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 syngeneic transplant (also called isograft)?
Transplant between identical twins. Usually no problem with rejection
What is allogeneic transplant?
Takes place between genetically nonidentical members of the same species - always a risk of rejection
What is cadaveric transplantation?
Use organs from a dead donor
What is xenogeneic transplant?
Takes place between different species. Highest risk of rejection
What are criteria for solid organ transplantation?
Good evidence that damage is irreversible
Alternative treatments are not applicable
Disease must not recur
What are examples of organs that can be transplanted?
Heart - heart failure Lung transplant Liver Pancreas Kidney
How can we reduce risk of transplant rejection?
Donor and recipient must be ABO compatible
Recipient must not have anti-donor human leukocyte antigen antibodies
Donor should be selected with close as possible humon leukocyte antigen match to recipient
Patient must take immunosuppressive drugs
What is hyperacute rejection?
Within hours of transplantation, preformed antibodies bind to either ABO blood group or HLA class I antigens on graft. Triggers a type II hypersensitivity response and graft is destroyed through vascular thrombosis
How is hyperacute rejection prevented?
Careful ABO and HLA cross-matching
What is acute rejection?
Donor dendritic cells stimulate allogeneic response in a local lymph node, T cells proliferate and migrate to donor organ
How long does acute rejection take to happen?
Within days or weeks of transplant
What type of hypersensitivity reaction is acute rejection?
Type IV
What is chronic rejection?
Element of allogeneic reaction mediated by T cells, results in repeated acute rejection
What can cause chronic rejection?
Pre-existing autoimmune disease
How long does chronic rejection take to occur?
Months or years after transplant
What is graft versus host disease?
Donor T cells respond to allogeneic recipient antigens, common in stem cell transplant but also happens in solid organ transplant
How long does acute GVHD take to occur?
Up to 4 weeks after stem cell transplant
What immunosuppresive drugs can be used after transplant?
Corticosteroids - low maintenance dose, high dose to treat rejection
T-cell signalling blockade
IL-2 blockade
Antiproliferatives
What drugs are used on T-cell signalling blockade?
Cyclosporine
Tacrolimus
What drugs are used in IL-2 blockade?
Monoclonal antibodies against IL-2 receptor - basiliximab - used for acute graft rejection
Rapamycin - maintenance drug to prevent rejection
What antiproliferative drugs are used for immunosuppression?
Azathioprine
Mycophenolate
Mofetil
Methotrexate
What are side effects of cyclosporin?
Recurrent viral, bacterial and fungal INFECTIONS Increased risk of certain CANCERS NEPHROTOXIC properties Diabetes Hypertension
What are side effects of rapamycin?
Raised lipid and chiolesterol levels Hypertension Anaemia Diarrhoea Rash Acne Thrombocytopenia Decreases in platelets and haemoglobin