2. Effector mechanisms of humoral immunity 1

3.  Physiologic function of Abs is defence against extracellular microbes and microbial toxins  Defects in Ab production result in increased susceptibility to infections  Ab mediated elimination of Ags requires participation of other effector systems  Produced Abs in lymphoid organs, perform their effector functions at sites distant from their production  Many of the effector functions of Abs are mediated by the heavy chain constant regions of Igs and different isotypes serve different effector functions  The requirement for Ag binding ensures that Abs activate various effector mechanisms only when they are needed

4. Neutralization of microbes and microbial toxins 3

5. 4

6. 5

7. Opsonization 6

9. Antibody-dependent cell- mediated cytotoxicity 8

11. 10

12. 11

13. Host benefit: –opsonization to enhance phagocytosis –phagocyte attraction and activation –lysis of bacteria and infected cells –regulation of antibody responses –clearance of immune complexes –clearance of apoptotic cells Host detriment: –Inflammation, anaphylaxis

14. C1(qrs), C2, C3, C4, C5, C6, C7, C8, C9 factors B, D, H and I, properdin (P) mannose binding lectin (MBL), MBL associated serine proteases (MASP-1 MASP-2) C1 inhibitor (C1-INH, serpin), C4-binding protein (C4-BP), decay accelerating factor (DAF), Complement receptor 1 (CR1), protein- S (vitronectin)

15. CLASSICAL PATHWAY ALTERNATIVE PATHWAY activation of C5 LYTIC ATTACK PATHWAY antibody dependent LECTIN PATHWAY antibody independent Activation of C3 and generation of C5 convertase

16. C4 C2 C3 C1 complex Ca ++ C1r C1s C1q

17. Ca ++ C1r C1s C1q C4 C4a b

18. C4b Mg ++ C4a Ca ++ C1r C1s C1q C2 C2b a C2 a _____ C4b2a is C3 convertase

19. C4b Mg ++ C4a Ca ++ C1r C1s C1q C2b C2 a C3 C3a b ________ C4b2a3b is C5 convertase; it leads into the Membrane Attack Pathway

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

21. C6 C9C9 C8 C7 C5

22. C3b C2 a C4b C5 b C5a

23. C5 b C6 C7

24. C5 b C6 C7 C8 C9C9 C9C9 C9C9 C9C9 C9C9 C9C9 C9C9 C9C9 C9C9

25.  CR-I promote phagocytosis  CR-II coreceptor for B cell activation  CR-III phagocytosis  CR-IV phagocytosis 24

27. ProductBiological EffectsRegulation C3a (anaphylatoxin) mast cell degranulation; enhanced vascular permeability; anaphylaxis carboxy- peptidase- B (C3-INA)

28. ProductBiological EffectsRegulation 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

30. a( hereditary (relatively rare) b)acquired deficiency c) increased consumption d) decreased production  Complement protein levels are usually increased, along with other unrelated proteins called acute phase proteins, during acute or chronic inflammation 29

31.  Recurrent microbial infections (usually bacterial)  Autoimmune diseases, including SLE and vasculitis  Hereditary angioedema  Acquired angioedema  Various types of kidney disease, including: glomerulonephritis, lupus nephritis, membranous nephritis, IgA nephropathy  Malnutrition  Septicemia  Serum sickness (immune complex disease) 30