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<span>Functions</span> </div> </a> <ul id="toc-Functions-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Overview" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Overview"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>Overview</span> </div> </a> <button aria-controls="toc-Overview-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Overview subsection</span> </button> <ul id="toc-Overview-sublist" class="vector-toc-list"> <li id="toc-Classical_pathway" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Classical_pathway"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1</span> <span>Classical pathway</span> </div> </a> <ul id="toc-Classical_pathway-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Alternative_pathway" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Alternative_pathway"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2</span> <span>Alternative pathway</span> </div> </a> <ul id="toc-Alternative_pathway-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Lectin_pathway" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Lectin_pathway"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.3</span> <span>Lectin pathway</span> </div> </a> <ul id="toc-Lectin_pathway-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Complement_protein_fragment_nomenclature" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Complement_protein_fragment_nomenclature"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.4</span> <span>Complement protein fragment nomenclature</span> </div> </a> <ul id="toc-Complement_protein_fragment_nomenclature-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Viral_inhibition" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Viral_inhibition"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.5</span> <span>Viral inhibition</span> </div> </a> <ul id="toc-Viral_inhibition-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Review" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Review"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.6</span> <span>Review</span> </div> </a> <ul id="toc-Review-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Activation_of_complements_by_antigen-associated_antibody" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Activation_of_complements_by_antigen-associated_antibody"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>Activation of complements by antigen-associated antibody</span> </div> </a> <ul id="toc-Activation_of_complements_by_antigen-associated_antibody-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Regulation" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Regulation"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>Regulation</span> </div> </a> <ul id="toc-Regulation-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Role_in_disease" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Role_in_disease"> <div class="vector-toc-text"> <span class="vector-toc-numb">6</span> <span>Role in disease</span> </div> </a> <button aria-controls="toc-Role_in_disease-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Role in disease subsection</span> </button> <ul id="toc-Role_in_disease-sublist" class="vector-toc-list"> <li id="toc-Complement_deficiency" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Complement_deficiency"> <div class="vector-toc-text"> <span class="vector-toc-numb">6.1</span> <span>Complement deficiency</span> </div> </a> <ul id="toc-Complement_deficiency-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Deficiencies_in_complement_regulators" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Deficiencies_in_complement_regulators"> <div class="vector-toc-text"> <span class="vector-toc-numb">6.2</span> <span>Deficiencies in complement regulators</span> </div> </a> <ul id="toc-Deficiencies_in_complement_regulators-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Diagnostic_tools" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Diagnostic_tools"> <div class="vector-toc-text"> <span class="vector-toc-numb">6.3</span> <span>Diagnostic tools</span> </div> </a> <ul id="toc-Diagnostic_tools-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Modulation_of_the_body_by_complement_with_infection" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Modulation_of_the_body_by_complement_with_infection"> <div class="vector-toc-text"> <span class="vector-toc-numb">7</span> <span>Modulation of the body by complement with infection</span> </div> </a> <ul id="toc-Modulation_of_the_body_by_complement_with_infection-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Role_in_the_brain" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Role_in_the_brain"> <div class="vector-toc-text"> <span class="vector-toc-numb">8</span> <span>Role in the brain</span> </div> </a> <ul id="toc-Role_in_the_brain-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">9</span> <span>References</span> </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-External_links" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#External_links"> <div class="vector-toc-text"> <span class="vector-toc-numb">10</span> <span>External links</span> </div> </a> <ul id="toc-External_links-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" class="vector-dropdown vector-page-titlebar-toc vector-button-flush-left" > <input type="checkbox" id="vector-page-titlebar-toc-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-page-titlebar-toc" class="vector-dropdown-checkbox " aria-label="Toggle the table of contents" > <label id="vector-page-titlebar-toc-label" for="vector-page-titlebar-toc-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--icon-only " aria-hidden="true" ><span class="vector-icon mw-ui-icon-listBullet mw-ui-icon-wikimedia-listBullet"></span> <span class="vector-dropdown-label-text">Toggle the table of contents</span> </label> <div class="vector-dropdown-content"> <div id="vector-page-titlebar-toc-unpinned-container" class="vector-unpinned-container"> </div> </div> </div> </nav> <h1 id="firstHeading" class="firstHeading mw-first-heading"><span class="mw-page-title-main">Complement system</span></h1> <div id="p-lang-btn" class="vector-dropdown mw-portlet mw-portlet-lang" > <input type="checkbox" id="p-lang-btn-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-p-lang-btn" class="vector-dropdown-checkbox mw-interlanguage-selector" aria-label="Go to an article in another language. Available in 48 languages" > <label id="p-lang-btn-label" for="p-lang-btn-checkbox" class="vector-dropdown-label cdx-button cdx-button--fake-button cdx-button--fake-button--enabled cdx-button--weight-quiet cdx-button--action-progressive mw-portlet-lang-heading-48" aria-hidden="true" ><span class="vector-icon mw-ui-icon-language-progressive mw-ui-icon-wikimedia-language-progressive"></span> <span class="vector-dropdown-label-text">48 languages</span> </label> <div class="vector-dropdown-content"> <div class="vector-menu-content"> <ul class="vector-menu-content-list"> <li class="interlanguage-link interwiki-ar mw-list-item"><a href="https://ar.wikipedia.org/wiki/%D9%86%D8%B8%D8%A7%D9%85_%D9%85%D9%86%D8%A7%D8%B9%D9%8A_%D9%85%D8%AA%D9%85%D9%85" title="نظام مناعي متمم – Arabic" lang="ar" hreflang="ar" data-title="نظام مناعي متمم" data-language-autonym="العربية" data-language-local-name="Arabic" class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-az mw-list-item"><a href="https://az.wikipedia.org/wiki/Komplement_sistemi" title="Komplement sistemi – Azerbaijani" lang="az" hreflang="az" data-title="Komplement sistemi" data-language-autonym="Azərbaycanca" data-language-local-name="Azerbaijani" class="interlanguage-link-target"><span>Azərbaycanca</span></a></li><li class="interlanguage-link interwiki-bg mw-list-item"><a href="https://bg.wikipedia.org/wiki/%D0%9A%D0%BE%D0%BC%D0%BF%D0%BB%D0%B5%D0%BC%D0%B5%D0%BD%D1%82" title="Комплемент – Bulgarian" lang="bg" hreflang="bg" data-title="Комплемент" data-language-autonym="Български" data-language-local-name="Bulgarian" class="interlanguage-link-target"><span>Български</span></a></li><li class="interlanguage-link interwiki-bs mw-list-item"><a href="https://bs.wikipedia.org/wiki/Komplementni_sistem" title="Komplementni sistem – Bosnian" lang="bs" hreflang="bs" data-title="Komplementni sistem" data-language-autonym="Bosanski" data-language-local-name="Bosnian" class="interlanguage-link-target"><span>Bosanski</span></a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Sistema_del_complement" title="Sistema del complement – Catalan" lang="ca" hreflang="ca" data-title="Sistema del complement" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target"><span>Català</span></a></li><li class="interlanguage-link interwiki-cs mw-list-item"><a href="https://cs.wikipedia.org/wiki/Komplement_(biologie)" title="Komplement (biologie) – Czech" lang="cs" hreflang="cs" data-title="Komplement (biologie)" data-language-autonym="Čeština" data-language-local-name="Czech" class="interlanguage-link-target"><span>Čeština</span></a></li><li class="interlanguage-link interwiki-da mw-list-item"><a href="https://da.wikipedia.org/wiki/Komplementsystemet" title="Komplementsystemet – Danish" lang="da" hreflang="da" data-title="Komplementsystemet" data-language-autonym="Dansk" data-language-local-name="Danish" class="interlanguage-link-target"><span>Dansk</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Komplementsystem" title="Komplementsystem – German" lang="de" hreflang="de" data-title="Komplementsystem" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-et mw-list-item"><a href="https://et.wikipedia.org/wiki/Komplemendis%C3%BCsteem" title="Komplemendisüsteem – Estonian" lang="et" hreflang="et" data-title="Komplemendisüsteem" data-language-autonym="Eesti" data-language-local-name="Estonian" class="interlanguage-link-target"><span>Eesti</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Sistema_del_complemento" title="Sistema del complemento – Spanish" lang="es" hreflang="es" data-title="Sistema del complemento" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-eu mw-list-item"><a href="https://eu.wikipedia.org/wiki/Osagarriaren_sistema" title="Osagarriaren sistema – Basque" lang="eu" hreflang="eu" data-title="Osagarriaren sistema" data-language-autonym="Euskara" data-language-local-name="Basque" class="interlanguage-link-target"><span>Euskara</span></a></li><li class="interlanguage-link interwiki-fa mw-list-item"><a href="https://fa.wikipedia.org/wiki/%D8%B3%D8%A7%D9%85%D8%A7%D9%86%D9%87_%DA%A9%D9%85%D9%BE%D9%84%D9%85%D8%A7%D9%86" title="سامانه کمپلمان – Persian" lang="fa" hreflang="fa" data-title="سامانه کمپلمان" data-language-autonym="فارسی" data-language-local-name="Persian" class="interlanguage-link-target"><span>فارسی</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/Syst%C3%A8me_du_compl%C3%A9ment" title="Système du complément – French" lang="fr" hreflang="fr" data-title="Système du complément" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/Complemento_(inmunidade)" title="Complemento (inmunidade) – Galician" lang="gl" hreflang="gl" data-title="Complemento (inmunidade)" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target"><span>Galego</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%EB%B3%B4%EC%B2%B4" title="보체 – Korean" lang="ko" hreflang="ko" data-title="보체" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target"><span>한국어</span></a></li><li class="interlanguage-link interwiki-hy mw-list-item"><a href="https://hy.wikipedia.org/wiki/%D4%B1%D6%80%D5%B5%D5%A1%D5%B6_%D5%AF%D5%B8%D5%B4%D5%BA%D5%AC%D5%A5%D5%B4%D5%A5%D5%B6%D5%BF%D5%AB_%D5%B0%D5%A1%D5%B4%D5%A1%D5%AF%D5%A1%D6%80%D5%A3" title="Արյան կոմպլեմենտի համակարգ – Armenian" lang="hy" hreflang="hy" data-title="Արյան կոմպլեմենտի համակարգ" data-language-autonym="Հայերեն" data-language-local-name="Armenian" class="interlanguage-link-target"><span>Հայերեն</span></a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Sistem_komplemen" title="Sistem komplemen – Indonesian" lang="id" hreflang="id" data-title="Sistem komplemen" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target"><span>Bahasa Indonesia</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Sistema_del_complemento" title="Sistema del complemento – Italian" lang="it" hreflang="it" data-title="Sistema del complemento" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-he mw-list-item"><a href="https://he.wikipedia.org/wiki/%D7%9E%D7%A2%D7%A8%D7%9B%D7%AA_%D7%94%D7%9E%D7%A9%D7%9C%D7%99%D7%9D" title="מערכת המשלים – Hebrew" lang="he" hreflang="he" data-title="מערכת המשלים" data-language-autonym="עברית" data-language-local-name="Hebrew" class="interlanguage-link-target"><span>עברית</span></a></li><li class="interlanguage-link interwiki-ka mw-list-item"><a href="https://ka.wikipedia.org/wiki/%E1%83%99%E1%83%9D%E1%83%9B%E1%83%9E%E1%83%9A%E1%83%94%E1%83%9B%E1%83%94%E1%83%9C%E1%83%A2%E1%83%98%E1%83%A1_%E1%83%A1%E1%83%98%E1%83%A1%E1%83%A2%E1%83%94%E1%83%9B%E1%83%90" title="კომპლემენტის სისტემა – Georgian" lang="ka" hreflang="ka" data-title="კომპლემენტის სისტემა" data-language-autonym="ქართული" data-language-local-name="Georgian" class="interlanguage-link-target"><span>ქართული</span></a></li><li class="interlanguage-link interwiki-kk mw-list-item"><a href="https://kk.wikipedia.org/wiki/%D0%9A%D0%BE%D0%BC%D0%BF%D0%BB%D0%B5%D0%BC%D0%B5%D0%BD%D1%82" title="Комплемент – Kazakh" lang="kk" hreflang="kk" data-title="Комплемент" data-language-autonym="Қазақша" data-language-local-name="Kazakh" class="interlanguage-link-target"><span>Қазақша</span></a></li><li class="interlanguage-link interwiki-ku mw-list-item"><a href="https://ku.wikipedia.org/wiki/S%C3%AEstema_temamker" title="Sîstema temamker – Kurdish" lang="ku" hreflang="ku" data-title="Sîstema temamker" data-language-autonym="Kurdî" data-language-local-name="Kurdish" class="interlanguage-link-target"><span>Kurdî</span></a></li><li class="interlanguage-link interwiki-lmo mw-list-item"><a href="https://lmo.wikipedia.org/wiki/Sistema_del_complement" title="Sistema del complement – Lombard" lang="lmo" hreflang="lmo" data-title="Sistema del complement" data-language-autonym="Lombard" data-language-local-name="Lombard" class="interlanguage-link-target"><span>Lombard</span></a></li><li class="interlanguage-link interwiki-hu mw-list-item"><a href="https://hu.wikipedia.org/wiki/Komplementrendszer" title="Komplementrendszer – Hungarian" lang="hu" hreflang="hu" data-title="Komplementrendszer" data-language-autonym="Magyar" data-language-local-name="Hungarian" class="interlanguage-link-target"><span>Magyar</span></a></li><li class="interlanguage-link interwiki-mk mw-list-item"><a href="https://mk.wikipedia.org/wiki/%D0%A1%D0%B8%D1%81%D1%82%D0%B5%D0%BC_%D0%BD%D0%B0_%D0%BA%D0%BE%D0%BC%D0%BF%D0%BB%D0%B5%D0%BC%D0%B5%D0%BD%D1%82" title="Систем