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YR2: Immunology > Transplantation > Flashcards

Transplantation Flashcards

1
Q

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

A

Life-saving: other life-supportive methods have reached end of their use e.g. Liver
Life-enhancing: other life-supportive methods are less good e.g. Kidneys + dialysis: organ is not vital but improves QoL

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2
Q

What are the 5 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 2 types of deceased donor?

A

Donor after brain death: brain dead but heart-beating (organs in optimal condition)
Donor after cardiac death: non-heart beating donors (longer warm ischaemia time)

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6
Q

What must be confirmed with DBD donors?

A

Irremediable structural brain damage of known cause

Lack of brain stem reflexes (e.g. pupillary reflex absent)

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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
Disease of the transplant organ

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8
Q

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

A

Rapidly cooled + perfused
Absolute max. cold ischaemia time for kidneys is 60 hours
Much shorter for other organs

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9
Q

What is the difference between transplant selection and transplant allocation?

A

Selection: eligibility to access waiting list
Allocation: access to organ once available

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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 + 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 
Waiting time  
HLA match + age combined
Donor-recipient age difference
Location of patient relative to donor    
HLA-DR homozygosity    
HLA-B homozygosity
Blood group match
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13
Q

Describe some other strategies for increasing transplantation activity.

A

Use marginal donors e.g. elderly, co-morbid, DCD
Transplantation across compatibility barriers
Exchange programmes: organ swaps for better tissue matching
Future: xenotransplantation + stem cell research

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14
Q

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

A

ABO blood group

HLA coded on Chr6

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15
Q

What are the two classes of HLA, which HLA subtypes are in each class and what cells are they found on?

A

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

HLA Class II: DP, DQ, DR = present on specialised immune cells (APC’s)

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16
Q

What are the most polymorphic and thus important HLA subtypes in organ compatibility?

A

A
B
DR
The fewer the number of mismatches /6, the better the outcome for the recipient

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17
Q

What are the 2 types of organ rejection?

A

T cell-mediated rejection

Antibody-mediated rejection (B cells)

18
Q

How is rejection diagnosed? How is it treated?

A

Histological examination of graft biopsy

Immunosuppressive drugs

19
Q

How is rejection classified based on the time of onset?

A

Hyperacute (immediate)
Acute (weeks/ months)
Chronic (years)

20
Q

How may organ rejection present?

A

Deteriorating graft function e.g. rise in creatinine with kidney transplant
Pain + tenderness over graft
Fever

21
Q

How can rejection be prevented?

A

Maximise HLA compatibility
Life-long immunosuppressive therapy
Treatment of rejection

22
Q

List 5 treatments for Antibody-mediated rejection.

A 
Anti-CD20 antibodies  
Bortezomib (proteasome inhibitor)  
Anti-complement antibodies  
Plasma exchange  
Intravenous immunoglobulin
23
Q

What is normally used for baseline immunosuppression following transplantation?

A

Signal transduction blockade, usually a CNI inhibitor
Antiproliferative agent (e.g. azathioprine)
Corticosteroids

24
Q

Describe the treatment of episodes of acute rejection.

A

T cell mediated: steroids + anti-T cell agents

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

25
Q

What is a major risk of the extensive immunosuppressive therapy that is given to patients following transplantation?

A

Increased risk of infections + tumours

26
Q

Give 3 general reasons that may cause organ failure

A

Infection
Trauma
Tumour

27
Q

What can be transplanted from a living donor?

A

Bone marrow
Kidney
Liver

28
Q

Describe the different types of red blood cell and antibodies

A

Type A: A RBCs + Anti-B antibodies
Type B: B RBC’s + Anti A antibodies
Type AB: AB RBC’s + No antibodies
Type O: Anti A + Anti B antibodies

29
Q

Where are ABO blood groups expressed?

A

RBCs

Endothelial lining of blood vessels in transplanted organs

30
Q

How can ABO-incompatible transplantation still have successful outcomes?

A

By removing antibodies in recipient by plasma exchange

Although antibodies return to an extent, there is accommodation of the organ

31
Q

Describe the recognition of foreign antigen by T lymphocytes

A

Foreign protein digested by APC
Resulting peptides presented on surface of APC in HLA peptide groove
T lymphocyte can recognise foreign molecule if in context of HLA

32
Q

Describe the nature of HLA expression

A 
Highly polymorphic (lots of alleles at each locus) e.g. A1-A341
Each individual has 2 types for each HLA molecule e.g. A3 + A21
33
Q

List 3 characteristics of T cell mediated rejection on a biopsy

A

Lymphocytic interstitial infiltration
Ruptured tubular basement membrane
Tubilitis (immune cells attacking tubular epithelial cells)

34
Q

Describe the mechanisms involved in T cell mediated rejection

A

Infiltration by host CD4+ cells
Recruitment of CD8+ killer cells- release toxins, stimulate apoptosis
Recruitment of macrophages- phagocytosis, release cytokines

35
Q

When do antibodies against graft HLA and AB antigens arise?

A 
Pre-transplantation = sensitised (previous transplant/ transfusion/ exposure to foreign antigen in foetus)
Post-transplantation = de novo
36
Q

Describe the process of antibody mediated rejection

A

Host antibodies bind to graft antigens + recruit complement
Activation of complement pathway- punches holes in graft cells
Recruit inflammatory cells with Fc receptors that recognise graft antigens- phagocytosis + secretion of proteolytic enzymes

37
Q

How do the antibody and T cell mediated rejection mechanisms differ?

A

Antibody: Mainly intravascular

T cell: Mainly interstitium + tubules

38
Q

How do immunosuppressive drugs work to prevent graft rejection?

A

Target T cell activation + proliferation

Target B cell activation + proliferation + antibody production

39
Q

List 3 treatments for T cell-mediated rejection.

A

CNI inhibitors
Drugs that deplete T cells generally e.g. anti-CD52
Steroids

40
Q

What is done to try to prevent rejection pre-transplantation?

A

T cell depletion or Cytokine blockade

41
Q

What infections does post transplantation immunosuppression increase risk of?

A

Conventional (bacterial, viral, fungal)

Opportunistic (normally harmless e.g. Cytomegalovirus)

42
Q

What malignancies does post transplantation immunosuppression increase risk of?

A

Skin cancer

Post transplant lymphoproliferative disorder (Epstein Barr virus driven)

YR2: Immunology (5 decks)

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