Common pathways for complement activation. Recognition of antigen-antibody complexes by C1q initiates the ‘classical pathway’. Binding of carbohydrate antigens by mannose-binding lectin (MBL) or MBL-associated serine proteases (MASPs) initiates the ‘lectin pathway’. Both pathways lead to the formation of the C3 convertase, C4b2a. Complement activation through the ‘alternative pathway’ involves the spontaneous hydrolysis of plasma C3, generating a second C3 convertase, C3(H2O)Bb. Proteolysis of C3 then leads to production of the C3b fragment, which binds to C3 convertases to generate C5 convertases. After the cleavage of C5, the C5b fragment binds C6-C9 to generate the membrane attack complex (MAC). The coagulation cascade leads to complement activation via the ‘extrinsic pathway’; this route does not depend on the presence of C3 convertases. Anaphylatoxins C5a, C3a and C4a are generated through cleavage of C5, C3 and C4, respectively. Soluble and membrane-bound negative regulators of complement and their site of action are indicated in green. The functional significance of certain activation steps is shown in red.