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)
