Week 3 Immunology and Transplantation Flashcards
(22 cards)
What is the difference between HLA class I and HLA class II
HLA class I:
Present on most cells in the body. This presents antigens of internally processed proteins. If they are recognised as viral then the cell is recognised by cytotoxic T-cells as infected and destroyed
HLA class II:
Present in antigen presenting cells and expresses antigens picked up from the environment to T-helper cells so that they can make antibodies etc.
What are HLA-A, HLA-B and HLA-C types of?
HLA class I
What are HLA-DP, HLA-DQ and HLA-DR types of?
HLA Class II
What is HLA matching used for?
WHere is it less important?
Used for kidney transplants.
Less important for liver transplants.
What HLAs are use for HLA profiling? What scored would they get?
HLA-A (2 alleles)
HLA-B (2 alleles)
HLA-DR (2 alleles)
Missmatch score from 0-6 depending on how many are matched. 0 is a perfect match, 6 is all are missmatched.
Hint: Dr AB gonna cut into your abs to harvest your kidney
What needs to be given along with a transplant?
Immunosupression
Which organs are cadaveric transplants more common for and which are living transplants more common for?
Living: Friend or Relative - Kidney
Cadaveric: Most other organs
What is an immunological x-match?
This tests for compatobility. You mix serum of recipiant with lympocytes of the donor. You then add compliment to trigger an immune response if present.
What does a positive immunological crossmatch (X-match) mean?
A positive immunological crossmatch (X-match) means that the recipient’s immune system has antibodies that react against the donor’s cells, specifically targeting HLA antigens on those cells.
Not suitable for transplant
In terms of transplants what does sensitisation mean?
This is where the recipiant has already been exposed to a foreign HLA e.g. transfusion or pregnancy. This means they can be sensitised to certain foreigh HLA types and already have antibodies against them.
This will lead to hyperacute rejection.
What is a hyperacute rejection?
*Occurs when the Tx carries antigens to which the
recipient is already sensitised
*Cytotoxic antibodies bind endothelial cells and
induces complement activation, platelet aggregation
and intravascular thrombus formation
*The Tx is often destroyed ‘on the operating table’
What is an acute rejection?
This is a rejection that occurs over days to weeks and is due to a new immune response to donor HLA antigens
Features:
*Rise in creatinine (often only indication)
*Reduced urine output
*Tender transplant
*Fever
Treatment for acute rejection?
Immunosupression
Anti T-cell antibody
If it is an antibody mediated acute rejection consider a plasma exchange
Which of these are antibody mediated and which are t-cell mediated:
Hyperacute rejection
Acute rejection
Hyperacute: antibody mediated
Acute: normally t-cell mediated, can be antibody mediated
Why should you do an immunological crossmatch and why should you do a HLA match test before a tansplant?
Which is more important?
HLA Matching helps reduce the chance of acute rejection through developing a new immune response. Though it is not essential.
Immunological crossmatch is essential to test for sensitisation and chance of hyperacute rejection.
If you seuspect acute kidney rejection what differentials do you need to exclude?
*Dehydration (clinical examination, BP, weight)
*Renal obstruction (ultrasound)
*Vascular catastrophe (Doppler)
*Drug toxicity (tacrolimus levels)
If you suspect chronic kidney trnasplant rejection what differentials do you need ot exclude?
- Recurrent disease (membranous, MCGN)
- Obstruction (ultrasound)
- Renal artery stenosis (Doppler of renal artery
+/- MRI angiography)
What are the features of chronic kidney transplant rejection?
Features:
* Progressive renal dysfunction
* Interstitial fibrosis and vascular disease on
renal biopsy
What’s the pathogenesis of chronic kidney rejection?
Multifactorial: immune and non-immune
mechanisms:
* Increased HLA mismatch (1-2-1 vs 0-0-1)
* Previous acute rejection
* Poor drug compliance (low tacrolimus levels)
* Prolonged cold ischaemia time of kidney prior to
surgery (CIT of living donor «_space;cadaveric donor)
* Graft failure - patient old or has other poor health affecting kidney function
Management of chronic kidney transplant rejection?
None
Normally require dialysis or another transplant
What is the relationship between transplants and cancer?
Occurance and particularly reoccurance of tumours are increased through immunosupression
Side effects of immunosupression beyond infection
- Calcineurin inhibitors are nephrotoxic!
Plasma levels of tacrolimus are measured
regularly - Increased risk of diabetes (steroids and
tacrolimus) - Hypertension (steroids and CNI)
- Osteoporosis (steroids)
- Tumours
