Human complement system (Complement system)

The human complement system is a sophisticated network of over 30 plasma and cell-surface proteins that serves as a primary effector of the innate immune system. It is organized into three distinct activation 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. Beyond lysis, the system facilitates opsonization for phagocytosis and generates potent anaphylatoxins (C3a, C5a) that drive inflammatory cell recruitment and activation. While vital for host defense, dysregulation or overactivation of the complement cascade is a central driver in various rare and chronic diseases, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Therapeutic intervention typically involves monoclonal antibodies, small molecules, or peptides that target key nodes like C5 or C3 to mitigate tissue damage. However, systemic inhibition of the complement system significantly increases patient susceptibility to life-threatening infections by encapsulated bacteria, necessitating strict vaccination protocols and monitoring.

Other names

Complement cascadeComplementInnate immune complement system

Inhibition of specific complement components (e.g., C1s, C3, C5, Factor B, Factor D) or antagonism of complement receptors (e.g., C5aR1) to prevent cascade activation, opsonization, and the formation of the membrane attack complex (MAC).