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Y2 Immunology > Transplantation > Flashcards

Transplantation Flashcards

1
Q

When are organs transplanted

A

when they are failing or have failed, or for reconstruction

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2
Q

Give examples of organs that can be transplanted

A 
Cornea
Skin 
Heart 
Lungs 
Kidney 
Liver
Bone Marrow
Small bowel 
Pancreas
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3
Q

What are the 4 types of transplant

A

Autograft
Isograft
Allograft
Xenograft

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4
Q

What is an autograft

A

within the same individual e.g. skin from buttock to face

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5
Q

What is an isograft

A

between genetically identical individuals of the same species

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6
Q

What is an allograft

A

between different individuals of the same species

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7
Q

What is a xenograft

A

between individuals of different species e.g. pig or cow heart valves

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8
Q

What are the two types of decreased donor

A

After brain death (DBD)

After cardiac death (DCD)

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9
Q

Describe the DBDs

A

Brain injury has caused death before terminal apnoea has resulted in cardiac arrest and circulatory standstill

E.g. Intracranial haemorrhage; road traffic accident (catastrophic cerebral haemorrhage)

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10
Q

What must be done with DBDs before harvesting

A

Brain death must be confirmed before the organs are harvested and cooled
Confirm using neurological criteria
Circulation established through resuscitation

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11
Q

What is the criteria for DBDs

A

Irremediable structural brain damage from a known cause
Demonstrable lack of brainstem function

Apnoeic coma not due to:

  • depressant drugs
  • metabolic / endocrine disturbance
  • hypothermia
  • neuromuscular blockers
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12
Q

How is lack of brainstem function demonstrated for DBDs

A

Eyes unresponsive (pupillary light reflex, corneal reflex, and cold caloric reflex test)
Cranial nerve motor reflexes absent
Gag reflex absent
No respiratory movements on disconnection from ventilator

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13
Q

What are some reasons for exclusion of a DBD

A

Viral infection, especially HIV, HBV, HCV
Malignancy
Drug abuse, overdose, or poisoning
Disease of the organ itself

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14
Q

What is the number 1 obstacle to donation and what is the rate for this

A

A braindead person’s family refusing to consent for his/her organs to be transplanted
43% refusal rate

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15
Q

What are some potential strategies for increasing transplantation

A

including more marginal donors (i.e. slightly relaxing some criteria for the deceased’s organs)

Exchange programmes to acquire better tissue matches

Xenotransplantation and stem cell research for the future

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16
Q

Describe DCDs

A

death is diagnosed and confirmed using cardio-respiratory criteria; 5 minutes observation of irreversible cardiorespiratory arrest
Controlled or uncontrolled
Longer period of warm ischaemia time

17
Q

What re the 7 elements of organ allocation for the kidney

A 
Waiting time
HLA match and age combined
Donor-recipient age difference
Location of patient relative to donor
HLA-DR homozygosity
HLA-B homozygosity
Blood group match
18
Q

What are the most relevant protein variations in clinical transplantation

A

ABO blood group

HLA (human leukocyte antigens) coded on chromosome 6 by Major Histocompatibility complex (MHC)

19
Q

What is the consequence of not ABO cross matching between donor and recipient

A

Hyperacute rejection occurs as the foreign cells are lysed by complement and/or phagocytosed all with massive inflammation, platelet activation etc..

20
Q

How is ABO-incompatible matching overcome in transplantation

A

remove the recipient’s A/B antibodies (plasma exchange) with good outcomes

21
Q

Where are class I and II HLA expressed

A 
Class I (A, B, C)- all cells
Class II (DR, DQ, DP) - immune cells (can be unregulated on other cells)
22
Q

Describe HLA molecules

A

Highly polymorphic – lots of alleles for each locus

Each individual has most often 2 types for each HLA molecule (for example: A3 and A21)

23
Q

What does exposure to a foreign HLA molecule result in

A

Immune response mediated by both B cells and T cells.

The immune reaction can cause immune graft damage and failure = rejection

24
Q

How important is HLA matching in organ donation and what is the criteria for it

A

HLA does not have to be perfectly matched (as that’s impractical) but there must be <6 mismatches

25
Q

How is organ rejection diagnosed

A

histological examination of a graft biopsy

26
Q

How is organ rejection treated

A

Immunosuppressive drugs

27
Q

Which organs’ rejection can be tested clinically and how

A

Kidney - creatinine
Pancreas - serum amylase/lipase/glucose

Hearts cannot be

28
Q

What does a standard immunosuppressive regime entail

A

An induction agent
Basline immunosuppression
Treatment of episodes of acute rejection

29
Q

Give examples of induction agents

A

e.g. cytokine blockade, T cell depletion

30
Q

Give examples of agents used for baseline immunosuppression

A

Signal transduction blockade e.g. calcineurin inhibitor (cyclosporin), mTOR inhibitor
Antiproliferative agent e.g. azathioprine
Corticosteroids

31
Q

How are acute rejection episodes treatment

A

Cellular: steroids, anti-T cell agents

Antibody-mediated: IVIg (intravenous immunoglobulin), anti-C5, plasma exchange

32
Q

Describe the T cell lymphocyte response to pathogens and to donor cells

A

Foreign bodies taken up by APCs and presented on the membrane. T lymphocytes only recognise foreign proteins in the context of self cells

In donor cells, they shed their own HLA molecules which are presented on APCs

33
Q

What are the mechanisms fo T-cell mediated rejection

A

Graft infiltration by alloreactive CD4+ cells
“Cytotoxic” T cells
Macrophages

34
Q

Describe how cytotoxic T cells bring about T-cell mediated rejection

A

Release of toxins to kill target e.g. Granzyme B
Punch holes in target cells via perforin
Apoptotic cell death via Fas -Ligand

35
Q

Describe how macrophages bring about T-cell mediated rejection

A

Phagocytosis
Release of proteolytic enzymes
Production of cytokines
Production of oxygen radicals and nitrogen radicals

Y2 Immunology (5 decks)

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