π‘οΈ The complement system is a crucial part of the innate immune system, made of plasma proteins working together to boost antibody and phagocyte function.
It promotes pathogen clearance, inflammation, and can directly lyse microbes via the membrane attack complex.
π Key Concepts
- Components of the Complement System :
- βοΈ Over 30 proteins and fragments.
- Includes complement proteins (C1βC9), regulators, and receptors.
π£οΈ Pathways of Complement Activation
- π Classical Pathway :
- Triggered by antibodies bound to antigens.
- C1q recognises antigenβantibody complexes β activates C1r & C1s.
- Produces C3 convertase (C4b2a) β splits C3 into C3a & C3b.
- π Lectin Pathway :
- Triggered by mannose-binding lectin (MBL) or ficolins on pathogen carbohydrates.
- Activates MASPs β cleave C4 & C2 β C3 convertase (C4b2a).
- π Alternative Pathway :
- Triggered directly by pathogen surfaces.
- Spontaneous C3 hydrolysis β C3bBb convertase (stabilised by properdin).
βοΈ Functions of the Complement System
- ποΈ Opsonization :
- C3b coats pathogens β recognised & phagocytosed by macrophages/neutrophils.
- π₯ Cell Lysis :
- MAC (C5b6789) punches holes in membranes β pathogen death.
- π₯ Inflammation :
- Anaphylatoxins (C3a, C4a, C5a) recruit & activate immune cells, intensifying inflammation.
- π§Ή Immune Complex Clearance :
- Immune complexes bind RBCs β transported to liver/spleen for macrophage removal.
π§― Regulation of the Complement System
- Regulatory Proteins :
- π§© Factor H β regulates alternative pathway, inactivates C3b.
- π« CD55 (DAF) β accelerates decay of C3/C5 convertases.
- π CD59 (Protectin) β blocks MAC formation on host cells.
- π C1 Inhibitor (C1-INH) β inactivates C1r, C1s, MASPs (classical/lectin control).
π₯ Clinical Relevance
- 𧬠Complement Deficiencies :
- Inherited defects β recurrent infections & autoimmunity (e.g. C3, C5βC9 deficiencies).
- π Paroxysmal Nocturnal Haemoglobinuria (PNH) :
- Loss of GPI-anchored CD55 & CD59 β unregulated complement attack on RBCs.
- Symptoms: haemolysis, haemoglobinuria, fatigue, thrombosis.
- π€ Autoimmune Diseases :
- Complement contributes to tissue injury in SLE, RA, etc.
- π Therapeutics :
- Complement inhibitors (e.g. eculizumab) treat PNH, aHUS, and other complement-driven disorders.
π Summary
π§© The complement system = innate defence + antibody booster.
Core roles: opsonisation, lysis, inflammation, immune complex clearance.
Balance is vital β too little β infection risk; too much β autoimmunity & tissue damage.