2009B15 Describe the complement system.

Definition

·   Series of 11 zymogens i.e. inactive precursors

·   Part of innate humoral immune system

·   Produced by the liver

Key features

·   Inhibition by regulator proteins e.g. C1 esterase inhibitor (deficient in hereditary angioedema)

·   Multiple activation pathways converge at cleavage of C3 into C3a and C3b

·   Activation results in formation of membrane attack complex (MAC)

Classical pathway

·   Activation by

o Antigen-antibody complexes (IgM >> IgG)

o Aggregated antibodies

o CRP

·   C3 convertase: C4b2b

Alternative pathway

·   Continuous low level activation

·   Spontaneous thioester hydrolysis of C3

·   C3 convertase: C3bBb

Lectin pathway

·   Homologous to the classical pathway

·   Mannose-binding lectin is the opsonin

·   Mannose present on surfaces of parasites, Candida, viruses etc.

·   C3 convertase: C4b2b

Final common pathway

·   End result of each activation pathway

·   C5b6789 combine to form MAC:

o Membrane pore -> lysis

o Opsonisation for phagocytosis by neutrophils, macrophages

o Chemotaxis

o Mast cell degranulation