Transplantation Flashcards
What is an autograft?
tissue from one body part to another.
What is an isograft?
Transplant of tissue between genetically identical individuals
What is an allograft?
Transplant of tissue between members of the same species
What is a xenograft?
transplant between members of different species; pig heart valves.
What is Host-verus-Graft reaction?
Where the transplanted tissues is attacked by the immune system of the host. Graft rejection occurs, which then induces memory (specific and can be transferred by T cells)
How is the reaction mediated?
Recognition of graft antigens by alloreactive T-cells. The strongest antigen recognised as foreign is the MHC. Minor transplantation antigens also present such as the ABO blood group; not as important as MHC.
what is the direct pathway of rejection?
Where recipient T-cells with TCRs bind to allo-MHC and multiple non-tolerant self-peptides of the donor cells.
What is the indirect pathway of rejection?
Allo-MHC of the donor cell is endocytosed by recipient APCs which then process the allo-MHC by proteolytic cleavage and then present the allo-peptide on the self-MHC-II to the TCR of the recipient T cell.
What are the strongest transplant antigens?
MHC-molecules; highly polymorphic. They determine whether or not tissues are comparable between individuals.
What are the mechanisms of rejection?
immediate or hyperacute rejection can occur if the recipient has pre-existing antibodies against the tranplantation antigens. These antigens induce an adaptive immune response.
Describe the rejection of human renal allograft.
It is an acute reaction; kidneys contain relatively few leukocytes so they are difficult to remove in transplants. Transplanted renal tissue will then contain immune system cells. Donor tissue begins attacking recipient tissue; Graft versus host reaction.
Describe the GvH
When a graft contains HLA-incompatible T cells (bone marrow transplant) which then attack host tissues leading to life threatening GvH disease. This can be prevented by removing the T lymphocytes from the marrow and treating the patients with immunosuppressive drugs such as cyclosporin.
What are the four types of rejection reactions?
Hyperacute, accelerated, acute, chronic.
What is involved in a hyperacute reaction?
caused by preformed anti-donor antibodies and complement, occurs within a few minutes or hours
What is involved in an accelerated reaction?
caused by reactivation of sensitised T cells and occurs within a few days
What is involved in an acute reaction?
primary activation of T cells, within a few days or weeks.
What is involved in a chronic reaction?
causes are unclear; antibodies, immune complexes, slow cellular reaction, recurrence of disease, occurs within months and years; underlying condition.
What is involved in tissue typing?
matching HLA antigens which can by typed by serological techniques and more usually with PCR using allele-specific oligonucleotide primers. MAtching is more likely to occur between related individuals. Tissue typeing centres focus on HLA-A/B and DR
Will a perfect match be made?
Unless between MZ twins, but some immune responses will always occur and will need to be suppressed; drugs such as cyclosporin, tacrolimus.
What do cyclosporin and tacrolimus do?
They inhibit cytokine (IL-2) production. These drugs are non-antigen specific and carry a danger of general immunodeficiency leading to an increased risk of infection.
How can the donor deficiency be solved?
Through xenografts from pigs; poses particular problems in the form aof natural human antibodies to sugars expressed on the surface of pig cells. Pigs have been genetically modified to remove the target of these antibodies, but concerns remain regarding the feasibility of xenotransplantation.; sugars alpha-GAL on surface of pig cells (also present on cells of natural flora). Knockout alpha-1-3 galactosyltransferase results in a non-hyperacute rejection.
