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Major Histocompatibility Complex(MHC)

Major Histocompatibility Complex(MHC)

MHC I MHC II MHC III

MHC I MHC II MHC III

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Transplantation

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Cells Expressing Class I and Class II MHC

Class I MHC

Class IIMHC

All nucleated cells express class I MHC

Cells expressing class II MHC also express class I MHC

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Significance of the MHCSignificance of the MHC

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

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

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Genetic barriers to transplantationGenetic 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)

• 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 transplantationPrinciples of transplantation

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Minor histocompatibility antigensand 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

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) diseaseGraft versus host (GVH) disease

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GVH disease in humansGVH disease in humans

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Inflammation

lysis

ADCC

lysis

IL2, IFN

TNF, NO2

IL2, IL4, IL5

IL2, TNF, IFN

rejection

Mechanisms of graft rejectionMechanisms of graft rejection

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Immunosuppressive agentsImmunosuppressive agents

application(s)mode of actionagent

corticosteroids, prednisone

anti-inflammatory, altering T-cell and PMN traffic

organ transplant, hypersensitivity, autoimmunity

rapamycin Inhibition of T cell activation by IL-2

organ transplant

cyclosporine, ticrolimus

inhibition of IL-2 production by T cells

organ transplant,

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Immunosuppressive agentsImmunosuppressive agents

application(s)mode of actionagent

azathioprine, 6-MP purine metabolism

organ transplant

methotrexate folate metabolism organ transplant

cyclophosphamide, melphalan

alkylation of DNA, RNA and proteins

autoimmune diseases, organ transplant

x-irradiation Lymphopenia malignancy/marrow transplantation

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Removal of T cells from marrow graftRemoval of T cells from marrow graft

Magnet

Magnetic antibodies