MHC and transplant rejection

Where is MHC class I and II found?

MHC classI= on all cells except RBC's MHC class II= on APC's

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On what chromosome if HLA coded?

chromosome 6

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What T-cells respond to MHC class I+II?

MHC I= CD8+ T-cells MHCII= CD4+ T-cells

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Outline Positive and Negative selection to MHC restriction

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Draw out the 2 classes of MHC - know their composition

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What is allorecognition?

The ability of an individual organism to distinguish its own tissues from those of another.

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Define allogeneic

relating to or denoting tissues or cells which are genetically dissimilar and hence immunologically incompatible, although from individuals of the same species.

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Define autologous

(of cells or tissues) obtained from the same individual.

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What is the immunological synapse (draw it out)

between the APC and CD4+ T-cell

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Describe the direct and indirect pathway of an allogenic APC and autologous APC

draw out the diagram

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What are the effector functions when an allogeneic APC interacts with a CD4+ T-cell ?

1)antibody production through B-cell stimulation 2)cytotoxicity via CD8+ T-cells releasing perforin+ granzyme B 3)DTH via CD4+ T-cell activation releasing cytokines and activating macrophages

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How is HLA typed?

Serological – cell based Molecular Extraction of DNA Amplification Detection of sequence polymorphisms (i.e. tissue type) Hybridisation to probes Sequencing

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What is the need for HLA typing?/ why do it?

1)Less rejection episodes 2)Better graft survival 3)National kidney waiting lists 4)Less sensitisation 5)Establish relationships

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What are the 3 methods to detect antibodies?

1)Complement dependent cytotoxicity test (CDC) 2)Flow cytometry 3)HLA Beads

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Why would you detect antibodies?

sensitising events -- 1)previous transplant 2)pregnancy 3)blood transfusion

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Why is it important to detect/ screen for antibodies?

prevent hyper acute rejection

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What are the 3 types of rejection?

1) acute antibody mediated rejection 2)acute cellular rejection 3)chronic antibody mediated rejection

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Why do you get hyper acute rejection? (4)

1)preformed antibodies 2)xenograftrejection- Anti-Galα1-3Gal 3)ABO incompatible transplantation- ABO antibodies 4)HLA incompatible transplantation- anti-HLA

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Why do you preform a pre transplant crossmatch?

To avoid hyper acute rejection

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What is acute cellular rejections?

T-cell dependant --> Directed against foreign HLA molecules Effect of HLA mismatch Typically 7- 10 days after transplant

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Get Revising

MHC and transplant rejection

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