Question
Role of complement in immune response
Answer
Complement system: a group of about 30 heat-labile plasma/serum proteins (C1–C9 and regulatory proteins) that, upon sequential activation, mediate several key effector functions of both innate and adaptive immunity.
Pathways of activation:
- Classical pathway — triggered by antigen-antibody (IgM or IgG) complexes binding C1q.
- Alternative pathway — triggered directly by microbial surfaces (e.g., bacterial cell wall components), independent of antibody.
- Lectin pathway — triggered by mannose-binding lectin (MBL) binding to mannose residues on microbial surfaces.
All three pathways converge on the formation of C3 convertase, cleaving C3, leading to the common terminal pathway.
Roles of complement in the immune response:
- Opsonization — C3b (and its degradation product iC3b) coats the surface of pathogens, promoting their recognition and phagocytosis by macrophages/neutrophils bearing complement receptors (CR1, CR3) — one of the most important functions of complement.
- Chemotaxis/inflammation — anaphylatoxins C3a and C5a attract neutrophils and other inflammatory cells to the site of infection, and also trigger mast cell/basophil degranulation, increasing vascular permeability (contributing to the inflammatory response).
- Membrane Attack Complex (MAC) formation — the terminal complement components (C5b, C6, C7, C8, C9) assemble to form a pore in the target cell membrane, causing direct lysis of the pathogen (particularly effective against Gram-negative bacteria).
- Clearance of immune complexes — complement (C3b/C4b) binds to circulating immune complexes and facilitates their transport to and clearance by the liver/spleen via complement receptor-bearing erythrocytes and phagocytic cells, preventing pathological deposition (e.g., in glomeruli/vessel walls).
- Bridging innate and adaptive immunity — C3d binding to antigen enhances B-cell activation by co-engaging the B-cell receptor and the complement receptor CR2 (CD21), lowering the threshold for B-cell activation and antibody production.
- Viral neutralization — complement can directly neutralize some enveloped viruses by disrupting the viral envelope, and can also opsonize virus particles for phagocytic clearance.
Clinical relevance: complement deficiencies predispose to recurrent pyogenic infections (early component deficiencies) and increased susceptibility to Neisseria infections (deficiency of terminal MAC components C5-C9); dysregulated complement activation contributes to disease in conditions such as paroxysmal nocturnal haemoglobinuria and certain autoimmune/renal diseases.