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Y2 Immuno (MCD) > Transplantation > Flashcards

Transplantation Flashcards

1
Q

What is the difference between life-saving and life-enhancing transplantation?

A

Life-saving – other life-supportive methods are not fully developed or other life-supportive methods have reached the end of their possible use e.g. liver

Life-enhancing – other life-supportive methods are less good e.g. Kidneys and dialysis – the organ is not vital but it improves the quality of life e.g. cornea

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2
Q

What are the different types of transplants?

A

Autograft – within the same individual

Isografts – between genetically identical individuals of the same species

Allograft – between different individuals of the same species

Xenograft – between individuals of different species

Prothetic graft – artificial material e.g. plastic, metal

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3
Q

Give an example of an autograft.

A

Coronary artery bypass graft

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4
Q

What tissues can xenografts be used for?

A

Heart valves

Skin

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5
Q

What are the two types of deceased donor?

A

Donor after brain death – brain dead but heart-beating

Donor after cardiac death –non-heart beating donors

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6
Q

What must be confirmed with DBD donors?

A

Irremediable structural brain damage of known cause

Apnoeic coma that is NOT due to depressant drugs, hypothermia, neuromuscular blockers etc.

Must be able to demonstrate a lack of brain stem function (e.g. pupils both fixed to light)

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7
Q

What must be excluded before harvesting organs from a deceased donor?

A

Viral infection
Malignancy
Drug abuse, overdose or poison

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8
Q

How are the organs maintained once they’ve been removed?

A

They are rapidly cooled and perfused

NOTE: absolute maximum cold ischaemia time for the kidneys is 60 hours

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9
Q

What is the difference between transplant selection and transplant allocation?

A

Selection – access to the waiting list

Allocation – access to the organ

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10
Q

What is the nationwide system of transplant allocation based on?

A

Equity – fairness

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

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11
Q

What are the 5 tiers of patients on the organ transplant waiting list based on?

A

Paediatric or adult

Highly sensitised or not

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12
Q

What are the 7 elements that are used to decide upon organ allocation?

A

Main 3:
Waiting time

HLA match and age combined

HLA-B homozygosity

Other 4:

HLA-DR homozygosity

Donor-recipient age difference

Location of patient relative to donor

Blood group match

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13
Q

What are the main obstacles to donation?

A

Contraindication for use of that organ

Family not approached for consent

Family declined consent

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14
Q

Describe some other strategies for increasing transplantationactivity.

A

Use marginal donors e.g. elderly and sick

Transplantation across compatibility barriers

Exchange programmes – organ swaps for better tissue matching

Future – xenotransplantation + stem cell research

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15
Q

What are the main antigens that must be considered when determining the compatibility of an organ for transplant?

A

ABO blood group

HLA

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16
Q

On which chromosome is the HLA gene encoded?

A

Chromosome 6

17
Q

What are the two classes of HLA and which HLA subtypes are in each class?

A

HLA Class I – A, B and C = present on all cells

HLC Class II – DP, DQ, DR = present on specialised immune cells

18
Q

What are the most important HLA subtypes in organ compatibility?

A

A
B
DR
NOTE: the fewer the number of mismatches, the better the outcome for the recipient

19
Q

What are the two types of organ rejection?

A

T cell-mediated rejection

Antibody-mediated rejection (B cells)

20
Q

How is rejection diagnosed?

A

Histological examination of graft biopsy

21
Q

How is rejection classified based on the time of onset?

A

Hyperacute
Acute
Chronic

22
Q

How may organ rejection present?

A

Deteriorating graft function e.g. rise in creatinine with kidney transplant

Pain and tenderness over graft

Fever

23
Q

How can rejection be prevented?

A

Maximise HLA compatibility

Life-long immunosuppressive therapy

24
Q

List some treatments for Antibody-mediated rejection.

A

Anti-CD20 antibodies

Bortezomib (proteasome inhibitor)

Anti-complement antibodies

Plasma exchange

IVIg

Splenectomy

25
Q

What is normally used for baseline immunosuppression following transplantation?

A

Signal transduction blockade: usually a calcineurin inhibitor (tacrolimus or cyclosporin)

Antiproliferative agent (e.g. azathioprine)

Corticosteroids

26
Q

Describe the treatment of episodes of acute rejection.

A

T cell mediated: steroids and anti-T cell agents

Antibody mediated: IVIg, plasma exchange, anti-CD20, anti-complement

27
Q

What are the risks of the extensive immunosuppressive therapy that is given to patients following transplantation?

A

Increased risk of infection (including opportunistic infection)

Malignancy

Drug toxicity

28
Q

What can be translplanted from a living donor?

A

bone marrow, kidney, liver

29
Q

Why are transplantations required?

A

rgans are transplanted when they are failing or have failed, or for reconstruction

30
Q

How does blood group effect transplantation rejection?

A

A and B proteins with carbohydrate chains on red blood cells but also endothelial lining of blood vessels in transplanted organ

O has neither A or B

Antibodies are produced to all blood group antigens not expressed

If receive organ with other antigens on then your antibodies will attack it

31
Q

How can ABO-incompatible transplantation be overcome?

A

Remove the antibodies in the recipient (plasma exchange)

Good outcomes (even if the antibody comes back)

32
Q

What’s the mechanism of t cell mediated rejection?

A

T cell activation by APC

Graft infiltration by alloreactive CD4+ cells

Cytotoxic t cells:
Release of 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

33
Q

What’s the mechanism of antibody mediated rejection?

A

Antibody against graft HLA and AB antigen

Antibody activates complement and macrophages

34
Q

What are the 2 ways of antibody production against a transplant?

A

Pre-transplantation (“sensitised”)

Post-transplantation (“de novo”)

35
Q

What is the stadard immunosupressive regime pre-implantation?

A

Induction agent for T-cell depletion or cytokine blockade.

Y2 Immuno (MCD) (5 decks)

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