Major Histocompatibility Complex MHC

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Major Histocompatibility Complex(MHC)

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

2
Progress in organ transplantation
3
Significance of the MHC

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

4
Genetic barriers to transplantation

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

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The laws of transplantation
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Histocompatibility antigensand graft survival

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

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Graft versus host disease
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Graft versus host disease
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The human MHC genes
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The mouse MHC genes
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Polymorphism of MHC genes
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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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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)

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Cytotoxic T lymphocyte (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
type of rejection
cause
time taken
minutes- hours
preformed anti-donor antibodies and complement
hyperacute
reactivation of sensitized T cells (secondary
response)
days
accelerated
primary activation of T cells
acute
days-weeks
unclear causes cross reactive Ab, immune
complexes, slow cellular reaction, tolerance
breakdown, disease recurrence
months-years
chronic
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HLA matching and graft survival
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Blood transfusion and graft survival
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Immunosuppresseive agents
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Immunosuppresseive agents
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Removal of T cells from marrow graft
Magnetic antibodies
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HLA and disease association
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Organ transplant activityUSA, 1988
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Serological tissue typingthe scheme
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Tissue typing by themixed lymphocyte reaction
(MLR)
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Tissue typingthe MLR scheme
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Lymphocyte proliferation during MLR