Transplantation Flashcards
name the types of graft
xenograft
allografy
isograft
autograft
what is a xenograft?
tissue graft or organ transplant from a donor of a different species from the recipient
what is an allograft?
the transplant of an organ or tissue from one individual to another of the same species with a different genotype
what is an isograft?
from a donor who is genetically identical to the recipient
do isograft receivers still need immunouppression and why?
yes because they will have been exposed to different things e.g. blood transfusion
what is an autograft?
a graft of tissue from one point to another of the same individual’s body
what is MHC?
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.
what is 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)
describe the inheritance of HLS
codominantly
two alleles 6 loci
name the major requirements for tissue typing?
HLA-DR, DP, DQ
HLA-A, B, C
ABO
describe class 1 HLA
The class I molecules are responsible for presenting antigenic peptides from within the cell (eg, antigens from the intracellular viruses, tumour antigens, self antigens) to CD8 T cells
descibe class 2 HLA
the class II molecules present extracellular antigens such as bacteria to CD4 T cells
where are HLA class I found?
all nucleated cells
what recognised HLA I
CD8+
Tc cells
where are HLA class II found?
APCs
what recognised HLA II?
CD4+
Th cells
what kind of HLA is most important in rejection?
class II
draw a molecule of HLA1 and 2
see notes
The MHC genes are codominantly expressed, which means that each individual expresses these genes from both the alleles on the cell surface. what does this mean in regards to transplant?
they are inherited as haplotypes or 2 half sets (one from each parent).t This makes a person half identical to each of his or her parents with respect to the MHC complex. This also leads to a 25% chance that an individual might have a sibling who is HLA identical. Only 30% of transplant recipients have an HLA identical donor.
what are privileged sites?
no vascularisation so:
no sensitisation/no tolerance
no requirement for tissue matching
no immunosuppression
give examples of transplants wth privileged sites
corneal
heart valves
types of living donor
related or unrelated
altruistic
types of deceased donor
brain death
cadaveric death
with living donors there is:
less rejection quicker last longer healthier easier to manage
what is graft rejection?
Transplant rejection occurs when transplanted tissue is rejected by the recipients immune system, which destroys the transplanted tissue.
causes of graft rejection
• ABO or HLA incompatible • Pre-formed immunity – sensitisation • Failed immunosuppression o Including non-compliance • Infections/environmental triggers o CMV esp
describe hyperacute rejection
This can happen in seconds as a result of ABO/HLA antibodies. It causes complement activation damaging blood vessels. Inflammation and thrombosis results.
risk factors for hyperacute rejection
previous failed transplants
pregnancies
blood transfusions
what kind of transplants are esp at risk of hyperacute rejection?
kidney
describe the sensitisation phase in acute rejection
- CD4 and CD8 cells recognise alloantigens
- T-cell receptors react with APCs via MHC molecules
- Co-stimulation via CD28, CD80 and CD4/40 surface ligands
describe acute rejection
Occurs in days to months up to 6 months Acute rejection usually occurs in the 1st 6 months of transplantation. It can be a mix of cell and antibody mediated rejection. Cellular infiltration of graft by TC cells, B-cells, NK cells and macrophages. Endothelial inflammation and parenchymal cell damage. Host T cells recognise intact allo-MHS molecules on the surface of tissues. Unlike T and B cells, NK cells are activated by the absence of MHC molecules on the surface of target cells (“missing self” hypothesis). The recognition is mediated by various NK inhibitory receptors triggered by specific alleles of MHC class I antigens on cell surfaces. Often develops into chronic.
describe chronic rejection
Chronic rejection is the commonest cause of graft failure occurring after 6 months. It is antibody mediated with other innate components. There is myointimal proliferation in arteries. Cytokines and antibodies cause a chronic inflammatory process that proliferates cell walls to protect themselves and due to turnover. This in turn blocks off blood vessels and leads to ischaemia and fibrosis
what is the treatment of rejection?
• Corticosteroids
• Anti-thymocyte globulin
o Must find out about horse or rabbit allergies
• Plasma exchange
o Antibody mediated rejection
o IV Ig added so that they don’t get common infections
apart from rejection, list the other complications of transplantation
- Infection (including zoonotic)
- Neoplasia (skin, lymphoma)
- Drug side effects
- Recurrence of original disease
- Surgical, ethical problems
how can you prevent transplant rejection?
- ABO matching
- Tissue typing (Class I and II HLA)
- Prophylactic immunosuppression
- (humanised or silenced xenografts)
list the types of immunosuppressants and what they do
• Corticosteroids (Prednisolone) o Widespread anti-inflammatory • Calcineurin Inhibitors (Tacrolimus) o Block IL-2 Gene Transcription • Anti-proliferatives (MMF) o Prevent Lymphocyte Proliferation
graft vs host disease is primarily found in what kind of transplant?
bone marrow
requirements of graft vs host disease
o Immunocompetent cells in graft
o Defective recipient immunity
Figure 7 Complications of Renal Transplantation
o HLA differences between donor and recipient
prevention of graft vs host disease
o Donor / recipient matching
o Donor marrow T cell depletion
what does unmodified xenografts result in?
hyperacute rejection
natural IgM human anti-swune antibody result sin what in unmodified xenografts?
graft endothelial galactose residuses
prevention of xenograft hyperacute rejection
1) Remove antibody from recipient
2) Genetically modified (‘silenced’) pigs
3) ‘Humanised’ transgenic pigs
