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Effector mechanisms of humoral immunity

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  1. Effector mechanisms of humoral immunity The Complement System (C’) Activation pathways Effector functions Regulation of complement activation

  2. Jules Bordet (1870-1961) 1919. Nobel prize For complement-mediated bacteriolysis Complement system (complements i.e. assists functions of antibody)

  3. Complement system Consists of serum and cell surfaceproteins involved in defense against pathogens and tissue damage mediated by antibodies Effector mechanism of both innate and adaptive humoral immunity

  4. Complement system • Over 30 serum and cell surface proteins: • Complement components • (in serum inactive, activated sequentially as a cascade) • Complement receptors • (cell surface, recognize activated components) • Regulatory proteins of complement • (both in serum and cell surface, inhibit activated components)

  5. Complement system Pathways of activation - Classical - Alternative - Lectin

  6. Activation and functions of complement (overview)

  7. Activation pathway Early steps Late steps Classical C1, C4, C2 C3, C5, C6, C7, C8, C9 C3, C5, C6, C7, C8, C9 MBL, C4, C2 Lectin Alternatve C3, B, D (P) C3, C5, C6, C7, C8, C9

  8. Ag-Ab complex (microorganism and IgG or IgM Ab) a C1 Classical C4 b C2 Lectin MBL C3 convertase C5 convertase microorganism D B Effector functions (elimination of pathogen) Alternatve C3 microorganism Early steps Late steps

  9. Early steps of complement activation B D MBL MASP P

  10. Late steps of complement activation

  11. MEMBRANE ATTACK COMPLEX C6 C7 C8 C9 IgG IgM Lysis C5-C9 MAC Bacterium C5a C5b C5 Activated C1 C2 C4 C3 CONVERTASE C4b2b3b C4a C4b C2b C2a C4b2b C5 CONVERTASE C3 C3b C3a C1

  12. MEMBRANE ATTACK COMPLEX C6 C7 C8 C9 Lysis C5-C9 MAC Bacterium C5a C5b C5 C2 C4 C3 CONVERTASE C4b2b3b C4a C4b C2b C2a C4b2b C5 CONVERTASE C3 C3b C3a MBL MASP

  13. C3a C3b C3 Alternative C5 convertase Ba Bb C3bB C3bBb C3b C3bBb3b Alternative C3 convertase Factor B Factor D Bacterium C5-C9 MAC C5b C5 C5a MEMBRANE ATTACK COMPLEX C9 C8 C7 C6 C3 Properdin Lysis

  14. Effector functions of activated complement • - Cytolysis (MAC)

  15. Cytolysis (MAC)

  16. Effector functions of activated complement • - Cytolysis (MAC) • - Opsonization (C3b, C4b)

  17. Opsonization and phagocytosis (C3b, C4b)

  18. Effector functions of activated complement • - Cytolysis (MAC) • - Opsonization (C3b, C4b) • - Stimulation of inflammation (C5a, C3a, C4a)

  19. Stimulation of inflammatory rections (C5a, C3a, C4a) Activation of mast cells and neutrophils (anaphylatoxins)

  20. Effector functions of activated complement • - Cytolysis (MAC) • - Opsonization (C3b, C4b) • - Stimulation of inflammation (C5a, C3a, C4a) • - Stimulation of humoral response (C3d)

  21. Stimulation of humoral immunity (B cells)

  22. Effector functions of activated complement • - Cytolysis (MAC) • - Opsonization (C3b, C4b) • - Stimulation of inflammation (C5a, C3a, C4a) • - Stimulation of humoral response (C3d) • - Immune complex clearance (C3b)

  23. Immune complex clearance (C3b)

  24. Immune complex clearance (C3b)

  25. Regulatory proteins of complement

  26. Regulatory proteins of complement

  27. Complement system (animation) http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_1.html

  28. Laboratory tests for complement assesment Quantification of compoments (C3, C4, MBL - RID, nephelometry) - concentration: g/L (mg/ml) Functional tests for classical and alternative pathway of activation

  29. 1. Activation of complement system is a. mannose binding lectin (MBL) 2. Complement activation pathways are b. effector mechanism of innate and adaptive immunity 3. Central role in complement activation belongs to c. factor B, factor D, properdin 4. First component in lectin pathway is d. classical, alternative and lectin 5. Activators of classical pathway are e. C1, C4, C2 6. Components of alternative pathway are f. IgM and IgG bound to antigen 7. Proteins involved in early steps of classical pathway are g. C3 component Important opsonin is h. MAC 8. 9. Inflammatory reactions are induced by i. C3b 10. Osmotic lysis of microbes are mediated by j. C3a, C4a and C5a 1._____ b 2._____ d 3._____ g 4._____ a 5._____ f 6.____ c 7.____ e 8.____ i 9.____ j 10.____ h