Complement Pathway

As part of the immune system, the complement cascade can be activated by three different pathways. The classical pathway takes place when antibody/antigen complexes interact with C1, a multimolecular complex consisting of C1q, C1r and C1s. The lectin pathway occurs when MBL binds to specific carbohydrate structures present on the surface of a variety of microorganisms. Both C1s and MASP cleave C2 and C4, which then forms C3 convertase (C4b2a). Initiated by yeast cell walls, biomaterials and tPA, the alternative pathway starts with activation of Factor D, then Factor B, and C3 Convertase (C3bBb). All three pathways merge at C3, which is then converted into C3a and C3b. C3b addition to either of C3 convertases changes its specificity into a C5 convertase, which cleaves C5 to form C5a and C5b. Addition of C6, C7, C8 and multiple C9 units to C5b forms the membrane attack complex (MAC), which binds to the cell surface and initiates membrane lysis. Components such as C1q, C3a, C3b, C3d, C4a, and C5a have additional functions through interaction with their respective receptors. There are many regulatory factors involved in the three pathways, such as Serpin G1 (C1 inhibitor), DAF/CD55 (dissociation of C3 convertases), MCP/CD46 (cofactor for serum factor I, inactivation of C3b and C4b), and CD59 (inhibitor of MAC formation).