Immunology - Transplantation

Question 1

What are the 5 types of transplant

Answer 1

• Autograph - within the same tissue
• Isograph - between genetically identical individuals of the same species
• Allographs - Between different individuals of the same species
• Xenographs - between individuals of different species
• Prosthetic graft - plastic, metal

Question 2

What is the future of transplantation

Answer 2

Performing autographs by growing organs

Question 3

What would an allograph be used for

Answer 3

• Solid organs
• Small bowel
• Free cells (bone marrow, pancreas islets)
• Temporary
• Privileged sites (Cornea)
• Framework (bone, cartilage, tendon)
• Composite (face, hands)

Question 4

What is the most common transplant in the UK?

Answer 4

Kidney - 3600 out of 5100 per year

Next most common are liver, heart, then pancreas

Question 5

What are the types of allograft donor

Answer 5

• Deceased donor
• Living donor (bone marrow, liver, kidney)
  - genetically related or unrelated (spouse, altruistic)

Question 6

What are the two variants of deceased donors?

Answer 6

DBD - donor after brain stem death

DCD - donor after circulatory death

Question 7

List some information about DBD

Answer 7

• Majority of organ donors
• Brain injury before cardiac arrest
• intracranial haemorrhage, road traffic accident
• Circulation established through resuscitation
• Confirm death using neurological criteria
• Harvest organs and cool to minimise ischaemic damage

Question 8

List some information about DCD

Answer 8

• Death diagnosed and confirmed using cardio-respiratory criteria
• Controlled - patients who have cardio-respiratory aid removed when in catastrophic brain injury and in best interest
• Uncontrolled
• Longer period of warm ischaemia time

Question 9

List exclusion criteria for deceased donors

Answer 9

• Viral infection
• Malignancy
• Drug abuse, overdose or poison
• Disease of transplanted organ

Question 10

How long can organs be kept between harvesting and transplant

Answer 10

• Organs need to be rapidly cooled and perfused
• maximum time for kidneys is 60 hrs, ideally less than 24 hrs
• For other organs the amount of time is much less

Question 11

What is used for transplant allocation

Answer 11

• National guidelines
• Evidence based computer algorithms
• Equity (what is fair, time on waiting list)
• Can be changed for super-urgent transplants (imminent death)
• Efficiency - what is the best use for the organ in terms of patients survival and graft survival

Question 12

Strategies to increase transplantation activity

Answer 12

• deceased donation from marginal donors - DCD, elderly, co-morbidities
• Living donation - transplantation across tissue compatibility barriers, exchange programmes: organ swap for better tissue matching

Question 13

What is the half-life for adult kidney transplants

Answer 13

Living donor - 12 years on average

Deceased donors - 9 years on average

Question 14

How does HLA matching alter the outcome of a transplant

Answer 14

Each individual has 2 types of each HLA molecule of which there are A, B and DR HLA. This can give between 0 and 6 mismatches and the more mismatches the worse the outcome

Question 15

What are the different types of rejection

Answer 15

• Hyperacute rejection (very rare)
• Acute rejection - T-cell mediated
• Chronic rejection - antibody mediated rejection

Question 16

Explain T cell mediated rejection

Answer 16

Graft infiltration by alloreactive CD4+ cells.
Cytotoxic T cells
- release toxins to kill target (granzyme B)
- Punch holes in target cells (perforin)
- Apoptotic cell death (Fas-ligand)
Macrophages
- phagocytosis
- release of proteolytic enzymes
- production of cytokines
- production of oxygen radicals and nitrogen radicals

Question 17

Describe antibody mediated rejection

Answer 17

Antibodies formed against graft HLA and AB antigen.
Antigens can arise:
- Pre-transplantation (sensitised) - caused by previous transfusions, grafts or pregnancy
- Post-transplantation (de novo)

Question 18

What do you measure for monitoring graft rejection

Answer 18

Kidney transplant - rise in creatinine, fluid retention, hypertension
Liver transplant - rise in LFTs, coagulopathy
Lung transplant - breathlessness, pulmonary infiltrate

Question 19

How to minimise rejection

Answer 19

• Maximise HLA compatibility

- Life long immunosuppressive drugs

Question 20

How to treat rejection

Answer 20

More drugs

Question 21

State the different types of immunosuppressive drugs

Answer 21

Drugs that target T cell activation and proliferation

Drugs that target B cell activation and proliferation, and antibody production

Question 22

Describe the standard immunosuppressive regime

Answer 22

Pre-transplantation - induction agent (T-cell depletion or cytokine blockade)
From time of implantation - base line immunosuppression
If needed - Treatment of episodes of acute rejection

Question 23

What are the risks of post-transplantation infections

Answer 23

Increased risk for conventional infections (bacterial, viral, fungal)
Opportunistic infections - normally harmless agents give sever infections because of immune compromise (CMV, BK virus, pneumocytis carinii)

Question 24

What cancers are transplant patients at an increased risk for

Answer 24

Skin cancer

Post transplant lymphoproliferative disorder - EBV driven