31 - MHC and clinical transplantation

What is an isograft?

Transplant between identical twins

What is an allograft?

The transplant of an organ or tissue from one individual to another of the same species with a different genotype

What is a xenograft?

Transplants between different species

What gene codes for HLAs?

MHC

What cells have MHC I on its surface?

All nucleated cells

What T cell does MHC I interact with?

CD8+ T cells

What cells have MHC II on its surface?

APC

What T cell does MHC II interact with?

CD4+ T cells

What 3 genes of the MHC code for MHC I?

1) HLA-A

2) HLA-B

3) HLA-C

What 4 genes of MHC code for MHC II?

1) HLA-DP

2) HLA-DM

3) HLA-DQ

4) HLA-DR

What chromosome is the HLA gene on?

Chromosome 6

In which 2 regions are HLA molecules most variable?

1) Protein groove

2) Alpha helix

Describe allorecognition following a transplant?

Donor APCs from organ migrate to the lymph nodes where they are detected as foreign by the CD4+ and CD8+ T cells, initiating immune response

What are co-stimulatory molecules?

Bind as well to initiate a stronger immune response

What 3 genes are considered in HLA typing?

1) HLA-A

2) HLA-B

3) HLA-DR

How does HLA inheritance work?

Individuals inherit multiple types of MHC class I and MHC class II genes from parents

How many HLA haplotypes does each human have?

2 (one from each parent)

What is the probability that two siblings have identical set of haplotypes?

0.25

What 1,1,1 mismatch?

Where a mismatch is found at one of each of the HLA genes when comparing haplotypes

What method is used for HLA typing?

Genetic sequencing

What is the cellular complement dependant cytotoxicity test?

A sample of patient's serum is added to a sample of leukocytes with a specific HLA - any losing cells indicates complement response

What is the flow cytometry cytotoxicity test?

After the sample of patient's serum is added to a sample of leukocytes, fluorescent antibodies are added to bind to plasma antibodies before being passed through a detector

What is the solid phase cytotoxicity test?

Synthetic beads covered in different HLA antigens are added to a sample of patient's serum and then passed through a detector

What causes hyperacute rejection?

Preformed antibodies (ABO mismatch) binding to the organ

What antibodies does type A blood have?

Anti-B

What antibodies does type B blood have?

Anti-A

What antibodies does type O blood have?

Anti-A and Anti-B

What antibodies does type AB blood have?

None

What causes acute cellular rejection?

T cell dependent reactivity against HLA molecules (normal immune response)