Immune aspects of kidney transplant

Question 1

Do transplantations between non-identical twins show rejection?

Answer 1

No - share bone marrow in utero

Question 2

What does HLA stand for?

Answer 2

Human leukocyte antigen

Question 3

What does HLA do?

Answer 3

Responsible for the activation of the immune response

Stimulate T and B cell responses

Question 4

What class of HLA are expressed on all nucleated somatic cells?

Answer 4

Class I HLA-B

Question 5

What happens in organ rejection?

Answer 5

HLA recognises proteins on the transplanted organ as non-self and attacks it by mounting an immune response

Question 6

What are 3 types of HLA molecules?

Answer 6

HLA-A, -B and -DR

Question 7

What do -A, -B and -DR represent on HLA molecules?

Answer 7

Important alleles

Question 8

Where are HLA-DR found?

Answer 8

On immune cells

Question 9

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

Answer 9

2 alleles

Question 10

How do we use the HLA molecule to determine the compatibility between potential donor and recipient?

Answer 10

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

Question 11

What is the relationship between HLA and MHC?

Answer 11

HLA = MHC in humans

Question 12

What determines the alleles that code for the HLA subtypes?

Answer 12

Alleles are inherited from your parents

Question 13

What is the role of HLA-DR?

Answer 13

Binds to specialised antigen presenting cells

Stimulates activation and proliferation of T cells

Releases cytokines which stimulate the immune response

Question 14

What effect does HLA mismatching have on success of transplantation?

Answer 14

The more different the HLA - the greater the immune response - the more immunosuppression is needed - the higher the probability of rejection of the graft

Question 15

What is transplant rejection?

Answer 15

Process by which the immune response attacks the donor organs

Question 16

What are the three types of transplant rejection?

Answer 16

1. Hyperacute
2. Acute
3. Chronic

Question 17

What is the timeline of hyperacute transplant rejection?

Answer 17

Minutes - hours

Question 18

Why does hyperacute transplant rejection occur?

Answer 18

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

Pregnancy
Blood transfusion
Previous transplantation

Question 19

Describe a method to test for preformed antibodies in a host

Answer 19

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

Question 20

What do preformed antibodies attack?

Answer 20

Donor HLA antigens

Blood group antigens

Question 21

How do preformed antibodies lead to transplant rejection?

Answer 21

Preformed antigens stick to endothelial cells

Trigger complement and clot formation

Form inflammation within the vessel

Occlude the transplanted organ blood supply = ischaemia

Question 22

What is the timeline of acute transplant rejection?

Answer 22

Days - weeks

Question 23

What leads to acute transplant rejection?

Answer 23

Can be

Cell-mediated -> T cells, macrophages and monocytes

Antibody mediated -> bind to HLA molecules or other antigens present in the blood vessels

Question 24

What leads to organ rejection in acute transplant rejection?

Answer 24

Triggering of the complement cascade acts as an amplification signal of inflammation and coagulation

Eventually leads to organ rejection

Question 25

What is the timeline of chronic transplant rejection?

Answer 25

Months - years

Question 26

What mechanisms leads to chronic transplant rejection?

Answer 26

Cellular and humoral rejection T cell mediated response to donor cells Complement activation

Question 27

Very little can be done to slow down chronic transplant rejection TRUE or FALSE

Answer 27

True

Question 28

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

Answer 28

50%

Question 29

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

Answer 29

Paired donation Desensitisation crossmatch positive Plasmapheresis

Question 30

What is paired donation?

Answer 30

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

Question 31

How does desensitisation crossmatch positive work?

Answer 31

Remove the antibodies after observed HLA mismatch

Question 32

How does plasmapheresis work?

Answer 32

Perform before transplantation Removal, treatment and return of plasma from the blood circulation Decrease the antibodies that might attack the transplanted to negligible levels

Question 33

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

Answer 33

If the donor and recipient are blood group mismatched then they suffer hyperacute rejection Preformed antibodies against these antigens

Question 34

What are blood group antigens?

Answer 34

Big antigen system expressed on the blood vessel wall

Question 35

What is accommodation?

Answer 35

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

Question 36

What is the consequence of accommodation?

Answer 36

Number of antobodies increases to before plasmapheresis But there are no adverse effects since antibodies do not instigate inflammation

Question 37

What is the definition of tolerance in context to transplantation?

Answer 37

When the recipient becomes tolerant to the antigens presented by the donor organ So no autoantibodies are produced against the transplanted organ

Question 38

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

Answer 38

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

Question 39

What was Peter Medawar's experiment?

Answer 39

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

Question 40

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

Answer 40

The regulatory cells regulate the immune response To prevent rejection Minimise withdrawal of immunosuppressive drugs

Question 41

What is the future of reducing organ rejection?

Answer 41

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