Transplant immunology Flashcards
What is an orthotopic graft?
donor tissue mobilised into natural anatomical location eg liver.
Old organ removed –> new one implanted in its place
What is a heterotropic graft?
donor tissue mobilised into unnatural anatomical location eg kidney.
Old organ remains and new one implanted alongside
What is an autograft?
donor is the recipient eg skin
What is an isograft?
donor is genetically identical to recipient eg in identical twins
What is an allograft?
donor is the same species as the recipient (usually matched but not genetically identical). This is the most common - eg graft from living or deceased donor
What is a xenograft?
donor is of different species eg porcine or bovine heart valves
What conditions tend to make an individual ineligible for tissue donation?
Active cancer
HIV/ HepC (though sometimes used and then recipient also treated for disease)
Ebola virus
CJD
Which types of graft do not provoke an immune recation?
Isografts and autografts
Relocating genetically identical tissue (self or twin) then this will not prompt a response
Which types of graft will provoke an immune response?
Allografts and Xenografts - foreign antigens
Which type of graft is largely spared of rejection/ it doesn’t matter if recipient and donor aren’t so well matched?
Avascular transplants eg cornea.
There is no lymphatic drainage to the cornea so it does not come into contact with the immune system, meaning chance of rejection is much smaller.
Which three components of the immune system mediate graft rejection?
ABO incompatibility (crucial) HLA incompatibility (fairly important) Minor histocompatibility complexes (more minor role)
What are the three types of rejection and their timescales?
Hyperacute rejection (minutes to hours) Acute rejection (weeks to months) Chronic rejection (years)
What type of graft rejection occurs within minutes to hours?
Hyperacute
Usually apparent almost immediately whilst patient is still in theatre
What type of graft rejection occurs within weeks to months?
Acute
What type of graft rejection usually occurs within years?
Chronic
Often inevitable
How does hyperacute rejection occur?
Tends to be by preformed antibodies eg ABO incompatibility
Binding of antibodies mediates immune response
The graft becomes inflamed and organ failure occurs
Graft must be removed immediately to avoid overwhelming systemic inflammation
How does acute rejection occur?
Can be either humoral or cell mediated antibody or T cell mediated
Antibodies are not preformed
Due to HLA incompatability
T cell mediated- T cells recognise these cells or fragments of antigen as non-self
Mediates immune response against HLA antigen of donor
Either cytotoxic or B cell antibody response
Signs may include graft failure and tenderness
How does chronic rejection occur?
Due to long term low grade cell mediated immunity
This may also be mediated to minor histocompatibility complexes
Endovascular inflammation (mediated by T cells, alloantibodies, macrophages and cytokines)
Smooth muscle hyperplasia and fibrosis occurs
Also known as allograft vasuclopathy
Matching of which HLA is most important for renal transplants?
HLA DR
What are the three immunosuppressant agents given to help reduce graft rejection?
Anti-proliferative
Glucocorticoid
Calcineurin inhibitor
How do calcineurin inhibitors work?
Inhibit calcineurin which impairs IL2 production, reducing the T cell response
eg Tacrolimus
How do glucocorticoids work?
They inhibit phospholipase A2 via lipocortin-1
Anti inflammatory as they reduce eicosanoid synthesis (arachidonic acid pathway), reduce cytokine secretion and reduce adhesion molecules.
They induce endonucleases that mediate apoptosis within white BCs
