Renal transplantation Flashcards
What is the reason for blood group matching and tissue type matching for transplants?
To have as closely related a tissue type as possible so that the recipients body does not recognise the transplant as non-self and destroy it ==> to reduce the chances of rejection
What would happen if you transplanted a kidney from a blood group A person to a blood group B person ?
The person whos receiving the kidney (blood group B) would have anti A antibodies which would result in hyperacute rejection of the kidney
What are human lecuocyte antigens (HLA)?
- Cell surface proteins expressed on cells.
- Which active the immune system if non self (not the ones the recipients cells express) and cause rejection
What are the 3 main types of HLA ?
- HLA A
- HLA B
- HLA DR
Each of these 3 types have hundreds of sub-types - this is why its difficult to find a match
HLA A and B = MHC class I
HLA DR = MHC class II
How many HLA types does a patient have ?
At each of A, B and DR there are 2 HLA types - 1 inherited from each parent
Therefore a patients tissue type might be:
- HLA A2,24 B45,80 DR 7,41
What are donor specific HLA antibodies ?
- A patient may have been exposed to a HLA Ag previously and formed Ab to this.
- Due to e.g. blood transfusions, pregnancies, previous transplants
- These preformed antibodies cause hyperacute rejection if they are against the HLA antigens of the transplant tissue
Describe the process of transplant rejection
- HLA antigen (on the transplant tissue cells) bind to antigen presenting cells (dendritic cells)
- The antigen then gets expressed on the outside of the MHC molecule on the dendritic cell
- It then binds to the T cell receptor, you then get activation of T cell receptor on a CD4 (T helper cell)
- It is the CD4 (T-helper cells)
- The activation of the T-helper cell results in a number of things, you get activation and increase in the number of NK cells and Cytotoxic T cells which directly attack non-self. T helper cells also produce cytokines which then activate B cells which proliferate and form antibodies which then bind to the transplant resulting in complement activation and cell lysis
- NK cells and cytotoxic cells attacking the transplant is called cellular rejection
- The antibodies causing damage is called antibody mediated rejection
What is meant by the balancing act in terms of treatment to prevent rejection of the transplant?
Balancing between immunosuppressing the patinet enough to prevent rejection and immunosuppressing them too much and causing infections, cancers etc
What are some of the infections/conditions which transplant patients are at risk of?
- Lymphoma
- Skin cancer especially
- Pneumocystis jirovecii - the pneumonia immunosuppressed people get e.g. HIV patients, transplant patients
- CMV - this is the most important viral infection post transplant
- Recurrent UTI
What happens if there is too little immunosuppression following a transplant ?
- Rejection
- Graft dysfunction
- Graft loss
What are the 3 different types of transplant rejection ?
- Hyperacute
- Acute
- Chronic
How soon does hyperacute rejection occur and what is it due to ?
- Occurs in mins to hours
- Due to preformed HLA antibodies
- This is not able to be treated and the kidney needs to be taken out
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How soon does acute rejection occur and what is it due to ?
- Acute rejection – this is usually early on (<6months) but can be if someone a few years after transplant decides to just stop taking the immunosuppressive treatments which then results in rejection
- This is a T cell or B cell mediated response
How is acute graft rejection treated ?
By increasing immunosuppression
How soon does chronic rejection occur and what is it due to ?
This is due to very slow subtle damage to the kidney (> 6months) so instead of hyperacute which is the machine gun, you have a sniper slowly chipping away - we don’t yet know how to treat this
