Category: immune_innate
Plasma protease cascade with three activation arms converging on C3 cleavage → C5 cleavage → MAC (C5b-9 membrane attack complex). Classical: C1q recognizes antibody-antigen → C1r/s → C4 + C2 → C3 convertase. Alternative: spontaneous C3 tickover, accelerated by surfaces lacking host regulators (DAF, MCP, FH). Lectin: MBL recognizes microbial mannose → MASP → same C4/C2 cleavage. PNH (paroxysmal nocturnal hemoglobinuria) lacks GPI-anchored DAF + CD59 on RBCs → uncontrolled alternative-pathway complement activation → intravascular hemolysis. ECULIZUMAB (anti-C5) prevents C5 cleavage → no MAC formation → PNH + atypical HUS treatment. RAVULIZUMAB is longer-half-life eculizumab analog. Iptacopan is a newer oral factor B inhibitor (alternative pathway).