на комплемент – Macedonian" lang="mk" hreflang="mk" data-title="Систем на комплемент" data-language-autonym="Македонски" data-language-local-name="Macedonian" class="interlanguage-link-target"><span>Македонски</span></a></li><li class="interlanguage-link interwiki-ms mw-list-item"><a href="https://ms.wikipedia.org/wiki/Sistem_komplemen" title="Sistem komplemen – Malay" lang="ms" hreflang="ms" data-title="Sistem komplemen" data-language-autonym="Bahasa Melayu" data-language-local-name="Malay" class="interlanguage-link-target"><span>Bahasa Melayu</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/Complementsysteem" title="Complementsysteem – Dutch" lang="nl" hreflang="nl" data-title="Complementsysteem" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target"><span>Nederlands</span></a></li><li class="interlanguage-link interwiki-ja mw-list-item"><a href="https://ja.wikipedia.org/wiki/%E8%A3%9C%E4%BD%93" title="補体 – Japanese" lang="ja" hreflang="ja" data-title="補体" data-language-autonym="日本語" data-language-local-name="Japanese" class="interlanguage-link-target"><span>日本語</span></a></li><li class="interlanguage-link interwiki-no mw-list-item"><a href="https://no.wikipedia.org/wiki/Komplementsystem" title="Komplementsystem – Norwegian Bokmål" lang="nb" hreflang="nb" data-title="Komplementsystem" data-language-autonym="Norsk bokmål" data-language-local-name="Norwegian Bokmål" class="interlanguage-link-target"><span>Norsk bokmål</span></a></li><li class="interlanguage-link interwiki-pl mw-list-item"><a href="https://pl.wikipedia.org/wiki/Dope%C5%82niacz_(biologia)" title="Dopełniacz (biologia) – Polish" lang="pl" hreflang="pl" data-title="Dopełniacz (biologia)" data-language-autonym="Polski" data-language-local-name="Polish" class="interlanguage-link-target"><span>Polski</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Sistema_do_complemento" title="Sistema do complemento – Portuguese" lang="pt" hreflang="pt" data-title="Sistema do complemento" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-kaa mw-list-item"><a href="https://kaa.wikipedia.org/wiki/Komplement" title="Komplement – Kara-Kalpak" lang="kaa" hreflang="kaa" data-title="Komplement" data-language-autonym="Qaraqalpaqsha" data-language-local-name="Kara-Kalpak" class="interlanguage-link-target"><span>Qaraqalpaqsha</span></a></li><li class="interlanguage-link interwiki-ro mw-list-item"><a href="https://ro.wikipedia.org/wiki/Sistemul_complement" title="Sistemul complement – Romanian" lang="ro" hreflang="ro" data-title="Sistemul complement" data-language-autonym="Română" data-language-local-name="Romanian" class="interlanguage-link-target"><span>Română</span></a></li><li class="interlanguage-link interwiki-ru badge-Q17437796 badge-featuredarticle mw-list-item" title="featured article badge"><a href="https://ru.wikipedia.org/wiki/%D0%A1%D0%B8%D1%81%D1%82%D0%B5%D0%BC%D0%B0_%D0%BA%D0%BE%D0%BC%D0%BF%D0%BB%D0%B5%D0%BC%D0%B5%D0%BD%D1%82%D0%B0" title="Система комплемента – Russian" lang="ru" hreflang="ru" data-title="Система комплемента" data-language-autonym="Русский" data-language-local-name="Russian" class="interlanguage-link-target"><span>Русский</span></a></li><li class="interlanguage-link interwiki-simple mw-list-item"><a href="https://simple.wikipedia.org/wiki/Complement_system" title="Complement system – Simple English" lang="en-simple" hreflang="en-simple" data-title="Complement system" data-language-autonym="Simple English" data-language-local-name="Simple English" class="interlanguage-link-target"><span>Simple English</span></a></li><li class="interlanguage-link interwiki-sk mw-list-item"><a href="https://sk.wikipedia.org/wiki/Komplement_(imunita)" title="Komplement (imunita) – Slovak" lang="sk" hreflang="sk" data-title="Komplement (imunita)" data-language-autonym="Slovenčina" data-language-local-name="Slovak" class="interlanguage-link-target"><span>Slovenčina</span></a></li><li class="interlanguage-link interwiki-sl mw-list-item"><a href="https://sl.wikipedia.org/wiki/Sistem_komplementa" title="Sistem komplementa – Slovenian" lang="sl" hreflang="sl" data-title="Sistem komplementa" data-language-autonym="Slovenščina" data-language-local-name="Slovenian" class="interlanguage-link-target"><span>Slovenščina</span></a></li><li class="interlanguage-link interwiki-ckb mw-list-item"><a href="https://ckb.wikipedia.org/wiki/%D8%B3%DB%8C%D8%B3%D8%AA%D9%85%DB%8C_%D8%AA%DB%95%D9%88%D8%A7%D9%88%DA%A9%DB%95%D8%B1" title="سیستمی تەواوکەر – Central Kurdish" lang="ckb" hreflang="ckb" data-title="سیستمی تەواوکەر" data-language-autonym="کوردی" data-language-local-name="Central Kurdish" class="interlanguage-link-target"><span>کوردی</span></a></li><li class="interlanguage-link interwiki-sr mw-list-item"><a href="https://sr.wikipedia.org/wiki/Sistem_komplementa" title="Sistem komplementa – Serbian" lang="sr" hreflang="sr" data-title="Sistem komplementa" data-language-autonym="Српски / srpski" data-language-local-name="Serbian" class="interlanguage-link-target"><span>Српски / srpski</span></a></li><li class="interlanguage-link interwiki-sh mw-list-item"><a href="https://sh.wikipedia.org/wiki/Sistem_komplementa" title="Sistem komplementa – Serbo-Croatian" lang="sh" hreflang="sh" data-title="Sistem komplementa" data-language-autonym="Srpskohrvatski / српскохрватски" data-language-local-name="Serbo-Croatian" class="interlanguage-link-target"><span>Srpskohrvatski / српскохрватски</span></a></li><li class="interlanguage-link interwiki-fi mw-list-item"><a href="https://fi.wikipedia.org/wiki/Komplementti_(biologia)" title="Komplementti (biologia) – Finnish" lang="fi" hreflang="fi" data-title="Komplementti (biologia)" data-language-autonym="Suomi" data-language-local-name="Finnish" class="interlanguage-link-target"><span>Suomi</span></a></li><li class="interlanguage-link interwiki-sv mw-list-item"><a href="https://sv.wikipedia.org/wiki/Komplement_(biologi)" title="Komplement (biologi) – Swedish" lang="sv" hreflang="sv" data-title="Komplement (biologi)" data-language-autonym="Svenska" data-language-local-name="Swedish" class="interlanguage-link-target"><span>Svenska</span></a></li><li class="interlanguage-link interwiki-ta mw-list-item"><a href="https://ta.wikipedia.org/wiki/%E0%AE%A8%E0%AE%BF%E0%AE%B0%E0%AE%AA%E0%AF%8D%E0%AE%AA%E0%AF%81%E0%AE%AA%E0%AF%8D%E0%AE%AA%E0%AF%81%E0%AE%B0%E0%AE%A4%E0%AE%99%E0%AF%8D%E0%AE%95%E0%AE%B3%E0%AF%8D" title="நிரப்புப்புரதங்கள் – Tamil" lang="ta" hreflang="ta" data-title="நிரப்புப்புரதங்கள்" data-language-autonym="தமிழ்" data-language-local-name="Tamil" class="interlanguage-link-target"><span>தமிழ்</span></a></li><li class="interlanguage-link interwiki-tr mw-list-item"><a href="https://tr.wikipedia.org/wiki/Kompleman_sistemi" title="Kompleman sistemi – Turkish" lang="tr" hreflang="tr" data-title="Kompleman sistemi" data-language-autonym="Türkçe" data-language-local-name="Turkish" class="interlanguage-link-target"><span>Türkçe</span></a></li><li class="interlanguage-link interwiki-uk mw-list-item"><a href="https://uk.wikipedia.org/wiki/%D0%A1%D0%B8%D1%81%D1%82%D0%B5%D0%BC%D0%B0_%D0%BA%D0%BE%D0%BC%D0%BF%D0%BB%D0%B5%D0%BC%D0%B5%D0%BD%D1%82%D1%83" title="Система комплементу – Ukrainian" lang="uk" hreflang="uk" data-title="Система комплементу" data-language-autonym="Українська" data-language-local-name="Ukrainian" class="interlanguage-link-target"><span>Українська</span></a></li><li class="interlanguage-link interwiki-vi mw-list-item"><a href="https://vi.wikipedia.org/wiki/B%E1%BB%95_th%E1%BB%83" title="Bổ thể – Vietnamese" lang="vi" hreflang="vi" data-title="Bổ thể" data-language-autonym="Tiếng Việt" data-language-local-name="Vietnamese" class="interlanguage-link-target"><span>Tiếng Việt</span></a></li><li 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searchaux" style="display:none">Part of the immune system that enhances the ability of antibodies and phagocytic cells</div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">This article is about an aspect of the immune system. For other uses, see <a href="/wiki/Complement_(disambiguation)" class="mw-redirect mw-disambig" title="Complement (disambiguation)">Complement</a>.</div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/w/index.php?title=File:Complement_pathway.svg&lang=en" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/9/98/Complement_pathway.svg/310px-Complement_pathway.svg.png" decoding="async" width="310" height="373" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/98/Complement_pathway.svg/465px-Complement_pathway.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/98/Complement_pathway.svg/620px-Complement_pathway.svg.png 2x" data-file-width="1680" data-file-height="2024" /></a><figcaption>Scheme of the complement system</figcaption></figure> <p>The <b>complement system</b>, also known as <b>complement cascade</b>, is a part of the <a href="/wiki/Humoral" class="mw-redirect" title="Humoral">humoral</a>, <a href="/wiki/Innate_immune_system" title="Innate immune system">innate immune system</a> and enhances (complements) the ability of <a href="/wiki/Antibodies" class="mw-redirect" title="Antibodies">antibodies</a> and <a href="/wiki/Phagocytic_cell" class="mw-redirect" title="Phagocytic cell">phagocytic cells</a> to clear <a href="/wiki/Microbes" class="mw-redirect" title="Microbes">microbes</a> and damaged cells from an organism, promote <a href="/wiki/Inflammation" title="Inflammation">inflammation</a>, and attack the <a href="/wiki/Pathogen" title="Pathogen">pathogen</a>'s <a href="/wiki/Cell_membrane" title="Cell membrane">cell membrane</a>.<sup id="cite_ref-:1_1-0" class="reference"><a href="#cite_note-:1-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Despite being part of the innate immune system, the complement system can be recruited and brought into action by antibodies generated by the <a href="/wiki/Adaptive_immune_system" title="Adaptive immune system">adaptive immune system</a>. </p><p>The complement system consists of a number of small, inactive, liver synthesized <a href="/wiki/Protein_precursor" title="Protein precursor">protein precursors</a> circulating in the <a href="/wiki/Blood" title="Blood">blood</a>. When stimulated by one of several triggers, <a href="/wiki/Protease" title="Protease">proteases</a> in the system <a href="/wiki/Protease" title="Protease">cleave specific proteins</a> to release <a href="/wiki/Cytokine" title="Cytokine">cytokines</a> and initiate an amplifying cascade of further cleavages. The end result of this <i>complement activation</i> or <i>complement fixation</i> cascade is stimulation of <a href="/wiki/Phagocyte" title="Phagocyte">phagocytes</a> to clear foreign and damaged material, <a href="/wiki/Inflammation" title="Inflammation">inflammation</a> to attract additional phagocytes, and <a href="/wiki/Immunologic_activation" title="Immunologic activation">activation</a> of the cell-killing <a href="/wiki/Membrane_attack_complex" class="mw-redirect" title="Membrane attack complex">membrane attack complex</a>. About 50 proteins and protein fragments make up the complement system, including <a href="/wiki/Plasma_protein" title="Plasma protein">plasma proteins</a>, and <a href="/wiki/Cell_membrane_receptor" class="mw-redirect" title="Cell membrane receptor">cell membrane receptors</a>. They account for about 10% of the <a href="/wiki/Globulin" title="Globulin">globulin</a> fraction of blood serum.<sup id="cite_ref-2" class="reference"><a href="#cite_note-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> </p><p>Three biochemical pathways activate the complement system: the <a href="/wiki/Classical_complement_pathway" title="Classical complement pathway">classical complement pathway</a>, the <a href="/wiki/Alternative_complement_pathway" title="Alternative complement pathway">alternative complement pathway</a>, and the <a href="/wiki/Lectin_pathway" title="Lectin pathway">lectin pathway</a>.<sup id="cite_ref-Abbas_2010_3-0" class="reference"><a href="#cite_note-Abbas_2010-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> The alternative pathway accounts for the majority of terminal pathway activation and so therapeutic efforts in disease have revolved around its inhibition.<sup id="cite_ref-:0_4-0" class="reference"><a href="#cite_note-:0-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="History">History</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=1" title="Edit section: History"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In 1888, <a href="/wiki/George_Nuttall" title="George Nuttall">George Nuttall</a> found that sheep blood <a href="/wiki/Serum_(blood)" title="Serum (blood)">serum</a> had mild killing activity against the <a href="/wiki/Bacterium" class="mw-redirect" title="Bacterium">bacterium</a> that causes <a href="/wiki/Anthrax" title="Anthrax">anthrax</a>.<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> The killing activity disappeared when he heated the blood.<sup id="cite_ref-Chaplin2005_6-0" class="reference"><a href="#cite_note-Chaplin2005-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> In 1891, <a href="/wiki/Hans_Ernst_August_Buchner" title="Hans Ernst August Buchner">Hans Ernst August Buchner</a>, noting the same property of blood in his experiments, named the killing property "alexin", which means "to ward off" in Greek.<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Nesargikar2012_8-0" class="reference"><a href="#cite_note-Nesargikar2012-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> By 1894, several laboratories had demonstrated that serum from guinea pigs that had recovered from <a href="/wiki/Cholera" title="Cholera">cholera</a> killed the cholera bacterium <i>in vitro</i>. Heating the serum destroyed its killing activity. Nevertheless, the heat-inactivated serum, when injected into guinea pigs exposed to the cholera bacteria, maintained its ability to protect the animals from illness. <a href="/wiki/Jules_Bordet" title="Jules Bordet">Jules Bordet</a>, a young <a href="/wiki/Belgians" title="Belgians">Belgian</a> scientist in <a href="/wiki/Paris" title="Paris">Paris</a> at the <a href="/wiki/Pasteur_Institute" title="Pasteur Institute">Pasteur Institute</a>, concluded that this principle has two components, one that maintained a "sensitizing" effect after being heated and one (alexin) whose toxic effect was lost after being heated.<sup id="cite_ref-9" class="reference"><a href="#cite_note-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> The heat-stable component was responsible for immunity against specific microorganisms, whereas the heat-sensitive component was responsible for the non-specific antimicrobial activity conferred by all normal sera. In 1899, <a href="/wiki/Paul_Ehrlich" title="Paul Ehrlich">Paul Ehrlich</a> renamed the heat-sensitive component "complement".