Complement system

The complement system is a network of more than 30 plasma and membrane-bound proteins that constitute an effector arm of innate immunity, activated through three converging pathways — classical (antibody-dependent), lectin, and alternative — all leading to cleavage of C3 and C5 and ultimately the formation of the membrane attack complex (C5b-9). Core functions include opsonisation of pathogens for phagocytosis, direct lysis of gram-negative bacteria and enveloped viruses, recruitment of inflammatory cells via anaphylatoxins C3a and C5a, and clearance of apoptotic debris. With aging, complement dysregulation — including diminished activation capacity alongside paradoxical chronic low-level activation — has been implicated in age-related macular degeneration (AMD), where variants in complement factor H (CFH) substantially modify genetic risk, and in neuroinflammation, where complement-mediated synaptic pruning may become pathologically excessive in conditions such as Alzheimer's disease.

Last reviewed: May 2, 2026