Complement activation pathways. Activation of the classical, lectin, and alternative pathways results in the generation of C3 convertases that cleave C3 to C3b (which deposits on the cell surface) and C3a (an anaphylatoxin that recruits and activates effector cells). C3b deposition may rapidly amplify through a positive feedback loop (shown by the dotted line). C3b may also trigger activation of C5 through generation of C5 convertase, which cleaves C5 and results in the generation of C5a (an anaphylatoxin) and assembly of the membrane attack complex (MAC; C5b-9). The key regulators of the amplification or feedback loop include factor H (FH), factor I (FI), membrane cofactor protein (MCP, CD46), and complement receptor 1 (CR1, CD35). Excessive activation via this loop secondary to a decrease in regulatory activity or a gain of function in a component like C3 or factor B due to genetic variants in these proteins predisposes to atypical hemolytic uremic syndrome. B, factor B; D, factor D; P, properdin. Reproduced from Java.²⁷