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→Complement Fixation Pathways
[[Image:Complement Classical Pathway.png|thumb|right|250px|'''Classical pathway in detail''' - R.J.Francis, RVC 2012]]
[[Image:Complement Classical Pathway.png|thumb|right|250px|'''Classical pathway in detail''' - R.J.Francis, RVC 2012]]
This pathway of the complement system is triggered by the binding of antibody to antigen. The only subclasses that can activate complement this way are the
This pathway of the complement system is triggered by the binding of antibody to antigen. The only subclasses that can activate complement this way are the
[[IgM]] and certain [[IgG]]. The first step of complement activation is the binding of C1 to two Fc regions of the antibodies (IgM is such a strong activator of complement as it contains '''five''' Fc regions, while IgG contains '''one'''). C1 is actually a complex of C1q, C1r and C1s. C1q looks like a bunch of 6 tulips with each "flower" consisting of a globular protein head and a collagen "stem". C1q is required to trigger the cascade because two of it is the globular heads binds the two Fc regions. C1r and C1s then become activated when the C1q heads are antibody-bound. When they are activated they form the enzyme '''C1 esterase''' (it is a serine protease).
[[IgM]] and certain [[IgG]]. The first step of complement activation is the binding of C1 to two Fc regions of the antibodies (IgM is such a strong activator of complement as it contains '''five''' Fc regions, while IgG contains '''one'''). C1 is actually a complex of C1q, C1r and C1s. C1q looks like a bunch of 6 tulips with each "flower" consisting of a globular protein head and a collagen "stem". <font color="green">C1q is required to trigger the cascade because two of it is the globular heads binds the two Fc regions.</font color> C1r and C1s then become activated when the C1q heads are antibody-bound. When they are activated they form the enzyme '''C1 esterase''' (it is a serine protease).
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It is the C1 esterase which then first digests components C4 to C4a and C4b, and C2 to C2a and C2b. It is the C4b which first binds to the antigen, and then forms a complex with C2a (some textbooks (tend to be more recent) quote this as "C2b" depending on nomenculture used) to produce the active enzyme '''C3 convertase (classical pathway)'''. The binding of one C1q molecule produces one C1 esterase molecule that can then cause the binding of many hundreds of the C4b¯2a molecules (or in some textbooks "C4b¯2b"). The role of the convertase is to digest C3 into C3a and C3b. This part of the pathway is self-propagating as the production of C3b can now be amplified by the same mechanism as the alternative pathway (below).
It is the C1 esterase which then first digests components C4 to C4a and C4b, and C2 to C2a and C2b. It is the C4b which first binds to the antigen, and then forms a complex with C2a (some textbooks (tend to be more recent) quote this as "C2b" depending on nomenculture used) to produce the active enzyme '''C3 convertase (classical pathway)'''. The binding of one C1q molecule produces one C1 esterase molecule that can then cause the binding of many hundreds of the C4b¯2a molecules (or in some textbooks "C4b¯2b"). The role of the convertase is to digest C3 into C3a and C3b. This part of the pathway is self-propagating as the production of C3b can now be amplified by the same mechanism as the [[Complement#Alternative Pathway| alternative pathway]] (below).
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