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MCD Immunology > Transplantation > Flashcards

Transplantation Flashcards

1
Q

What is an autograft?

A

When the graft is within the same individual

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2
Q

What is an isograft?

A

Between genetically identical individuals of same species

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3
Q

What is an allograft?

A

Between different individuals of same species

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4
Q

What is a xenograft?

A

Between individuals of different species

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5
Q

Give common examples of autografts being used

A

Coronary artery surgery- left internal thoracic, radial artery or saphenous vein are grafted to coronary artery
Reconstructive surgery e.g. skin grafts

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6
Q

How are stem cells used as a graft?

A

From the bone marrow, cells are aspirated and stem cells are purified to irradiate malignant or deficient BM cells. The cells are then recolonised with purified stem cells
In vitro use of pluripotent stem cells to make other tissues

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7
Q

When are xenografts most commonly used?

A

Heart valve replacement where pig or cow valves are used

Can also be used as a biological plaster for example burns victims

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8
Q

What types of allografts are there?

A 
Transplants:
Solid organs
Small bowel
Free cells
Temporary- blood and skin
Privileged sites- cornea
Framework- bone, cartilage, tendons and nerves
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9
Q

What are the two classifications for deceased allograft donors?

A

DBD (donor after brain death)- patients have confirmed brain death but still have beating heart
DCD (donor cardiac death)- patients have longer period of warm ischaemia time therefore organs are of less good quality however are suitable of kidney donations

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10
Q

What features are required for DBD donors?

A 
Patients must have displayed:
Irremediable structural brain damage of known cause
Apneic coma not due to:
- depressant drugs
- metabolic or endocrine disturbance
-hypothermia
-neuromuscular blockers
Demonstrated lack of brain stem function
- Pupils both fixed to light 
- Corneal reflex absent
- No eye movements with cold caloric test
- No cranial nerve motor responses
- no gag reflex
- No respiratory movements on disconnection
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11
Q

What is the exclusion criteria for donation?

A

Viral infection- HIV, HBV and HCV
Malignancy
Drug abuse, overdose or poison
Disease of transplanted organ

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12
Q

How are donors and recipient matched?

A

HLA typing

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13
Q

In what situations do corneas fail?

A

Degenerative disease, infections and trauma

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14
Q

In what situations does skin fail?

A

Burn, trauma and infections

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15
Q

In what situations do kidneys fail?

A

Diabetes, hypertension, glomerulonephritis and hereditary conditions

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16
Q

In what situations does the heart fail?

A

Coronary artery or valve disease, cardiomyopathy and congenital defects

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17
Q

In what situations does the liver fail?

A

Cirrhosis (viral hepatitis, alcohol , autoimmune, hereditary conditions)

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18
Q

In what situations do the lungs fail?

A

Chronic obstructive pulmonary disease/emphysema, interstitial fibrosis/intersitial lung disease, cystic fibrosis, pulmonary hypertension

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19
Q

In what situation does the pancreas fail?

A

Type 1 diabetes

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20
Q

In what situation does the bone marrow fail?

A

Tumours and hereditary disease

21
Q

In what situation does the small bowel fail?

A

Mainly children (short gut), hereditary conditions or related to prematurity

22
Q

What factors are involved when considering organ allocation?

A 
Ethical determinants-
Urgency
Time on waiting list
Biological determinants-
Cold ischaemia time
Organ size
Histocompatibility
23
Q

What is NHSBT?

A

NHS blood and transplant provides a reliable efficient supply of blood, organs and associated services to the NHS

24
Q

What are geographical differences in cadaveric donor rates due?

A

Lower rates of road traffic accidents

Inefficiencies and inconsistencies in identification of potential donors

25
Q

What strategies are there to increase transplantation activity?

A

Deceased donation- use of marginal donors i.e. donation following cardiac death. the elderly and sick
Living donation- donating across the tissue compatibility barriers, organ exchange programmes

26
Q

In terms of clinical transplantation, what are the most relevant protein variations?

A

ABO blood group

Polymorphic HLA coded on chromosome 6 by MHC

27
Q

Where are A and B proteins found?

A

On red blood cells as well as endothelial lining of blood vessels

28
Q

If a patient has A proteins what would you expect to find?

