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Major Histocompatability Complex

Major Histocompatability Complex. Molecular chaparones Hugh B. Fackrell. Major Histocompatability Complex. Assigned Reading Content Outline Performance Ojectives Key terms Key Concepts Short Answer Questions. 4. Assigned Reading. Chapter: 9 pp 223-248 Janis Kuby’s Immunology 3rd Ed.

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Major Histocompatability Complex

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  1. Major Histocompatability Complex Molecular chaparones Hugh B. Fackrell

  2. Major Histocompatability Complex • Assigned Reading • Content Outline • Performance Ojectives • Key terms • Key Concepts • Short Answer Questions 4

  3. Assigned Reading • Chapter: 9 pp 223-248 • Janis Kuby’s Immunology 3rd Ed 5

  4. General Characteristics of MHC MHC Molecules & Genes MHC-I MHC-II MHC-III Genomic maps of MHC Cellular Distribution of MHC Regulation of MHC Expression MHC and Immune Responsiveness MHC and Disease Content Outline 6

  5. General Characteristics of MHC • MHC vs HLA • Congenic mice • Genetic Co dominance • Location & function of MHC regions • MHC haplotypes 7

  6. MHC vs HLA • MHC: Major Histocompatability complex • mouse genetic complex • HLA: Human Leucocyte Antigen • human genetic complex Similar functions: different terms

  7. MHC genes (mouse) • Class 1 genes K D L R Qa Tla • Class 2 genes A A E E • Class 3 genes C4 Slp 61

  8. HLA genes (human) • HLA 1 B C A • HLA 2 SB SB • HLA 3 C4f C4S C2 Bf 62

  9. MHC antigens codominate 53

  10. Congenic Mice • Two strains of mice that are genetically identical except at one locus • developed by successive back crosses to one parent • each progeny tested for specific difference • if difference still present then back cross again

  11. MHC: Assays • Serotyping • Mixed lymphocyte Reaction 36

  12. Public vs Private Ag 58

  13. Antibody production during Transplants 60

  14. Antibodies during transplants (2) 59

  15. Serological Tissue Typing 37

  16. Mixed Lymphocyte Reaction 38

  17. Mixed Lymphocyte Reaction

  18. Haplotype Restricted Cytotoxicity 56

  19. MHC Molecules & Genes • Structure of MHC-I • Structure of MHC-II • Gene Organization • Peptide Binding 8

  20. MHC-I 9

  21. MHCI Carbohydrates 40

  22. MHC I: : 3D structure 41

  23. HLA I: Structure 42

  24. MHC I: Biological function 44

  25. MHC-II • Polymorphic • Immunocytes • Class II molecules 10

  26. HLA 2: Structure 43

  27. MHC II: Ag Presentation Detail 48

  28. Idependent vs Associative recognition 55

  29. MHCII: Function 50

  30. MHCII: Biologogical function (2) 46

  31. MHC II: Biological function 47

  32. MHC II: Ag Presentation 49

  33. 13

  34. MHC III • Collection of genes associated with MHC • Do not code for MHC I or MHC II • Code for associated immunological molecules • complement • interferon • Tumour necrosis factor

  35. Gene C2, C4a,C4b, Bf COL11A2 CYP21,CYP21P G7a/b HSP LMP2, LMP7 TAP1,TAP2 TNF-a, TNF-b Encoded Protein Complement collagen Steroid 21-hydroxylases Valyl-tRNA synthetase Heat Shock Protein Proteasome-like subunits Peptide transports subunits Tumour Necrosis factor Class III MHC Products

  36. Genomic maps of MHC • MHC-I • MHC-II • MHC-III 11

  37. Organization of Mouse Genes 52

  38. Cellular Distribution of MHC 12

  39. Regulation of MHC Expression • 5’ promotor sequences • Positive and negative control of transcription • CIITA-Transactivator • RFX Bare lymphocyte Syndrome 13

  40. Regulation of MHC Expression • Class I level of expression different in various cell types • Class II- gene expression limited to certain cell types 13

  41. MHC and Immune Responsiveness • Determinant selection model • Hole in the repertoire model 14

  42. MHC and Disease 15

  43. Distribution of MHC Antigens • MHC I All nucleated cells & Platelets (mouse RBCs) • MHC II lymphocytes, monocytes, macrophages 63

  44. DONE!!

  45. Performance Objectives

  46. Key Terms • alleles, alloantigens. bone marrow chimeras, Class I molecules, Class I regions, Class II molecules, • Class II regions, Class III molecules, Class III regions, Determinant selection model, • H-2 complex and its regions D region, I region, K region, L region, S region 17

  47. hole in the repertoire models,locus, Immune response genes, congenic mice, Human Leukocyte Antigens, Major histocompatibility complex, MHC restriction, negative thymic selection • positive thymic selection, public specificities, private specificities, region, Specificities, superantigens 18

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