Major Histocompatibility Complex (MHC)

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Major Histocompatibility Complex(MHC)

• What is MHC?
• HLA
• H-2
• Minor histocompatibility antigens

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Significance of the MHC

• role in immune response
• role in organ transplantation
• role in predisposition to disease

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Progress in organ transplantation
4
Genetic barriers to transplantation

• autologous in the same individual (autograft)
• isologous between genetically Identical
  individuals (isograft), i.e., identical twins
  (inbred animals)
• homologous between individuals of the same
  species (allograft)
• heterologous between individuals different
  species (xenograft)

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Principles of transplantation
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Minor histocompatibility antigensand graft
survival

• minor histocompatibility antigens also cause
  rejection
• The rejection time is variable but longer than
  that for major histocompatibility antigen
• They have additive effects

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Graft versus host (GVH) disease
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GVH disease in humans
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The human MHC genes
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The mouse MHC genes
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Polymorphism of MHC antigens (based on phenotype)
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Polymorphism of MHC genes(based on DNA sequence/
PCR)
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The inheritance of MHC genes
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MHC products expressed on cells
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Crossing overresults in new haplotypes
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MHC products expressed on cells
If Jack and Jill have four children Bo, Kim, Mo
and Lee Theyll all inherit antigens of the
parental MHC Oft their haplotypes will be of the
father or mother Unless during meiosis, a
crossover should occur
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Differential expression of MHC antigens

• Class-I expressed on all nucleated cells in man,
  and also on erythrocytes in mice.

• Class-II expressed primarily on antigen
  presenting cells (dendritic cells, macrophages
  and B cells, etc.)

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Alloreactivity of T cells MLR and CTL generation
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Alloreactivity of T cells
Alloreaction (MLR)
Thymus
Positive Selection
Proliferation and Differentiation
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Mechanisms of graft rejection
Inflammation
ADCC
lysis
rejection
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Tempo of rejection reaction
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A, B DR matching and graft survival
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Blood transfusion and graft survival
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Immunosuppressive agents
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Immunosuppressive agents
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Removal of T cells from marrow graft
Magnetic antibodies
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HLA and disease association
Disease Associated alleles Frequency in Frequency in Relative risk
Disease Associated alleles patients control Relative risk
Ankylsoing spondylitis Reiters disease Acute anterior uveitis Psoriasis vulgaris Dermatitis herpetiformis B27 B27 B27 CW6 DR3 9 79 52 87 85 9 9 9 33 26 87.4 37.0 10.4 13.3 15.4