Transplantation Flashcards

Question

What is the role of the donor transplant coordinator?

Answer 1

- Registered nurses with experience in critical care - Employment to shift from transplant centres to NHS BT - Potential donors A&E/ICU - Carry out family interviews (part of bereavement services)

Answer 2

1. Deceased donation: Marginal donors – DCD, elderly, sick 2. Living donation: transplantation across tissue compatibility barriers and exchange programmes (organ swaps for better tissue matching) 3. The future: xenotransplantation and stem cell research

Answer 3

- The half life of a kidney from a deceased donor is around 10 years - From a living donor, this increases to 13/14 years - The transplant kidney does not last forever – this comes down to the immunology of transplantation

Answer 4

- ABO blood group is important for blood transfusions and organ transplantation - HLA coded on chromosome 6 by Major Histocompatibility Complex (MHC) - These antigens play an important role in immunology and tissue rejection

Answer 5

- Recipient has pre-formed anti-B antibodies that bindto the B antigen present on the endothelial cells - This leads to activation of complement and thrombosis - The is immediate, acute rejection (mediated by antibodies)

Answer 6

Remove the antibodies in the recipient (plasma exchange) Good outcomes (even if the antibody comes back)

Answer 7

- In the context of transplantation, rather than presenting a foreign viral/bacterial peptide, the APC presents a fragment of the donor’s HLA peptide in the context of the recipient’s HLA molecule - This leads to T cell activation for T cells that are allo-specific, and can recognise the antigen in this context

Answer 8

- Class I (A, B, C): expressed on all cells - Class II (DR, DQ, DP): expressed antigen-presenting cells but also can be upregulated on other cells Highly polymorphic – lots of alleles for each locus (for example: A1, A2, A341… etc.) Each individual has most often 2 types for each HLA molecule (for example: A3 and A21)

Answer 9

You can have between 0 and 6 mismatches with a potential donor. This is really key to the outcome of the graft. The more mismatches you have, the less well the organ will do when it is transplanted. This is why living donation is encouraged, particularly from related family members.

Answer 10

- 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 - Rejection is the most common cause of graft failure - Diagnosis is usually through a histological examination of a graft biopsy

Answer 11

Immunosuppressive drugs (prevent and treat rejection post-transplantation)

Answer 12

- Rejection can be T-cell mediated or antibody-mediated | - Rejection may be hyper-acute, acute or chronic

Answer 13

- When an organ is transplanted, both the recipient and donor APCs will take up fragments of the donated organ antigens - They then circulate to the lymph nodes. - At the lymph nodes, APC sit and present antigen - T cells circulate through the lymphatic system, and have contact with the APCs in this way until some T cells that can mount an allo-specific response against the specific antigens come into contact - These specific T cells recycle to the organ, and will infiltrate it - They also recruit inflammatory cells to help them cause organ damage - Although the initial response is through CD4 positive T cells, they then begin to recruit other cells - This is the effector phase: CD4 cells recruit CD8+ T cells and macrophages - In this phase, the immune cells cause injury to the graft - This is through a variety of mechanisms: secretion of enzymes, production of free radicals, apoptosis etc.

Answer 14

- Antibody against graft HLA and AB antigen - Antibodies arise: pre-transplantation (“sensitised”), post-transplantation (“de novo”) - Antibody-mediated rejection has a different picture to T-cell mediated rejection, because it is predominantly an intravascular process - It stays within the capillaries - The endothelium is the main site that is being targeted - We can detect the complement system on the endothelial cell surface, to establish the diagnosis of antibody-mediated rejection biopsies

Answer 15

Deteriorating graft function detection: - Kidney transplant: Rise in creatinine, fluid retention, hypertension - Liver transplant: Rise in LFTs, coagulopathy - Lung transplant: breathlessness, pulmonary infiltrate - Heart (no good test for dysfunction, regular biopsies done)

Answer 16

- Immunosuppressive drugs target both T cell and B cell activation and proliferation - They also target antibody production (in antibody-mediated rejection) - Drugs targeting T cell rejection target the initial interaction between the APC and the T cell - The T cell receptor interaction, as well as the co-stimulatory mechanisms, are targeted - Once the T cell is activated, it produces cytokines (e.g. IL-2), which have a paracrine effect - Drugs that have been developed target all of these mechanisms, and more - Some drugs block nucleotide synthesis, and others antagonise various receptors

Answer 17

We have different strategies to remove antibodies (e.g. plasma exchange can be used to physically remove immunoglobulins from the blood). This is used with intravenous immunoglobulins to replenish the antibodies we need.

Answer 18

Pre-transplantation: Induction agent (T-cell depletion or cytokine blockade) From time of implantation: - Base line immunosuppression - Signal transduction blockade, usually a CNI inhibitor (Tacrolimus or Cyclosporin) - Sometimes mTOR inhibitor (Rapamycin) - Antiproliferative agent (MMF or Azathioprine) - Corticosteroids If needed: treatment of episodes of acute rejection - T-cell mediated: steroids, anti-T cell agents - Antibody-mediated: IVIG, plasma exchange, anti-CD20, anti-complement

Answer 19

Immunosuppression controls rejection at the price of development of infection, drug toxicity and tumours.

Answer 20

- Increased risk for conventional infections: bacterial, viral, fungal - Opportunistic infections: Cytomegalovirus, BK virus and pneumocystis carinii - Management of these infections requires lowering of immunosuppression, but this triggers rejection - This is very much a balance - Transplant patients are particularly vulnerable to skin cancers (especially Elderly and Caucasion) - Post transplant lymphoproliferative disorder – Epstein Barr virus driven - There are other post-transplantation malignancies associated with immunosuppression (e.g. Kaposi’s

Answer 21

We can deplete B cells by using rituximab (anti-CD20),

Transplantation Flashcards

(45 cards)