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Reminders

Reminders. Case Studies: Due Wed., March 19 Exam 3- Wed., March 26 Chapters 3, 5, & 6. The genetics of the MHC. The significance of the polygenic & polymorphic characteristics of MHC. continued. Polymorphism in MHC & AcuteTransplant Rejection.

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Reminders

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  1. Reminders • Case Studies: • Due Wed., March 19 • Exam 3- Wed., March 26 • Chapters 3, 5, & 6.

  2. The genetics of the MHC The significance of the polygenic & polymorphic characteristics of MHC. continued.

  3. Polymorphism in MHC & AcuteTransplant Rejection • Transplanted organs from donors bearing MHC molecules that differ from those of the recipient by as little as 1 AA are invariably rejected. • Allogeneic T cells react with non-self cells displaying foreign MHC! • Allogeneic- individual of the same species who differ in alleles due to polymorphism.

  4. Parham- figure 5.14 p. 137 (Section 5-11) Irradiate or mitomycin C treated 1-10% of the T cells will recognize non-self-MHC.

  5. Janeway Allogeneic T cell Response

  6. Significance of Polygeny & Polymorphism to populations

  7. Most humans are heterozygous for the MHC.

  8. Co-evolution of pathogen & humans impacts MHC polymorphism: Directional selection Balanced selection

  9. Coevolution of pathogen & host • New alleles of MHC may confer advantages when a population is exposed to new infectious disease. • Outbreed population with polymorphism will have more individuals resistant to an infectious disease. • Small isolated populations with less polymorphism can become susceptible to disease.

  10. New allele can be formed by: • Point Mutations • Recombination HLA-B 5301 found in African population resistant towards malaria HLA-B 4601- found in southeast Asian population & is associated with nasopharyngeal carcinoma

  11. Co-evolution of host & pathogen: • HIV: • HLA-B14, B27, B57 & HLA-C8 & C14 have slower progression of AIDs. • HLA-A29, HLA-B22, HLA-B35, HLA-C16, and HLA-DR11 are associated with fast progression of AIDs.

  12. Small isolated populations may have less MHC diversity. • New Guinea- 60% population- HLA-A11 • Epstein Barr virus isolates- mutation in peptide leading to susceptible population.

  13. T cell Development Chapter 5

  14. Progenitor T Lymphocytes travel from the BM to the thymus for T cell development.

  15. How important is the thymus? • DeGeorg’s Syndrome & Nude Mice: • Severely Immunocompromised. • The thymus is extremely important during embryonic development & early part of life!

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