Transplant and Graft rejection

Question 1

Define Autograft

Answer 1

Grafts from one organism to the same organism, e.g. a skin graft from the same individual

Question 2

Define Allografts

Answer 2

Grafts from one organism to another in the same species, e.g. kidney transplant

Question 3

Define Xenograft

Answer 3

Grafts from a different species, e.g. heart valve transplants from pig to human.

Question 4

What is the main reason for graft rejection?

Answer 4

Immune system - recognises the graft as foreign and mounts and immune response (does not occur with autografts)

In Allografts - the tissue presents foreign HLA molecules and foreign peptides in the HLA molecules - the graft can be recognised as foreign and destroyed

Question 5

What is another name for HLA molecules and what do they present?

Answer 5

Major histocompatibility antigen

The antigen peptides they present are called = Minor histocompatibility antigen

Question 6

What does tissue typing involve?

Which HLA type is particularly important to match

Answer 6

• It is carried out for HLA A,B and DR loci
• It is particularly important to match the DR loci as mismatch here increases the risk of graft rejection significantly

Question 7

Well matched tranplants have X percentage higher survival at 1 year

Answer 7

15%

Question 8

Give examples of patient subgroups at higher risk of graft rejection

Answer 8

• Women (due to pregnancy)
• People who have previously received multiple blood transfusions

Question 9

Why do corneal transplants have a particularly high success rate?

Answer 9

• Anatomically avascular
• Sits over the AC which is an Immunologically privileged site

Question 10

What is immune privilege?

Answer 10

Areas that are excluded from the normal immune system function

They contain autoantigen that the immune system is not exposed to

Question 11

How do immune privileged areas differ from other tissues/sites?

Answer 11

1. The immune communication with the rest of the body is limited as there is no lymphatic supply
2. There is a high level of anti-inflammatory markers e.g TGF- B
3. Increased expression of FASL - which induces apoptosis of infiltrating FAS expressing activated lymphocytes

Question 12

Give 5 examples of immune privileged sites

Answer 12

1. The eye
2. The brain
3. The foetus
4. The placenta
5. The Gonads

Question 13

What is Graft versus host disease?

how can it present?

Answer 13

The opposite of graft rejection (host versus graft disease)

The graft tissue contains immune cells that recognise the host as foreign

It can cause a severe inflammatory response including rashes, diarrhoea, liver disease

Question 14

How can GVHD be tested for prior to a transplant?

Answer 14

Mixed lymphocyte reaction test - important for BM transplants

• Lymphocytes from the donor are mixed with irradiated donors from the host
• If the potential donor lymphocytes replicate then it means there is a potential alloreactive response - the donor will then be discontinued

Question 15

What is DIRECT allorecognition?

Answer 15

The GRAFT dendritic cells present the foreign MHC and co-stimulatory molecules to HOST T cells

Question 16

What is INDIRECT allorecognition?

Answer 16

The HOST dendritic cells uptake the foreign antigen and present to naiive HOST alloreactive T cells

Question 17

Which type of cells are mainly responsible for the activation of alloreactive T cells through the direct pathway?

Answer 17

In solid tissue allografts, numerous class-II-expressing, bone-marrow-derived cells of the dendritic and macrophage type are present, and these cells, termed passenger leukocytes, are primarily responsible for the activation of alloreactive T cells through the direct pathway.

Question 18

The cornea - cant phrase a question LOL just read

Answer 18

The absence of passenger cells within the normal cornea correlates very well with the relative inability of orthotopic corneal allografts to activate direct alloreactive T cells.

Because corneal allografts activate and may eventually succumb to the effector function of indirect alloreactive T cells, APCs other than passenger leukocytes, that is, of recipient origin, must be responsible for initial T-cell activation.

Question 19

What are the 4 types of rejection and when do they occur?

Answer 19

• Hyperacute: 2- 5 days
• Acute: 7-21 days
• Chronic: After 3 months
• Acute on Chronic

Question 20

How does hyperacute rejection occur?

Answer 20

Circulating antibodies are are present to antigens on the graft tissue within minutes

If the recipient is sensitised to the antigen - graft destruction occurs via Cell mediated mechanisms will commence

Question 21

How does acute rejection occur?

Answer 21

Mainly a Cell mediated response

Question 22

How does Chronic rejection occur?

Answer 22

• Disturbance in graft tolerance leads to rejection
• Main mediators: Antibodies, complement

Question 23

How does acute on chronic rejection occur?

Answer 23

T cells are instigators

Occurs if the recipient immune system is altered e.g. immunosuppression