Immunology - Transplantation Flashcards
What are the 5 types of transplant
- 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
What is the future of transplantation
Performing autographs by growing organs
What would an allograph be used for
- Solid organs
- Small bowel
- Free cells (bone marrow, pancreas islets)
- Temporary
- Privileged sites (Cornea)
- Framework (bone, cartilage, tendon)
- Composite (face, hands)
What is the most common transplant in the UK?
Kidney - 3600 out of 5100 per year
Next most common are liver, heart, then pancreas
What are the types of allograft donor
- Deceased donor
- Living donor (bone marrow, liver, kidney)
- genetically related or unrelated (spouse, altruistic)
What are the two variants of deceased donors?
DBD - donor after brain stem death
DCD - donor after circulatory death
List some information about DBD
- 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
List some information about DCD
- 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
List exclusion criteria for deceased donors
- Viral infection
- Malignancy
- Drug abuse, overdose or poison
- Disease of transplanted organ
How long can organs be kept between harvesting and transplant
- 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
What is used for transplant allocation
- 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
Strategies to increase transplantation activity
- deceased donation from marginal donors - DCD, elderly, co-morbidities
- Living donation - transplantation across tissue compatibility barriers, exchange programmes: organ swap for better tissue matching
What is the half-life for adult kidney transplants
Living donor - 12 years on average
Deceased donors - 9 years on average
How does HLA matching alter the outcome of a transplant
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
What are the different types of rejection
- Hyperacute rejection (very rare)
- Acute rejection - T-cell mediated
- Chronic rejection - antibody mediated rejection
Explain T cell mediated rejection
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
Describe antibody mediated rejection
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)
What do you measure for monitoring graft rejection
Kidney transplant - rise in creatinine, fluid retention, hypertension
Liver transplant - rise in LFTs, coagulopathy
Lung transplant - breathlessness, pulmonary infiltrate
How to minimise rejection
- Maximise HLA compatibility
- Life long immunosuppressive drugs
How to treat rejection
More drugs
State the different types of immunosuppressive drugs
Drugs that target T cell activation and proliferation
Drugs that target B cell activation and proliferation, and antibody production
Describe the standard immunosuppressive regime
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
What are the risks of post-transplantation infections
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)
What cancers are transplant patients at an increased risk for
Skin cancer
Post transplant lymphoproliferative disorder - EBV driven
