The APC. Unlike the classical pathway of complement that requires specific antibody-antigen binding to initiate activation, the APC is in a state of continuous activation (termed “tick-over”). Covalently bound C3b serves as the nidus for formation of the amplification C3 convertase of the APC, consisting of C3b, activated factor B (Bb) (the enzymatic subunit of the complex), and factor P (properdin, a stabilizing protein). The C3 convertase amplifies the APC by cleaving many molecules of C3 to C3b (with release into the fluid phase of the C3a anaphylatoxin). These activated C3b molecules form additional C3 convertases and also C5 convertases (C3bBbC3bP) that lead eventually to generation of the cytolytic membrane attack complex (C5b-9n). Because the APC is primed for attack continuously, elaborate mechanisms for self-recognition and for protection of the host against APC-mediated injury have evolved. Both fluid-phase (factor H and factor I) and membranebound proteins (MCP, DAF, and MIRL) are involved in this process. APC regulatory proteins that have been shown to be mutant in patients with aHUS are indicated with an asterisk. The GPI-AP regulatory proteins, DAF (CD55) and MIRL (CD59), are deficient in PNH, accounting for the complement-mediated hemolysis characteristic of the disease.