21. Transplantation Flashcards
What is meant by rejection with regards to transplants
What is meant by an autologous transplant
Damage done by the immune system to a transplanted organ
Tissue returning to an individual after a period outside the body (typically frozen)
What is meant by an syngenic transplant
What is meant by an allogenic transplant
What is meant by a xenogeneic transplant
Transplant between identical twins. Also called an isograft
Takes place between a genetically nonidentical members of the same species, risk of rejection
takes place between species, has the highest risk of rejection
How can you minimise the risk of rejection?
Donor and recipient must be ABO compatible
Recipient must not have anti donor human leukocyte antigens
Donor should be selected with as close as possible HLA match to the recipient
Patient must take immunnosuppressive treatment
What is hyperacute rejection?
Rejection within hours of transplantation
Preformed antibodies bind to either ABO blood group or HLA class I antigens on the graft
Antibody binding triggers a type II hypersensitivity reaction and the graft is destroyed by vascular thrombosis
Rare as preventable through ABO and HLA cross matching
What is acute rejection?
Type IV (cell mediated) delayed hypersensitivity reaction Takes place within days or weeks or transplantation Donor dendritic cells stimulate an allogenic response to a local lymph node and T cells proliferate and migrate into the transplanted organ. Minimising the HLA mismatch of the donor is the key to a successful transplantation
What is chronic rejection?
Rejection months or years after transplant typically when injury to the vessel wall leads to initial smooth muscle proliferation luminal occlusion
What is tolerance?
A state of unresponsiveness to molecules the immune system has the capacity to recognise and attack
In the context of transplantation this means there is no response to alloantigens present on the transplanted tissue but response to pathogens aren’t affected
What is the immunopathology of graft rejection
Donor MHC molecules on passenger leucocytes (dendritic cells) within the graft are recognised by the recipients CD4+ cells
CD4+ cells recruit effector cells responsible for tissue damage of rejection:macrophages, CD8, T cells, NK cells and B lymphocytes
How do they select who receives a transplant
ABO compatible
Negative serum cross match with donor T lymphocytes
HLA match- as near as possible especially D loci
How do stem cells transplantation
Hematopoietic stem cells are used to restore myeloid and lymphoid cells. Autologous stem cell transplant carry the lowest risk
Allogenic stem cells can be much riskier as 20 % mortality rate
Why would you have an allogenic stem cell transplantation
Haematologic malignancy
Cases where myeloid cell production is reduced or notably abnormal such as aplastic anaemia
Primary immunodeficiency such as severe combined immunodeficiency
Where do stem cells exist?
Bone marrow- aspiration of a considerable amount of donor marrow under general anaesthetic
peripheral blood- harvested after treating th e donor with colony stimulating factors to increase the numbers of circulating stem cells
Cord blood- contains a large number of stem cells which can be frozen before use
Immature lymphocytes are less likely to cause GVHD
What is meant by conditioning in a stem cell transplant?
High dose chemo
High dose radiotherapy
Destroy the recipient’s stem cells and allow the engraftment of donor cells
What is meant by graft vs host disease
When donor T cells respond to allogeneic recipient antigens
Mismatches in major or minor histocompatibility antigens
All patients who receive stem cell transplantation are given immunosuppresive drugs to prevent graft vs host disease
Can be severe(70% mortality) and involves the gut, skin, liver and lungs)
Give som examples of immunosuppressice drugs
Corticosteroids- act on antigen presenting cells
T-cell signalling blockade- cyclosporine and tacrolimus interact with T cell signalling cascade
Monoclonal antibodies against IL-2 receptors (Basiliximab, daclizumab) used to treat acute graft rejection
Rapamycin can be given orally and interact switch IL-2 receptor. used to prevent graft rejection
Antiproliferatives (azathioprine, mycophenolate, mofetil and methotrexate) inhibit DNA production
