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→Classical Pathway
===Classical Pathway===
===Classical Pathway===
[[Image:Complement Classical Pathway.png|thumb|right|250px|'''Classical pathway in detail''']]
[[Image:Complement Classical Pathway.png|thumb|right|250px|'''Classical pathway in detail''']]
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''' (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". 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''' (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 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 the C3 convertase (classical pathway). 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 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 the C3 convertase (classical pathway). 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).
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The main action of the C3b molecule is to form the C4b¯2a¯3b complex, or the '''C5 convertase (classical pathway)'''. The C5 convertase then activates C5 and initiates the [[#Membrane Attack Complex|membrane attack complex]] (MAC) as shown below. Other actions include the fragmentation of the C3b due to the actions of [[#Factors I and H|Factors I and H]] which forms C3bi, which provides an opsonin for [[Phagocytosis|phagocytosis]].
The main action of the C3b molecule is to form the C4b¯2a¯3b complex, or the '''C5 convertase (classical pathway)'''. The C5 convertase then activates C5 and initiates the [[#Membrane Attack Complex|membrane attack complex]] (MAC) as shown below. Other actions include the fragmentation of the C3b due to the actions of [[#Factors I and H|Factors I and H]] which forms C3bi, which provides an opsonin for [[Phagocytosis|phagocytosis]].
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Along with the actions of the fragments mentioned above, Ca fragments C3a, C4a and C5a, and Cb fragment C2b also form a chemotactic response. This brings [[Neutrophils|neutrophils]] to the area of complement activation through the process of [[Neutrophils|extravasation]] through the increase in cell adhesion molecules on the endothelium and an increase in vascular permeability; and chemotaxis which is the direct cellular movement. The fragments can also cause [[Mast Cells|mast cell]] and [[Basophils|basophil]] degranulation. These therefore induce '''acute inflammation'''.
Along with the actions of the fragments mentioned above, Ca fragments C3a, C4a and C5a, and Cb fragment C2b also form a chemotactic response. This brings [[Neutrophils|neutrophils]] to the area of complement activation through the process of [[Neutrophils|extravasation]] through the increase in cell adhesion molecules on the endothelium and an increase in vascular permeability; and chemotaxis which is the direct cellular movement. The fragments can also cause [[Mast Cells|mast cell]] and [[Basophils|basophil]] degranulation. These therefore induce '''acute inflammation'''.
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