bacteria Patient serum bacteria Heated patient serum bacteria

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bacteria Patient serum bacteria Heated patient serum bacteria No immune fresh serum Cell Lysis

bacteria Patient serum bacteria Heated patient serum bacteria No immune fresh serum Cell Lysis No Lysis Heated patient serum Cell Lysis 1

Pathways of complement activation CLASSICAL PATHWAY antibody dependent LECTIN PATHWAY ALTERNATIVE PATHWAY antibody independent

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

Components of the Classical Pathway C 1 r C 1 s Ca++ C 1

Components of the Classical Pathway C 1 r C 1 s Ca++ C 1 q C 2 C 1 complex C 3 C 4

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Classical Pathway Generation of C 3 -convertase C 1 r C 1 s Ca++

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

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

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

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

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

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 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

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

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

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

 • PTXs + C 1 q complement activation Binding to C 1 q

• PTXs + C 1 q complement activation Binding to C 1 q Receptors on phagocytes opsonization

Components of the alternative pathway D C 3 B P

Components of the alternative pathway D C 3 B P

Spontaneous C 3 activation Generation of C 3 convertase H 2 O C 3

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

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

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

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

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

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

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

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

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

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;

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)

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,

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). 45

 Th e effects of these deficiencies highlight the importance of the early complement

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 46

 A deficiency in MBL, the first component of the lectin pathway, has been

A deficiency in MBL, the first component of the lectin pathway, has been shown to be relatively common, and results in serious pyrogenic (fever-inducing) 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. 47