Editing Complement system (section)

== History ==
In 1888, [[George Nuttall]] found that sheep blood [[serum (blood)|serum]] had mild killing activity against the [[bacterium]] that causes [[anthrax]].<ref>{{Cite journal |vauthors=Nuttall G |date=1888 |title=Experimente über die bakterien feindlichen Einflüsse des tierischen Körpers |trans-title=Experiments on the antibacterial influences of animal substances |url=https://babel.hathitrust.org/cgi/pt?id=uc1.b3063944&view=1up&seq=361 |journal=Zeitschrift für Hygiene |language=German |volume=4 |pages=353–394}}English translation [https://apps.dtic.mil/sti/pdfs/AD0880296.pdf here]</ref> The killing activity disappeared when he heated the blood.<ref name="Chaplin2005">{{Cite journal |vauthors=Chaplin H |year=2020 |title=Review: the burgeoning history of the complement system 1888-2005 |journal=Immunohematology |volume=21 |issue=3 |pages=85–93 |doi=10.21307/immunohematology-2019-398 |pmid=16178664 |doi-access=free}}</ref>  In 1891, [[Hans Ernst August Buchner]], noting the same property of blood in his experiments, named the killing property "alexin", which means "to ward off" in Greek.<ref>Buchner named "alexin" during an address to a meeting of the Medical Society (''Aerztlichen Verein'') in Munich, Germany on 3 June 1891.  Buchner's address was published in: {{Cite journal |vauthors=Buchner H |date=23 June 1891 |title=Kurze Uebersicht über die Entwicklung der Bacterienforschung seit Naegeli's Eingreifen in dieselbe |trans-title=Brief overview of the development of bacteriology since Naegeli's involvement in it |url=https://babel.hathitrust.org/cgi/pt?id=uc1.c2621491&view=1up&seq=459 |journal=Münchener Medizinische Wochenschrift |language=German |volume=38 |issue=25 |pages=435–437, (26): 454–456}}  From p. 437:  ''"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."'' (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).)
* Buchner's address was reprinted in condensed form in:  {{cite journal | vauthors = Buchner H |title=Kurze Uebersicht über die Entwicklung der Bacterienforschung seit Naegeli's Eingreifen in dieselbe |journal=Centralblatt für Bakteriologie und Parasitenkunde |date=1891 |volume=10 |pages=349–352 |url=https://www.biodiversitylibrary.org/item/210617#page/365/mode/1up |language=German}}  From p. 350:  ''"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."'' (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).)</ref><ref name="Nesargikar2012">{{Cite journal |vauthors=Nesargikar PN, Spiller B, Chavez R |date=June 2012 |title=The complement system: history, pathways, cascade and inhibitors |journal=European Journal of Microbiology & Immunology |volume=2 |issue=2 |pages=103–11 |doi=10.1556/EuJMI.2.2012.2.2 |pmc=3956958 |pmid=24672678}}</ref>  By 1894, several laboratories had demonstrated that serum from guinea pigs that had recovered from [[cholera]] killed the cholera bacterium ''in vitro''.  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.  [[Jules Bordet]], a young [[Belgians|Belgian]] scientist in [[Paris]] at the [[Pasteur Institute]], 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.<ref>{{Cite journal |vauthors=Bordet J |date=1895 |title=Les leucocytes et les propriétés actives du sérum chez les vaccinés |trans-title=Leucocytes and the active properties of serum in vaccinated [animals] |url=https://www.biodiversitylibrary.org/item/31494#page/420/mode/1up |journal=Annales de l'Institut Pasteur |language=French |volume=9 |pages=462–506}}</ref> 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, [[Paul Ehrlich]] renamed the heat-sensitive component "complement".<ref>{{Cite journal |vauthors=Ehrlich P, Morgenroth J |date=29 May 1899 |title=Ueber Haemolysine |trans-title=On hemolysin |url=https://babel.hathitrust.org/cgi/pt?id=uc1.c2892587&view=1up&seq=517 |journal=Berliner klinische Wochenschrift |language=German |volume=36 |issue=22 |pages=481–486}}  From p. 483:  ''"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."''  (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.)</ref><ref name="Chaplin2005" />

Ehrlich introduced the term "complement" as part of his larger theory of the immune system.<ref>{{Cite journal |vauthors=Kaufmann SH |date=July 2008 |title=Immunology's foundation: the 100-year anniversary of the Nobel Prize to Paul Ehrlich and Elie Metchnikoff |journal=Nature Immunology |volume=9 |issue=7 |pages=705–12 |doi=10.1038/ni0708-705 |pmid=18563076 |s2cid=205359637}}</ref> According to this theory, the immune system consists of cells that have specific receptors on their surface to recognize [[antigens]]. Upon immunization with an [[antigen]], more of these receptors are formed, and they are then shed from the cells to circulate in the blood. Those [[Immune receptor|receptors]], which we now call "[[Antibody|antibodies]]", 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.{{citation needed|date=May 2015}}