What is the complement system?
A system of soluble and membrane-bound plasma proteins that act as innate immune effector molecules to detect and destroy microorganisms.
Which arm of immunity does complement belong to?
Innate immunity (but it links innate and adaptive immunity)
Why are complement proteins synthesised in an inactive form?
To prevent uncontrolled activation and damage to host tissues
What are the 3 main outcomes of complement activation?
Opsonisation, inflammation, and lysis
Name the 3 complement activation pathways?
What triggers the classical pathway?
Antibody- antigen complexes (IgG or IgM)
What triggers the lectin pathway?
Binding of MBL or ficolins to microbial carbohydrate structures
What triggers the alternative pathway?
Spontaneous C3 activation amplified on pathogen surfaces
What key component do all 3 pathways converge on?
C3
What are the initiator molecules in the classical pathway?
C1q (with C1r and C1s)
What are the initiator molecules in the lectin pathway?
Mannose-binding lectin (MBL) and ficolins
What role does C1q play?
It recognises and binds antibody- antigen complexes
What are C1r and C1s?
Serine proteases that cleave C4 and C2
What are MASPs?
MBL- associated serine proteases that activate complement in the lectin pathway
What is a convertase?
An enzyme complex that cleaves complement proteins to drive the cascade
What is the C3 convertase of the classical and lectin pathways?
C4b2a
What is the C3 convertase of the alternative pathway?
C3bBb
What does C3 convertase do?
Cleaves C3 into C3a and C3b
How is the C5 convertase formed in the classical pathway?
C4b2a + C3b = C4b2a3b
How is the C5 convertase formed in the alternative pathway?
C3bBb + C3b = C3bBb3b
What is opsonisation?
The coating of pathogens with molecules that enhance phagocytosis
What is the main complement opsonin?
C3b
How does C3b enhance phagocytosis?
It binds to complement receptors on phagocytes, improving pathogen recognition and uptake
What are anaphylatoxins?
Small component fragments that induce inflammation