Complement Cascade 🛡️
Innate immune defense: opsonization, inflammation & membrane attack complex
Biology & cascade steps
Classical pathway is triggered when C1q recognises antibody-antigen complexes (IgG or IgM): C1q → C1r/C1s serine proteases → C4 cleavage (C4a+C4b) → C2 cleavage → C3 convertase C4b2a → massive C3 amplification → C3b opsonization → C5 cleavage → MAC assembly (C5b-6-7-8-9).
Alternative pathway is constitutively active via spontaneous C3 "tick-over" hydrolysis in plasma. C3(H₂O) + Factor B + Factor D → C3bBb convertase → Properdin (P) stabilises → amplification loop.
Lectin pathway is triggered by Mannose-Binding Lectin (MBL) recognising carbohydrate patterns on pathogens → MASP-1/MASP-2 activate → cleave C4 and C2 (same as classical from here).
Opsonization: C3b covalently binds pathogen surface, flagging it for phagocytosis by macrophages/neutrophils via CR1 receptors.
MAC (Membrane Attack Complex): C5b+C6+C7+C8+(C9)ₙ form a transmembrane pore → ion gradient collapses → lysis of Gram-negative bacteria.
Inhibitors: DAF/CD55 accelerates convertase decay; CD59 blocks C9 insertion. Deficiency → PNH (paroxysmal nocturnal haemoglobinuria).