Immunology - Transplantation Flashcards
What is rejection?
Damage done by the immune system to a transplanted organ
What is an autologous transplant?
Tissue returning to the same individual after a period outside the body, usually in a frozen state
What is a syngeneic transplant?
transplant between identical twins; there is usually no problem with graft rejection
Also called isograft
What is allogeneic transplant?
Takes place between genetically nonidentical members of the same species; there is always a risk of rejection
What is xenogeneic transplantation?
Takes place between different species and carries the highest risk of rejection
What is an autograft?
From one part of the body to another
What criteria must be met before transplantation?
There must be good evidence that the damage is irreversible
That alternative treatments are not applicable
The disease must not recur
How can risk of rejection be minimised?
The donor and recipient must be ABO compatible
The recipient must not have anti-donor human leukocyte antigen (HLA) antibodies
The donor should be selected with as close as possible HLA match to the recipient
The patient must take immunosuppressive treatment
What is hyperacute rejection?
Preformed antibodies binding 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
How soon after transplantation does hyperacute rejection occur?
Within hours
How can hyperacute rejection be prevented?
through careful ABO and HLA cross-matching
What is acute rejection?
Type IV (cell-mediated) delayed hypersensitivity reaction Donor dendritic cells stimulate an allogeneic response in a local lymph node and T cells proliferate and migrate into the donor kidney
How soon after transplantation does acute rejection occur?
Days to weeks
What is the main cause of acute rejection?
HLA incompatability
How soon after transplantation does chronic rejection occur?
Months or years
Which type of stem cell is used to restore myeloid and lymphoid cells?
Haematopoietic stem cells
How is an autologous SCT carried out?
Marrow is removed, frozen, and reinfused after potent chemotherapy has been given
Autologous transplants carry minimal immunological risk
What are additional risks with allogeneic SCT due to?
GVHD
When is allogenic SCT carried out?
Haematological malignancy
Cases when myeloid cell production is reduced or notably abnormal, such as in aplastic anaemia
Primary immunodeficiencies such as severe combined immunodeficiency (SCID)
Sources of stem cells
Bone marrow
Peripheral blood
Cord blood
When does GVHD occur?
When donor T cells respond to allogeneic recipient antigens
Mismatches in major or minor histocompatibility antigens
Which SCT patients are given immunosuppression?
All of them, even if donor and recipient are HLA identical
Immunosuppressive drugs
Corticosteroids
T-cell signalling blockade
IL-2 blockade
Antiproliferatives
What do corticosteroids act on?
Low doses - antigen presenting cells
Higher dose - direct effect on T cells
T-cell signalling blockade drugs
Cyclosporin and tacrolimus
IL-2 blockade drugs
Monoclonal antibodies
Rapamycin
How do antiproliferatives work?
Inhibit DNA production
Prevent lymphocyte proliferation, but they are not specific for T cells and can cause myelotoxicity
Side effects of cyclosporin
Infections Increased risk of certain cancers Nephrotoxicity Diabetes Hypertension
Side effects of Rapamycin
Raised lipid and cholesterol levels Hypertension Anaemia Diarrhoea Rash Acne Thrombocytopenia Decrease in platelets and haemoglobin
Which cells are responsible for the effects of chronic rejection?
T cells