A

Naturally occurring anti-B antibodies (opposite with B proteins)

29
Q

What would you expect to find in a patient that is O?

A

No antigens so they would have both anti-A and anti-B antibodies

30
Q

How do anti-A/B antibodies cause an immune reaction when they come in contact with protein that they are against?

A

The antibody will bind to antigens on donor endothelium and then:
Activates complement -> complement mediated lysis, opsonisation and increased vascular permeability
Recruitment of phagocytes
Disruption of endothelium > platelet activation, inflammation and thrombosis
- This is known as hyper acute rejection

31
Q

In terms of ABO what has been possible in recent years?

A

It has become possible to remove antibodies in the organ recipient with good outcomes- used for kidney, heart and liver

32
Q

What are the cell surface proteins of HLA important in?

A

They have a highly variable portion that is important in defence against infection and neoplasia

33
Q

How do HLA molecules enable an immune response?

A

The HLA molecules are recognised as “self” therefore no immune response is mounted. However HLA molecules present foreign antigens to T cells therefore enabling the immune response

34
Q

What are the two classes of HLA antigens?

A 
Class I (A,B and C) which are expressed on all cells. These are most important with regards to organ transplantation
Class II (DR, DQ +DP) which are expressed on immune cells but can be unregulated on other cells
35
Q

What is the haplotype inheritance like?

A

Children each have a haplotype match with each parent so amongst siblings:
25% 2 haplotype match
50% 1 haplotype match
25% 0 haplotype match

36
Q

What happens if there is a mismatch in HLA antigens?

A

Recipient’s immune system will mount a reaction against the donors HLA as if it were an infection/cancer. This results in rejection= the destruction of the graft by cellular and antibody-mediated immune processes, eventually resulting in graft failure

37
Q

What transplants is HLA matching most important in?

A

Kidney and bone marrow transplant

Less important in heart, lung and liver

38
Q

What is the most common cause of graft failure and what can it be due to?

A

Transplant rejection- may be T cell mediated or antibody mediated

39
Q

What is the gold standard for diagnosis of transplant rejection?

A

Histological examination of a biopsy

40
Q

What is used to reduce risk of rejection?

A

Prophylactic immunosuppression

41
Q

When does acute T-cell mediated rejection occur?

A

Following recognition of donor HLA antigens by CD4+ T cells, which are then activated and mount a type IV hypersensitivity response

42
Q

What does the production of cytokines in an acute T cell mediated rejection do?

A

Helps CD8+ cell action (cytotoxic)
Helps B cells (mounts antibody response)
Recruit and activate macrophages and neutrophils

43
Q

What does acute antibody-mediated rejection involve?

A

Antibody production and complex formation with graft HLA and AB antigens (these antibodies may be present before transplantation due to previous antigen contact)

44
Q

What do the antibody complexes do in acute antibody-mediated rejection?

A 
Activate complement (via classical pathway>cell lysis, opsonisation etc) and macrophages (. phagocytosis)
They also disrupt the endothelium, causing platelet activation, inflammation and thrombosis
45
Q

How is rejection diagnosed in kidney, liver and pancreas?

A

Regular blood tests (creatinine, liver function and amylase)

Followed by graft biopsy and histological interpretation

46
Q

How is rejection prevented?

A

Maximise HLA compatibility

Suppress the immune reaction of the recipient- immunosuppression

47
Q

What do immunosuppressive drugs target?

A

T cell activation and proliferation

B cell activation and proliferation and antibody production

48
Q

What does modern transplant immunosuppression involve?

A

Induction agent to deplete immune cells before transplantation
Base-line immunosuppression: variable
Treatment of episodes of acute rejection

49
Q

What other post-transplant risks is there?

A 
Post-transplant conventional infection:
Viral: CMV, VZV and EBV
Fungal: aspergillus
Bacterial: TB, listeria
Parasitic: Pneumocystis
Toxoplasma
Other common infections

Post-transplantation malignancy including skin cancer
Drug toxicity due to high use of immunosuppressive drugs such as steroids including hypertension, hyperlipidaemia and CVD

MCD Immunology (5 decks)

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