2. Complement system

3. references

4. C was discovered several years ago as a heat labile of normal plasma that augment opsonozation of bacteria by Ab.coplement the antibacterial activity of Ab C was discovered several years ago as a heat labile of normal plasma that augment opsonozation of bacteria by Ab.coplement the antibacterial activity of Ab Consist of approximately 30 serum molecules Consist of approximately 30 serum molecules 10% of the total serum proteins 10% of the total serum proteins One of the major defense system of the body One of the major defense system of the body

5. Major function of the complement system Control of inflammatory reaction and chemotaxis Control of inflammatory reaction and chemotaxis Clearance of the immune complexes Clearance of the immune complexes Cellular activation and antimicrobial defense Cellular activation and antimicrobial defense It is a major effector in immuno- pathological diseases It is a major effector in immuno- pathological diseases

6. Complement components C1(C1q, C1r, C1s ) factor B C1(C1q, C1r, C1s ) factor B C2(C2a, C2b) factor D C2(C2a, C2b) factor D C3(C3a, C3b) DAF, CD55 C3(C3a, C3b) DAF, CD55 C4(C4a, C4b) CR1,CD35 C4(C4a, C4b) CR1,CD35 C5(C5a, C5b) factor H C5(C5a, C5b) factor H C6 factor I C6 factor I C7 C7 C8 C8 C9 C9

7. Complement activation 1-classical pathway which is activated by Ab bound to Ag 1-classical pathway which is activated by Ab bound to Ag 2-the lectin pathway activated by carbohydrates 2-the lectin pathway activated by carbohydrates 3-Alternative pathway activated in the presence of various microbial pathogen 3-Alternative pathway activated in the presence of various microbial pathogen The protein of the system act in enzyme cascade The protein of the system act in enzyme cascade

8. Complement activation

9. consequences of the complement activation 1-it generate large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement 1-it generate large numbers of activated complement proteins that bind covalently to pathogens, opsonizing them for engulfment by phagocytes bearing receptors for complement

10. 2-the small fragments of some complement proteins act as chemo- attractants to recruit more phagocytes to the site of complement activation and also to activate these phagocytes 2-the small fragments of some complement proteins act as chemo- attractants to recruit more phagocytes to the site of complement activation and also to activate these phagocytes 3-the terminal complement components damage certain bacteria by creating pores in the bacterial membrane 3-the terminal complement components damage certain bacteria by creating pores in the bacterial membrane

11. Overview of the main components and effector actions of complement

12. C1 complex C1q bind to Ab complexed with Ag C1q bind to Ab complexed with Ag C1q can also bind directly to the surface of some pathogenes C1q can also bind directly to the surface of some pathogenes C1q bind to 2C1r and 2C1s zymogene C1q bind to 2C1r and 2C1s zymogene Binding of C1q heads to the pathogene surface cause enzymatic acivity of C1r, then cleave C1s to generate serine protease Binding of C1q heads to the pathogene surface cause enzymatic acivity of C1r, then cleave C1s to generate serine protease

13. C3 and thioester bond The α chain of C3 and C4 contain a thioester bond between cystein and a glutamine, fallowing cleavage to C3a & C3b,allowing C3b or C4b to form covalent bond with protein and carbohydrate The α chain of C3 and C4 contain a thioester bond between cystein and a glutamine, fallowing cleavage to C3a & C3b,allowing C3b or C4b to form covalent bond with protein and carbohydrate

14. Classical pathway of complement activation

15. proteins of the classical pathway of complement activation

16. The mannan binding lectin pathway is homologous to the classical pathway The MB-lectin pathway uses a protein very similar to C1q to trigger the complement cascade The MB-lectin pathway uses a protein very similar to C1q to trigger the complement cascade MB-lectin binds specifically to mannose residues on pathogens surfaces MB-lectin binds specifically to mannose residues on pathogens surfaces It is present at low conc. in normal plasma and during acute phase reaction its production increase by liver It is present at low conc. in normal plasma and during acute phase reaction its production increase by liver

17. Continue: MB-lectin forms a complex with two protease : MBL associated serine protease; MASP-1 and MASP-2 MB-lectin forms a complex with two protease : MBL associated serine protease; MASP-1 and MASP-2 Closely homologous to C1r and C1s and activated to cleave C4 and C2 Closely homologous to C1r and C1s and activated to cleave C4 and C2

18. Hydrolysis of C3 causes initiation of the alternative pathway Spontaneous hydrolysis of plasma C3 Spontaneous hydrolysis of plasma C3 C3b is produced at a significant rate by spontaneous cleavage (C3 tick over) through spontaneous hydrolysis of the thioester in the C3 to form C3(H2O), allowing binding factor B. factor D plasma protease cleave factor B to form C3(H2O)Bb a fluid C3 convertase, and can cleave C3 to C3a and C3b. Most of these C3b inactivated by H2O C3b is produced at a significant rate by spontaneous cleavage (C3 tick over) through spontaneous hydrolysis of the thioester in the C3 to form C3(H2O), allowing binding factor B. factor D plasma protease cleave factor B to form C3(H2O)Bb a fluid C3 convertase, and can cleave C3 to C3a and C3b. Most of these C3b inactivated by H2O

19. Alternative pathway of complement activation

20. Relationship between the factors of the alternative, classic and MBL

21. C5 convertase C5 convertase are formed when a large number of C3b on the surface of pathogene bind to C4b2b or C3bBb C5 convertase are formed when a large number of C3b on the surface of pathogene bind to C4b2b or C3bBb C5a is the most anaphylatoxine C5a is the most anaphylatoxine C5b initiate the assembly of the terminal complement component C5b initiate the assembly of the terminal complement component

22. Anaphylatoxins : C4a,C3a and C5a causes local inflammation C5a is more active than C3a which is more active than C4a C5a is more active than C3a which is more active than C4a C5a is a potent mast cell activation, degranulate mast cell mediators; histamin and TNFα induce inflammation C5a is a potent mast cell activation, degranulate mast cell mediators; histamin and TNFα induce inflammation C5a can enhance phagocytosis of opsonised microorganism C5a can enhance phagocytosis of opsonised microorganism

23. The terminal complement components

24. Membrane attack complex

25. Regulatory components

28. Functional protein classes in the complement system