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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?

Important alleles


Where are HLA-DR found?

On immune cells


How many alleles code for each HLA subtype (-A, -B, -DR)?

2 alleles


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?

1. Hyperacute

2. Acute

3. Chronic


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

Blood transfusion
Previous transplantation


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?

Can be

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

Complement activation


Very little can be done to slow down chronic transplant rejection




What percentage of grafts are lost due to chronic transplant rejection?



What are methods by which we have managed to increase transplant donations?

Paired donation

Desensitisation crossmatch positive



What is paired donation?

If living donors are not suitable for the recipient - check to see if they are suitable for another recipient

Non compatible donors can ve switched between the two recipients


How does desensitisation crossmatch positive work?

Remove the antibodies after observed HLA mismatch


How does plasmapheresis work?

Perform before transplantation

Removal, treatment and return of plasma from the blood circulation

Decrease the antibodies that might attack the transplanted to negligible levels


How can ABO-blood group mismatch lead to organ rejection?

If the donor and recipient are blood group mismatched then they suffer hyperacute rejection

Preformed antibodies against these antigens


What are blood group antigens?

Big antigen system expressed on the blood vessel wall


What is accommodation?

Endothelial cells lining blood vessels become down regulated to the effect of autoantibodies


What is the consequence of accommodation?

Number of antobodies increases to before plasmapheresis

But there are no adverse effects since antibodies do not instigate inflammation


What is the definition of tolerance in context to transplantation?

When the recipient becomes tolerant to the antigens presented by the donor organ

So no autoantibodies are produced against the transplanted organ


What would be the consequences of tolerance in context to transplantation?

Indefinite graft survival

No need for:

- Immunosuppression - no drug related side effects, infections or nephrotoxicity

- No chronic rejection - no need for re-transplantation

- Impact organ shortage


What was Peter Medawar's experiment?

Cells from brown-haired mouse where injected into white-haired embryo

Skin from the brown donor animal grafted onto the white recipient

Mouse grew both white and brown hair due to tolerance

White mouse became tolerant to the antigens from the brown mouse as cells were injected into the embryo


How can injection of CD4+CD25+ regulatory T cells increase organ survival.

The regulatory cells regulate the immune response

To prevent rejection

Minimise withdrawal of immunosuppressive drugs


What is the future of reducing organ rejection?

In vitro expansion and reinfusion of autologous CD4+CD25+ REGULATORY cells in patients with increased autoimmune reactivity