<sup id="cite_ref-10" class="reference"><a href="#cite_note-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Chaplin2005_6-1" class="reference"><a href="#cite_note-Chaplin2005-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>Ehrlich introduced the term "complement" as part of his larger theory of the immune system.<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> According to this theory, the immune system consists of cells that have specific receptors on their surface to recognize <a href="/wiki/Antigens" class="mw-redirect" title="Antigens">antigens</a>. Upon immunization with an <a href="/wiki/Antigen" title="Antigen">antigen</a>, more of these receptors are formed, and they are then shed from the cells to circulate in the blood. Those <a href="/wiki/Immune_receptor" title="Immune receptor">receptors</a>, which we now call "<a href="/wiki/Antibody" title="Antibody">antibodies</a>", were called by Ehrlich "amboceptors" to emphasise their bifunctional binding capacity: They recognise and bind to a specific antigen, but they also recognise and bind to the heat-labile antimicrobial component of fresh serum. Ehrlich, therefore, named this heat-labile component "complement", because it is something in the blood that "complements" the cells of the immune system. Ehrlich believed that each antigen-specific amboceptor has its own specific complement, whereas Bordet believed that there is only one type of complement. In the early 20th century, this controversy was resolved when it became understood that complement can act in combination with specific antibodies, or on its own in a non-specific way.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (May 2015)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading2"><h2 id="Functions">Functions</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=2" title="Edit section: Functions"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Membrane_Attack_Complex_(Terminal_Complement_Complex_C5b-9).png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/6/60/Membrane_Attack_Complex_%28Terminal_Complement_Complex_C5b-9%29.png/220px-Membrane_Attack_Complex_%28Terminal_Complement_Complex_C5b-9%29.png" decoding="async" width="220" height="252" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/6/60/Membrane_Attack_Complex_%28Terminal_Complement_Complex_C5b-9%29.png/330px-Membrane_Attack_Complex_%28Terminal_Complement_Complex_C5b-9%29.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/6/60/Membrane_Attack_Complex_%28Terminal_Complement_Complex_C5b-9%29.png/440px-Membrane_Attack_Complex_%28Terminal_Complement_Complex_C5b-9%29.png 2x" data-file-width="1596" data-file-height="1830" /></a><figcaption>Membrane attack complex (Terminal Complement Complex C5b-9)</figcaption></figure> <p>Complement triggers the following immune functions:<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p> <ol><li><b><a href="/wiki/Complement_membrane_attack_complex" title="Complement membrane attack complex">Membrane attack</a></b> – by rupturing the <a href="/wiki/Cell_wall" title="Cell wall">cell wall</a> of <a href="/wiki/Bacteria" title="Bacteria">bacteria</a>. (<a href="/wiki/Classical_Complement_Pathway" class="mw-redirect" title="Classical Complement Pathway">classical complement pathway</a>)</li> <li><b><a href="/wiki/Phagocytosis" title="Phagocytosis">Phagocytosis</a></b> – by <a href="/wiki/Opsonin" title="Opsonin">opsonizing</a> antigens. C3b has most important opsonizing activity. (<a href="/wiki/Alternative_complement_pathway" title="Alternative complement pathway">alternative complement pathway</a>)</li> <li><b><a href="/wiki/Inflammation" title="Inflammation">Inflammation</a></b> – by attracting <a href="/wiki/Macrophage" title="Macrophage">macrophages</a> and <a href="/wiki/Neutrophil" title="Neutrophil">neutrophils</a>. (<a href="/wiki/Lectin_pathway" title="Lectin pathway">lectin pathway</a>)</li></ol> <div class="mw-heading mw-heading2"><h2 id="Overview">Overview</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=3" title="Edit section: Overview"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Most of the <a href="/wiki/Protein" title="Protein">proteins</a> and <a href="/wiki/Glycoprotein" title="Glycoprotein">glycoproteins</a> that constitute the complement system are synthesized by <a href="/wiki/Hepatocytes" class="mw-redirect" title="Hepatocytes">hepatocytes</a>. But significant amounts are also produced by tissue <a href="/wiki/Macrophage" title="Macrophage">macrophages</a>, blood <a href="/wiki/Monocyte" title="Monocyte">monocytes</a>, and <a href="/wiki/Epithelial_cells" class="mw-redirect" title="Epithelial cells">epithelial cells</a> of the <a href="/wiki/Genitourinary_system" title="Genitourinary system">genitourinary system</a> and <a href="/wiki/Gastrointestinal_tract" title="Gastrointestinal tract">gastrointestinal tract</a>. The three pathways of activation all generate homologous variants of the <a href="/wiki/Protease" title="Protease">protease</a> <a href="/wiki/C3-convertase" title="C3-convertase">C3-convertase</a>. The classical complement pathway typically requires <a href="/wiki/Antigen-antibody_complex" class="mw-redirect" title="Antigen-antibody complex">antigen-antibody complexes</a> for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous <a href="/wiki/Complement_component_3" title="Complement component 3">complement component 3</a> (C3) hydrolysis, foreign material, pathogens, or damaged cells. The <a href="/wiki/Mannose" title="Mannose">mannose</a>-binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). In all three pathways, C3-convertase cleaves and activates component C3, creating C3a and C3b, and causes a cascade of further cleavage and activation events. C3b binds to the surface of pathogens, leading to greater internalization by <a href="/wiki/Phagocyte" title="Phagocyte">phagocytic cells</a> by <a href="/wiki/Opsonization" class="mw-redirect" title="Opsonization">opsonization</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (July 2022)">citation needed</span></a></i>]</sup> </p><p>In the alternative pathway, C3b binds to Factor B. Factor D releases Factor Ba from Factor B bound to C3b. The complex of C3b(2)Bb is a protease which cleaves C5 into C5b and C5a. <a href="/wiki/C5-convertase" title="C5-convertase">C5 convertase</a> is also formed by the classical pathway when C3b binds C4b and C2b. <a href="/wiki/Complement_component_5a" title="Complement component 5a">C5a</a> is an important <a href="/wiki/Chemokine" title="Chemokine">chemotactic protein</a>, helping recruit inflammatory cells. C3a is the precursor of an important <a href="/wiki/Cytokine" title="Cytokine">cytokine</a> (<a href="/wiki/Adipokine" title="Adipokine">adipokine</a>) named <a href="/wiki/Acylation_stimulating_protein" title="Acylation stimulating protein">ASP</a> (although this is not universally accepted <sup id="cite_ref-pmid=_23383423_13-0" class="reference"><a href="#cite_note-pmid=_23383423-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup>) and is usually rapidly cleaved by <a href="/wiki/Carboxypeptidase_B" title="Carboxypeptidase B">carboxypeptidase B</a>. Both C3a and C5a have <a href="/wiki/Anaphylatoxin" title="Anaphylatoxin">anaphylatoxin</a> activity, directly triggering <a href="/wiki/Degranulation" title="Degranulation">degranulation</a> of <a href="/wiki/Mast_cell" title="Mast cell">mast cells</a> as well as increasing vascular permeability and <a href="/wiki/Smooth_muscle" title="Smooth muscle">smooth muscle</a> contraction.<sup id="cite_ref-pmid=_23383423_13-1" class="reference"><a href="#cite_note-pmid=_23383423-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> C5b initiates the <a href="/wiki/Complement_membrane_attack_complex" title="Complement membrane attack complex">membrane attack pathway</a>, which results in the <a href="/wiki/Complement_membrane_attack_complex" title="Complement membrane attack complex">membrane attack complex</a> (MAC), consisting of C5b, <a href="/wiki/Complement_component_6" title="Complement component 6">C6</a>, <a href="/wiki/Complement_component_7" title="Complement component 7">C7</a>, <a href="/wiki/C8_complex" title="C8 complex">C8</a>, and polymeric <a href="/wiki/Complement_component_9" title="Complement component 9">C9</a>.<sup id="cite_ref-Baron_14-0" class="reference"><a href="#cite_note-Baron-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> MAC is the cytolytic endproduct of the complement cascade; it forms a transmembrane channel, which causes <a href="/wiki/Osmosis" title="Osmosis">osmotic</a> lysis of the target cell. <a href="/wiki/Kupffer_cells" class="mw-redirect" title="Kupffer cells">Kupffer cells</a> and other macrophage cell types help clear complement-coated pathogens. As part of the innate immune system, elements of the complement cascade can be found in species earlier than vertebrates; most recently in the <a href="/wiki/Protostome" title="Protostome">protostome</a> <a href="/wiki/Horseshoe_crab" title="Horseshoe crab">horseshoe crab</a> species, putting the origins of the system back further than was previously thought.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (July 2022)">citation needed</span></a></i>]</sup> </p> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:09_Hegasy_Complement_System_Wiki_EN_CCBYSA.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/c/ca/09_Hegasy_Complement_System_Wiki_EN_CCBYSA.png/220px-09_Hegasy_Complement_System_Wiki_EN_CCBYSA.png" decoding="async" width="220" height="156" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/c/ca/09_Hegasy_Complement_System_Wiki_EN_CCBYSA.png/330px-09_Hegasy_Complement_System_Wiki_EN_CCBYSA.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/c/ca/09_Hegasy_Complement_System_Wiki_EN_CCBYSA.png/440px-09_Hegasy_Complement_System_Wiki_EN_CCBYSA.png 2x" data-file-width="3508" data-file-height="2480" /></a><figcaption>Reaction cascade of the complement system: classical, alternative, and lectin pathways, amplification loop, terminal pathway, and membrane attack complex.</figcaption></figure> <div class="mw-heading mw-heading3"><h3 id="Classical_pathway">Classical pathway</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=4" title="Edit section: Classical pathway"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Classical_complement_pathway" title="Classical complement pathway">Classical complement pathway</a></div> <figure typeof="mw:File/Thumb"><a href="/wiki/File:Complement-pathways.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/b/b0/Complement-pathways.png/350px-Complement-pathways.png" decoding="async" width="350" height="484" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/b0/Complement-pathways.png/525px-Complement-pathways.png 1.5x, //upload.wikimedia.org/wikipedia/commons/b/b0/Complement-pathways.png 2x" data-file-width="604" data-file-height="836" /></a><figcaption>The classical and alternative complement pathways</figcaption></figure> <p>The <a href="/wiki/Classical_complement_pathway" title="Classical complement pathway">classical pathway</a> is triggered by activation of the C1-complex. The <b>C1-complex</b> is composed of 1 molecule of <a href="/wiki/Complement_component_1q" title="Complement component 1q">C1q</a>, 2 molecules of C1r and 2 molecules of C1s, or <i>C1qr<sup>2</sup>s<sup>2</sup></i>. This occurs when C1q binds to <a href="/wiki/IgM" class="mw-redirect" title="IgM">IgM</a> or <a href="/wiki/Immunoglobulin_G" title="Immunoglobulin G">IgG</a> complexed with <a href="/wiki/Antigen" title="Antigen">antigens</a>. A single pentameric IgM can initiate the pathway, while several, ideally six, IgGs are needed. This also occurs when <a href="/wiki/Complement_component_1q" title="Complement component 1q">C1q</a> binds directly to the surface of the pathogen. Such binding leads to conformational changes in the C1q molecule, which leads to the activation of two <a href="/wiki/Complement_component_1r" title="Complement component 1r">C1r</a> molecules. C1r is a serine protease. They then cleave <a href="/wiki/Complement_component_1s" title="Complement component 1s">C1s</a> (another serine protease). The C1r<sup>2</sup>s<sup>2</sup> component now splits <a href="/wiki/Complement_component_4" title="Complement component 4">C4</a> and then <a href="/wiki/Complement_component_2" title="Complement component 2">C2</a>, producing C4a, C4b, C2a, and C2b (historically, the larger fragment of C2 was called C2a but is now referred to as C2b). C4b and C2b bind to form the classical pathway C3-convertase (C4b2b complex), which promotes cleavage of C3 into C3a and C3b. C3b later joins with C4b2b to make C5 convertase (C4b2b3b complex).<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Alternative_pathway">Alternative pathway</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=5" title="Edit section: Alternative pathway"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Alternative_complement_pathway" title="Alternative complement pathway">Alternative complement pathway</a></div> <p>The <a href="/wiki/Alternate_complement_pathway" class="mw-redirect" title="Alternate complement pathway">alternative pathway</a> is continuously activated at a low level, analogous to a car engine at idle, as a result of spontaneous <a href="/wiki/Complement_component_3" title="Complement component 3">C3</a> hydrolysis due to the breakdown of the internal <a href="/wiki/Thioester" title="Thioester">thioester</a> bond (C3 is mildly unstable in aqueous environment). The alternative pathway does not rely on pathogen-binding antibodies like the other pathways.<sup id="cite_ref-Abbas_2010_3-1" class="reference"><a href="#cite_note-Abbas_2010-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> C3b that is generated from C3 by a C3 convertase enzyme complex in the fluid phase is rapidly inactivated by <a href="/wiki/Factor_H" title="Factor H">factor H</a> and <a href="/wiki/Complement_factor_I" title="Complement factor I">factor I</a>, as is the C3b-like C3 that is the product of spontaneous cleavage of the internal thioester. In contrast, when the internal thioester of C3 reacts with a hydroxyl or amino group of a molecule on the surface of a cell or pathogen, the C3b that is now covalently bound to the surface is protected from factor H-mediated inactivation. The surface-bound C3b may now bind <a href="/wiki/Complement_factor_B" title="Complement factor B">factor B</a> to form C3bB. This complex in the presence of <a href="/wiki/Factor_D" title="Factor D">factor D</a> will be cleaved into Ba and Bb. Bb will remain associated with C3b to form C3bBb, which is the alternative pathway C3 convertase.