The classic activation pathway

The classic activation pathway depends on the interaction of three complement proteins (C1, C4, and C2) with antigen-bound antibody to activate the initial cleavage of C3. C1, the first complement component, consists of three subcomponents, C1q, C1r, and C1s, which form a complex in the presence of calcium. Antigen–antibody complexes (containing IgG1, IgG2, IgG3, or IgM) can activate C1 to its enzymatically active form.

Activated C1 then cleaves its two complement substrates, C4 and C2, to form a bimolecular complex, C4b2ba. This complex, known as C3 convertase, is capable of cleaving C3 to initiate activation of the effector sequence. Once C3 is activated, there is subsequent activation of the terminal components of the pathway. Complement enhances the immune response. The attachment of C3 to an antigen has been demonstrated to affect various phases of the acquired immune response. C3 is involved in (i) the promotion of antigen uptake, processing, and presentation by B cells to antigen-specific T cells; (ii) direct activation of B cells; and (ii) facilitation of B cell interactions.