Major histocompatibility complex mhc
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Major Histocompatibility Complex (MHC). What is MHC? HLA H-2 (in the mouse) Minor histocompatibility antigens. There may be polymorphic antigens other than MHC that differ between the donor and the recipient.

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Major Histocompatibility Complex (MHC)

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Major histocompatibility complex mhc

Major Histocompatibility Complex(MHC)

  • What is MHC?

    • HLA

    • H-2 (in the mouse)

    • Minor histocompatibility antigens

Major histocompatibility complex mhc

  • There may be polymorphic antigens other than MHC that differ between the donor and the recipient.

  • These antigens induce weak or slower ( more gradual) rejection reactions than do MHC molecules and are called Minor histocompatibility antigens.

Major histocompatibility complex mhc

  • Minor histocompatibility antigens are proteins that are processed an presented to host T cells association with self MHC molecules on host APCs (by indirect pathway).

Significance of the mhc

Significance of the MHC

  • role in immune response

  • role in organ transplantation

  • role in predisposition to disease

Genetic barriers to transplantation

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)

Principles of transplantation

Principles of transplantation

Minor histocompatibility antigens and graft survival

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

Graft versus host gvh disease

Graft versus host (GVH) disease

Gvh disease in humans

GVH disease in humans

The human mhc genes

The human MHC genes

The mouse mhc genes

The mouse MHC genes

Polymorphism of mhc antigens based on phenotype

Polymorphism of MHC antigens (based on phenotype)

Polymorphism of mhc genes based on dna sequence pcr

Polymorphism of MHC genes(based on DNA sequence/ PCR)

Mhc products expressed on cells

MHC products expressed on cells

If Jack and Jill have four children; Bo, Kim, Mo and Lee

They’ll all inherit antigens of the parental MHC

Oft their haplotypes will be of the father or mother

Unless during meiosis, a crossover should occur

The inheritance of mhc genes

The inheritance of MHC genes

Mhc products expressed on cells1

MHC products expressed on cells

Crossing over results in new haplotypes

Crossing overresults in new haplotypes

Differential expression of mhc antigens

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.)

Major histocompatibility complex mhc




Alloreactivity of T cells:

MLR and CTL generation

Major histocompatibility complex mhc

Alloreactivity of T cells






Proliferation and Differentiation

Mechanisms of graft rejection


IL2, TNF, IFN 

IL2, IL4, IL5


IL2, IFN 

Mechanisms of graft rejection





Tempo of rejection reaction

type of rejection


time taken

minutes- hours

preformed anti-donor antibodies and complement


reactivation of sensitized T cells (secondary response)



primary activation of T cells



unclear causes: cross reactive Ab, immune complexes, slow cellular reaction, tolerance breakdown, disease recurrence



Tempo of rejection reaction

Immunosuppressive agents


mode of action


organ transplant, hypersensitivity, autoimmunity

organ transplant,

corticosteroids, prednisone

cyclosporine, ticrolimus

anti-inflammatory, altering T-cell and PMN traffic

inhibition of IL-2 production by T cells

Inhibition of T cell activation by IL-2

organ transplant


Immunosuppressive agents

Immunosuppressive agents1


mode of action


purine metabolism

organ transplant

azathioprine, 6-MP

organ transplant


folate metabolism

autoimmune diseases, organ transplant

cyclophosphamide, melphalan

alkylation of DNA, RNA and proteins



malignancy/marrow transplantation

Immunosuppressive agents

Major histocompatibility complex mhc


Removal of T cells from marrow graft

Magnetic antibodies

Hla and disease association

HLA and disease association

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