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Year 2 Collin > Immunology 3 - Transplantation > Flashcards

Immunology 3 - Transplantation Flashcards

1
Q

What are the 2 types of transplantation?

A
  1. Life saving - liver, heart, small bowel

2. Life enhancing - if other life supportive methods less good (e.g. kidney - dialysis / pancreas)

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2
Q

What are the different types of transplantation

A
  1. Autografts - within the same individual - e.g. CABG, reconstructive
  2. Isografts - between genetically identical individuals of the same species (identical twins)
  3. Allografts - between different individuals of the same species (most common)
  4. Xenografts - between individuals of different species
  5. Prosthetic graft
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3
Q

What are the 2 types of allograft donor

A
  1. Deceased donor - divided into donor after brainstem death and donor after circulatory death
  2. Living donor - bone marrow, kidney, liver. Can be genetically related donor or unrelated
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4
Q

Describe DBD - Donor after brain stem death

A

Majority of organ donors - brain injury caused death before terminal apnoea resulted in cardiac arrest.

e.g. IC haemorrhage road traffic accident.

Organs harvested and cooled to minimise ischaemic damage

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5
Q

Describe DCD - donor after circulatory death

A

Death diagnosed and confirmed using cardiorespiratory criteria

Longer period of warm ischaemia time

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6
Q

In deceased donors, what must be excluded before using the organ

A
  1. Viral infection
  2. Malignancy
  3. Drug abuse, OD
  4. Disease of transplanted organ

Removed organs = rapidly cooled and perfused (maximum cold time for kidney = 60h)

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7
Q

Transplantation allocation is based on?

A
  1. Equity - time on waiting list, urgency

2. Efficiency - patient survival, etc

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8
Q

Name 3 elements to consider when allocating organs

A
  1. Waiting time
  2. HLA match and age combined
  3. Donor-recipient age difference
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9
Q

How does the half life of kidney transplants vary?

A

If living donor - lasts longer (2x) than deceased donor (roughly 15 years)

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10
Q

What are the 2 main groups of molecules that cause rejection

A
  1. ABO blood group

2. HLA on Chr 6

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11
Q

A and B proteins are located on RBC. Where else are they located

A

Endothelial lining of blood vessels in transplanted organ

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12
Q

Describe ABO incompatible transplantation

A
  1. Antibodies removed in recipient (plasma exchange)
  2. Good outcome - even if antibody comes back
  3. Done in kidney, heart, liver transplants
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13
Q

How do T cells recognise antigens

A

They recognise T cells in the context of HLA molecules presented by APCa

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14
Q

What are the 2 types of HLA

A
  1. Class 1 - A, B, C - expressed on all cells
  2. Class 2 - DR, DQ, DP; expressed on APCs but also unregulated on other cells

They are highly polymorphic - lots of alleles for each locus. Each individual has 2 types for each HLA molecule

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15
Q

How do MHC Class 1 and Class 2 molecules differ

A

Peptide binding groove:

In MHC Class 1 -both alpha chains (1 & 2)

In MHC Class 2 - alpha (1) and beta (1)

(Class 1 also has a b2-microglobulin chain)

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16
Q

Which are the highly polymorphic HLA molecules

A

HLA-A, HLA-B, HLA-C, HLA-DR

17
Q

Explain the mismatching in parent - child.

wb sibling to sibling

A

Parent to child = equal to or greater than 3/6 matches

Sibling to sibling:

25%= 6 mismatches
50% = 3 mismatches
25% = 0 mismatches
18
Q

What is rejection

A
  1. Exposure to foreign HLA molecules –> results in an immune reaction to foreign epitopes —> rejection.

Can cause immune graft damage and failure

19
Q

What is the treatment for rejection

A

Immunosuppressive drugs

20
Q

Describe the different types of rejection

A
  1. Hyperacute rejection (rare) - rapidly after graft implanted
  2. Acute rejection - few weeks/months after transplant
  3. Chronic rejection - slow deterioration
  4. T-cell mediated rejection
  5. Antibody mediated rejection
21
Q

Describe T cell mediated rejection

A

T cell recognises foreign HLA epitopes on APCs. T cells recognise these foreign antigens on local secondary lymphoid organs - lymph nodes.

Then T cells circulate to graft and encounter the HLA molecule that will stimulate them on the surface of the endothelium of the graft.

T cells undergo tethering, rolling, arrest, diapedesis, through endothelial cell lining into interstitium - start attacking tubule with HLA epitopes they recognise - causing tubulitis (in kidney)

22
Q

CD4 helper cells recruit which other 2 cells as part of the infiltrate?

A

Cytotoxic T cells and macrophages

23
Q

Describe antibody-mediated rejection

A

B cell dominant (obvs)

Antibody against graft HLA (mainly) or AB antigen (rarely)

Antibodies may arise:

  1. Pre-transplantation (“sensitised”)
  2. Post transplantation (“de novo”)
24
Q

How do antibodies destroy infections?

A

Activates complement, activates macrophages (Fc receptors)

25
Q

Antibody rejection is mainly ….

A

Intravascular

26
Q

T cell rejection is mainly?

A

Tubulointerstitial

27
Q

What are signs of deteriorating graft function

A

Kidney - rise in creatinine, fluid retention, hypertension

Liver - rise in LFTs, coagulopathy

Lung transplant - breathlessness, pulmonary infiltrate

28
Q

How do we try and prevent rejection

A
  1. Maximise HLA compatibility

2. Life-long immunosuppressive drugs

29
Q

Which immunosuppressive drugs target T cells?

A

Calcineurin inhibitors: e.g. cyclosporine, tacrolimus

Cell cycle / nucleotide synthesis inhibitors: azathioprine

and steroids which have a more generic action

Also induction agents - reduce the number of antibodies - e.g. anti-CD52 mAb

IL-2 inhibitors - anti-IL2 receptor drugs

30
Q

Which immunosuppressive drugs target B cells?

A

We only target B cells if patient has antibodies against graft

Can do splenectomy or plasma exchange or intravenous immunoglobulin (IVIG)

Can use:

  1. anti-CD20 drugs
  2. Bortezomib (proteosome inhibitor - kills of antibody producing plasma cells)
  3. Anti-C5 drugs (drugs inhibiting complement activation)
31
Q

Name 3 opportunistic viruses that may arise post transplantation

A
  1. Cytomegalovirus
  2. BK Virus
  3. Pneumocytis carinii
32
Q

Name some common pst transplantation malignancies

A
  1. Skin cancer
  2. Post transplant lymphoproliferative disorder - EBV driven
  3. Others

Year 2 Collin (114 decks)

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