(13) MHC and transplantation Flashcards
(40 cards)
Where has blood group substance been revealed by immunofluorescent staining?
In the cell membranes of all vascular endothelial cells, and certain epithelial cells
Normal individuals have naturally occuring isoagglutinins of which type?
Normal individuals have naturally occurring anti-A or anti-B isoagglutinins
How is blood group related to transplant?
Poor outcome of transplants performed between blood group incompatible individuals
Who discovered the MHC?
Peter Alfred Gorer
Describe the discovery of the MHC?
- tumour transplantation between mouse strains
- sarcoma tissue from strong’s albino A strain grew in F2 cross and backcross generations between the A strain and the resistant C57 black strain
- all susceptible animals possessed an antigen derived form their albino acceptors “antigen II”
- anti-antigen II antibody produced in C57 black mic by transfer of sarcoma tissue from the A strain
- maximal titres of anti-antigen II antibody corresponded with time of complete tumour regression
- “…genes govern the transplantability of the tumour and determine isoantigenic differences’
What was the experiment done by Peter Medawar concerning MHC?
- skin allograft rejection in burns victims
- rabbit skin graft model
gave different donor strains to incompatible recipient, measured time taken for graft to become necrotic
What were the results from Medawar’s experiment?
- recipient strain = X, donor strain = Y, graft loss = 10-14 days (1st set response)
- recipient strain = X’, donor strain = Y, graft loss = 5-7 days (2nd set response)
- recipient strain = X’, donor strain = Z, graft loss = 10-14 days (1st set response)
MHC responsible for these observations
The MHC is a set of genes found in who?
All vertebrate species
What is the role of the MHC?
- immune function
- diseases susceptibility
- reproductive success
- role in histocompatibility, major influence on graft survival
Where are the proteins encoded by the MHC expressed and what do they present?
They are expressed at the cell surface and function to present ‘self’ and ‘non-self’ antigens for inspection by T cell antigen receptors
How many MHC molecules are on the average mammalian cell?
50,000-100,000
It is the most prolific cell surface protein/antigen
Are MHC proteins polymorphic?
Highly polymorphic
Most polymorphic system in the human genome
Where is the human MHC genes found?
6p21.3
the short arm of chromosome 6
How big is the human MHC?
3.6Mbp
The MHC is divided into 3 regions. Which proteins/antigens do each of these 3 different regions encode?
class I region = HLA-A, B, C (‘classical’) antigens
class II region = HLA-DR, DQ, DP antigens
class III region = HSP70, TNF, C4A, C4B, C2, BF, CYP21
HLA-DR is encoded by what region of the MHC?
Class II region
What are the antigens encoded by MHC called?
HLA
Human leucocyte antigens
Where are class I antigens found?
On all nucleated cells
Class I HLA antigens mainly serve to present which antigens?
Endogenous antigens (result of changes in the cell eg. virus)
Where are class II antigens found?
Primarily expressed on B lymphocytes but expression can be induced on T lymphocytes and other cells
Class II HLA antigens mainly serve to present which antigens?
Exogenous antigens
What type of proteins are HLA antigens?
Membrane-bound glycoproteins
What are class I HLA-A, B, C molecules composed of?
MHC encoded 45kd heavy chain non-covalently associated with non-polymorphic B2 microglobulin
What are class II HLA-DR, DP, DQ molecules composed of?
MHC encoded 31-34kd associated A chain non-covalently associated with 26-29kd B chain