<sup id="cite_ref-16" class="reference"><a href="#cite_note-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p><p>The C3bBb complex is stabilized by binding oligomers of <a href="/wiki/Properdin" title="Properdin">factor P</a> (properdin). The stabilized C3 convertase, C3bBbP, then acts enzymatically to cleave much more C3, some of which becomes covalently attached to the same surface as C3b. This newly bound C3b recruits more B, D and P activity and greatly amplifies the complement activation. When complement is activated on a cell surface, the activation is limited by endogenous complement regulatory proteins, which include <a href="/wiki/CD35" class="mw-redirect" title="CD35">CD35</a>, <a href="/wiki/CD46" title="CD46">CD46</a>, <a href="/wiki/CD55" class="mw-redirect" title="CD55">CD55</a> and <a href="/wiki/CD59" title="CD59">CD59</a>, depending on the cell. Pathogens, in general, don't have complement regulatory proteins (there are many exceptions, which reflect adaptation of microbial pathogens to vertebrate immune defenses). Thus, the alternative complement pathway is able to distinguish self from non-self on the basis of the surface expression of complement regulatory proteins. Host cells don't accumulate cell surface C3b (and the proteolytic fragment of C3b called iC3b) because this is prevented by the complement regulatory proteins, while foreign cells, pathogens and abnormal surfaces may be heavily decorated with C3b and iC3b. Accordingly, the alternative complement pathway is one element of <a href="/wiki/Innate_immunity" class="mw-redirect" title="Innate immunity">innate immunity</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (May 2015)">citation needed</span></a></i>]</sup> </p><p>Once the alternative C3 convertase enzyme is formed on a pathogen or cell surface, it may bind covalently another C3b, to form C3bBbC3bP, the C5 convertase. This enzyme then cleaves C5 to C5a, a potent <a href="/wiki/Anaphylatoxin" title="Anaphylatoxin">anaphylatoxin</a>, and C5b. The C5b then recruits and assembles C6, C7, C8 and multiple C9 molecules to assemble the <a href="/wiki/Membrane_attack_complex" class="mw-redirect" title="Membrane attack complex">membrane attack complex</a>. This creates a hole or pore in the membrane that can kill or damage the pathogen or cell.<sup id="cite_ref-:1_1-1" class="reference"><a href="#cite_note-:1-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Lectin_pathway">Lectin pathway</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=6" title="Edit section: Lectin pathway"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Lectin_pathway" title="Lectin pathway">Lectin pathway</a></div> <p>The <a href="/wiki/Lectin" title="Lectin">lectin</a> pathway is homologous to the classical pathway, but with the opsonin, <a href="/wiki/Mannose-binding_lectin" class="mw-redirect" title="Mannose-binding lectin">mannose-binding lectin</a> (MBL), and <a href="/wiki/Ficolin" title="Ficolin">ficolins</a>, instead of C1q. This pathway is activated by binding of MBL to mannose residues on the pathogen surface, which activates the MBL-associated serine proteases, <a href="/wiki/MASP1_(protein)" title="MASP1 (protein)">MASP-1</a>, and MASP-2 (very similar to C1r and C1s, respectively), which can then split C4 into C4a and C4b and C2 into C2a and C2b. C4b and C2b then bind together to form the classical C3-convertase, as in the classical pathway. Ficolins are homologous to MBL and function via MASP in a similar way. Several <a href="/wiki/Single-nucleotide_polymorphism" title="Single-nucleotide polymorphism">single-nucleotide polymorphisms</a> have been described in M-ficolin in humans, with effect on ligand-binding ability and serum levels. Historically, the larger fragment of C2 was named C2a, but it is now referred to as C2b.<sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup> In invertebrates without an adaptive immune system, ficolins are expanded and their binding specificities diversified to compensate for the lack of pathogen-specific recognition molecules.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (July 2022)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading3"><h3 id="Complement_protein_fragment_nomenclature">Complement protein fragment nomenclature</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=7" title="Edit section: Complement protein fragment nomenclature"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Immunology textbooks have used different naming assignments for the smaller and larger fragments of C2 as C2a and C2b. The preferred assignment appears to be that the smaller fragment be designated as C2a: as early as 1994, a well known textbook recommended that the larger fragment of C2 should be designated C2b.<sup id="cite_ref-Janeway1994_18-0" class="reference"><a href="#cite_note-Janeway1994-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> However, this was amplified in their 1999 4th edition, to say that:<sup id="cite_ref-janeway1999_19-0" class="reference"><a href="#cite_note-janeway1999-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> "It is also useful to be aware that the larger active fragment of C2 was originally designated C2a, and is still called that in some texts and research papers. Here, for consistency, we shall call all large fragments of complement <b>b</b>, so the larger fragment of C2 will be designated C2b. In the classical and lectin pathways the C3 convertase enzyme is formed from membrane-bound C4b with C2b."<sup id="cite_ref-janeway1999_19-1" class="reference"><a href="#cite_note-janeway1999-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup> </p><p>This nomenclature is used in another literature:<sup id="cite_ref-abbas_20-0" class="reference"><a href="#cite_note-abbas-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> The assignment is mixed in the latter literature, though. Some sources designate the larger and smaller fragments as C2a and C2b respectively<sup id="cite_ref-Peakman_21-0" class="reference"><a href="#cite_note-Peakman-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-22" class="reference"><a href="#cite_note-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Sims_23-0" class="reference"><a href="#cite_note-Sims-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-24" class="reference"><a href="#cite_note-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Roitt_25-0" class="reference"><a href="#cite_note-Roitt-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-anderson2003_26-0" class="reference"><a href="#cite_note-anderson2003-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Parham_27-0" class="reference"><a href="#cite_note-Parham-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-murphy2008_28-0" class="reference"><a href="#cite_note-murphy2008-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Atkinson_29-0" class="reference"><a href="#cite_note-Atkinson-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> while other sources apply the converse.<sup id="cite_ref-Janeway1994_18-1" class="reference"><a href="#cite_note-Janeway1994-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-janeway1999_19-2" class="reference"><a href="#cite_note-janeway1999-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Janeway_2001_30-0" class="reference"><a href="#cite_note-Janeway_2001-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-doan2007_31-0" class="reference"><a href="#cite_note-doan2007-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-DeFranco_32-0" class="reference"><a href="#cite_note-DeFranco-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> However, due to the widely established convention, C2b here is the larger fragment, which, in the classical pathway, forms C4b2b (classically C4b2a). It may be noteworthy that, in a series of editions of Janeway's book, 1st to 7th, in the latest edition<sup id="cite_ref-murphy2008_28-1" class="reference"><a href="#cite_note-murphy2008-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> they withdraw the stance to indicate the larger fragment of C2 as C2b. </p> <div class="mw-heading mw-heading3"><h3 id="Viral_inhibition">Viral inhibition</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=8" title="Edit section: Viral inhibition"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Fixation of the <a href="/wiki/Mannan-binding_lectin" title="Mannan-binding lectin">MBL</a> protein on viral surfaces has also been shown to enhance neutralization of viral pathogens.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Review">Review</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=9" title="Edit section: Review"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <table class="wikitable"> <tbody><tr> <th>Activation pathway</th> <th>Classic</th> <th>Alternative</th> <th>Lectin </th></tr> <tr> <td>Activator</td> <td>Ag–Ab Complex</td> <td>spontaneous hydrolysis of C3</td> <td>MBL-Mannose Complex </td></tr> <tr> <td>C3-convertase</td> <td>C4b2b</td> <td>C3bBb</td> <td>C4b2b </td></tr> <tr> <td>C5-convertase</td> <td>C4b2b3b</td> <td>C3bBbC3b</td> <td>C4b2b3b </td></tr> <tr> <td>MAC development</td> <td colspan="3">C5b+C6+C7+C8+C9 </td></tr></tbody></table> <div class="mw-heading mw-heading2"><h2 id="Activation_of_complements_by_antigen-associated_antibody">Activation of complements by antigen-associated antibody</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=10" title="Edit section: Activation of complements by antigen-associated antibody"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In the classical pathway, C1 binds with its C1q subunits to Fc fragments (made of CH2 region) of IgG or IgM, which has formed a complex with antigens. C4b and C3b are also able to bind to antigen-associated IgG or IgM, to its Fc portion.<sup id="cite_ref-abbas_20-1" class="reference"><a href="#cite_note-abbas-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Roitt_25-1" class="reference"><a href="#cite_note-Roitt-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-murphy2008_28-2" class="reference"><a href="#cite_note-murphy2008-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> </p><p>Such immunoglobulin-mediated binding of the complement may be interpreted as that the complement uses the ability of the immunoglobulin to detect and bind to non-self antigens as its guiding stick. The complement itself can bind non-self pathogens after detecting their <a href="/wiki/Pathogen-associated_molecular_patterns" class="mw-redirect" title="Pathogen-associated molecular patterns">pathogen-associated molecular patterns</a> (PAMPs),<sup id="cite_ref-murphy2008_28-3" class="reference"><a href="#cite_note-murphy2008-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> however, utilizing specificity of the antibody, complements can detect non-self targets much more specifically.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (July 2022)">citation needed</span></a></i>]</sup> </p><p>Some components have a variety of binding sites. In the classical pathway, C4 binds to Ig-associated C1q and C1r<sup>2</sup>s<sup>2</sup> enzyme cleaves C4 to C4b and 4a. C4b binds to C1q, antigen-associated Ig (specifically to its Fc portion), and even to the microbe surface. C3b binds to antigen-associated Ig and to the microbe surface. Ability of C3b to bind to antigen-associated Ig would work effectively against antigen-antibody complexes to make them soluble.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (May 2015)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading2"><h2 id="Regulation">Regulation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=11" title="Edit section: Regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>The complement system has the potential to be extremely damaging to host tissues, meaning its activation must be tightly regulated. The complement system is regulated by <a href="/wiki/Complement_control_protein" title="Complement control protein">complement control proteins</a>, which are present at blood plasma and host cell membrane.<sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup> Some complement control proteins are present on the membranes of self-cells preventing them from being targeted by complement. One example is <a href="/wiki/CD59" title="CD59">CD59</a>, also known as protectin, which inhibits C9 polymerization during the formation of the <a href="/wiki/Membrane_attack_complex" class="mw-redirect" title="Membrane attack complex">membrane attack complex</a>. The classical pathway is inhibited by <a href="/wiki/C1-inhibitor" title="C1-inhibitor">C1-inhibitor</a>, which binds to C1 to prevent its activation.<sup id="cite_ref-:2_35-0" class="reference"><a href="#cite_note-:2-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> Another example, is a plasma protein called, <a href="/wiki/Factor_H" title="Factor H">Factor H</a> (FH), which has a key role in down-regulating the alternative pathway.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> Factor H, along with another protein called <a href="/wiki/Complement_factor_I" title="Complement factor I">Factor I</a>, inactivates C3b, the active form of C3. This process prevents the formation of C3 convertase and halts the progression of the complement cascade. C3-convertase also can be inhibited by <a href="/wiki/Decay_accelerating_factor" class="mw-redirect" title="Decay accelerating factor">decay accelerating factor</a> (DAF), which is bound to erythrocyte plasma membranes via a <a href="/wiki/Glycophosphatidylinositol" class="mw-redirect" title="Glycophosphatidylinositol">GPI</a> anchor.<sup id="cite_ref-:2_35-1" class="reference"><a href="#cite_note-:2-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Role_in_disease">Role in disease</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=12" title="Edit section: Role in disease"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading3"><h3 id="Complement_deficiency">Complement deficiency</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=13" title="Edit section: Complement deficiency"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Complement_deficiency" title="Complement deficiency">Complement deficiency</a></div> <p>It is thought that the complement system might play a role in many diseases with an immune component, such as <a href="/wiki/Barraquer%E2%80%93Simons_syndrome" title="Barraquer–Simons syndrome">Barraquer–Simons syndrome</a>, <a href="/wiki/Asthma" title="Asthma">asthma</a>, <a href="/wiki/Lupus_erythematosus" title="Lupus erythematosus">lupus erythematosus</a>, <a href="/wiki/Glomerulonephritis" title="Glomerulonephritis">glomerulonephritis</a>, various forms of <a href="/wiki/Arthritis" title="Arthritis">arthritis</a>, <a href="/wiki/Autoimmune_heart_disease" title="Autoimmune heart disease">autoimmune heart disease</a>, <a href="/wiki/Multiple_sclerosis" title="Multiple sclerosis">multiple sclerosis</a>, <a href="/wiki/Inflammatory_bowel_disease" title="Inflammatory bowel disease">inflammatory bowel disease</a>, <a href="/wiki/Paroxysmal_nocturnal_hemoglobinuria" title="Paroxysmal nocturnal hemoglobinuria">paroxysmal nocturnal hemoglobinuria</a>, <a href="/wiki/Atypical_hemolytic_uremic_syndrome" title="Atypical hemolytic uremic syndrome">atypical hemolytic uremic syndrome</a> and ischemia-reperfusion injuries,<sup id="cite_ref-pmid_15087815_37-0" class="reference"><a href="#cite_note-pmid_15087815-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid19443638_38-0" class="reference"><a href="#cite_note-pmid19443638-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> and rejection of transplanted organs.