Pathways activating and inhibiting complement. The three complement activation pathways converge at the formation of the enzyme C3 convertase (or C4b/C2a), activation of which leads to the formation of C3b, the ligand of complement receptor 1 (CR1, also known as CD35). Activation of the complement pathway can ultimately lead to the release of inflammatory mediators, opsonisation of pathogens, and the membrane attack complex (MAC). The C1 complex of the classical complement pathway is comprised of C1q, C1r, and C1s. The endogenous complement C1 inhibitor/C1-esterase inhibitor (C1-Inh), which regulates the activation of the C1 complex, is decreased in AD. C5b, C6, C7, C8, and C9 form the MAC complex in the alternative complement activation pathway. CD59, an endogenous regulator of the MAC complex, is decreased in AD whilst C9 may be increased. Levels of Factor H, a regulatory glycoprotein of the alternative complement cascade, may also be perturbed in AD.
