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Complement systemComplement system
C was discovered several years ago as a C was discovered several years ago as a heat labile of normal plasma that augment heat labile of normal plasma that augment opsonozation of bacteria by opsonozation of bacteria by Ab.coplement Ab.coplement the antibacterial activity of Abthe antibacterial activity of Ab
Consist of approximately 30 serum Consist of approximately 30 serum moleculesmolecules
10% of the total serum proteins10% of the total serum proteins One of the major defense system of the One of the major defense system of the
bodybody
Major function of the complement Major function of the complement systemsystem
Control of inflammatory reaction and Control of inflammatory reaction and chemotaxischemotaxis
Clearance of the immune complexesClearance of the immune complexes Cellular activation and antimicrobial Cellular activation and antimicrobial
defensedefense It is a major effector in immuno-It is a major effector in immuno-
pathological diseasespathological diseases
Complement componentsComplement components
C1(C1q, C1r, C1s ) factor BC1(C1q, C1r, C1s ) factor B C2(C2a, C2b) factor DC2(C2a, C2b) factor D C3(C3a, C3b) DAF, CD55C3(C3a, C3b) DAF, CD55 C4(C4a, C4b) CR1,CD35C4(C4a, C4b) CR1,CD35 C5(C5a, C5b) factor H C5(C5a, C5b) factor H C6 factor IC6 factor I C7C7 C8C8 C9C9
Complement activationComplement activation
1-classical pathway which is activated 1-classical pathway which is activated by Ab bound to Agby Ab bound to Ag
2-the lectin pathway activated by 2-the lectin pathway activated by carbohydratescarbohydrates
3-Alternative pathway activated in the 3-Alternative pathway activated in the presence of various microbial presence of various microbial pathogenpathogen
The protein of the system act in The protein of the system act in enzyme cascadeenzyme cascade
consequences of the complement consequences of the complement activationactivation
1-it generate large numbers of 1-it generate large numbers of activated complement proteins that activated complement proteins that bind covalently to pathogens, bind covalently to pathogens, opsonizingopsonizing them for engulfment by them for engulfment by phagocytes bearing receptors for phagocytes bearing receptors for complement complement
2-the small fragments of some 2-the small fragments of some complement proteins act as complement proteins act as chemo-chemo-attractants attractants to recruit more phagocytes to recruit more phagocytes to the site of complement activation to the site of complement activation and also to activate these phagocytesand also to activate these phagocytes
3-the terminal complement 3-the terminal complement components components damage certain bacteriadamage certain bacteria by creating pores in the bacterial by creating pores in the bacterial membrane membrane
Overview of the main components Overview of the main components and effector actions of complementand effector actions of complement
C1 complexC1 complex C1q bind to Ab C1q bind to Ab
complexed with Agcomplexed with Ag C1q can also bind C1q can also bind
directly to the surface directly to the surface of some pathogenesof some pathogenes
C1q bind to 2C1r and C1q bind to 2C1r and 2C1s zymogene2C1s zymogene
Binding of C1q heads Binding of C1q heads to the pathogene to the pathogene surface cause surface cause enzymatic acivity of enzymatic acivity of C1r, then cleave C1s C1r, then cleave C1s to generate serine to generate serine protease protease
C3 and thioester bondC3 and thioester bond
The The αα chain of C3 and chain of C3 and C4 contain a C4 contain a thioester thioester bond between cystein bond between cystein and a glutamine, and a glutamine, fallowing cleavage to fallowing cleavage to C3a & C3b ,allowing C3a & C3b ,allowing C3b or C4b to form C3b or C4b to form covalent bond with covalent bond with protein and protein and carbohydratecarbohydrate
proteins of the classical pathway of proteins of the classical pathway of complement activationcomplement activation
The mannan binding lectin pathway is The mannan binding lectin pathway is
homologous to the classical pathwayhomologous to the classical pathway The MB-lectin pathway uses a protein very The MB-lectin pathway uses a protein very
similar to C1q to trigger the complement similar to C1q to trigger the complement cascadecascade
MB-lectin binds specifically to mannose MB-lectin binds specifically to mannose residues on pathogens surfacesresidues on pathogens surfaces
It is present at low conc. in normal plasma It is present at low conc. in normal plasma and during acute phase reaction its and during acute phase reaction its production increase by liver production increase by liver
Continue:Continue:
MB-lectin forms a MB-lectin forms a complex with two complex with two protease : MBL protease : MBL associated serine associated serine protease; MASP-1 protease; MASP-1 and MASP-2and MASP-2
Closely Closely homologous to C1r homologous to C1r and C1s and and C1s and activated to cleave activated to cleave C4 and C2C4 and C2
Hydrolysis of C3 causes initiation of Hydrolysis of C3 causes initiation of the alternative pathwaythe alternative pathway
Spontaneous hydrolysis of plasma C3Spontaneous hydrolysis of plasma C3 C3b is produced at a significant rate by C3b is produced at a significant rate by
spontaneous cleavage spontaneous cleavage (C3 tick over)(C3 tick over) through spontaneous hydrolysis of the through spontaneous hydrolysis of the thioester in the C3 to form thioester in the C3 to form C3(H2O),C3(H2O), allowing allowing binding factor B.binding factor B. factor D plasmafactor D plasma protease cleave factor B to form protease cleave factor B to form C3(H2O)BbC3(H2O)Bb a fluid C3 convertase, and can a fluid C3 convertase, and can cleave C3 to C3a and C3b. Most of these cleave C3 to C3a and C3b. Most of these C3b inactivated by H2O C3b inactivated by H2O
Relationship between the factors of Relationship between the factors of the alternative, classic and MBLthe alternative, classic and MBL
C5 convertaseC5 convertase C5 convertase are C5 convertase are
formed when a large formed when a large number of C3b on the number of C3b on the surface of pathogene surface of pathogene bind to C4b2b or bind to C4b2b or C3bBbC3bBb
C5a is the most C5a is the most anaphylatoxineanaphylatoxine
C5b initiate the C5b initiate the assembly of the assembly of the terminal complement terminal complement componentcomponent
Anaphylatoxins : C4a,C3a and C5a Anaphylatoxins : C4a,C3a and C5a causes local inflammationcauses local inflammation
C5a is more active C5a is more active than C3a which is than C3a which is more active than C4amore active than C4a
C5a is a potent mast C5a is a potent mast cell activation, cell activation, degranulate mast cell degranulate mast cell mediators; histamin mediators; histamin and TNFand TNFαα induce induce inflammationinflammation
C5a can enhance C5a can enhance phagocytosis of phagocytosis of opsonised opsonised microorganismmicroorganism