152 - Transplants Flashcards
Autograft
Graft from one body part to another, in one individual
Isograft
Between genetically identical individuals (EG monozygotic twins
Allograft
Between different members of the same species
Xenograft
Between members of different species (EG porcine heart valves)
Syngeneic
Identical twins
Immunogenicity against sequential grafts
First graft, if not MHC matched, will be rejected.
If there is a second graft from the same donor, the graft will be rejected much more quickly (secondary response of the immune system)
What mediates transplant rejection?
T cells
Chromosome on which HLA genes are
Chromosome 6
Most important HLAs for graft acceptance
A, B and DR are more important than C, DP and DQ
Australian renal transplant waiting list
1500 patients
Types of rejection
1
2
3
1) Antibody-mediated
2) Acute
3) Chronic
Antibody-mediated rejection mediators
Preformed anti-donor antibodies and complement
Acute rejection mediators
T-cells (primary activation)
Chronic rejection mediators
Unclear. Antibodies, immune complexes, slow cellular reaction, recurrence of disease.
Groups who can have anti-HLA antibodies
1
2
3
1) Blood recipients
2) Pregnancy
3) Transplant
Immunological and non-immunological causes of chronic rejection
Immunological: Acute rejection Non-immunological: Viruses: Ischaemia-reperfusion injury
Ischaemia-reperfusion injury
When an organ is removed, put on ice and then transplanted. This is damaging to organ, and might lead to it being rejected
Intimal fibrosis in kidneys, liver and lungs in transplant rejection
Kidney: Chronic allograft nephropathy
Liver: Vanishing bile duct syndrome
Lungs: Bronchiolitis obliterans syndome
Ways to prevent allograft rejection
1
2
3
- Matching ABO antigens (not just expressed on erythrocytes)
- Matching MHC alleles
- Immunosuppressive drugs
First drug that could immunosuppress in allografts
Azathioprine
More modern immunosuppressants in grafts
Cyclosporine.
Prednisolone.
Effect of cyclosporine
Kills recently-activated T-cells (calcineurin inhibitor).
Downregulates IL-2 expression.
Side effect of cyclosporine
Nephrotoxicity
Azathioprine effects
1
2
3
- Antiproliferative (azathioprine, mycophenalate, rapamycin)
- Inhibit DNA and RNA synthesis
- Blocks IL-2 production and lymphocyte expansion
Organ regeneration 1 2 3 4 5
1) Take donor lung
2) Decellularise with detergent
3) Establish acellular vasculature, airways and alveoli
4) Seed scaffold with epithelial and endothelial cells
5) Perfuse and ventilate in bioreactor
