3: Transplantation

Question 1

Types of transplantation

Answer 1

Autografts - same individual
Isografts - between genetically identical individuals
Allografts - between different individuals of same species
Xenografts - between different species
Prosthetic graft - plastic/metal

Question 2

Most commonly transplanted organs?

Answer 2

Kidney
Liver
Cardiothoracic
Pancreas

Question 3

Types of donor in allograft?

Answer 3

Deceased

Living (bone marrow, kidney, liver)

Question 4

Types of decease donors?

Answer 4

Brain stem death - confirmed death using neurological criteria

Circulatory death - confirmed death using cardio-respiratory criteria

Question 5

What else do you check for in deceased donors?

Answer 5

Exclude

• Viral infection
• malignancy
• drug abuse/overdose or poison
• disease of transplanted organ

Question 6

What happens to removed organs

Answer 6

Rapidly cooled and perfused

Question 7

Organisation of transplant services?

Answer 7

Transplant SELECTION (waiting list)
Transplant ALLOCATION

Question 8

Problems with transplant allocation

Answer 8

Equity - time on waiting list

Efficiency - what is the best use of organ in terms of patient survival and graft survival?

Question 9

What are the most important protein variations in clinical transplantation?

Answer 9

ABO blood group

HLA

Question 10

Explain ABO blood group

Answer 10

A and B proteins carbohydrate chains bound on red cells
Also found in endothelial lining of blood vessels in transplanted organ

Blood type A = Extra N-acetyl galactosamine
Blood type B = Extra Galactose

Question 11

Explain ABO blood group

Answer 11

A and B proteins carbohydrate chains bound on red cells

Also found in endothelial lining of blood vessels in transplanted organ

Question 12

What happens when donor blood type is different?

Answer 12

Blood type A produces Anti-B antibodies
Blood type B produces Anti-A antibodies

If type A patient gets organ from type B patient,
anti-B antibodies bind to B group antigens on endothelial cells of donor organ = Antibody mediated rejection

Question 13

How would you do an ABO-incompatible transplantation?

Answer 13

Remove antibodies in recipient (plasma exchange)
Good outcomes
Kidney, heart, liver

Question 14

Explain T-cell mediated graft rejection

Answer 14

Antigens from donor graft cell taken up by recipient APC
Recipient APC meets T-cell at secondary lymphoid organ and presents donor antigen to T-cell causing Type 4 hypersensitivity reaction

T-cells will not induce a reaction unless the foreign antibody is presented to them by an antigen-presenting cell via HLA

Question 15

How does HLA matching work?

Answer 15

Patient’s notes include HLA mismatching
Tells you the HLA-A, HLA-B and HLA-DR mismatches between recipient and donor
(HLA A/B/C/DR are the most polymorphic HLA types)

The more mismatches you have, the poorer the outcome

Exposure to foreign HLA results in immune reaction -> immune graft damage and failure -> REJECTION

Question 16

Most common cause of graft failure?

Answer 16

Rejection

Question 17

Treatment for graft rejection?

Answer 17

Immunotherapy

Question 18

Types of graft rejection?

Answer 18

Hyperacute
Acute
Chronic
T-cell mediated
Antibody-mediated

Question 19

What can T-cells recruit after graft infiltration?

Answer 19

Cytotoxic T-cells (Release toxins)

Macrophages

Question 20

Explain antibody-mediated rejection

Answer 20

Antibodies against graft HLA and AB antigen

Antibodies can arise PRE-transplantation (naturally occuring) or POST-transplantation (de novo)

Question 21

What is the standard immunosuppressive regime?

Answer 21

Pre-transplant - Use induction agent (T-cell depletion or cytokine blockade)

From time of implantation - Baseline immunosuppression (signal transduction blockade CYCLOSPORIN, antiproliferative AZATHIOPRINE, corticosteroids)

If needed - Treat episodes of acute rejection

Question 22

What are the other complications of transplants arise from immunosuppressive therapy?

Answer 22

Infection
Post-transplant malignancy (skin cancer, lymphoproliferative disorder)
Drug toxicity