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 MANNOSEBINDING 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

DEGRADATION OF SPONTANEOUSLY PRODUCED C 3 B C 3 c I C 3 b C 3 dg i. C 3 b

C 3 B STABILIZATION AND C 5 ACTIVATION C 3 a C 3 b finds an activator (protector) membrane P C 3 b This is stable C 5 convertase D of the alternative pathway Bb C 3 b

C 3 B REGULATION ON SELF AND ACTIVATOR SURFACES C 3 b

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 CACTIVATION PRODUCTS Product C 3 a (anaphylatoxin) Biological Effects Regulation mast cell degranulation; carboxypeptidase- B enhanced vascular (C 3 -INA) permeability; anaphylaxis

BIOLOGICAL PROPERTIES OF CACTIVATION 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 CACTIVATION 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

COMPLEMENT LEVEL Complement levels may be decreased due to: a) hereditary (relatively rare) b)acquired deficiency 1) increased consumption 2) decreased production ﺳﻄﺢ پﺮﻭﺗﺌیﻦ ﻫﺎی کﻤپﻠﻤﺎﻥ ﻣﻌﻤﻮﻻ ﻫﻤﺮﺍﻩ ﺑﺎ پﺮﻭﺗﺌیﻦ ﻫﺎی ﻓﺎﺯ ﺣﺎﺩ . ﺩﺭﺯﻣﺎﻥ ﺍﻟﺘﻬﺎﺏ ﺣﺎﺩ یﺎ ﻣﺰﻣﻦ ﺍﻓﺰﺍیﺶ ﻣی یﺎﺑﺪ 44