The complement system is part of the innate immune system that helps defend the body against pathogens. It was discovered in 1894 and consists of proteins that flow freely in the blood and can quickly reach sites of infection. When activated, complement proteins trigger inflammation, attract immune cells, coat pathogens for destruction, and can even directly kill pathogens. There are three pathways of complement activation - the classical, lectin, and alternative pathways. Complement activation leads to the formation of the membrane attack complex that causes lysis of pathogen cell membranes.

1. COMPLEMENT THE LINK BETWEEN NON-SPECIFIC AND SPECIFIC IMMUNITY

3. resistant active immunization blood sample Bordet's Classical Experiment serum (antisera) Fresh serum Serum (Heat inactivated at 56º C)

4. Hans Joaquim Muller-Eberhard (May 5, 1927- March 3, 1998).

8. Pathways of Complement Activation CLASSICAL PATHWAY LECTIN PATHWAY ALTERNATIVE PATHWAY Activation of C5 MEMBRANE ATTACK COMPLEX (MAC) antibody dependent (Ac-Ag) antibody Independent (No Ac-Ag) Activation of C3 and generation of C5 convertase

9. Classical Pathway. C1 C1r C1s 1 2 3 4 5 6 Collagen- like tails C1q

10. Classical Pathway. Intact C1

11. Classical Pathway. Intact C1

12. Classical Pathway. Interaction with Ac Ac Ac Cell membrane Ag

14. Classical Pathway Ab C1qrs C4 b C4a

15. Ab C1qrs C4 b C2 b a

16. C4b2b (C3 convertase) Ab C1qrs C2 b C4 b

18. C2 b C4 b C3 C3 C3 C3

19. b C4b2b3b (C5 convertase) C2 b C4 b C3 C3 C3 C3 a

20. Generation of C5 convertase leads to the activation of the lytic pathway Lytic pathway

21. b C2 b C4 b C3 C3 b C5 b a C5 b a

22. b C8 C9 Lysis and cell death C5b C6 C7

23. Membrane Attack Complex

24. Membrane Attack Complex

26. Membrane Attack Complex

27. Membrane Attack Complex

29. Alternative Pathway C3 is spontaneously formed in serum C3 b C3 b C3 b C3 b C3 b C3 b

30. LPS LPS Bacterial surface Lipopolysaccharide C3 b C3 b

31. LPS Bacterial surface C3bBb (C3 convertase) b C8 C9 C3 b B a D C3 b P C5b C6 C7

33. Mannose-Binding Protein Pathway Macrophages

34. Mannose-Binding Protein Pathway Bacterial Surface (rich in carbohydrates) MBP MASP-1 MASP-2 C4 b C4a

35. Mannose-Binding Protein Pathway Bacterial Surface (rich in carbohydrates) MBP MASP-1 MASP-2 b C4 b C2 b a

38. Opsonization and Phagocytosis

39. Biological Effects of C5a

42. Biological Properties of C-activation Products Product Biological Effects Regulation C2b (prokinin) edema C1-INH C3a (anaphylatoxin) mast cell degranulation; enhanced vascular permeability; anaphylaxis carboxy-peptidase- B (C3-INA)

43. Biological Properties of C-activation Products Product Biological Effects Regulation as C3, but less potent (C3-INA) C4a (anaphylatoxin) opsonization; phagocytosis C4b (opsonin) C4-BP, factor I C3b (opsonin) opsonization; phagocyte activation factors H & I

44. Biological Properties of C-activation Products Product Biological Effects Regulation anaphylactic as C3, but much more potent; attracts & activates PMN causes neutrophil aggregation, stimulation of oxidative metabolism and leukotriene release C5a ( chemotactic factor ) carboxy-peptidase-C (C3-INA) C5b67 protein-S chemotaxis, attaches to other membranes

46. C1-inhibitor deficiency: angioedema