7 - transplantation Flashcards
define rejection?
damage done by the immune system to a transplanted organ
define autologous transplant?
tissue returning to the same individual after a period outside the body, usually in a frozen state
define syngeneic transplant?
transplant between identical twins; there is
usually no problem with graft rejection i.e. isograft
define allogenic transplant?
takes place between genetically nonidentical members of
the same species; there is always a risk of rejection
define cadaveric transplant?
uses organs from a dead donor
define xenogenic transplant?
takes place between different species and carries the highest risk of rejection
3 criteria which must be met for solid organ transplant?
good evidence that damage is irreversible, alternative treatments are not applicable, disease must not recur
4 examples of solid organ transplant?
skin, heart, kidney, cornea
problem with solid organ transplants?
rejection
4 ways in which rejection is minimised in solid organ transplants?
ABO compatible donor, recipient must not have anti-donor HLA antibodies,
donor should have closest possible match for HLA, patient must have immunosuppressive treatment
name 5 cadaveric transplants?
cornea, liver, kidney, pancreas, heart
name 3 live transplants?
liver, kidney, stem cells
2 indications for liver transplant?
alcoholic liver disease, 1y biliary cirrhosis
indication for kidney transplant?
renal failure
2 indications for stem cells transplant?
malignancy, haematologic conditions
when does hyperacute rejection occur?
within hours of transplant
what causes the graft to be destroyed by vascular thrombosis in hyperacute rejection?
antibody binding to ABO group/ HLA class I antigens causes type II hypersensitivity reaction
how can hyperacute rejection be prevented?
careful ABO/ HLA cross-matching
what type of reaction is acute rejection?
type IV delayed hypersensitivity reaction
when does acute rejection take place?
within days/ weeks of transplant
main cause of acute rejection?
HLA incompatibility
what is the survival of the kidney related to?
the degree of mismatching, especially at the HLA-DR loci
2 phases of graft rejection?
afferent phase and efferent phase
describe the afferent phase of graft rejection?
donor MHC molecules on ‘passenger leucocytes’ within the graft are recognised by the recipient’s CD4+ T cells = allorecognition
describe the efferent phase of graft rejection?
CD4+ T cells recruit effector cells responsible for the tissue damage of rejection; macrophages, CD8+ T cells, NK cells and B
lymphocytes
when does chronic rejection take place?
months/ years after transplant
how does chronic rejection occur?
allogenic reaction is mediated by T cells - results in repeated acute rejection
what type of disease can cause chronic rejection?
autoimmune disease
what drugs prevent rejection?
immunosuppressive drugs
-ve aspect of immunosuppressive drugs?
lack the specificity - therefore prevent immune responses to other infectious agents
kidney transplant - final checks?
donor’s B cells are mixed with patient’s serum to cross match the samples
3 sources of stem cells?
bone marrow, peripheral blood, cord blood
what are haematopoietic stem cells used for?
used to restore myeloid and lymphoid cells
what is the risk of autologous stem cell transplants compared with allogenic stem cell transplants and why?
autologous stem cells transplants are less of a risk - due to GVHD.
name 3 circumstances where allogenic stem cell transplant is carried out?
hematologic malignancy, myeloid cell production is reduced, SCID
what occurs during conditioning?
Destroy the recipient’s stem cells and allows the engraftment of donor cells
what is GVHD?
graft versus host disease
when does GVHD occur?
when donor T cells respond to allogeneic recipient antigens
what prevents GVHD?
immunosuppressants
what 2 organs does chronic GVHD affect?
skin, liver
name 2 ways in which corticosteroids are used as immunosuppressives in terms of rejection?
at low doses - to prevent early stages of graft rejection,
at high doses - to treat episodes of rejection
which 2 drugs are used in T-cell signalling blockade?
cyclosporine and tacrolimus
name 2 monoclonal antibodies used for blocking the IL-2 receptor?
basiliximab, daclizumab
what is rapamycin used to treat?
used to prevent graft rejection - does so by blocking IL-2 receptor
what are antiproliferatives used for?
to stop DNA production and prevent lymphocyte proliferation
why do antiproliferatives cause bone marrow suppression - i.e. myelotoxicity?
they are not specific for T cells
name 5 possible side effects of cyclosporin?
infections (bac, vir, fun), nephrotoxicity, increased risk of certain cancers, hypertension, diabetes
name 5 possible side effects of rapamycin?
raised lipid/ cholesterol levels, hypertension, anaemia, diarrhoea, acne
most common transplant?
kidney
name 3 antiproliferatives?
Azathioprine, mycophenolate
mofetil, methotrexate