<sup id="cite_ref-pmid_14499254_39-0" class="reference"><a href="#cite_note-pmid_14499254-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> </p><p>Complement regulation is suggested to play a role in pregnancy. Improper alternative complement pathway activation may mediate recurrent immune-mediated fetal loss.<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup> </p><p>The complement system is also becoming increasingly implicated in diseases of the central nervous system such as <a href="/wiki/Alzheimer%27s_disease" title="Alzheimer's disease">Alzheimer's disease</a> and other neurodegenerative conditions such as spinal cord injuries.<sup id="cite_ref-42" class="reference"><a href="#cite_note-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-44" class="reference"><a href="#cite_note-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> </p><p>Deficiencies of the terminal pathway predispose to both <a href="/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune disease</a> and <a href="/wiki/Infection" title="Infection">infections</a> (particularly <a href="/wiki/Neisseria_meningitidis" title="Neisseria meningitidis">Neisseria meningitidis</a>, due to the role that the <a href="/wiki/Membrane_attack_complex" class="mw-redirect" title="Membrane attack complex">membrane attack complex</a> ("MAC") plays in attacking <a href="/wiki/Gram-negative" class="mw-redirect" title="Gram-negative">Gram-negative</a> bacteria).<sup id="cite_ref-45" class="reference"><a href="#cite_note-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> </p><p>Infections with <i>N. meningitidis</i> and <i><a href="/wiki/N._gonorrhoeae" class="mw-redirect" title="N. gonorrhoeae">N. gonorrhoeae</a></i> are the only conditions known to be associated with deficiencies in the MAC components of complement.<sup id="cite_ref-Ram2010_46-0" class="reference"><a href="#cite_note-Ram2010-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> 40–50% of those with MAC deficiencies experience recurrent infections with <i>N. meningitidis</i>.<sup id="cite_ref-Lewis2014_47-0" class="reference"><a href="#cite_note-Lewis2014-47"><span class="cite-bracket">[</span>47<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Deficiencies_in_complement_regulators">Deficiencies in complement regulators</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=14" title="Edit section: Deficiencies in complement regulators"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Mutations in the genes of complement regulators, especially <a href="/wiki/Factor_H" title="Factor H">factor H</a>, have been associated with atypical <a href="/wiki/Hemolytic_uremic_syndrome" class="mw-redirect" title="Hemolytic uremic syndrome">hemolytic uremic syndrome</a>,<sup id="cite_ref-:0_4-1" class="reference"><a href="#cite_note-:0-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid16189652_48-0" class="reference"><a href="#cite_note-pmid16189652-48"><span class="cite-bracket">[</span>48<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-pmid16575689_49-0" class="reference"><a href="#cite_note-pmid16575689-49"><span class="cite-bracket">[</span>49<span class="cite-bracket">]</span></a></sup> and C3 glomerulopathy.<sup id="cite_ref-:0_4-2" class="reference"><a href="#cite_note-:0-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Both of these disorders are currently thought to be due to complement overactivation either on the surface of host cells or in plasma, with the molecular location of genetic variation in complement proteins providing clues into the underlying disease processes.<sup id="cite_ref-:0_4-3" class="reference"><a href="#cite_note-:0-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Moreover, several <a href="/wiki/Single_nucleotide_polymorphism" class="mw-redirect" title="Single nucleotide polymorphism">single nucleotide polymorphisms</a> and mutations in the complement factor H gene (the most common of which results in the protein change p.Y402H) have been associated with the common eye disease <a href="/wiki/Age-related_macular_degeneration" class="mw-redirect" title="Age-related macular degeneration">age-related macular degeneration</a>.<sup id="cite_ref-:0_4-4" class="reference"><a href="#cite_note-:0-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> Polymorphisms of <a href="/wiki/Complement_component_3" title="Complement component 3">complement component 3</a>, <a href="/wiki/Complement_factor_B" title="Complement factor B">complement factor B</a>, and <a href="/wiki/Complement_factor_I" title="Complement factor I">complement factor I</a>, as well as deletion of complement factor H-related 3 and complement factor H-related 1, also affect a person's risk of developing <a href="/wiki/Age-related_macular_degeneration" class="mw-redirect" title="Age-related macular degeneration">age-related macular degeneration</a>.<sup id="cite_ref-:0_4-5" class="reference"><a href="#cite_note-:0-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-BradleyDT2011_50-0" class="reference"><a href="#cite_note-BradleyDT2011-50"><span class="cite-bracket">[</span>50<span class="cite-bracket">]</span></a></sup> </p><p>Mutations in the C1 inhibitor gene can cause <a href="/wiki/Hereditary_angioedema" title="Hereditary angioedema">hereditary angioedema</a>, a genetic condition resulting from reduced regulation of <a href="/wiki/Bradykinin" title="Bradykinin">bradykinin</a> by C1-INH.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (May 2015)">citation needed</span></a></i>]</sup> </p><p><a href="/wiki/Paroxysmal_nocturnal_hemoglobinuria" title="Paroxysmal nocturnal hemoglobinuria">Paroxysmal nocturnal hemoglobinuria</a> is caused by complement breakdown of <a href="/wiki/Red_blood_cell" title="Red blood cell">RBCs</a> due to an inability to make GPI. Thus the RBCs are not protected by GPI anchored proteins such as DAF.<sup id="cite_ref-51" class="reference"><a href="#cite_note-51"><span class="cite-bracket">[</span>51<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Diagnostic_tools">Diagnostic tools</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=15" title="Edit section: Diagnostic tools"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Diagnostic tools to measure complement activity include the <a href="/wiki/Total_complement_activity" title="Total complement activity">total complement activity</a> test.<sup id="cite_ref-52" class="reference"><a href="#cite_note-52"><span class="cite-bracket">[</span>52<span class="cite-bracket">]</span></a></sup> </p><p>The presence or absence of complement fixation upon a challenge can indicate whether particular antigens or antibodies are present in the blood. This is the principle of the <a href="/wiki/Complement_fixation_test" title="Complement fixation test">complement fixation test</a>.<sup class="noprint Inline-Template Template-Fact" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citation_needed" title="Wikipedia:Citation needed"><span title="This claim needs references to reliable sources. (July 2024)">citation needed</span></a></i>]</sup> </p> <div class="mw-heading mw-heading2"><h2 id="Modulation_of_the_body_by_complement_with_infection">Modulation of the body by complement with infection</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=16" title="Edit section: Modulation of the body by complement with infection"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Excessive complement activity contributes to severe Covid-19 symptoms and disease.<sup id="cite_ref-53" class="reference"><a href="#cite_note-53"><span class="cite-bracket">[</span>53<span class="cite-bracket">]</span></a></sup> Although complement is intended to protect the body systems, under stress there can be more damage than protection. Research has suggested that the complement system is manipulated during <a href="/wiki/Human_Immunodeficiency_Virus" class="mw-redirect" title="Human Immunodeficiency Virus">HIV</a>/<a href="/wiki/Acquired_Immunodeficiency_Syndrome" class="mw-redirect" title="Acquired Immunodeficiency Syndrome">AIDS</a>, in a way that further damages the body.<sup id="cite_ref-54" class="reference"><a href="#cite_note-54"><span class="cite-bracket">[</span>54<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Role_in_the_brain">Role in the brain</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=17" title="Edit section: Role in the brain"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Research from over the last decade has shown that complement proteins of the classical complement pathway have an important role in <a href="/wiki/Synaptic_pruning" title="Synaptic pruning">synaptic pruning</a> in the brain during early development.<sup id="cite_ref-55" class="reference"><a href="#cite_note-55"><span class="cite-bracket">[</span>55<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-56" class="reference"><a href="#cite_note-56"><span class="cite-bracket">[</span>56<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Complement_system&action=edit&section=18" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 30em;"> <ol class="references"> <li id="cite_note-:1-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-:1_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-:1_1-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFJaneway_JrTraversWalportShlomchik2001" class="citation book cs1">Janeway Jr CA, Travers P, Walport M, Shlomchik MJ (2001). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/books/NBK27100">"The complement system and innate immunity"</a>. <i>Immunobiology: The Immune System in Health and Disease</i>. New York: Garland Science<span class="reference-accessdate">. Retrieved <span class="nowrap">25 February</span> 2013</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=The+complement+system+and+innate+immunity&rft.btitle=Immunobiology%3A+The+Immune+System+in+Health+and+Disease&rft.place=New+York&rft.pub=Garland+Science&rft.date=2001&rft.aulast=Janeway+Jr&rft.aufirst=CA&rft.au=Travers%2C+P&rft.au=Walport%2C+M&rft.au=Shlomchik%2C+MJ&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fbooks%2FNBK27100&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-2"><span class="mw-cite-backlink"><b><a href="#cite_ref-2">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGlovsky2019" class="citation journal cs1">Glovsky MM (9 November 2019). Talavera F, Dreskin SC, Kaliner MA (eds.). <a rel="nofollow" class="external text" href="https://emedicine.medscape.com/article/136368-overview">"Complement-Related Disorders: Background, Pathophysiology, Activation"</a>. <i>Medscape</i>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Medscape&rft.atitle=Complement-Related+Disorders%3A+Background%2C+Pathophysiology%2C+Activation&rft.date=2019-11-09&rft.aulast=Glovsky&rft.aufirst=MM&rft_id=https%3A%2F%2Femedicine.medscape.com%2Farticle%2F136368-overview&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-Abbas_2010-3"><span class="mw-cite-backlink">^ <a href="#cite_ref-Abbas_2010_3-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Abbas_2010_3-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAbbasLichtmanPillai2010" class="citation book cs1">Abbas AK, Lichtman AH, Pillai S (2010). <a rel="nofollow" class="external text" href="https://archive.org/details/cellularmolecula00abba_1/page/272"><i>Cellular and Molecular Immunology</i></a> (6th ed.). Elsevier. pp. <a rel="nofollow" class="external text" href="https://archive.org/details/cellularmolecula00abba_1/page/272">272–288</a>. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-1-4160-3123-9" title="Special:BookSources/978-1-4160-3123-9"><bdi>978-1-4160-3123-9</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Cellular+and+Molecular+Immunology&rft.pages=272-288&rft.edition=6th&rft.pub=Elsevier&rft.date=2010&rft.isbn=978-1-4160-3123-9&rft.aulast=Abbas&rft.aufirst=AK&rft.au=Lichtman%2C+AH&rft.au=Pillai%2C+S&rft_id=https%3A%2F%2Farchive.org%2Fdetails%2Fcellularmolecula00abba_1%2Fpage%2F272&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-:0-4"><span class="mw-cite-backlink">^ <a href="#cite_ref-:0_4-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-:0_4-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-:0_4-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-:0_4-3"><sup><i><b>d</b></i></sup></a> <a href="#cite_ref-:0_4-4"><sup><i><b>e</b></i></sup></a> <a href="#cite_ref-:0_4-5"><sup><i><b>f</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFTzoumasHallamHarrisLako2020" class="citation journal cs1">Tzoumas N, Hallam D, Harris CL, Lako M, Kavanagh D, Steel DH (November 2020). "Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants". <i>Survey of Ophthalmology</i>. <b>66</b> (2): 378–401. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.survophthal.2020.10.008">10.1016/j.survophthal.2020.10.008</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/33157112">33157112</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:226274874">226274874</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Survey+of+Ophthalmology&rft.atitle=Revisiting+the+role+of+factor+H+in+age-related+macular+degeneration%3A+Insights+from+complement-mediated+renal+disease+and+rare+genetic+variants&rft.volume=66&rft.issue=2&rft.pages=378-401&rft.date=2020-11&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A226274874%23id-name%3DS2CID&rft_id=info%3Apmid%2F33157112&rft_id=info%3Adoi%2F10.1016%2Fj.survophthal.2020.10.008&rft.aulast=Tzoumas&rft.aufirst=N&rft.au=Hallam%2C+D&rft.au=Harris%2C+CL&rft.au=Lako%2C+M&rft.au=Kavanagh%2C+D&rft.au=Steel%2C+DH&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-5"><span class="mw-cite-backlink"><b><a href="#cite_ref-5">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFNuttall1888" class="citation journal cs1 cs1-prop-foreign-lang-source">Nuttall G (1888). <a rel="nofollow" class="external text" href="https://babel.hathitrust.org/cgi/pt?id=uc1.b3063944&view=1up&seq=361">"Experimente über die bakterien feindlichen Einflüsse des tierischen Körpers"</a> [Experiments on the antibacterial influences of animal substances]. <i>Zeitschrift für Hygiene</i> (in German). <b>4</b>: 353–394.