major histocompatibility complex (mhc)
Post on 06-Jan-2016
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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
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