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Janeway 9.49 part 2

Janeway 9.49 part 2. Roitt 12.22. Roitt 4.1. A Cascade of Proteases Is A Biological Amplifier. Protease cascades as biological amplifiers. Ucker, 2000. Classical Activation Pathway. C4b. C3b. The Classical Activation Pathway. The small fragments act as soluble mediators. C3a. C2b.

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Janeway 9.49 part 2

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  1. Janeway 9.49 part 2

  2. Roitt 12.22

  3. Roitt 4.1

  4. A Cascade of Proteases Is A Biological Amplifier Protease cascades as biological amplifiers Ucker, 2000

  5. Classical Activation Pathway C4b C3b The Classical Activation Pathway The small fragments act as soluble mediators C3a C2b C5a C4a C3 C5 C6 C7 C8 C9 C2 C4 C1 MAC Ab C5b C6 C7 C8 C9 C2a Membrane The large fragments function by binding to membranes (esp. pathogen membranes) Ucker, 2002

  6. Roitt 4.2

  7. Janeway 9.36

  8. Janeway 9.34

  9. Janeway 9.35

  10. Janeway 9.32

  11. Janeway 9.37(i)

  12. Thioester mediated binding of C4b THIOESTER-MEDIATED BINDING OF C4b TO THE SURFACE OF APATHOGEN C4a C4 C4b C4b Pathogen Ucker, 2000

  13. Janeway 9.37(i-iii) Note C2a / C2b nomenclature is reversed here (figure taken from Janeway et al.)

  14. Roitt 4.7

  15. Thioester mediated binding of C3b THIOESTER-MEDIATED BINDING OF C3b TO THE SURFACE OF APATHOGEN C3a C3 C3b C3b Pathogen Ucker, 2000

  16. Roitt 4.16

  17. Roitt 4.8

  18. Roitt 12.10

  19. Amplification Loop Amplification Loop B C3b C3a C3bB D C3 Ba Properdin stabilization C3 C3 C3bBb (C3 convertase) One C3 convertase molecule cleaves many C3 molecules. C3b interacts with factor B, and more C3 convertase is generated. Hanley, 1998

  20. Roitt 12.13A

  21. Roitt 12.13

  22. Two Major Pathways for Complement Activation Classical Pathway Alternative Pathway C1 + Ag-Ab, C4, C2 Factors B, D, P , C3, + Bacteria C3 Initiation (C4b2a) C3 Convertase C3 Convertase (C3bBb) Amplification Loop Amplification (and production of biologically active fragments) C3a C3a C3 C3b C3b b (C4b2aC3b) C5 Convertase C5 Convertase (C3bBbC3b) C5 --> C5a + C5b C5b + C5a <-- C5 Membrane + C6 + C7 + C8 + C9 attack C5b6789 [MAC] Hanley, 1998

  23. Roitt 4.13 panel 1

  24. Janeway 9.49 part 2

  25. Complement is a self-limiting cycle Ucker, 2000

  26. Regulators Of Complement Activation • Regulators Of Complement Activation • Regulators of C3 convertase assembly and destruction:C4b-BP, MCP, CR1, Factor H, DAF (assembly),Factor I (destruction) • Regulators of the lytic pathway (MAC assembly inhibitors):HRF, MRL • Regulators of C1 esterase activity:C1INH(Deficiency = Hereditary Angioneurotic Edema) Ucker, 2000

  27. Roitt 4.7

  28. Roitt 4.12

  29. Roitt 12.11

  30. Roitt 4.13

  31. Complement Control Proteins (adapted from Janeway 9.50)

  32. Complement Receptors (adapted from Roitt 4.15)

  33. Leukocyte Adhesion Deficiency • Defects In Complement Receptor Proteins • Leukocyte Adhesion Deficiency Type I • Cells lack CR3 and CR4, which are Integrins (adhesion molecules) in addition to being Complement Receptors (CRs), hence the “LAD”phenotype. • CR3 and CR4 are composed of distinct  chains (CD11b and CD11c, respectively) complexed with a common 2 chain (CD18). • CR3 - M2- CD11b / CD18 (also known as Mac1) • CR4 - X2- CD11c / CD18 • Type I LAD is a deficiency of the 2 chain. • The major functional manifestation of LAD is the defective vascular adhesion of PMNs, with consequent defective extravasation. Ucker, 2000

  34. Roitt 12.19

  35. Roitt 18.16

  36. Roitt 12.22

  37. Deficiencies of components within the same pathway result in similar clinical manifestations. B C1 C4 D Properdin C2 C3 (I, H) Pyogenic infections Immune Complex Disease Neisserial infections Severe pyogenic infections Immune Complex Disease C5 C6 C7 Neisserial infections C8 C9 Hanley, 1998

  38. Janeway 9.31

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