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Year 2 MCD Immunology > 2: Transplantation > Flashcards

2: Transplantation Flashcards

1
Q

When are organ transplanted?

A

When organgs

  • are failing or
  • have failed, or
  • for reconstruction

•

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2
Q

What are the two different types of transplants that can be performed?

A
  1. Life Saving
    1. all other treatments treatments have reached end of use
      • Heart
      • Liver
  2. Life-enhancing
    1. other life-supportive methods less good
      • Kindey-dialysis
      • Pancreas T1DM
    2. organ not vital but improved quality of life: cornea, reconstructive surgery
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3
Q

What are the different types of transplantation (refering to donor-recipient relation)

A
  • Autografts
    • within the same individual
  • Isografts
    • between genetically identical individuals of the same species
  • Allografts
    • between different individuals of the same species
  • Xenografts
    • between individuals of different species
  • Prosthetic graft
    • plastic, metal
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4
Q

What are the different types of donors that can donate in allograft transplantations?

A

Allograft= recipiant is different individuum from same species

Donors can be

  • Deceased
    • DBD (donor after brain stem death)–> neurological criterial for death
    • DCD (donor after circulatory death) –> circulatory criteria for death
  • Living donor
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5
Q

What are the criteria that need to be met for being an organ donor?

A

Once death has been confimed

  1. Excluding of Infections (e.g. HIV, HBV)
  2. malignany
  3. drug abuse, overdose or poison
  4. disease of the transplanted organ
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6
Q

Which organisation distributes transplant organs in the UK?

A

NHS Blood and Transplant (NHSBT)

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7
Q

What are the two steps that have to be undertaken to recieve a transplant organ?

A
  • •Transplant selection: listing (waiting list) at a transplant centre after multidisciplinary assessment –> done by doctors
  • Transplant allocation: how organs are allocated as they become available –> NHSBT
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8
Q

What are the criteria used for allocating a transplant organ to a patient

A

•National guidelines withEvidence based computer algorithm

  • Equity – what is fair?
    • –Time on waiting list
    • –Super-urgent transplant - imminent death (liver, heart)
    • –What else? (e.g. very rare phenotypes higher on list because otherwise would never get a chance)

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

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9
Q

What are the “A”s and “B”s that the AB0 bloos system referes to?

A

•proteins with carbohydrate chains on red blood cells but also endothelial lining of blood vessels in transplanted organ

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10
Q

What would happen if an organ with the blood group of A woud be transplanted to someone with blood group B (and anti-A antibodies

A

Antibodies would bind to endothelial A antigens and cause

  • complement activation
  • Blood clotting and thrombus formation
    • immediate loss of organ due to vascular damage (no perfustion possible)
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11
Q

How are AB0 incompatible transplants performed today?

A

Remove the antibodies in the recipient (plasma exchange)

  • Good outcomes (even if the antibody comes back)
  • Kidney, heart, liver
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12
Q

What are the three importatnt Class I and Class II HLA antigens for transplantation?

A
  • Class I (A,B,C)– expressed on all cells
  • Class II (DR, DQ, DP) (on Antigen-Presenting cells)
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13
Q

What are the three antigens that are involved in performing HLA matching)

A

Main three (but others are also important) are

  1. HLA-A
  2. HLA-B
  3. HLA-DR
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14
Q

Explain the concept of (mis)matching of antigens in transplantations

A

Three molecules are taken into consideration:

  • HLA-A, HLA-B, HLA-DR

Every HLA: 2 Alleles (one from each parent)

so: A maximum of 6 Mismatches can be there (2 for each HLA gene)

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15
Q

What is the main problem in transplantations?

What is the overall mechanism behind it?

A

Rejection

  • Exposure to foreign HLA molecules results in an immune reaction to the foreign epitopes
  • The immune reaction can cause immune graft damage and failure = rejection
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16
Q

How is organ rejection after transplantation diagnosed?

A

Mainly: Via histological examination of a graft biopsy

    • Clinical signs (e.g. monitor kidney function, liver enzymes etc.)
  • Hear only possible with biopsy
17
Q

What are the two ways you can classify rejections?

A
  1. Time-linked classification
    • Hyper-acute (directly when organ is implanted)
    • Actue (weeks to months)
    • Chronic (years-happens in almost all recipients)
  2. Type of immune reaction
    1. T-cell mediated
    2. Antibody mediated
18
Q

What happens during T-cell mediated rejection?

A
  1. Antigen-Presenting cells present the foreign HLA molecules (on their own HLA molecules) to T-cells in lymphocytes
  2. Get activated and cause migration into tissues and
    • Recrtuitement of pro-inflammatory cells that cause tissue damage

Interstitial inflammation

19
Q

Which inflammatory cells are invove in T-cell mediated rejection?

What is their respective role?

A
  • CD4+ -T-cells
    • infiltrate the graft
  • CD8+
    • cytotoxic: kill cells in graft
  • Macrophages
    • phagocytosis and proteolysis of cells
20
Q

When can antibodies that are involved in organ rejection form?

How do you call them?

A

They can be there pre-transplantation (in “sensitised” patients)

Or after transplantation (de novo)

21
Q

Explain the process of antigen-mediated organ rejection

A

Antibodies against HLA and AB antigens

  • antibodies bind to antigens presnent on endothelial donor cells
    • leading to complement and macrophage activation and

Intra-vascular pathology

22
Q

How do you prevent rejection of organs?

A
  1. maximise HLA compatibility
  2. Life-long immunosuppressive drugs
23
Q

What are the targets of the immunosupressant drugs given in acture and preventative treatment of organ rejection

A
  1. Targeting T cell activation and proliferation
    • mainly signaling pathways that lead to activation or interaction between antigen presenting cell and T-cell
  2. Targeting B cell activation and proliferation, and therefore antibody production
    • anti-CD20 antibodies –> destroy B cells
    • Plasma exchange (get rid of antibodies)
      *
24
Q

What are the targets for immunosupressant drugs pre-transplantation?

A

•Induction agent (T-cell depletion or cytokine blockade)

25
Q

What are the treatments in the base-line immunosupressing of tranplant patients? (after recieving an organ)

A
  • Signal transduction blockade, usually a CNI (calcineurin) inhibitor: Tacrolimus or Cyclosporin; sometimes mTOR inhibitor (Rapamycin) –> inhibits activation of T cells
  • Antiproliferative agent: MMF or Azathioprine (T-cell antiproliferative)
  • Corticosteroids
26
Q

What are the drugs that are used in the treatmtnet of acture rejection of a transplant organ?

A
  • T-cell mediated: steroids, anti-T cell agents
  • Antibody-mediated: IVIG, plasma exchange, anti-CD20, anti-complement
27
Q

What are the main risks that are associated with immunosupression in patients that have recieved an organ transplant?

A
  1. Drug toxicity
  2. Development of malignancies
  3. Increased risk of infections
28
Q

What kind of infections are people on immunosupressive therapy after recieving an orgn transplant more suseptible to?

A
  • Increased risk for conventional infections
    • Bacterial, viral, fungal
  • Opportunistic infections – normally relatively harmless infectious agents give severe infections because of immune compromise
    • Cytomegalovirus
    • BK virus
    • Pneumocytis carinii (jirovecii)
29
Q

What are the common types of post-tranlation malignancies?

A
  • Skin cancer
  • Post transplant lymphoproliferative disorder – Epstein Barr virus driven
  • others

Year 2 MCD Immunology (6 decks)

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