Flashcards in Immune aspects of kidney transplant Deck (41)
Do transplantations between non-identical twins show rejection?
No - share bone marrow in utero
What does HLA stand for?
Human leukocyte antigen
What does HLA do?
Responsible for the activation of the immune response
Stimulate T and B cell responses
What class of HLA are expressed on all nucleated somatic cells?
Class I HLA-B
What happens in organ rejection?
HLA recognises proteins on the transplanted organ as non-self and attacks it by mounting an immune response
What are 3 types of HLA molecules?
HLA-A, -B and -DR
What do -A, -B and -DR represent on HLA molecules?
Where are HLA-DR found?
On immune cells
How many alleles code for each HLA subtype (-A, -B, -DR)?
How do we use the HLA molecule to determine the compatibility between potential donor and recipient?
Compare the alleles that make up the HLA subtypes between the recipient and donor
For example, for the HLA-A
Donor = two alleles that code for this molecule are HLA-A1 and HLA-A1
Recipient = two alleles that code for this molecule are HLA-A1 and HLA-A2
Matching = 1
Do the same for HLA-B and HLA-DR
Complete match = 0, 0, 0
Complete mismatch= 2, 2, 2
What is the relationship between HLA and MHC?
HLA = MHC in humans
What determines the alleles that code for the HLA subtypes?
Alleles are inherited from your parents
What is the role of HLA-DR?
Binds to specialised antigen presenting cells
Stimulates activation and proliferation of T cells
Releases cytokines which stimulate the immune response
What effect does HLA mismatching have on success of transplantation?
The more different the HLA - the greater the immune response - the more immunosuppression is needed - the higher the probability of rejection of the graft
What is transplant rejection?
Process by which the immune response attacks the donor organs
What are the three types of transplant rejection?
What is the timeline of hyperacute transplant rejection?
Minutes - hours
Why does hyperacute transplant rejection occur?
Pre formed antibodies are present in the body
Due to the antibodies being exposed to ANY foreign HLA in the past
Exposure to foreign HLA happens in
Describe a method to test for preformed antibodies in a host
1. Take serum from the recipient in which there would be preformed antibodies
2. Mix serum with donor cells
3. Add complement to lyse the antibodies stuck to the donor cells
4. Detect whether these are preformed antibodies
What do preformed antibodies attack?
Donor HLA antigens
Blood group antigens
How do preformed antibodies lead to transplant rejection?
Preformed antigens stick to endothelial cells
Trigger complement and clot formation
Form inflammation within the vessel
Occlude the transplanted organ blood supply = ischaemia
What is the timeline of acute transplant rejection?
Days - weeks
What leads to acute transplant rejection?
Cell-mediated -> T cells, macrophages and monocytes
Antibody mediated -> bind to HLA molecules or other antigens present in the blood vessels
What leads to organ rejection in acute transplant rejection?
Triggering of the complement cascade acts as an amplification signal of inflammation and coagulation
Eventually leads to organ rejection
What is the timeline of chronic transplant rejection?
Months - years
What mechanisms leads to chronic transplant rejection?
Cellular and humoral rejection
T cell mediated response to donor cells
Very little can be done to slow down chronic transplant rejection
TRUE or FALSE
What percentage of grafts are lost due to chronic transplant rejection?
What are methods by which we have managed to increase transplant donations?
Desensitisation crossmatch positive