(13) MHC and transplantation Flashcards Preview

2. CP - Core Immunology > (13) MHC and transplantation > Flashcards

Flashcards in (13) MHC and transplantation Deck (40):

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?

1. recipient strain = X, donor strain = Y, graft loss = 10-14 days (1st set response)

2. recipient strain = X', donor strain = Y, graft loss = 5-7 days (2nd set response)

3. 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?


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?


(the short arm of chromosome 6)


How big is the human MHC?



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?


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


Which part of the HLA molecule presents the antigen to the T cells?

The peptide-binding groove


How are MHC inherited?

Mendelian inheritance - 1 in 4 chance of mismatch with sibling, 1 in 2 chance of partial match, 1 in 4 chance of match

En-bloc from each parental chromosome. Each individual inherits two antigens at a given locus

Codominant expression. All of the inherited antigens are displayed on the cell surface (HLA phenotype)


Describe HLA polymorphism

- MHC is highly polymorphic
- large number of allelic variants at each locus
- allelic variation maintained at population level due to survival advantage
- significant in terms of capacity of individual to mount an immune response in response to an antigenic challenge


In HLA nomenclature, what are the 3 levels of specificity?

- broad eg. HLA-A19
- split eg. HLA-A29(A19)
- allele eg. HLA-A*29:01

serology (broad)
serology (split)
molecular (low)
molecular (high)


In HLA nomenclature, what does an * mean?

* = molecular
no * = serology


What are the 3 categories of response when the immune system experiences foreign HLA in transplant tissue?

- direct recognition
- indirect recognition
- semi-direct recognition


What happens in direct recognition in response to transplant tissue (foreign HLA)?

- graft + damaged endothelium due to surgical stress
- T cell binding direct to graft
- donor DCs presenting to recipient T cells
- T cell proliferation


What happens in indirect recognition in response to transplant tissue (foreign HLA)?

- graft peptides
- movement of recipient APC
- processing of donor peptides (lymph node)
- T cells migrate to the graft (immune response)


What happens in semi-direct recognition in response to transplant tissue (foreign HLA)?

- movement of recipient APC
- donor APC
- recipient and donor APC interaction
- migration of 'new' APC to lymph node to present to T cells


Which type of recognition (direct, indirect, semi-direct) occurs straight away in transplantation?


Unique to transplantation


What is sensitisation and give examples of events

Any event which elicits an HLA directed immune response

- pregnancy
- blood transfusion
- transplantation


How can you determine HLA profile?

- serum screening
- cross matching (directly test recipient serum against donor cells)


cRF% is a measure of what?



If you have a 0% cRF, what does this mean?

Any donor can be used


What does 50% cRF mean?

50% sensitised

lost 50% chance of finding donor

but better than 100% cRF (100% not actually possible, but have to find donor exactly matching)


What happens in hyperacute rejection?

- activate clotting cascade
- activate complement
- lost integrity of vascular endothelium
- organ engorges with blood and becomes necrotic