5. Activation product of complement proteins (nomenclature) When enzymatically cleaved, the larger moiety , binds to the activation complex or membrane and the smaller peptide is released in the microenvironment Letter “b” is usually added to the larger, membrane-binding, peptide and “a” to the smaller peptide ( e.g. , C3b/C3a, C4b/C4a, C5b/C5a), EXCEPT C2 (the larger, membrane-binding moiety is C2a; the smaller on is C2b) Activated component are usually overlined: e.g. C1qrs
6. Pathways of complement activation CLASSICAL PATHWAY ALTERNATINE PATHWAY LECTIN PATHWAY activation of C5 LYTIC ATTACK PATHWAY antibody dependent antibody independent Activation of C3 and generation of C5 convertase
7. Components of the Classical Pathway C4 C2 C3 C1 complex Ca ++ C1r C1s C1q
8. Classical Pathway Generation of C3-convertase C4 Ca ++ C1r C1s C1q C4a b
9. Classical Pathway Generation of C3-convertase C4b Mg ++ C4a C2 C4b2a is C3 convertase Ca ++ C1r C1s C1q C2b a C2 a
10. Classical Pathway Generation of C5-convertase C4b Mg ++ C4a C2b C3 C 4b2a3b is C 5 convertase; it leads into the Membrane Attack Pathway Ca ++ C1r C1s C1q C2 a C3a b
12. Mannose-binding lectin pathway C4 C2 C4b2a is C3 convertase; it will lead to the generation of C5 convertase MASP MASP2 MBL C4b C4a C4b C2b C2a C2a
24. C3b stabilization and C5 activation C3 C5 B D P This leads to membrane attack pathway C3b C3b finds an activator (protector) membrane C3a b b C5a b
25. C5- convertase of the two pathways C3b B b C3b C5-convertase of the Alternative Pathway C5-convertase of the Classical and lectin Pathways C4b C2a C3b
26. Generation of C5 convertase leads to the activation of the Lytic pathway Lytic pathway
37. Biological properties of C-activation products Product Biological Effects Regulation as C3, but less potent (C3-INA) C4a (anaphylatoxin) opsonization; phagocytosis C4b (opsonin) C4-BP, factor I C3b (opsonin) opsonization; phagocyte activation factors H & I
38. Biological properties of C-activation products Product Biological Effects Regulation anaphylactic as C3, but much more potent; attracts & activates PMN causes neutrophil aggregation, stimulation of oxidative metabolism and leukotriene release C5a ( chemotactic factor ) carboxy-peptidase-C (C3-INA) C5b67 protein-S chemotaxis, attaches to other membranes