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Zeitschrift+f%C3%BCr+Hygiene&rft.atitle=Experimente+%C3%BCber+die+bakterien+feindlichen+Einfl%C3%BCsse+des+tierischen+K%C3%B6rpers&rft.volume=4&rft.pages=353-394&rft.date=1888&rft.aulast=Nuttall&rft.aufirst=G&rft_id=https%3A%2F%2Fbabel.hathitrust.org%2Fcgi%2Fpt%3Fid%3Duc1.b3063944%26view%3D1up%26seq%3D361&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span>English translation <a rel="nofollow" class="external text" href="https://apps.dtic.mil/sti/pdfs/AD0880296.pdf">here</a></span> </li> <li id="cite_note-Chaplin2005-6"><span class="mw-cite-backlink">^ <a href="#cite_ref-Chaplin2005_6-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Chaplin2005_6-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFChaplin2020" class="citation journal cs1">Chaplin H (2020). <a rel="nofollow" class="external text" href="https://doi.org/10.21307%2Fimmunohematology-2019-398">"Review: the burgeoning history of the complement system 1888-2005"</a>. <i>Immunohematology</i>. <b>21</b> (3): 85–93. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.21307%2Fimmunohematology-2019-398">10.21307/immunohematology-2019-398</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16178664">16178664</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Immunohematology&rft.atitle=Review%3A+the+burgeoning+history+of+the+complement+system+1888-2005&rft.volume=21&rft.issue=3&rft.pages=85-93&rft.date=2020&rft_id=info%3Adoi%2F10.21307%2Fimmunohematology-2019-398&rft_id=info%3Apmid%2F16178664&rft.aulast=Chaplin&rft.aufirst=H&rft_id=https%3A%2F%2Fdoi.org%2F10.21307%252Fimmunohematology-2019-398&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-7"><span class="mw-cite-backlink"><b><a href="#cite_ref-7">^</a></b></span> <span class="reference-text">Buchner named "alexin" during an address to a meeting of the Medical Society (<i>Aerztlichen Verein</i>) in Munich, Germany on 3 June 1891. Buchner's address was published in: <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBuchner1891" class="citation journal cs1 cs1-prop-foreign-lang-source">Buchner H (23 June 1891). <a rel="nofollow" class="external text" href="https://babel.hathitrust.org/cgi/pt?id=uc1.c2621491&view=1up&seq=459">"Kurze Uebersicht über die Entwicklung der Bacterienforschung seit Naegeli's Eingreifen in dieselbe"</a> [Brief overview of the development of bacteriology since Naegeli's involvement in it]. <i>Münchener Medizinische Wochenschrift</i> (in German). <b>38</b> (25): 435–437, (26): 454–456.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=M%C3%BCnchener+Medizinische+Wochenschrift&rft.atitle=Kurze+Uebersicht+%C3%BCber+die+Entwicklung+der+Bacterienforschung+seit+Naegeli%27s+Eingreifen+in+dieselbe&rft.volume=38&rft.issue=25&rft.pages=435-437%2C+%2826%29%3A+454-456&rft.date=1891-06-23&rft.aulast=Buchner&rft.aufirst=H&rft_id=https%3A%2F%2Fbabel.hathitrust.org%2Fcgi%2Fpt%3Fid%3Duc1.c2621491%26view%3D1up%26seq%3D459&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span> From p. 437: <i>"Es handelt sich demnach um Eiweisskörper einer neuen Kategorie, die mit irgend welchen bisher bekannten sich nicht identificieren lassen, und die man am besten deshalb mit einem neuen Namen, etwa als "Alexine" (d.h. Schutzstoffe, von αλέξειν abwehren, schützen) bezeichnet."</i> (So it's a matter of protein of a new type, which cannot be identified with any [protein] which [has been] known until now, and which one therefore designates best with a new name, perhaps as "alexine" (i.e., protective stuff, from αλέξειν fight off, defend).) <ul><li>Buchner's address was reprinted in condensed form in: <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBuchner1891" class="citation journal cs1 cs1-prop-foreign-lang-source">Buchner H (1891). <a rel="nofollow" class="external text" href="https://www.biodiversitylibrary.org/item/210617#page/365/mode/1up">"Kurze Uebersicht über die Entwicklung der Bacterienforschung seit Naegeli's Eingreifen in dieselbe"</a>. <i>Centralblatt für Bakteriologie und Parasitenkunde</i> (in German). <b>10</b>: 349–352.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Centralblatt+f%C3%BCr+Bakteriologie+und+Parasitenkunde&rft.atitle=Kurze+Uebersicht+%C3%BCber+die+Entwicklung+der+Bacterienforschung+seit+Naegeli%27s+Eingreifen+in+dieselbe&rft.volume=10&rft.pages=349-352&rft.date=1891&rft.aulast=Buchner&rft.aufirst=H&rft_id=https%3A%2F%2Fwww.biodiversitylibrary.org%2Fitem%2F210617%23page%2F365%2Fmode%2F1up&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span> From p. 350: <i>"Es handelt sich demnach um Eiweisskörper einer neuen Kategorie, die besonders durch grosse Labilität ausgezeichnet sind (bei 50-55°C erlischt rasch die Wirksamkeit), und die am besten mit einem neuen Namen, etwa als "Alexine" (d.h. Schutzstoffe, von αλέξειν abwehren, schützen) bezeichnet werden könnten."</i> (So it's a matter of protein of a new type, which is especially distinguished by great lability (at 50-55°C its efficacy suddenly ceases to exist), and which can best be designated with a new name, perhaps as "alexine" (i.e., protective stuff, from αλέξειν fight off, defend).)</li></ul> </span></li> <li id="cite_note-Nesargikar2012-8"><span class="mw-cite-backlink"><b><a href="#cite_ref-Nesargikar2012_8-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFNesargikarSpillerChavez2012" class="citation journal cs1">Nesargikar PN, Spiller B, Chavez R (June 2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956958">"The complement system: history, pathways, cascade and inhibitors"</a>. <i>European Journal of Microbiology & Immunology</i>. <b>2</b> (2): 103–11. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1556%2FEuJMI.2.2012.2.2">10.1556/EuJMI.2.2012.2.2</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3956958">3956958</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/24672678">24672678</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=European+Journal+of+Microbiology+%26+Immunology&rft.atitle=The+complement+system%3A+history%2C+pathways%2C+cascade+and+inhibitors&rft.volume=2&rft.issue=2&rft.pages=103-11&rft.date=2012-06&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3956958%23id-name%3DPMC&rft_id=info%3Apmid%2F24672678&rft_id=info%3Adoi%2F10.1556%2FEuJMI.2.2012.2.2&rft.aulast=Nesargikar&rft.aufirst=PN&rft.au=Spiller%2C+B&rft.au=Chavez%2C+R&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3956958&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-9"><span class="mw-cite-backlink"><b><a href="#cite_ref-9">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFBordet1895" class="citation journal cs1 cs1-prop-foreign-lang-source">Bordet J (1895). <a rel="nofollow" class="external text" href="https://www.biodiversitylibrary.org/item/31494#page/420/mode/1up">"Les leucocytes et les propriétés actives du sérum chez les vaccinés"</a> [Leucocytes and the active properties of serum in vaccinated [animals]]. <i>Annales de l'Institut Pasteur</i> (in French). <b>9</b>: 462–506.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Annales+de+l%27Institut+Pasteur&rft.atitle=Les+leucocytes+et+les+propri%C3%A9t%C3%A9s+actives+du+s%C3%A9rum+chez+les+vaccin%C3%A9s&rft.volume=9&rft.pages=462-506&rft.date=1895&rft.aulast=Bordet&rft.aufirst=J&rft_id=https%3A%2F%2Fwww.biodiversitylibrary.org%2Fitem%2F31494%23page%2F420%2Fmode%2F1up&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-10"><span class="mw-cite-backlink"><b><a href="#cite_ref-10">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFEhrlichMorgenroth1899" class="citation journal cs1 cs1-prop-foreign-lang-source">Ehrlich P, Morgenroth J (29 May 1899). <a rel="nofollow" class="external text" href="https://babel.hathitrust.org/cgi/pt?id=uc1.c2892587&view=1up&seq=517">"Ueber Haemolysine"</a> [On hemolysin]. <i>Berliner klinische Wochenschrift</i> (in German). <b>36</b> (22): 481–486.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Berliner+klinische+Wochenschrift&rft.atitle=Ueber+Haemolysine&rft.volume=36&rft.issue=22&rft.pages=481-486&rft.date=1899-05-29&rft.aulast=Ehrlich&rft.aufirst=P&rft.au=Morgenroth%2C+J&rft_id=https%3A%2F%2Fbabel.hathitrust.org%2Fcgi%2Fpt%3Fid%3Duc1.c2892587%26view%3D1up%26seq%3D517&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span> From p. 483: <i>"Es sprechen diese Versuche nach unseren früheren Erfahrungen dafür, dass auch hier in dem Serum ein Analogon des Immunkörpers, ein mit zwei haptophoren Gruppen versehener Complex, der als Zwischenkörper bezeichnet werde, und ein Addiment, das wir im Folgenden mit dem allgemeineren Ausdruck Complement bezeichnen wollen, besteht, und dass von den Blutkörperchen vorweigend der Zwischenkörper gebunden worden ist."</i> (According to our earlier experiences, these experiments indicate (1) that here too there exists in the serum an analog of the immune bodies — a complex [that's] provided with two haptophoric groups, [one of] which may be designated as an "intermediate body" and [the other, as] an addiment [i.e., a component of a hemolysin that's induced by an antigen (see p. 481)], which we will designate in the following with the more general term "complement" — and (2) that the intermediate body has been bound mainly by the blood cells.)</span> </li> <li id="cite_note-11"><span class="mw-cite-backlink"><b><a href="#cite_ref-11">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFKaufmann2008" class="citation journal cs1">Kaufmann SH (July 2008). "Immunology's foundation: the 100-year anniversary of the Nobel Prize to Paul Ehrlich and Elie Metchnikoff". <i>Nature Immunology</i>. <b>9</b> (7): 705–12. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fni0708-705">10.1038/ni0708-705</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/18563076">18563076</a>. <a href="/wiki/S2CID_(identifier)" class="mw-redirect" title="S2CID (identifier)">S2CID</a> <a rel="nofollow" class="external text" href="https://api.semanticscholar.org/CorpusID:205359637">205359637</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nature+Immunology&rft.atitle=Immunology%27s+foundation%3A+the+100-year+anniversary+of+the+Nobel+Prize+to+Paul+Ehrlich+and+Elie+Metchnikoff&rft.volume=9&rft.issue=7&rft.pages=705-12&rft.date=2008-07&rft_id=https%3A%2F%2Fapi.semanticscholar.org%2FCorpusID%3A205359637%23id-name%3DS2CID&rft_id=info%3Apmid%2F18563076&rft_id=info%3Adoi%2F10.1038%2Fni0708-705&rft.aulast=Kaufmann&rft.aufirst=SH&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-12"><span class="mw-cite-backlink"><b><a href="#cite_ref-12">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMurphyWeaver2017" class="citation book cs1">Murphy K, Weaver C (2017). "Innate Immunity: the First Lines of Defense". <i>Janeway's Immunobiology</i> (9th ed.). Garland Science. p. 49. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-8153-4505-3" title="Special:BookSources/978-0-8153-4505-3"><bdi>978-0-8153-4505-3</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Innate+Immunity%3A+the+First+Lines+of+Defense&rft.btitle=Janeway%27s+Immunobiology&rft.pages=49&rft.edition=9th&rft.pub=Garland+Science&rft.date=2017&rft.isbn=978-0-8153-4505-3&rft.aulast=Murphy&rft.aufirst=K&rft.au=Weaver%2C+C&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-pmid=_23383423-13"><span class="mw-cite-backlink">^ <a href="#cite_ref-pmid=_23383423_13-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-pmid=_23383423_13-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFKlosWendeWarehamMonk2013" class="citation journal cs1">Klos A, Wende E, Wareham KJ, Monk PN (January 2013). <a rel="nofollow" class="external text" href="https://doi.org/10.1124%2Fpr.111.005223">"International Union of Basic and Clinical Pharmacology. 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Complement peptide C5a, C4a, and C3a receptors"</a>. <i>Pharmacological Reviews</i>. <b>65</b> (1): 500–43. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1124%2Fpr.111.005223">10.1124/pr.111.005223</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23383423">23383423</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Pharmacological+Reviews&rft.atitle=International+Union+of+Basic+and+Clinical+Pharmacology.+%5Bcorrected%5D.+LXXXVII.+Complement+peptide+C5a%2C+C4a%2C+and+C3a+receptors&rft.volume=65&rft.issue=1&rft.pages=500-43&rft.date=2013-01&rft_id=info%3Adoi%2F10.1124%2Fpr.111.005223&rft_id=info%3Apmid%2F23383423&rft.aulast=Klos&rft.aufirst=A&rft.au=Wende%2C+E&rft.au=Wareham%2C+KJ&rft.au=Monk%2C+PN&rft_id=https%3A%2F%2Fdoi.org%2F10.1124%252Fpr.111.005223&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-Baron-14"><span class="mw-cite-backlink"><b><a href="#cite_ref-Baron_14-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGoldmanPrabhakar1996" class="citation book cs1">Goldman AS, Prabhakar BS (1996). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/books/NBK7795/#A238">"The Complement System"</a>. 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Euro Diagnostica. Archived from <a rel="nofollow" class="external text" href="http://www.complementsystem.se/classical-pathway">the original</a> on 2 June 2016<span class="reference-accessdate">. Retrieved <span class="nowrap">6 June</span> 2022</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=unknown&rft.jtitle=www.complementsystem.se&rft.atitle=Classical+Pathway+%28CP%29&rft_id=http%3A%2F%2Fwww.complementsystem.se%2Fclassical-pathway&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-16"><span class="mw-cite-backlink"><b><a href="#cite_ref-16">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRooijakkersWuRuykenvan_Domselaar2009" class="citation journal cs1">Rooijakkers SH, Wu J, Ruyken M, van Domselaar R, Planken KL, Tzekou A, et al. (July 2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729104">"Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor"</a>. <i>Nature Immunology</i>. <b>10</b> (7): 721–7. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fni.1756">10.1038/ni.1756</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729104">2729104</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19503103">19503103</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nature+Immunology&rft.atitle=Structural+and+functional+implications+of+the+alternative+complement+pathway+C3+convertase+stabilized+by+a+staphylococcal+inhibitor&rft.volume=10&rft.issue=7&rft.pages=721-7&rft.date=2009-07&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2729104%23id-name%3DPMC&rft_id=info%3Apmid%2F19503103&rft_id=info%3Adoi%2F10.1038%2Fni.1756&rft.aulast=Rooijakkers&rft.aufirst=SH&rft.au=Wu%2C+J&rft.au=Ruyken%2C+M&rft.au=van+Domselaar%2C+R&rft.au=Planken%2C+KL&rft.au=Tzekou%2C+A&rft.au=Ricklin%2C+D&rft.au=Lambris%2C+JD&rft.au=Janssen%2C+BJ&rft.au=van+Strijp%2C+JA&rft.au=Gros%2C+P&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC2729104&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-17"><span class="mw-cite-backlink"><b><a href="#cite_ref-17">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAmmitzbøllKjærSteffensenStengaard-Pedersen2012" class="citation journal cs1">Ammitzbøll CG, Kjær TR, Steffensen R, Stengaard-Pedersen K, Nielsen HJ, Thiel S, et al. (2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509001">"Non-synonymous polymorphisms in the FCN1 gene determine ligand-binding ability and serum levels of M-ficolin"</a>. <i>PLOS ONE</i>. <b>7</b> (11): e50585. