Pathways of complement activation CLASSICAL PATHWAY antibody dependent
Pathways of complement activation CLASSICAL PATHWAY antibody dependent LECTIN PATHWAY ALTERNATIVE PATHWAY antibody independent Activation of C 3 and generation of C 5 convertase activation of C 5 LYTIC ATTACK PATHWAY
Components of the Classical Pathway C 1 r C 1 s Ca++ C 1 q C 2 C 1 complex C 3 C 4
Classical Pathway Generation of C 3 -convertase C 1 r C 1 s Ca++ C 1 q C 4 b C 4 a
Classical Pathway Generation of C 3 -convertase C 4 a C 1 r C 1 s Ca++ C 1 q a 2 C C 2 b _____ Mg++ C 4 b 2 a is C 3 convertase C 4 b C 2 a
Classical Pathway Generation of C 5 -convertase C 4 a C 1 r C 1 s Ca++ C 1 q Mg++ C 2 b C 3 a ____ C 4 b 2 a 3 b is C 5 convertase; it leads into the Membrane Attack Pathway C 4 b C 2 a C 3 b
Lytic pathway Generation of C 5 convertase leads to the activation of the Lytic pathway
Components of the lytic pathway C 7 C 6 C 5 C 8 C 9
Lytic pathway C 5 -activation C 5 a C 5 b C 4 b C 2 a C 3 b
Lytic pathway assembly of the lytic complex C 6 C 7 C 5 b
Lytic pathway: insertion of lytic complex into cell membrane C 6 C 8 CC C 9 9 9 9 C 9 C C C 9 9 C 7 C 5 b
Components of mannose-binding lectin pathway C 4 MASP 2 MBL C 2 MASP 1
Mannose-binding lectin pathway C 2 b C 4 a MASP 1 MASP 2 MBL _____ C 4 b 2 a is C 3 convertase; it will lead to the generation of C 5 convertase C 4 b C 4 a 2 CC 2 C 4 b C 2 a
Components of the alternative pathway D C 3 B P
Spontaneous C 3 activation Generation of C 3 convertase H 2 O C 3 i D Bb C 3 a C 3 i. Bb complex has a very short half life
C 3 -activation the amplification loop If spontaneously-generated C 3 b is not degraded D C 3 a C 3 b Bb C 3 b
C 3 -activation the amplification loop D C 3 b C 3 a C 3 b Bb Bb C 3 b
C 3 -activation the amplification loop D Bb C 3 a C 3 a Bb C 3 b
C 3 -activation the amplification loop Bb C 3 a Bb C 3 b
C 3 -activation the amplification loop Bb C 3 a Bb C 3 b
ﺍﻧﻮﺍﻉ ﻣﻮﻟکﻮﻟﻬﺎی کﻨﺘﺮﻟی C 1 INH Membrane cofacto protein(MCP) Complement receptor-1(CR-1) Decay accelerating factor(DAF) factor H C 4 -binding protein(C 4 bp) CD 59 Factor I S-protein
Control of spontaneous C 3 activation via DAF prevents C 3 b factor B to C 3 b B DAF the binding of CR 1 Autologous cell membrane
Control of spontaneous C 3 activation via DAF dislodges factor Bb C 3 b Bb DAF C 3 b-bound Bb CR 1 Autologous cell membrane
Control of spontaneous C 3 activation via CR 1 Bb H Bb C 3 b DAF I i. C 3 b CR 1 DAF C 3 b Autologous cell membrane I i. C 3 b CR 1
C 5 -convertase of the two pathways C 5 -convertase of the Classical and lectin Pathways C 4 b C 2 a C 3 b C 5 -convertase of the Alternative Pathway C 3 b Bb C 3 b
Biological properties of C-activation products Product Biological Effects Regulation C 3 b (opsonin) opsonization; phagocyte activation factors H & I C 4 a as C 3, but less (anaphylatoxin) potent (C 3 -INA) C 4 b (opsonin) C 4 -BP, factor I opsonization; phagocytosis
Biological properties of C-activation products Product Biological Effects Regulation C 5 a (chemotactic factor) anaphylactic as C 3, but much more potent; attracts & activates PMN causes neutrophil aggregation, stimulation of oxidative metabolism and leukotriene release carboxypeptidase-B (C 3 -INA) C 5 b 67 chemotaxis, attaches to other membranes protein-S
The genetic deficiency of early components of the classical pathway (C 1 q, C 1 r/s, C 2, C 4) tend to be linked with autoimmune diseases whereas C 5 to C 9 may have enhanced susceptibilty to meningococcal disease. Deficiencies in complement predispose patients to infection via 2 mechanisms: (1) ineffective opsonization (2) defects in lytic activity (defects in MAC). 40
Th e effects of these deficiencies highlight the importance of the early complement reactions in generating C 3 b and C 3 b’s role in the solubilization and clearance of immune complexes. In addition, C 1 q has been shown to bind apoptotic blebs. In the absence of C 1 q binding, cells bearing these apoptotic blebs, or the blebs themselves, can act as autoantigens and lead to the development of autoimmune diseases Individuals with deficiencies in the early complement components may also suffer from recurrent infections by pyogenic (pus-forming) bacteria such as streptococci and staphylococci 41
A deficiency in MBL, the first component of the lectin pathway, has been shown to be relatively common, and results in serious pyrogenic (feverinducing) infections in babies and children. Children with MBL deficiency suffer from respiratory tract infections. People with C 3 deficiencies display the most severe clinical manifestations of any of the complement deficiency patients, reflecting the central role of C 3 in opsonization and in the formation of the MAC. 42
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