(PM3A) Transplantation Flashcards
What are the main drug classes used in transplantation?
(1) Glucocorticoids
(2) Anti-proliferatives
(3) Calcineurin inhibitors
Where does organ transplantation rejection arise from?
When transplanted organ has a profoundly different T cell antigen profile
Major histocompatibility complex (MHC) is largely different between individuals
What is allorecognition?
Ability of immune system to be able to distinguish other tissues
What are MHC?
Major histocompatibility complexes
Contain many immune-related genes
e.g. MHC class 1 + MHC class 2
What is the mechanism of action of an MHC?
(1) Epitope recognised by T cell receptors
(2) Antigen is broken down to expose epitope (peptide fragments)
(3) Epitope peptide binds to a self-molecule (an MHC)
(4) T cell receptor binds to form a complex with the epitope and MHC
How many MHC genes are there?
14
How many MHC class 1 genes does each individual have?
3
2 copies of each (6)
How many MHC class 2 genes does each individual have?
4
2 copies of each (8)
Why are the chances of two individuals having the same MHC alleles so small?
So many different potential combinations of MHC alleles
Why is MHC presentation in individuals so diverse?
The evolutionary need to present as many different peptide antigens as possible?
To be safe from many viruses/ pathogens
What are some mechanisms of action of organ transplantation rejection?
(1) Antibody-mediated cell killing
(2) T cell-mediated cell killing
(3) T cell-mediated inflammation
What is Graft vs Host disease?
Donor tissue acts against host tissue
via lymphocytes
A worry in bone marrow transplantation
What would be the only way to cure organ transplantation rejection?
Removal of antigen
i.e. a perfect MHC match (all 14 alleles)
What is the induction phase of organ/ tissue transplantation?
Blanket suppression of immune system
To allow for healing
What is the effector phase of organ/ tissue transplantation?
Ongoing immunosuppressants
Prevention of rejection of transplant