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2012PLoSO...750585A">2012PLoSO...750585A</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1371%2Fjournal.pone.0050585">10.1371/journal.pone.0050585</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509001">3509001</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23209787">23209787</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=PLOS+ONE&rft.atitle=Non-synonymous+polymorphisms+in+the+FCN1+gene+determine+ligand-binding+ability+and+serum+levels+of+M-ficolin&rft.volume=7&rft.issue=11&rft.pages=e50585&rft.date=2012&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3509001%23id-name%3DPMC&rft_id=info%3Apmid%2F23209787&rft_id=info%3Adoi%2F10.1371%2Fjournal.pone.0050585&rft_id=info%3Abibcode%2F2012PLoSO...750585A&rft.aulast=Ammitzb%C3%B8ll&rft.aufirst=CG&rft.au=Kj%C3%A6r%2C+TR&rft.au=Steffensen%2C+R&rft.au=Stengaard-Pedersen%2C+K&rft.au=Nielsen%2C+HJ&rft.au=Thiel%2C+S&rft.au=B%C3%B8gsted%2C+M&rft.au=Jensenius%2C+JC&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3509001&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-Janeway1994-18"><span class="mw-cite-backlink">^ <a href="#cite_ref-Janeway1994_18-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Janeway1994_18-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFJanewayTravers1994" class="citation book cs1">Janeway C, Travers P (1994). <i>Immunobiology: The Immune System in Health and Disease</i>. 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(May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-janeway1999-19"><span class="mw-cite-backlink">^ <a href="#cite_ref-janeway1999_19-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-janeway1999_19-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-janeway1999_19-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFJanewayTraversWalportCapra1999" class="citation book cs1">Janeway CA, Travers P, Walport M, Capra JD (1999). <i>Immunobiology: The Immune System in Health and Disease</i> (4th ed.). New York: Garland Publishing, Inc. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0-8153-3217-3" title="Special:BookSources/0-8153-3217-3"><bdi>0-8153-3217-3</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Immunobiology%3A+The+Immune+System+in+Health+and+Disease&rft.place=New+York&rft.edition=4th&rft.pub=Garland+Publishing%2C+Inc.&rft.date=1999&rft.isbn=0-8153-3217-3&rft.aulast=Janeway&rft.aufirst=CA&rft.au=Travers%2C+P&rft.au=Walport%2C+M&rft.au=Capra%2C+JD&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-abbas-20"><span class="mw-cite-backlink">^ <a href="#cite_ref-abbas_20-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-abbas_20-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAbbasLichtman2015" class="citation book cs1">Abbas AK, Lichtman AH (May 2015). <i>Cellular and Molecular Immunology</i> (5th ed.). Philadelphia: Saunders. p. 332. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-7216-0008-6" title="Special:BookSources/978-0-7216-0008-6"><bdi>978-0-7216-0008-6</bdi></a>. <q>Note that, in older texts, the smaller fragment is often called C2b, and the larger one is called C2a for historical reasons.</q></cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Cellular+and+Molecular+Immunology&rft.place=Philadelphia&rft.pages=332&rft.edition=5th&rft.pub=Saunders&rft.date=2015-05&rft.isbn=978-0-7216-0008-6&rft.aulast=Abbas&rft.aufirst=AK&rft.au=Lichtman%2C+AH&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-Peakman-21"><span class="mw-cite-backlink"><b><a href="#cite_ref-Peakman_21-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPeakmanVergani1997" class="citation book cs1">Peakman M, Vergani D (1997). <i>Basic and Clinical Immunology</i>. New York: Churchill Livingstone. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0-443-04672-7" title="Special:BookSources/0-443-04672-7"><bdi>0-443-04672-7</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Basic+and+Clinical+Immunology&rft.place=New+York&rft.pub=Churchill+Livingstone&rft.date=1997&rft.isbn=0-443-04672-7&rft.aulast=Peakman&rft.aufirst=M&rft.au=Vergani%2C+D&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-22"><span class="mw-cite-backlink"><b><a href="#cite_ref-22">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPaul1999" class="citation book cs1">Paul WE, ed. (1999). <i>Fundamental Immunology</i> (4th ed.). Philadelphia: Lippincott-Raven. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0-7817-1412-5" title="Special:BookSources/0-7817-1412-5"><bdi>0-7817-1412-5</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Fundamental+Immunology&rft.place=Philadelphia&rft.edition=4th&rft.pub=Lippincott-Raven&rft.date=1999&rft.isbn=0-7817-1412-5&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-Sims-23"><span class="mw-cite-backlink"><b><a href="#cite_ref-Sims_23-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSimsWiedmer2000" class="citation book cs1">Sims PJ, Wiedmer T (2000). "Complement biology". In Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, McGlave P (eds.). <i>Hematology: Basic Principles and Practic</i> (3rd ed.). New York; Edinburgh: Churchill-Livingstone. pp. 651–667. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0-443-07954-4" title="Special:BookSources/0-443-07954-4"><bdi>0-443-07954-4</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Complement+biology&rft.btitle=Hematology%3A+Basic+Principles+and+Practic&rft.place=New+York%3B+Edinburgh&rft.pages=651-667&rft.edition=3rd&rft.pub=Churchill-Livingstone&rft.date=2000&rft.isbn=0-443-07954-4&rft.aulast=Sims&rft.aufirst=PJ&rft.au=Wiedmer%2C+T&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-24"><span class="mw-cite-backlink"><b><a href="#cite_ref-24">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFFrankAtkinson2001" class="citation book cs1">Frank K, Atkinson JP (2001). "Complement system". In Austen KF, Frank K, Atkinson JP, Cantor H (eds.). <i>Samter's Immunologic Diseases</i>. Vol. 1 (6th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 281–298. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0-7817-2120-2" title="Special:BookSources/0-7817-2120-2"><bdi>0-7817-2120-2</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Complement+system&rft.btitle=Samter%27s+Immunologic+Diseases&rft.place=Philadelphia&rft.pages=281-298&rft.edition=6th&rft.pub=Lippincott+Williams+%26+Wilkins&rft.date=2001&rft.isbn=0-7817-2120-2&rft.aulast=Frank&rft.aufirst=K&rft.au=Atkinson%2C+JP&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-Roitt-25"><span class="mw-cite-backlink">^ <a href="#cite_ref-Roitt_25-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-Roitt_25-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRoittBrostoffMale2001" class="citation book cs1">Roitt I, Brostoff J, Male D (2001). <i>Immunology</i> (6th ed.). St. Louis: Mosby. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0-7234-3189-2" title="Special:BookSources/0-7234-3189-2"><bdi>0-7234-3189-2</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Immunology&rft.place=St.+Louis&rft.edition=6th&rft.pub=Mosby&rft.date=2001&rft.isbn=0-7234-3189-2&rft.aulast=Roitt&rft.aufirst=I&rft.au=Brostoff%2C+J&rft.au=Male%2C+D&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-anderson2003-26"><span class="mw-cite-backlink"><b><a href="#cite_ref-anderson2003_26-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAnderson2003" class="citation book cs1">Anderson DM (2003). <i>Dorland's Illustrated Medical Dictionary</i> (30th ed.). Philadelphia: W.B. Saunders. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0-7216-0146-4" title="Special:BookSources/0-7216-0146-4"><bdi>0-7216-0146-4</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Dorland%27s+Illustrated+Medical+Dictionary&rft.place=Philadelphia&rft.edition=30th&rft.pub=W.B.+Saunders&rft.date=2003&rft.isbn=0-7216-0146-4&rft.aulast=Anderson&rft.aufirst=DM&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-Parham-27"><span class="mw-cite-backlink"><b><a href="#cite_ref-Parham_27-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFParham2005" class="citation book cs1">Parham P (2005). <i>The Immune System</i>. New York: Garland. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/0-8153-4093-1" title="Special:BookSources/0-8153-4093-1"><bdi>0-8153-4093-1</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=The+Immune+System&rft.place=New+York&rft.pub=Garland&rft.date=2005&rft.isbn=0-8153-4093-1&rft.aulast=Parham&rft.aufirst=P&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-murphy2008-28"><span class="mw-cite-backlink">^ <a href="#cite_ref-murphy2008_28-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-murphy2008_28-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-murphy2008_28-2"><sup><i><b>c</b></i></sup></a> <a href="#cite_ref-murphy2008_28-3"><sup><i><b>d</b></i></sup></a></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFMurphyTraversWalportEhrenstein2008" class="citation book cs1">Murphy K, Travers P, Walport M, Ehrenstein M (2008). <i>Janeway's Immunobiology</i> (7th ed.). New York: Garland Science. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-8153-4123-9" title="Special:BookSources/978-0-8153-4123-9"><bdi>978-0-8153-4123-9</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Janeway%27s+Immunobiology&rft.place=New+York&rft.edition=7th&rft.pub=Garland+Science&rft.date=2008&rft.isbn=978-0-8153-4123-9&rft.aulast=Murphy&rft.aufirst=K&rft.au=Travers%2C+P&rft.au=Walport%2C+M&rft.au=Ehrenstein%2C+M&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-Atkinson-29"><span class="mw-cite-backlink"><b><a href="#cite_ref-Atkinson_29-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAtkinson2009" class="citation book cs1">Atkinson JP (2009). "Complement system". In Firestein GS, Budd RC, Harris Jr ED, McInnes IB, Ruddy S, Sergent JS (eds.). <i>Kelley's Textbook of Rheumatology</i>. Philadelphia, PA: Saunders/Elsevier. pp. 323–336. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-1-4160-3285-4" title="Special:BookSources/978-1-4160-3285-4"><bdi>978-1-4160-3285-4</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Complement+system&rft.btitle=Kelley%27s+Textbook+of+Rheumatology&rft.place=Philadelphia%2C+PA&rft.pages=323-336&rft.pub=Saunders%2FElsevier&rft.date=2009&rft.isbn=978-1-4160-3285-4&rft.aulast=Atkinson&rft.aufirst=JP&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-Janeway_2001-30"><span class="mw-cite-backlink"><b><a href="#cite_ref-Janeway_2001_30-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFJaneway_JrTraversWalportShlomchik2001" class="citation book cs1">Janeway Jr CA, Travers P, Walport M, Shlomchik MJ (2001). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/books/NBK27100/">"The complement system and innate immunity"</a>. <a rel="nofollow" class="external text" href="https://archive.org/details/immunobiology00char"><i>Immunobiology</i></a> (5th ed.). Garland Publishing. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-8153-3642-6" title="Special:BookSources/978-0-8153-3642-6"><bdi>978-0-8153-3642-6</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=The+complement+system+and+innate+immunity&rft.btitle=Immunobiology&rft.edition=5th&rft.pub=Garland+Publishing&rft.date=2001&rft.isbn=978-0-8153-3642-6&rft.aulast=Janeway+Jr&rft.aufirst=CA&rft.au=Travers%2C+P&rft.au=Walport%2C+M&rft.au=Shlomchik%2C+MJ&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fbooks%2FNBK27100%2F&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-doan2007-31"><span class="mw-cite-backlink"><b><a href="#cite_ref-doan2007_31-0">^</a></b></span> <span class="reference-text">Doan T, Melvold R, Viselli S, Waltenbaugh C (2007). <i>Lippincott's Illustrated Reviews: Immunology,</i> 320p. Lippincott Williams & Wilkins<sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-DeFranco-32"><span class="mw-cite-backlink"><b><a href="#cite_ref-DeFranco_32-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFDeFrancoLocksleyRobertson2007" class="citation book cs1">DeFranco AL, Locksley RM, Robertson M (2007). <i>Immunity : The Immune Response in Infectious and Inflammatory Disease</i>. London; Sunderland, MA: New Science Press; Sinauer Associates. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-9539181-0-2" title="Special:BookSources/978-0-9539181-0-2"><bdi>978-0-9539181-0-2</bdi></a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.btitle=Immunity+%3A+The+Immune+Response+in+Infectious+and+Inflammatory+Disease&rft.place=London%3B+Sunderland%2C+MA&rft.pub=New+Science+Press%3B+Sinauer+Associates&rft.date=2007&rft.isbn=978-0-9539181-0-2&rft.aulast=DeFranco&rft.aufirst=AL&rft.au=Locksley%2C+RM&rft.au=Robertson%2C+M&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span><sup class="noprint Inline-Template" style="white-space:nowrap;">[<i><a href="/wiki/Wikipedia:Citing_sources" title="Wikipedia:Citing sources"><span title="This citation requires a reference to the specific page or range of pages in which the material appears. (May 2015)">page needed</span></a></i>]</sup></span> </li> <li id="cite_note-33"><span class="mw-cite-backlink"><b><a href="#cite_ref-33">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFStoermerMorrison2011" class="citation journal cs1">Stoermer KA, Morrison TE (March 2011). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073741">"Complement and viral pathogenesis"</a>. <i>Virology</i>. <b>411</b> (2): 362–73. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.virol.2010.12.045">10.1016/j.virol.2010.12.045</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073741">3073741</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/21292294">21292294</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Virology&rft.atitle=Complement+and+viral+pathogenesis&rft.volume=411&rft.issue=2&rft.pages=362-73&rft.date=2011-03&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3073741%23id-name%3DPMC&rft_id=info%3Apmid%2F21292294&rft_id=info%3Adoi%2F10.1016%2Fj.virol.2010.12.045&rft.aulast=Stoermer&rft.aufirst=KA&rft.au=Morrison%2C+TE&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3073741&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-34"><span class="mw-cite-backlink"><b><a href="#cite_ref-34">^</a></b></span> <span 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Immunology</i>. <b>22</b> (2): 77–84. