Expansion
Classical, alternative and lectin pathways converging on C3
Expansion
Three activation pathways
- Classical: antigen-antibody complexes (IgM or IgG) binding C1
- Alternative: spontaneous C3 hydrolysis stabilised on microbial surfaces; part of innate immunity
- Lectin: mannose-binding lectin recognising microbial sugars
All converge on C3 convertase, splitting C3 into C3a and C3b.
Functions
- Opsonisation: C3b coating organisms for phagocytosis. The most important function
- Chemotaxis and inflammation: C3a and C5a are anaphylatoxins, causing mast cell degranulation and neutrophil recruitment
- Lysis: C5 to C9 form the membrane attack complex
Deficiencies are instructive:
- C5 to C9 (terminal) deficiency: recurrent Neisseria infection specifically, since the membrane attack complex is needed against these organisms. Also the risk with eculizumab, hence meningococcal vaccination
- C1 esterase inhibitor deficiency: hereditary angioedema, which does not respond to adrenaline or steroids
- Early classical component deficiency: lupus-like disease