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Immunology Y2 > Transplantation > Flashcards

Transplantation Flashcards

1
Q

What is an Autograft

A

Within the same individual (one part of the body to the other

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2
Q

What is an Isografts

A

Between genetically identical individuals of the same species

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3
Q

What is an Allografts

A

Between different individuals of the same species

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4
Q

What is an Xenografts

A

Between individuals of different species

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5
Q

What is an Prosthetic graft

A

Plastic, metal

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6
Q

Examples of areas of xenografts? (3)

A
  • Heart valves (pig/cow)

- Skin

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7
Q

Examples of areas of autografts? (3)

A
  • Reconstructive surgeries, coronary artery bypass surgery etc.
  • The future of autografts lies in the use of STEM CELLS to make full organs which function as they should
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8
Q

Examples of areas of allografts? (3)

A

Solid organs (kidney, liver, heart, lung, pancreas)

  • Small bowel
  • Free cells (bone marrow, pancreas islets)
  • Temporary blood, skin (burns)
  • Privileged sites cornea
  • Framework bone, cartilage, tendons, nerves
  • Composite hands, face, larynx, uterus
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9
Q

Difference between orthotopic and heterotopic transplantation?

A

ORTHOTOPIC transplantation Organ put in the place where it should be (this is the most common and done for heart, lungs and liver)
HETEROTOPIC transplantation Organ not put in the place where it should be (kidneys and pancreas)

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10
Q

What organ is suitable for donor after cardiac death

A
  • Suitable for kidney
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11
Q

What organ is suitable for donor after brain death

A

Most

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12
Q

What do you do to organs once harvested and why?

A
  • Harvest organs and cool to minimise ischaemic damage
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13
Q

How to demonstrate brain death? (6)

A 
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 (with PaCO2 >50 mmHg)
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14
Q

Cold time for kidney?

A
  • absolute maximum cold ischaemia time for kidney 60h (ideally <24h
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15
Q

2 things that must be considered before allocating an organ? Explain both

A
  • Equity – what is fair?
    Time on waiting list
    Super-urgent transplant - imminent death (liver, heart)

Efficiency – what is the best use for the organ in terms of patients’ survival and graft survival?

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16
Q

7 elements of prioritising an organ recipient?

A
  1. Waiting time
  2. HLA match and age combined
  3. Donor-recipient age difference
  4. Location of patient relative to donor
  5. HLA-DR homozygosity
  6. HLA-B homozygosity
  7. Blood group match
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17
Q

How is organ donation made fair and who regulates it?

A
  • Rules for organ allocation are established by medical community/health professionals/advisory groups/DH
  • NHSBT monitors allocation
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18
Q

What is the main obstacle to organ donation post brain death?

A

Family decline consent for donation (43%)

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19
Q

Ways government has tried to increase organ donation?

A

Organ Donation Taskforce (2008-2013)
Making a donor transplant coordinator
Improving public engagement
Improving quality of organ retrieval and organ transplantation standards, guidelines, training and resources

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20
Q

What do donor transplant nurses do

A
  • Employment to shift from transplant centres to NHSBT
  • Seek out potential donors in A&E /ICU
  • They carry out family interviews - part of bereavement services
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21
Q

Strategies to increase transplantation? (3)

A
  1. increased donation
     Marginal donors – DCD, elderly, sick with co-mobidities
  2. Living donation
     transplantation across tissue compatibility barriers
    Exchange programmes: organ swaps for better tissue matching
  3. The future?
     Xenotransplantation
     Stem cell research
22
Q

Half life of a kidney transplant?

A

10-14 years

23
Q

2 main things you have to match during organ transplantation?

A
  1. ABO blood group (however we have developed techniques to avoid this so it’s a bit of a historical problem)
  2. HLA (human leukocyte antigens) coded on chromosome 6 by Major Histocompatibility complex (MHC)
24
Q

How do we get around ABO-incompatible transplantations?

A
  • Remove the antibodies in the recipient (plasma exchange)

- We do see good outcomes (even if the antibody comes back)

25
Q

What happens if you incorrectly match blood groups?

A

If you give a blood group A person a blood group B heart:

  1. Circulating, pre-formed, recipient anti-B antibody binds to B blood group antigens on donor endothelium = antibody-mediated rejection
  2. Antibody activates complement and macrophages
26
Q

What are the MHC Class I subgroups?

A
  • Class I (A, B, C)– expressed on all cells
27
Q

What are the MHC Class II subgroups?

