Transplantation - Case Studies Flashcards
Why is it better to have a kidney from a live donor than a deceased donor?
More damage to the organ from a deceased organ.
DAMPs play a factor
What are factors that affect a successful kidney transplant?
1) No transmissible disease
2) Good health/renal function
3) No malignancy
4) Minimal damage
5) Rapid processing
What are chances of kidney rejection?
1/3 patients will reject the graft
What are the post kidney complications
Infective and Rejection
What are the three graft rejections?
- Hperacute (under 24 hours)
- Acute (in weeks/months)
- Chronic (over a number of years0
Why does hyperacute rejection occur?
- Pre-exisiting antibodies to the blodo group antigens/MHC
- Occurs via the classical pathway
How can pre existing antibodies occur to cause graft rejection?
- Previous pregnancy
- Prior transplant
- Prior blood transfusion
- Cross-reactive antibodies
Is hyperacute rejection treatable?
No. Organ rejection inevitable
What are the stages of Hyperacute rejection?
1) Pre-exisiting host antibodies are carried to kidney graft
2) Antibodies bidn to antigens of renal capillaries and activate complement
3) Complement split products attract neutrophils which release lytic enzymes
4) Neutrophil lytic enzymes destroy endothlial cells; platelets adhere to injured tissue, casuign vascular blockage
What is the stages in Acute rejection?
Sensitation and Effector
What is the Sensitation phase?
- Priming of T cells to donor alloantigens
- Signal 1 can occur from direct or indirect pathway
- Signal 2 can occur due to ‘Damage’, enahnces priming (co-stimulation)
How long does Sensitiation phase in Acute rejection last?
7 to 10 days
How long does Effector phase in Acute phase?
- Weeks or months
What is the Effector phase?
Delayed-type Hypersensitivity
What effector cells are invovled in the Effector phase?
Effector T cells
- CD4+ T cells
- CD8+ T cells
Macrophages, neutrophils, complement and Ab-mediated damage cells are involved as they are promoted
What cyotkines are expressed in Effector phase?
IL-2, IFN-gamma, TH2 type cytokines
What happens when Chronic Rejection occurs?
T Cells, antibodies and non-immune mechanisms (immunosuppressant drugs/hypoxia on transplant etc) cause long term damage
What is the risk factors for chronic rejection?
- Episodes of acute rejection
- Sub optimal HLA matching
- Prior sensitisation to donor HLA
- Renal/general health of recipient (E.g hypertension/smoking)
How can may Chronic rejection occur?
- Result of mulitple episodes of controlled acute rejection
What is apheresis?
- Blood cells collected from bone marrow or from blood or from cord blood
When a host is given the donor’s stem cells, what occurs?
Stem cells will seed the bone marrow of the host and create a new immune system educated in the patients own thymus and bone marrow
What is Condiitoning regimen?
Total body irration or myeloblative radiation and/or chemotherapy to destroy cells within the bone marrow, entirely or partially
What is the purpose of conditioning regimen?
- Clear harmful cells
- Mak space for the new stem cells
What is antibiotics/antivirals used during preparing the recipient?
- Prevent infection during the immunosuppressive window
- Remove potential souces of DAMP
What are the concerns of Allogenic bone marrow transplantion?
1) Rejection of the recipient by the graft (graft versus host disease; GVHD)
2) Failure of engraftment leading to prolonged immune suppression
3) Primary infection risk
4) Reactivation of latent virsues in the recipient or coming from the donor cells
What is GvHD?
The donor cells of the immune system recognise the host cells as foreign
How is GvHD prevented?
- HLA matching/immunosuppression
- MLR to see if the donor will respond to the recieipent
What is GvL?
Donor immune cell induced eliminated of residual leukemic burden
What is Chimersim?
A mixed state
What is full bone marrow chimerism?
Complete replacement of bone marrow with donor cells
What is partial chimerism?
Bone marrow is mixed, part donor and part host
What is the issue with xenogeneic transplantation?
- Ethics
- Presence of sugars on pigs that we see as foreign
- Absence of inhibitory proteins on pig cells