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fs41577-021-00665-1">10.1038/s41577-021-00665-1</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8672651">8672651</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/34912108">34912108</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nature+Reviews.+Immunology&rft.atitle=The+state+of+complement+in+COVID-19&rft.volume=22&rft.issue=2&rft.pages=77-84&rft.date=2022-02&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC8672651%23id-name%3DPMC&rft_id=info%3Apmid%2F34912108&rft_id=info%3Adoi%2F10.1038%2Fs41577-021-00665-1&rft.aulast=Afzali&rft.aufirst=B&rft.au=Noris%2C+M&rft.au=Lambrecht%2C+BN&rft.au=Kemper%2C+C&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC8672651&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> <li id="cite_note-54"><span class="mw-cite-backlink"><b><a href="#cite_ref-54">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFDattaRappaport2006" class="citation journal cs1">Datta PK, Rappaport J (November 2006). 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(May 2012). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528177">"Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner"</a>. <i>Neuron</i>. <b>74</b> (4): 691–705. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1016%2Fj.neuron.2012.03.026">10.1016/j.neuron.2012.03.026</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3528177">3528177</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/22632727">22632727</a>.</cite><span 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href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFGomez-ArboledasAcharyaTenner2021" class="citation journal cs1">Gomez-Arboledas A, Acharya MM, Tenner AJ (September 2021). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478425">"The Role of Complement in Synaptic Pruning and Neurodegeneration"</a>. <i>ImmunoTargets and Therapy</i>. <b>10</b>: 373–386. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.2147%2FITT.S305420">10.2147/ITT.S305420</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478425">8478425</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/34595138">34595138</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=ImmunoTargets+and+Therapy&rft.atitle=The+Role+of+Complement+in+Synaptic+Pruning+and+Neurodegeneration&rft.volume=10&rft.pages=373-386&rft.date=2021-09&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC8478425%23id-name%3DPMC&rft_id=info%3Apmid%2F34595138&rft_id=info%3Adoi%2F10.2147%2FITT.S305420&rft.aulast=Gomez-Arboledas&rft.aufirst=A&rft.au=Acharya%2C+MM&rft.au=Tenner%2C+AJ&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC8478425&rfr_id=info%3Asid%2Fen.wikipedia.org%3AComplement+system" class="Z3988"></span></span> </li> </ol></div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a 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style="width:1%">Pathways</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Classical_complement_pathway" title="Classical complement pathway">C</a></li> <li><a href="/wiki/Lectin_pathway" title="Lectin pathway">L</a></li> <li><a href="/wiki/Alternative_complement_pathway" title="Alternative complement pathway">A</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Activators/enzymes</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Early</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>C:</i> <a href="/wiki/C1_complex" title="C1 complex">C1</a> <ul><li><a href="/wiki/Complement_component_1q" title="Complement component 1q">C1q</a></li> <li><a href="/wiki/Complement_component_1r" title="Complement component 1r">C1r</a></li> <li><a href="/wiki/Complement_component_1s" title="Complement component 1s">C1s</a></li></ul></li> <li><a href="/wiki/Complement_component_4" title="Complement component 4">C4</a> <ul><li><a href="/wiki/C4A" title="C4A">C4a</a></li> <li><a href="/wiki/C4B" class="mw-redirect" title="C4B">C4b</a></li></ul></li> <li><a href="/wiki/Complement_component_2" title="Complement component 2">C2</a></li></ul> <ul><li><i>L:</i> <a href="/wiki/MASP1_(protein)" title="MASP1 (protein)">MASP1</a>/<a href="/wiki/MASP2_(protein)" title="MASP2 (protein)">MASP2</a></li> <li><a href="/wiki/Mannan-binding_lectin" title="Mannan-binding lectin">MBL</a></li></ul> <ul><li><i>A:</i> <a href="/wiki/Complement_factor_B" title="Complement factor B">Factor B</a></li> <li><a href="/wiki/Factor_D" title="Factor D">Factor D</a></li> <li><a href="/wiki/Properdin" title="Properdin">Factor P/Properdin</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Middle</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Complement_component_3" title="Complement component 3">C3</a> <ul><li><a href="/wiki/C3a_(complement)" title="C3a (complement)">C3a</a></li> <li><a href="/wiki/C3b" title="C3b">C3b</a>/<a href="/wiki/IC3b" title="IC3b">iC3b</a></li></ul></li> <li><a href="/wiki/Complement_component_5" title="Complement component 5">C5</a> <ul><li><a href="/wiki/Complement_component_5a" title="Complement component 5a">C5a</a></li> <li><a href="/wiki/Complement_component_5b" class="mw-redirect" title="Complement component 5b">C5b</a></li></ul></li></ul> <ul><li><a href="/wiki/C3-convertase" title="C3-convertase">C3-convertase</a></li> <li><a href="/wiki/C5-convertase" title="C5-convertase">C5-convertase</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Late</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Complement_membrane_attack_complex" title="Complement membrane attack complex">MAC</a> <ul><li><a href="/wiki/Complement_component_5b" class="mw-redirect" title="Complement component 5b">C5b</a></li> <li><a href="/wiki/Complement_component_6" title="Complement component 6">C6</a></li> <li><a href="/wiki/Complement_component_7" title="Complement component 7">C7</a></li> <li><a href="/wiki/C8_complex" title="C8 complex">C8</a></li> <li><a href="/wiki/Complement_component_9" title="Complement component 9">C9</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Inhibitors</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><i>CLA:</i> <a href="/wiki/C1-inhibitor" title="C1-inhibitor">C1-inhibitor</a></li> <li><a href="/wiki/Decay-accelerating_factor" title="Decay-accelerating factor">Decay-accelerating factor</a>/<a href="/wiki/CD59" title="CD59">CD59</a></li> <li><a href="/wiki/Complement_factor_I" title="Complement factor I">Factor I</a></li></ul> <ul><li><i>CL:</i> <a href="/wiki/C4b-binding_protein" title="C4b-binding protein">C4BP</a></li></ul> <ul><li><i>A:</i> <a href="/wiki/Factor_H" title="Factor H">Factor H</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Complement_receptor" title="Complement receptor">Complement receptors</a></th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Complement_receptor_1" title="Complement receptor 1">CR1</a></li> <li><a href="/wiki/Complement_receptor_2" title="Complement receptor 2">CR2</a></li> <li><a href="/wiki/Macrophage-1_antigen" title="Macrophage-1 antigen">CR3</a></li> <li><a href="/wiki/Integrin_alphaXbeta2" title="Integrin alphaXbeta2">CR4</a></li> <li><a href="/wiki/Integrin_alpha_M" title="Integrin alpha M">CD11b</a>/<a href="/wiki/CD11c" class="mw-redirect" title="CD11c">CD11c</a>/<a href="/wiki/CD18" class="mw-redirect" title="CD18">CD18</a></li> <li><a href="/wiki/Anaphylatoxin_receptors" title="Anaphylatoxin receptors">Anaphylatoxin</a> <ul><li><a href="/wiki/C3a_receptor" title="C3a receptor">C3a</a></li> <li><a href="/wiki/C5a_receptor" title="C5a receptor">C5a</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Function</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cytotoxicity" title="Cytotoxicity">Cytotoxicity</a>(by MAC)</li> <li><a href="/wiki/Immune_adherence" title="Immune adherence">immune adherence</a></li> <li>Inducing <a href="/wiki/Inflammation" title="Inflammation">inflammation</a></li> <li><a href="/wiki/Opsonization" class="mw-redirect" title="Opsonization">Opsonization</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Lymphocytic_adaptive_immune_system_and_complement" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Lymphocytic_immune_system" title="Template:Lymphocytic immune system"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Lymphocytic_immune_system" title="Template talk:Lymphocytic immune system"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Lymphocytic_immune_system" title="Special:EditPage/Template:Lymphocytic immune system"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Lymphocytic_adaptive_immune_system_and_complement" style="font-size:114%;margin:0 4em"><a href="/wiki/Lymphocyte" title="Lymphocyte">Lymphocytic</a> <a href="/wiki/Adaptive_immune_system" title="Adaptive immune system">adaptive immune system</a> and <a class="mw-selflink selflink">complement</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">Lymphoid</th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Antigens</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Antigen" title="Antigen">Antigen</a> <ul><li><a href="/wiki/Superantigen" title="Superantigen">Superantigen</a></li> <li><a href="/wiki/Allergen" title="Allergen">Allergen</a></li> <li><a href="/wiki/Antigenic_variation" title="Antigenic variation">Antigenic variation</a></li></ul></li> <li><a href="/wiki/Hapten" title="Hapten">Hapten</a></li></ul> <ul><li><a href="/wiki/Epitope" title="Epitope">Epitope</a> <ul><li><a href="/wiki/Linear_epitope" title="Linear epitope">Linear</a></li> <li><a href="/wiki/Conformational_epitope" title="Conformational epitope">Conformational</a></li></ul></li> <li><a href="/wiki/Mimotope" title="Mimotope">Mimotope</a></li></ul> <ul><li><a href="/wiki/Antigen_presentation" title="Antigen presentation">Antigen presentation</a>/<a href="/wiki/Antigen-presenting_cell" title="Antigen-presenting cell">professional APCs</a>: <a href="/wiki/Dendritic_cell" title="Dendritic cell">Dendritic cell</a></li> <li><a href="/wiki/Macrophage" title="Macrophage">Macrophage</a></li> <li><a href="/wiki/B_cell" title="B cell">B cell</a></li> <li><a href="/wiki/Immunogen" title="Immunogen">Immunogen</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Antibodies</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Antibody" title="Antibody">Antibody</a> <ul><li><a href="/wiki/Monoclonal_antibody" title="Monoclonal antibody">Monoclonal antibodies</a></li> <li><a href="/wiki/Polyclonal_antibodies" title="Polyclonal antibodies">Polyclonal antibodies</a></li> <li><a href="/wiki/Autoantibody" title="Autoantibody">Autoantibody</a></li> <li><a href="/wiki/Microantibody" title="Microantibody">Microantibody</a></li></ul></li> <li><a href="/wiki/Polyclonal_B_cell_response" title="Polyclonal B cell response">Polyclonal B cell response</a></li> <li><a href="/wiki/Allotype_(immunology)" title="Allotype (immunology)">Allotype</a></li> <li><a href="/wiki/Isotype_(immunology)" title="Isotype (immunology)">Isotype</a></li> <li><a href="/wiki/Idiotype" title="Idiotype">Idiotype</a></li></ul> <ul><li><a href="/wiki/Immune_complex" title="Immune complex">Immune complex</a></li> <li><a href="/wiki/Paratope" title="Paratope">Paratope</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Immunity vs.<br /> tolerance</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Action: <a href="/wiki/Immunity_(medical)" class="mw-redirect" title="Immunity (medical)">Immunity</a></li> <li><a href="/wiki/Autoimmunity" title="Autoimmunity">Autoimmunity</a></li> <li><a href="/wiki/Alloimmunity" title="Alloimmunity">Alloimmunity</a></li> <li><a href="/wiki/Allergy" title="Allergy">Allergy</a></li> <li><a href="/wiki/Hypersensitivity" title="Hypersensitivity">Hypersensitivity</a></li> <li><a href="/wiki/Inflammation" title="Inflammation">Inflammation</a></li> <li><a href="/wiki/Cross-reactivity" title="Cross-reactivity">Cross-reactivity</a></li> <li><a href="/wiki/Co-stimulation" title="Co-stimulation">Co-stimulation</a></li></ul> <ul><li>Inaction: <a href="/wiki/Immune_tolerance" title="Immune tolerance">Tolerance</a> <ul><li><a href="/wiki/Central_tolerance" title="Central tolerance">Central</a></li> <li><a href="/wiki/Peripheral_tolerance" title="Peripheral tolerance">Peripheral</a></li> <li><a href="/wiki/Clonal_anergy" title="Clonal anergy">Clonal anergy</a></li> <li><a href="/wiki/Clonal_deletion" title="Clonal deletion">Clonal deletion</a></li> <li><a href="/wiki/Immune_tolerance_in_pregnancy" title="Immune tolerance in pregnancy">Tolerance in pregnancy</a></li></ul></li> <li><a href="/wiki/Immunodeficiency" title="Immunodeficiency">Immunodeficiency</a></li> <li><a href="/wiki/Immune_privilege" title="Immune privilege">Immune privilege</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Immunogenetics" title="Immunogenetics">Immunogenetics</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Affinity_maturation" title="Affinity maturation">Affinity maturation</a> <ul><li><a href="/wiki/Somatic_hypermutation" title="Somatic hypermutation">Somatic hypermutation</a></li> <li><a href="/wiki/Clonal_selection" title="Clonal selection">Clonal selection</a></li></ul></li> <li><a href="/wiki/V(D)J_recombination" title="V(D)J recombination">V(D)J recombination</a></li> <li><a href="/wiki/Junctional_diversity" title="Junctional diversity">Junctional diversity</a></li> <li><a href="/wiki/Immunoglobulin_class_switching" title="Immunoglobulin class switching">Immunoglobulin class switching</a></li> <li><a href="/wiki/Major_histocompatibility_complex" title="Major histocompatibility complex">MHC</a>/<a href="/wiki/Human_leukocyte_antigen" title="Human leukocyte antigen">HLA</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Lymphocyte" title="Lymphocyte">Lymphocytes</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cell-mediated_immunity" title="Cell-mediated immunity">Cellular</a> <ul><li><a href="/wiki/T_cell" title="T cell">T cell</a></li></ul></li> <li><a href="/wiki/Humoral_immunity" title="Humoral immunity">Humoral</a> <ul><li><a href="/wiki/B_cell" title="B cell">B cell</a></li></ul></li> <li><a href="/wiki/Natural_killer_cell" title="Natural killer cell">NK cell</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Substances</th><td class="navbox-list-with-group navbox-list navbox-even hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Cytokine" title="Cytokine">Cytokines</a></li> <li><a href="/wiki/Opsonin" title="Opsonin">Opsonin</a></li> <li><a href="/wiki/Cytolysin" title="Cytolysin">Cytolysin</a></li></ul> </div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"><style data-mw-deduplicate="TemplateStyles:r1038841319">.mw-parser-output .tooltip-dotted{border-bottom:1px dotted;cursor:help}</style><link 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