Transplantation Flashcards
what is an isograft
tissue between genetically identical identicals
what is an autograft?
move tissue from one part of the body to another
what is an allograft?
tissue transplantation between different members of the same species
what is a xenograft?
transplantation between members of different species
what is the cell responsible for transplant rejection and how?
T cells - recognise non-self antigens presented on MHC complexes
which chromosome is the MHC located on?
short arm of chromosome 6
which cells do the class 1 and class 2 MHC presenting to
1 - CD8 T cells
2 - CD4 T cells
what is the major transplant antigen
MHC molecules
what are the most important alleles on the MHC to match for transplantation
A, B and DR
graft survival of a solid organ transplant is directly related to
HLA matching
what is the dose response relationship with HLA mismatching
the more mismatches…. the worsening of long term graft survival
why arent lung and heart transplants HLA matches?
due to urgency
types of transplantation rejection and their timing
hyperacute - minutes-hours
acute - days-weeks
chronic - months-years
what is the cause of hyperacute rejection
preformed anti-donor antibodies and complement
what is the cause of acute transplant rejection
primary activation of T cells
what is the cause of chronic transplant rejection
causes unclear
Ab, immune complexes, slow cellular reaction, recurrence of disease
what is another name for hyperacute rejection
antibody-mediated rejection
what kinds of people would you test to see if they had preformed antibodies against MHC groups
people who have had a blood transfusion
previous pregnancy
previous transplant
what is the mechanism behind antibody mediated rejection
- pre existing Ab are carried to graft
- Ab bind to antigen and activate C’
- C’ attracts neutrophils and release lytic enzymes
- destroys endothelial cells, platelets adhere to injured tissue –> vascular blockage
mechanism of acute rejection
- immune cells pass through the new organ
- recognises non-self organ
- takes antigen to draining lymph node on MHC
- presents to T cells via APC
- T cells activated and proliferated
- immune related destruction
how do you check whether you have acute rejection
take biopsies and look for T cell infiltrate
what are the multiple hits that can cause chronic rejection
ischaemia/reperfusion dyslipidaemia infection hypertension acute rejection
what is the hallmark of of chronic rejection
fibrosis
where does fibrosis normally occur in chronic rejection in renal, liver and lungs
around tubules
- renal - around renal tubules (chronic allograft nephropathy)
- liver - around bile duct (bile duct syndrome)
- lungs - around airways (BOS)
how do you try and prevent allograft rejection
Matching ABO antigens
matching MHC alleles
immunosuppressive drugs
what is the action of cyclosporin
selectively takes out recently activated T cells
what is the cocktail of drugs given to a transplant recipient
calcineurin inhibitors (eg cyclosporin)
anti-inflammatory (eg steroids)
anti-proliferative (eg azathioprine)
how does cyclosporine inhibit T cells
prevents IL2 transcription needed for proliferation
side effects of cyclosporon
nephrotoxicity
prone to viral infection
action of azathioprine
inhibit T cell proliferation
what is the concept of organ regeneration
organ put in detergent –> decellularize
then reconstitute the organ with the recipients own cells
transplant with no MHC
