complementmediated

Complement-mediated refers to processes driven by the complement system, a network of plasma proteins and membrane receptors that participate in innate and adaptive immunity. The system detects pathogens and immune complexes, promotes their clearance, and modulates inflammation. It acts in host defense but requires tight regulation to avoid damage to healthy tissues.

Activation and effector functions occur through three main pathways—classical, lectin, and alternative—that converge on C3 activation. This leads to the formation of C3 convertases, opsonization by C3b to enhance phagocytosis, and production of inflammatory mediators C3a and C5a. Further downstream, C5 convertase initiates assembly of the membrane attack complex (MAC, C5b-9), which can lyse susceptible cells. Complement-mediated processes also coordinate adaptive responses by enhancing antigen presentation and antibody responses.

Regulation is essential to prevent host injury. Regulatory proteins such as Factor H and Factor I control activation in fluid and on surfaces, while decay-accelerating factors (CD55/DAF) and membrane cofactor protein (CD46) limit amplification on host cells. CD59 inhibits MAC formation on human cell membranes. Defects or deficiencies in these regulators can lead to unrestrained complement activity and tissue injury.

Clinical relevance includes a spectrum of protective and pathogenic roles. Complement-mediated injury contributes to autoimmune and inflammatory diseases, including paroxysmal nocturnal hemoglobinuria, C3 glomerulopathy, atypical hemolytic uremic syndrome, and age-related macular degeneration. Therapeutic approaches target specific components (for example, C5 inhibitors like eculizumab) or early steps (C1 inhibitors, C3 inhibitors) to mitigate disease activity.

Overall, the concept of complement-mediated emphasizes how this system balances defense and damage, with implications for infection, autoimmunity, and transplantation.