Complement system (also known as complement cascade) (Not a single molecule; represents a multi-protein cascade system)

The complement system is a multi-component cascade of approximately 50 proteins circulating in blood and tissue fluids that functions as a critical arm of innate immunity[1][6]. It can be activated through three distinct biochemical pathways—classical, alternative, and lectin—which converge on common effector mechanisms[1][7]. The system mediates three primary defense functions: direct pathogen lysis via membrane attack complex formation, enhanced phagocytosis through opsonization by C3b and its fragments, and recruitment of inflammatory cells through release of anaphylatoxins (C3a, C5a)[1][5]. Individual complement components serve as therapeutic targets for diseases characterized by either deficiency (leading to recurrent infections) or overactivation (causing tissue damage in conditions like atypical hemolytic uremic syndrome and C3 glomerulopathy)[1][3][4]. Therapeutic strategies have primarily focused on inhibiting the alternative pathway and specific complement components like C3 and C5, with development efforts aimed at achieving selective immune enhancement while avoiding excessive immunosuppression[1].

Other names

Complement cascadeHumoral innate immune systemComplement activationComplement fixation

Complement therapeutics operate through multiple proposed mechanisms: Pathway inhibition - Blocking classical, alternative, or lectin pathway activation. Component-specific inhibition - Targeting individual complement proteins (C3, C5, factor B, factor H) to prevent cascade amplification. Regulatory protein modulation - Enhancing or mimicking endogenous complement regulatory proteins (CD35, CD46, CD55, CD59). Terminal complex inhibition - Blocking membrane attack complex formation by preventing C9 polymerization.