Transplant immunology

Question 1

What is an orthotopic graft?

Answer 1

donor tissue mobilised into natural anatomical location eg liver.
Old organ removed –> new one implanted in its place

Question 2

What is a heterotropic graft?

Answer 2

donor tissue mobilised into unnatural anatomical location eg kidney.
Old organ remains and new one implanted alongside

Question 3

What is an autograft?

Answer 3

donor is the recipient eg skin

Question 4

What is an isograft?

Answer 4

donor is genetically identical to recipient eg in identical twins

Question 5

What is an allograft?

Answer 5

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

Question 6

What is a xenograft?

Answer 6

donor is of different species eg porcine or bovine heart valves

Question 7

What conditions tend to make an individual ineligible for tissue donation?

Answer 7

Active cancer
HIV/ HepC (though sometimes used and then recipient also treated for disease)
Ebola virus
CJD

Question 8

Which types of graft do not provoke an immune recation?

Answer 8

Isografts and autografts

Relocating genetically identical tissue (self or twin) then this will not prompt a response

Question 9

Which types of graft will provoke an immune response?

Answer 9

Allografts and Xenografts - foreign antigens

Question 10

Which type of graft is largely spared of rejection/ it doesn’t matter if recipient and donor aren’t so well matched?

Answer 10

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.

Question 11

Which three components of the immune system mediate graft rejection?

Answer 11

ABO incompatibility (crucial)
HLA incompatibility (fairly important)
Minor histocompatibility complexes (more minor role)

Question 12

What are the three types of rejection and their timescales?

Answer 12

Hyperacute rejection (minutes to hours)
Acute rejection (weeks to months)
Chronic rejection (years)

Question 13

What type of graft rejection occurs within minutes to hours?

Answer 13

Hyperacute

Usually apparent almost immediately whilst patient is still in theatre

Question 14

What type of graft rejection occurs within weeks to months?

Answer 14

Acute

Question 15

What type of graft rejection usually occurs within years?

Answer 15

Chronic

Often inevitable

Question 16

How does hyperacute rejection occur?

Answer 16

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

Question 17

How does acute rejection occur?

Answer 17

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

Question 18

How does chronic rejection occur?

Answer 18

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

Question 19

Matching of which HLA is most important for renal transplants?

Answer 19

HLA DR

Question 20

What are the three immunosuppressant agents given to help reduce graft rejection?

Answer 20

Anti-proliferative
Glucocorticoid
Calcineurin inhibitor

Question 21

How do calcineurin inhibitors work?

Answer 21

Inhibit calcineurin which impairs IL2 production, reducing the T cell response
eg Tacrolimus

Question 22

How do glucocorticoids work?

Answer 22

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