Transplantation Flashcards
What is a 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 quality of life
What is the only organ yet to be successfully transplanted?
Am Brian
What makes for a more successful graft?
- Laying the foundations
- 10/10 chat
- wearing a suit
- [Also being closer genetically]
What is an autograft/isograft/allograft/xenograft?
- Autograft - skin graft etc
- Isograft – from identical twin (but still need immunosuppression)
- Allograft – from sibling who is not genetically the same – ie sister etc
- Xenograft– from a different species (pig for heart valves)
What is histocompatability?
- The major histocompatibility complex (MHC) is a set of cell surface proteins essential for the acquired immune system to recognize foreign molecules in vertebrates, which in turn determines histocompatibility.
- Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA).
- Codominantly expressed, meaning every individual expresses each of the inherited alleles, both paternal and maternal. The similarity or difference of one individual’s HLA alleles, and therefore MHC proteins, to another person’s is what makes the tissues either compatible or incompatible
- HLA A,B and DR and ABO blood group matching are the MAJOR requirements for tissue typing.
What is class 1 MHC?
The class I molecules are responsible for presenting antigenic peptides from within the cell (eg, antigens from the intracellular viruses, tumor antigens, self-antigens) to CD8 T cells
What is class 2 MHC?
The class II molecules present extracellular antigens such as extracellular bacteria to CD4 T cells
Which is more important in terms of matching?
- HLA matching is not a deal breaker – longitunidinal successful graft less likely however
- ABO – gives immediate response because we have certain antibodies against these – so very important to match
What are priviledged sites for transplant?
- Blood flow = Immunity exposed
- no sensitisation / no tolerance
- no requirement for tissue matching
- no immunosuppression
- Areas such as cornea of eye
What is graft rejection?
Ask Peter
jk jk lol
Transplant rejection occurs when transplanted tissue is rejected by the recipient’s immune system, which destroys the transplanted tissue
What are causes of graft rejection?
- ABO or HLA Incompatible
- Pre-formed Immunity (Sensitisation)
- Failed Immunosupression
- Including Non-compliance (often because people feel better when they are off the meds so are less likely to be compliant)
- Infections/Environmental Triggers
What is hyperacute rejection?
- Can happen in minutes
- ABO/HLA-antibodies
- Complement activation damages blood vessels
- Inflammation and thrombosis
- Kidney Transplants are particularily vulnerable
What is acute rejection?
- Days rather than minutes, can be up to 6 months within transplant
- 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 are the steps to acute rejection?
- Recognition: CD4 and CD8 cells recognise alloantigens
- APC reaction: T-cell receptors react with APCs via MHC Molecules
- Co-stimulation: Co-stimulation via CD28, CD80 and CD4/CD40 surface ligands
What is chronic rejection?
- Commonest cause of Graft Failure
- > 6 months
- Antibody mediated with other innate components
- Myointimal proliferation in arteries - This in turn blocks off blood vessels and leads to ischaemia an fibrosis
- IRREVERSIBLE
