Editing Classical complement pathway (section)

==Complement cascade==
[[File:Complement pathway.svg|270px|thumb|The classical complement pathway leading into a complement cascade that is shared with the alternative pathway.]]
The classical pathway is distinct from the other complement pathways in its unique activation triggers and cascade sequence. Activation of the complement pathway through the classical, [[Lectin pathway|lectin]] or [[alternative complement pathway]] is followed by a cascade of reactions eventually leading to the membrane attack complex.

===Initiation===
The classical complement pathway can be initiated by the binding of antigen-antibody complexes to the [[Complement component 1q|C1q]] protein. The globular regions of C1q recognize and bind to the [[Fragment crystallizable region|Fc]] region of antibody isotypes IgG or IgM.<ref name="Complement in disease">{{cite journal|last1=Vignesh|first1=Pandiarajan|last2=Rawat|first2=Amit|last3=Sharma|first3=Madhubala|last4=Singh|first4=Surjit|title=Complement in autoimmune diseases|journal=Clinica Chimica Acta|date=February 2017|volume=465|pages=123–130|doi=10.1016/j.cca.2016.12.017|pmid=28040558}}</ref> These globular regions of C1q can also bind to bacterial and viral surface proteins, apoptotic cells, and acute phase proteins.<ref>{{Cite book| title = Advances in Immunology Volume 46| last1 = Ahearn| first1 = Joseph M.| last2 = Fearon| first2 = Douglas T.| chapter = Structure and Function of the Complement Receptors, CR1 (CD35) and CR2 (CD21)| date = 1989-01-01| editor-last = Dixon| editor-first = Frank J.| volume = 46| pages = 183–219| doi = 10.1016/s0065-2776(08)60654-9| pmid = 2551147| isbn = 9780120224463}}</ref> In the absence of these activation factors, C1q is part of the inactive C1 complex which consists of six molecules of C1q, two molecules of [[C1r]], and two molecules of [[C1s]].<ref name="Overview of Complement" /><ref name="C1q" />

=== Formation of C4b convertase ===
The binding of C1q with pathogen surface or antigen-antibody immune complex leads to conformational changes and the activation of the serine protease C1r. The activated C1r then cleaves and activates the serine protease C1s.<ref name="Complement history" /><ref name="C1q" /> Activated C1s cleaves [[Complement component 4|C4]] into C4a and C4b. 

=== Regulation of C4b ===
The newly formed C4b cannot stay activated as a highly reactive thioester bond is revealed once C4 has been cleaved. The thioester bond is cleaved by water resulting in its cleavage permanently deactivating the C4b molecule. As a result of this C4b is restricted to only bind to pathogen surfaces. They would undergo rapid deactivation in the time it took to travel from the origin of activation where C1q is complexed with an antigen-antibody immune complex(IC) or where C1q is directly attached to the pathogens surface.<ref name=":1">{{Cite book |last=Janeway |first=Ca Jr |url=https://www.ncbi.nlm.nih.gov/books/NBK27100/ |title=Immunobiology: The Immune System in Health and Disease |chapter=The complement system and innate immunity |publisher=Garland Science |year=2001 |edition=5th |location=New York}}</ref>

=== Formation of C3-convertase. ===
Surface-bound C4b acts as a receptor for the binding of C2.<ref name=":1" /> The binding of C2 and C4b results in C2 being cleaved by C1s into C2a and C2b. C2b diffuses into the plasma as a protein inflammatory mediator while C2a remains attached with C4b, forming the C3-convertase (C4b2a). The function of the membrane-bound C3-convertase is the cleavage of many many molecules of C3 into C3a and C3b. C3a is a smaller fragment of C3 is a potent inflammatory mediator. 

=== C3b function and structure. ===
C3b can act as an opsonin. C3b is very similar to C4 in both structure and function also has a thioester bond that forces it to attach to surface nucleophile of the activator(namely the pathogen or IC). Phagocytes have receptors for C3b and as a result of receptor-ligand binding are able to more easily recognize and engulf pathogen molecules.    While the [[anaphylatoxin]] C3a interacts with its [[C3a receptor]] (C3aR) to recruit leukocytes, C3b contributes to further downstream complement activation.<ref name="Overview of Complement" /><ref name="Complement history" />

===Formation of C5 convertase and MAC===
C3b binds to the C3 convertase (C4b2a), to form C5 convertase (C4b2a3b). C5 convertase then cleaves C5 into C5a and C5b.<ref name="Complement history" /> Like C3a, C5a is also an anaphylatoxin that interacts with its cognate C5a receptor (C5aR) to attract leukocytes.<ref name="Overview of Complement" /> Subsequent interactions between C5b and other terminal components C6, C7, C8, and C9 form the membrane attack complex or the C5b-9 complex which forms pores on the target cell membranes to lysing.<ref name="Rus 103–112">{{Cite journal| last1 = Rus| first1 = Horea| last2 = Cudrici| first2 = Cornelia| last3 = Niculescu| first3 = Florin| date = 2005-11-01| title = The role of the complement system in innate immunity| journal = Immunologic Research| language = en| volume = 33| issue = 2| pages = 103–112| doi = 10.1385/IR:33:2:103| issn = 0257-277X| pmid=16234578| s2cid = 46096567}}</ref>