Transplantation Flashcards
Definition of transplant
The replacement of tissues or organs that have undergone an irreversible pathological process which threatens the patients life or to a significant degree, considerably hampers their QoL
Types of graft
Xenograft
Allograft
Isograft
Autograft
What is a xenograft?
A transplantation from a donor of a different species from the recipient
What is an allograft?
A transplant from one person to another
What is an isograft?
A transplant between two individuals who are genetically identical i.e. monozygotic twins
What is an autograft?
A transplant from one point to another of the same individuals body
What is immune tolerance?
A state of unresponsiveness of the immune system to SELF
Two types of immune tolerance
Central control (thymus) Peripheral control
What is involved in central control?
Inactivation of cells required for initiation of an immune response
What is involved in peripheral control?
Inhibition of expression of the immune response
Two classes of HLA
Class 1
- HLA- A,B,C
Class 2
- HLA- DR, DP, DQ
Where is class 1 of HLA found?
On all nucleated cells
What class of HLA is most important in rejection?
Class 2
What recognises class 1 HLA?
CD8 + / Tc cells
What recognises class 2 HLA?
CD4 + / Th cells
The major histocompatibility complex consists of…..
Human leukocyte antigen (HLA)
Chromosome 6
Features of privileged sites
No sensitisation / no tolerance
No requirement for tissue matching
No immunosuppression
Blood flow and immunity
If there is blood flow = immunity exposed
What is graft rejection?
Occurs when transplanted tissue is rejected by the recipients immune system, which destroys the transplanted tissue
Causes of transplant / graft rejection
ABO or HLA incompatible
Pre formed immunity (sensitisation)
Failed immunosuppression (including non compliance)
Infections / environmental triggers
When can immediate rejection happen?
Within minutes
Classes of rejection
Immediate
Acute
Chronic
Pathology of immediate rejection
ABO/HLA antibodies
Complement activation damages blood vessels
Inflammation and thrombosis
When does acute rejection happen?
Usually in 1st 6 months
Pathology of acute rejection
Sensitisation phase
1. recognition
2. APC reaction
3. co stimulation
Pre sensitised T cells hasten the process
Can be a mix of cell and antibody mediated
Cellular infiltration of graft by Tc cells, B cells, NK cells and macrophages
Endothelial inflammation and parenchymal cell damage
What is the commonest cause of graft failure?
Chronic graft failure
When does chronic graft failure occur?
> 6 months
Pathology of chronic graft failure
Antibody mediated with other innate components
Myointimal proliferation in arteries
Treatment of rejection
Corticosteriods
Anti-thymocyte globulin
Plasma exchange
Complications of transplantation
Rejection Infection (including zoonotic) Drug side effects Recurrence of original disease Surgical problems Ethical problems
Prevention of graft rejection
ABO matching
Tissue typing (Class I and II HLA)
Prophylactic immunosuppression
Humanised or silenced xenografts
What is used for immunosuppression?
Corticosteriods (prednisolone) - wide spread anti inflammatory Calcineurin inhibitors (tacrolimus) - block IL-2 gene transcription Anti proliferatives (MMF) - prevent lymphocyte proliferation
What is graft vs host disease principally a problem of?
Bone marrow transplant
Requirements for graft vs host disease
Immunocompetent cells in graft
Deficient recipient immunity
HLA differences between donor and recipient
Prevention of graft vs host disease
Donor / recipient matching
Donor marrow T cell depletion
Types of donors
Living - related / unrelated - altruistic Deceased donor - brain death (DBD) - cadaveric death (DCD)
Which types of donors have less rejection, are quicker, last longer and healthier and are easier to manage?
Living donors
