Transplantation And Immunosupressive Drugs Flashcards
What is transplantation?
Introduction of biological material into an organism
What are the types of donor?
Autologous
Syngeneic
Allogenic
Xenogenic
What is an autologous donor/patient relationship?
Transplant from one part of a patient to another
What is an syngeneic donor/patient relationship?
Transplant from a donor to a recipient that are genetically identical and therefore do not create immunogenic problems (identical twins)
What is an allogenic donor/patient relationship?
Donor and recipient are the same species but genetically different
What is an xenogenic donor/patient relationship?
Donor and recipient are different species
What are immune responses to transplant caused by?
MHC differences between donor and recipient
What is NGS used for?
To see differences between donor and recipient HLAs
What is another word for T-cell activation?
Allorecognition
What are the examples of indirect allorecognition?
Self HLA + self peptide
Self HLA + non-self peptide
What are the examples of direct allorecognition?
Matched HLA + peptide
Unmatched HLA + peptide
Which allorecognition will lead to no T cell activation?
Self HLA + self peptide
Matched HLA + peptide
Which allorecognition will lead to T cell activation?
Self HLA + non-self peptide
Unmatched HLA + peptide
What is increased with more HLA mismatches?
Chance of rejection
Why are dead donors bad?
Likely to be inflamed due to ischaemia, so more likely to be rejected as the inflammation will flag it up to the immune system
What are the types of rejection?
Hyperacute
Acute
Chronic
How quickly does hyperacute rejection happen?
Within a few hours of transplant
What is the method of hyperacute rejection?
Antibodies fix to endothelial cells
Complement fixation
Accumulation of innate immune cells
Endothelial damage, platelets accumulate and thrombi develop
What does hyperacute rejection require?
Pre-existing antibodies
What generally happens in acute rejection?
Inflammation results in activation of organ resident dendritic cells
What happens in acute rejection?
Inflammation results in activation of organ resident dendritic cells
Dendritic cells move to secondary lymphoid tissue where they encounter circulating effector T cells
Macrophages and CTL increase inflammation and destroy transplant
When does chronic rejection occur?
Months or years after transplant
What is the method of chronic rejection?
Alloantibodies recruit inflammatory cells to the blood vessel wall of the transplanted organ
Increased damage enables immune effectors to enter and damage tissue of the blood vessel wall
Blood vessel wall thickened and lumen narrowed -> loss of blood supply
-> donor derived cells die
Membrane fragments containing donor MHC are taken up by host DC
Donor MHC is processed into peptides which are presented by host MHC
How do antibodies cause damage to transplanted tissue?
Recognition of Fc region leading to:
- complement activation
- Antibody dependant cellular cytotoxicity (Fc receptors on NK cells)
- Phagocytosis (Fc receptors on macrophages)
What happens in haematopoietic stem cell transfer?
Transplanted HSCs can find their way to bone marrow after infusion and regenerate
What is graft versus host disease?
When transplanted tissue is immune cells themselves, there is risk of the donor immune cells attacking the host
What is the best approach to graft vs host disease treatment?
Prevention
What reduces the chance of GVHD?
Removing T cells from transplant or suppressing their function
When can GVHD be beneficial?
Removing original leukaemia may prevent disease relapse
What are the phases of immunosupression?
Induction, maintenance and rescue phases of treatment
What are the types of immunosuppressants?
General immune inhibitors
Cytotoxic
Inhibit T cell activation
What are examples of general immune inhibitors?
Corticosteroids
What are examples of cytotoxic immunosuppressants?
Methotrexate
What are examples of immunosuppressants that inhibit T cell activation?
Cyclosporine
How does cyclosporin work?
Blocks T cell proliferation and differentiation
What are the two types of immunosuppressive induction?
Antibody induction therapy
Triple drug regimen
What antibodies are used in antibody induction therapy?
Lymphocyte depleting rabbit anti-thymocyte globulins
What are the types of drugs used in the triple drug regimen?
Calcineurin inhibitor
Antiproliferative agent
Corticosteroid
What is the maintenance bit of the immunosuppressive regime?
Triple drug regimen at lower doses
What is T cell mediated rejection treated with?
Anti-thymocyte globulin (ATG) and steroids
What is B-cell mediated rejection treated with?
IVIg or anti-CD20 antibody and steroids
What can immunosuppressive drug toxicity lead to?
Organ failure
What are transplant patients more susceptible to?
Infection and malignancy
