Paper I
Question
List role of complement in health and disease
Answer
The complement system is a cascade of plasma proteins central to innate immune defence, activated via three pathways (classical, alternative, lectin) that converge on a common terminal pathway.
Role in health (protective functions):
- Opsonization — C3b coats pathogens, enhancing phagocytosis via complement receptors on phagocytes.
- Inflammation — anaphylatoxins (C3a, C5a) recruit and activate neutrophils/mast cells, promoting local inflammation and vascular permeability.
- Direct lysis — the membrane attack complex (C5b-9) forms pores in the membrane of Gram-negative bacteria and other target cells, causing osmotic lysis.
- Immune complex clearance — complement helps solubilize and clear circulating immune complexes, preventing their pathological tissue deposition.
- Bridge to adaptive immunity — C3d bound to antigen enhances B-cell activation via the complement receptor CR2.
Role in disease (pathological consequences):
- Complement deficiencies predispose to specific infections — deficiency of early classical pathway components (C1, C2, C4) is associated with increased risk of SLE-like autoimmune disease (impaired immune-complex clearance); deficiency of terminal components (C5-C9) predisposes specifically to recurrent Neisserial infections (gonococcal/meningococcal), since the membrane attack complex is particularly important for lysing these organisms; C3 deficiency causes severe, recurrent pyogenic infections.
- Hereditary angioedema — C1 esterase inhibitor deficiency causes uncontrolled complement (and kinin) activation, producing recurrent episodic angioedema.
- Immune-complex-mediated (Type III hypersensitivity) diseases — excessive/uncontrolled complement activation by deposited immune complexes contributes to tissue damage in SLE, post-streptococcal glomerulonephritis, and serum sickness.
- Paroxysmal nocturnal haemoglobinuria — deficiency of complement-regulatory proteins (CD55/CD59) on red cells leads to complement-mediated haemolysis.