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

CD4+TH1

CD8+preCTL

CD8+CTL

Alloreactivity of T cells:

MLR and CTL generation


Major histocompatibility complex mhc

Alloreactivity of T cells

Alloreaction

(MLR)

Thymus

Positive

Selection

Proliferation and Differentiation


Mechanisms of graft rejection

TNF, NO2

IL2, TNF, IFN 

IL2, IL4, IL5

lysis

IL2, IFN 

Mechanisms of graft rejection

Inflammation

ADCC

lysis

rejection


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

Tempo of rejection reaction


Immunosuppressive agents

agent

mode of action

application(s)

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

rapamycin

Immunosuppressive agents


Immunosuppressive agents1

agent

mode of action

application(s)

purine metabolism

organ transplant

azathioprine, 6-MP

organ transplant

methotrexate

folate metabolism

autoimmune diseases, organ transplant

cyclophosphamide, melphalan

alkylation of DNA, RNA and proteins

x-irradiation

Lymphopenia

malignancy/marrow transplantation

Immunosuppressive agents


Major histocompatibility complex mhc

Magnet

Removal of T cells from marrow graft

Magnetic antibodies


Hla and disease association

HLA and disease association


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