Fig. 1

Simplified overview of the active complement cascade. Foreign surface-bound antigen–antibody (Ag/Ab) complexes initiate the classic pathway, while polysaccharides, lipopolysaccharides, and/or IgA activate the alternative complement pathway. Damage-associated molecular patterns (DAMPs) like mannose-binding lectin (MBL), ficolins (Fcns), and certain collections (CLs) can directly trigger the classic pathway or initiate the lectin pathway. The three complement activation pathways collectively cleave C3 into C3b and C3a, triggering terminal pathway activation, mainly involving C5-C9, which assembles to form the membrane attack complex (MAC). Key complement regulatory factors include C1 inhibitor (C1-INH), factor H (FH), factor I (FI), CD46, C4BP, and CD59. C1-INH inhibits C1r activation of C1s, preventing C4 and C2 cleavage. Simultaneously, C1-INH can inhibit the binding of MBL to MASP-1 or MASP-2. Factor I and factor H, aided by C4BP and CD46, can phagocytize C3 from the alternative pathway, inhibiting its activation. CD59 prevents C9 from binding to C5b678 to form MAC