3 complement pathways
Classical, Lectin, Alternative
Which pathway involves antibodies
Classical:
C1q binds to pathogen Or Ag:Ab complex
What induces lectin pathway
MBL or ficolin binding to carbohydrates on pathogen surface
What induces alternative pathway
Soluble C3 undergoes spontaneous hydrolysis
Function of complement
- Bacterial cell wall lysis (MAC)
- Opsonisation
- Recruitment of neutrophils (chemotaxis)
- Activation of mast cells + basophils
- Removal of immune complexes
Function of C3b
- bind to C3 convertases to form C5 convertases
- opsonin
- binds to Factor B, which is cleaved to Bb (by factor D). Properdin stabilises C3b-Bb complex: inflammation, phagocytosis, neutralisation of viruses
Function of C5, 6, 7, 8, 9
Formation of MAC (membrane attack complex)
C5b + 6 + 7: bind to membrane via C7
C5b + 6 + 7 + 8: insert into cell membrane
C5b + 6 + 7 + 8 + 9: polymerises, forms pore in in membrane (with multiple C9 molecules).
Leads to cell lysis due to entry of water and Na+
Role of anaphylotoxins (C3a, C4a, C5a)
- local inflammatory response
- increase vascular permeability
- smooth muscle contraction
- induction of adhesion molcules
- recruitment of phagocytes to inflammation site
Describe complement mediated phagocytosis
- Cr1 on macrophage binds C3b on bacterium
- Endocytosis of bacterium by macrophage
- When antibody binds to Fc receptor, bacteria are phagocytosed
- Lysosomes fuse with these vesicles, delivering enzymes that degrade the bacteria
What happens to Ag:Ab complexes formed in circulation
CR1 on erythrocytes bind Ab:Ag complexes via bound C3b
Ag:Ab complexes removed to spleen and liver where cells remove the immune complexes from the erythrocyte surface
Complement proteins + protease involved in classical pathway
C1q, C4, C2
Protease: C1s
Complement proteins + protease involved in lectin pathway
C2, C4
Protease: MASP2
Complement proteins + protease involved in alternative pathway
C3
Protease: Factor D
Effect of CD59 on MAC formation
Prevents final assembly of MAC at the C8 to C9 stage
Where are most complements made
Liver (not stem cell).
Thus BM transplant would not be effective for complement deficiency patients.
(BM transplant would work for CGD where phagocytes do not have working NADPH oxidase)
