Human complement system components (Complement system)

The human complement system is a complex network of more than 30 plasma and cell-surface proteins that play a critical role in the innate immune response [StatPearls, 2023]. It operates through three primary pathways—classical, lectin, and alternative—which converge at the cleavage of C3 and lead to the formation of the membrane attack complex (MAC) for direct pathogen lysis [UniProt, 2024]. Beyond lysis, the system facilitates opsonization, chemotaxis, and the modulation of adaptive immunity [PubMed: PMC7460431]. Dysregulation or overactivation of the complement cascade is implicated in various rare and chronic diseases, including paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) [Nature Reviews Drug Discovery, 2021]. Therapeutic strategies focus on inhibiting specific components like C3, C5, or various proteases to mitigate tissue damage and systemic inflammation [NIH: NCATS]. However, because the system is vital for host defense, pharmacological inhibition carries a significant risk of infection by encapsulated bacteria, particularly Neisseria meningitidis [FDA Label: Empaveli, 2021].

Other names

Complement cascadeComplement proteinsComplement factors

Inhibition of specific complement proteins (e.g., C3, C5, Factor B, Factor D, C1s) or receptors (C5aR1) to prevent the formation of the membrane attack complex (MAC), reduce opsonization, or block pro-inflammatory signaling [Nature Reviews Drug Discovery, 2021].