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Antigen Processing & Presentation

Antigen Processing & Presentation. Hugh B. Fackrell. Antigen Processing & Presentation. Assigned Reading Content Outline Performance Objectives Key terms Key Concepts Short Answer Questions. Assigned Reading. Chapter: 10 pp 249-262 Janis Kuby’s Immunology 3rd Ed.

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Antigen Processing & Presentation

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  1. Antigen Processing & Presentation Hugh B. Fackrell

  2. Antigen Processing & Presentation • Assigned Reading • Content Outline • Performance Objectives • Key terms • Key Concepts • Short Answer Questions

  3. Assigned Reading • Chapter: 10 pp 249-262 • Janis Kuby’s Immunology 3rd Ed

  4. Self MHC Restriction of T Cells Role of Antigen Presenting Cells Two Presentation Pathways Cytosolic Pathway: Endogenous Antigens Endocytic Pathway: Exogenous Antigens Clinical Applications Content Outline

  5. MHC antigens codominate 53

  6. Mixed Lymphocyte Reaction 38

  7. Self MHC Restriction of T Cells • CD4+ & CD8+ cells • Antigen must be in cleft of MHC • MHC polymorphism • ~500 antigens/cleft

  8. Haplotype Restricted Cytotoxicity 56

  9. “Antigen Pulse” • “Antigen pulsed” macrophages • T helper (CD4+) cells can only be stimulated by macrophages with the same MHC Class II • Cytotoxic (CD8+) T cells can only be stimulated by macrophages with the same MHC Class I

  10. T Cell Activation

  11. MHC I: Biological function 44

  12. MHC II: Biological function 47

  13. MHCII: Biologogical function (2) 46

  14. MHCII: Function 50

  15. Role of Antigen Presenting Cells • Immunize with native protein • Boost with native protein • B cell & T cell response • Boost with denatured antigen • T cell response only • 2 different mechanisms APC for cell mediated & humoral

  16. Antigen Presenting Cells • Professional APC • Dendritic cells • Macrophages • B Cells • Non Professional APC • Fibroblasts • Glial cells • Thymic epithelial cells • Vascular endothelial cells

  17. Dendritic cells • Lot MHC-II • co-stimulate • activate T helpers

  18. Macrophages • Engulf microbe first • digest antigen • bind to MHC-II • co express with B7 membrane protein

  19. B Cells • Constitutively express MHC-II • activated • then express B7

  20. Two Presentation Pathways • Cytosolic- • MHC-I • endogenous antigens • Endocytic - • MHC-II • exogenous antigens

  21. Cytosolic Pathway: Endogenous Antigens • Ubiquitin & ATP • Bind to peptide • proteasomes • Bind ubiquitin • peptide transport • Assembly of peptides in MHC-I • Rough Endoplasmic reticulum • Export to membrane

  22. TAP proteins • Transports associated with Antigen Processing • TAP-1 TAP-2 • Transfer Peptides from proteosome to RER

  23. TAP-1 TAP-2

  24. Calnexin & MHC-1

  25. Assembly in RER • TAP-1 TAP-2 transport into ER • Bind to Calnexin MHC-I • Add peptide to MHC-I • Release calnexin • Transport to Gogli

  26. Endogenous PathwayMHC-i

  27. Endocytic Pathway: Exogenous Antigens • endocytic vesicles • peptide transport • Assembly of peptides in MHC-II

  28. Endocytic Route • From Outside- phagocytosis • From Inside • Make MHC-II • Bind Invariant chain • CLIP- digests invariant chain • Fuse • MHC-II & clipped I & peptide • peptide displaces clipped I chain

  29. Invariant chain & MHC-II

  30. Exogenous PathwayMHC-II

  31. Clinical Applications

  32. Performance Objectives

  33. Key Terms • antigen presenting cells[253],professional antigen presenting cells[253], • nonprofessional antigen presenting cells[253],cytosolic pathway[255],, • endocytic pathway[258], ubiquitin [255], proteosome[255],

  34. Transportors associated with antigen processing (TAP) [256], • molecular chaperones[257], calnexin[ 257], invariant (Ii) chain [258], • CLIP [259],

  35. Key Concepts • Describe self MHC restriction. • Compare the cytosolic pathway for antigen presentation with the endocytic pathway for antigen presentation • Compare professional with non professional antigen presenting cells.

  36. Draw a flow diagram comparing cytosolic and endocytic pathways for processing antigens [Fig 10-4] • Describe peptide generation by proteasomes. • Describe transport of antigenic peptides from the cytosol to the Rough Endoplasmic reticulum

  37. Draw a concept map for the separate antigen presenting pathways for endogenous and exogenous antigens. • Describe the assembly of MHC-II molecules within the rough endoplasmic reticulum. • Describe the development of a viral vaccine that uses the cytosolic pathway.

  38. Short Answer Questions

  39. Describe the development of a vaccine that used the endocytic pathway. • Name thee types of professional APCs. • For each type indicate whether it expresses MHC-II molecules and a co-stimulatory signal constitutively or must be activated before doing so. • Describe the role of ubiquitin in the processing of endogenous antigens.

  40. Describe the role of calnexin in the assembly of MHC-I. • T cells can react only with protein fragments. • What is this process called? • How does it occur? • Which pathway leads to antigen interaction with MHC-I molecules? • Which pathway leads to interaction with MHC-II molecules?

  41. DONE!!!

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