Genetics of HLA and transplantation Flashcards
What is special about the function of dendritic cells? [1]
Only cell that can activate niave T cells (CD4 or CD8)
Why do we have multiple HLAs? [1]
So we can present multiple different pathogens:
Describe the relation between HLAs and HIV
- What does HIV bind to? [3]
- HIV binds to CD4 and CCR5 of CXCR4
- Long term non-progressors: suppress viral loads to undetectable levels with elevated CD4 T cell counts in the abscence of ART
- The two main HLA molecules: HLA-B2705 or HLAB5701 cause this adapted response
Which HLA is associated with ankylosing spond? [1]
HLA-B27
Which HLA is associated with RA? [1]
HLA-DRB1 - if have from both mum and dad then have increased risk
Describe the direct pathway to alloantigen presentation in transplantation
- Donor APCs migrate from graft to secondary lymphoid organs in host.
- Present MHC to recipient T cells which become activated
- They go back to the graft and cause damage ):
Describe the indirect pathway for alloantigen presentation in tranplantation
- Recipient APCs go to graft, phagocytose a donor peptide and put on MHC
- Activate T cells in secondary lymphoid organs
Describe the semi-direct mechanism for alloantigen presentation in transplant
Recipient APCs present intact donor MHC to recipient T cells
Describe why a hyperacute graft rejection may occur [2]
Recipient have already been sensitised - e.g. pregnancy, previous blood transfusion or graft.
Pre-formed antibodies activates complements - causing cell lysis and tissue damage
Describe why an acute rejection of a graft occurs [2]
2-3 weeks after
Driven by direct pathway of allorecognition - alloreactive T cells infiltrate graft and cause tissue death
Causes parenchymal cell damage & interstitial inflammation
Describe the process of chronic graft rejection [1]
Driven by indirect pathway of allorecognition - alloreactive T cells and antibodies infiltrate graft - occlusion of blood vessels and fibrosis
Describe what is meant by graft-versus-host disease [1]
T lymphocytes in the donated tissue (graft) recognise the recipient (host) as foreign, and attack the recipient’s tissue and organs.
Particularly in stem cell transfer
Which drug can be used to treat GvHD? [1]
Belumosudil
Describe what is meant by Graft-versus Leukemia
Decreases relapse rate of leukemia after allogenoic bone marrow transplant
Donor marrow recognises antigens on the leukemic blast cells as non-self
How do you decrease graft failure during peri-transplant? [1]
Decrease time that donated organ is cold (max 4hrs for a heart)