A
  • Class II (DR, DQ, DP) – expressed antigen-presenting cells but also can be upregulated on other cells
28
Q

Which cells have MHC class II

A
  • Class II (DR, DQ, DP) – expressed antigen-presenting cells but also can be upregulated on other cells
29
Q

Which cells have MHC class I

A
  • Class I (A, B, C)– expressed on all cells
30
Q

Each individual has how many types of each HLA molecule and why?

A
  • Each individual has most often 2 types for each HLA molecule (one from mummy and one from daddy)
31
Q

How many of which alpha and beta chains are in MHC class 1 and 2

A

A1, 2 and 3 and B2microglobulin in class 1

A1, 2 and B1, 2

32
Q

Which three different HLA isotopes do we match

A

HLA-A, HLA-B and HLA-DR

33
Q

How do represent the number of mismatches of different isotopes

A

MM X:Y:Z meaning X number of mismatches at HLA-A, Y number at B and Z number at DR

34
Q

most common cause of graft failure is…?

A

Rejection

35
Q

How to diagnose graft rejection?

A
  • Diagnosis = histological examination of a graft biopsy
36
Q

How to treat graft rejection?

A

immunosuppressive drugs

37
Q

2 ways of splitting the type of rejection and the subcategories of each?

A

Rejection can be divided by how quickly it develops:

  • HYPERACUTE (immediate/days)
  • ACUTE (weeks/months)
  • CHRONIC (years)

It can also be divided into:

  • T-CELL MEDIATED
  • ANTIBODY-MEDIATED
38
Q

Explain T cell mediated transplant rejection

A
  • When an organ is transplanted, both recipient and donor antigen presenting cells will take up fragments of the donated organ’s HLA antigens
  • These will then circulate to the local lymph nodes where T-cells will circulate through
  • Some T-(helper) cells which are able to mount an allospecific response will come into contact with the APCs
  • These alloreactive T cells will then re-circulate until they reach the transplanted organ, infiltrate it
    Recruit T killer and cause cell apoptosis
    Then macrophages come along and finish the job
39
Q

What toxin do cytotoxic T cells release to damage cells? how do they cause apoptosis?

A

Granzyme B and perforin

Stimulate apoptosis by activating the fas ligand

40
Q

What is a defining feature of renal allograft rejection

A

Tubulitis

41
Q

Describe the antibody mediated mechanism of transplant rejection

A
  • Antibodies bind on antigens (AB or HLA) present on the donor’s endothelium
  • They recruit complement and activate it
  • This can lead to cell lysis (creation of membrane attack complex)
  • Antibodies can also directly recruit inflammatory cells which can cause injury to the endothelium
42
Q

How to differentiate between antibody and T cell mediated graft rejection histologically

A

WE CAN SEE THE DIFFERENCE BETWEEN ANTIBODY-MEDIATED AND T-CELL MEDIATED HISTOLOGICALLY BECAUSE THEY LOOK DIFFERENCE, ONE IS TUBULAR ONE IS A VASCULAR LOOKING THING

43
Q

What 3 signs indicate a deterioration in kidney transplant function

A

Rise in creatinine, fluid retention, hypertension

44
Q

What 2 signs indicate a deterioration in liver transplant function

A

Rise in LFTs, coagulopathy

45
Q

What 2 signs indicate a deterioration in lung transplant function

A

breathlessness, pulmonary infiltrate

46
Q

2 ways of preventing rejection

A
  • Maximise HLA compatibility (very difficult however)

- Life-long immunosuppressive drugs

47
Q

2 general targets of immunosuppressants?

A
  • Targeting T cell activation and proliferation

- Targeting B cell activation and proliferation, and antibody production

48
Q

3 ways of targeting T cell activation and proliferation with immunosuppressants?

A

Target the initial interaction between an APC and a T cell – target presentation of a peptide and binding to MHC, or can tarfet co-stimulation between APCs and T cells, or can target paracrine effect of cytokines

49
Q

5 ways of targeting B cell activation and proliferation and antibody function with immunosuppressants?

A

I.V. immunoglobulins (IVIG) and plasma exchange, anti-CD20 drugs, proteasome inhibitors, anti-C5 and finally, splenectomy

50
Q

What immunosuppressive regime is used pre-implantation? (2)

A

Induction agent (T-cell depletion or cytokine blockade)

51
Q

What immunosuppressive regime is used post-implantation? (4)

A
  • line immunosuppression for the rest of their life:
  • Signal transduction blockade, usually a CNI inhibitor: Tacrolimus or Cyclosporin; sometimes mTOR inhibitor (Rapamycin)
  • Antiproliferative agent: MMF or Azathioprine
  • Corticosteroids
52
Q

What opportunistic infections must you watch out for post-transplantation?

A

Cytomegalovirus, BK virus, Pneumocytis carinii

Immunology Y2 (5 decks)

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