Organ Transplant

Question 1

Define autologous transplant?

Answer 1

Donor and recipient are the same individual.

Question 2

Define syngenic transplant?

Answer 2

Donor and recipient are genetically identical twins.

Question 3

Define allogenic transplant? Give examples.

Answer 3

Donor and recipient are not genetically identical, but are from the same species.

E.g. Living donors: Haematopoietic stem cells, kidney, liver or lung lobe.
Deceased donors: Kidney, liver, pancreas, heart, lungs, cornea.

Question 4

Define xenogeneic transplant?

Answer 4

Donor and recipient are from different species. e.g. pig heart valve?

Question 5

Who are the NHSBT and what is their role?

Answer 5

NHS Blood and Transplant service are the directorate of organ donation and transplant.
They act to ensure;
- Organs donated are matched and allocated in a fair and unbias way.
- That there is equality of access for patients throughout the UK (i.e. not excluded based on where you live.
- Review critical need, waiting times and compatibility.

Question 6

Describe how transplant compatibility is measured?

Answer 6

1. Blood group compatibility.

2. HLA matching.

Question 7

Which blood group(s) have Anti-B antibodies in their plasma?

Answer 7

A & O

Question 8

What blood group(s) have Anti-A antibodies in their plasma?

Answer 8

B & O

Question 9

Which blood group(s) have Anti-O antibodies in their plasma?

Answer 9

None

Question 10

Which blood groups can receive A blood?

Answer 10

A & AB

Question 11

Which blood groups can receive B blood?

Answer 11

B & AB

Question 12

What blood groups can receive AB blood?

Answer 12

AB only

Question 13

What blood group can receive O blood?

Answer 13

A, B, AB & O

Question 14

What is the MHC?

Answer 14

Major Histocompatibility Complex.

A set of cell surface proteins that are APC’s which recognise foreign molecules and present them to T-cells.

Question 15

Describe the classes of MHC?

Answer 15

Class I MHC: Present on the surface of all nucleated cells in the body.
They have an alpha heavy chain bound to a B microchain. The Alpha heavy chain has the binding domain.
HLA-A, -B, -C are Class I and expressed on virtually all cells including platelets.
AA
AB

Class II MHC: Present on APC’s and are activated by T cells.
Have 2 polypeptide chains (alpha and beta). Each chain contributes to the binding domain.
HLA-DR, -DQ, -DP are class II and found on APC’s (dendritic cells, macrophages, B cells) and activated T cells.
BA
BA

Question 16

Which chromosome are the MHC genes found on?

Answer 16

6

Question 17

Describe tissue rejection issues in transplant?

Answer 17

The immune system of the recipient can mount an immune response to the donor tissue resulting in rejection. This is prevented using immunosupression drugs.

Bone marrow transplants differ as this involves the donors immune system being put into the recipient. The bone marrow can be translated and replace the recipients. This could lead to the recipients tissue being attacked by the new immune system.

Question 18

Describe Alloreactivity in relation to HLA matching?

Answer 18

1-10% of host T-cells can be alloreactive which means they can react with donor derived peptides and mount an immune response against the donor tissue.
T cells respond vigorously to non-self HLA, which is the main obstacle in transplantation.
Therefore HLA matching between donor and recipient is performed to try minimise this.
This is not always possible to to availability and timing issues, so compromises must be made so some mismatched are accepted and managed with immunosupression.

Question 19

What are donor specific antibodies? Give examples.

Answer 19

Antibodies produced by the recipient due to blood contact through previous occasions.

• Pregnancy: Mother has antibodies against the fathers HLA molecules.
• Blood transfusion: Recipient has antibodies against the donor.
• Previous transplant
• Viral infection: Antibodies produced in a viral infection can cross react HLA molecule of the donated organ.

Question 20

Describe HLA matching differences in kidney, liver and cardiothoracic transplantation?

Answer 20

Kidney
Aim to match HLA-A, B, DR low resolution.
Avoid transplant in the presence of donor specific antibodies.

Liver
Has no HLA mismatch problems.

Cardiothoracic
HLA matching recognised as important but not performed due to logistics (time?).
Avoid transplant in presence of donor specific antibodies.

Question 21

What would happen if an incompatible kidney was transplanted?

Answer 21

Pre-formed alloreactive antibodies target and attack the transplanted organ and blood vessels resulting in rejection.

Question 22

Describe hyper acute rejection?

Answer 22

Hyper-acute rejection can occur which happens minutes-hours after transplant. There is prevention of vascularisation of the graft and the organ dies of ischeamia.
Immune mediated by T and B cells.
Treated with modulation of immunosupression.

Question 23

What is chronic allograft nephropathy?
What causes it?
What is the result of chronic allograft nephropathy?

Answer 23

Progressive form of primarily immunologcal injury to graft, which more slowly compromises organ function than acute rejection.

Occurs due to;

• Immunological factors: poor HLA matching and presence of HLA alloantbodies or suboptimal immunosupression (including non-compliance of the patient.
• Non-immunological factors: Poorere graft quality (older patient), injury to graft (ischaemia, preservation injury), hypertension, hyperlipidemia, toxic effects of immunosupression, delayed graft function.

Results in graft ateriosclerosis leading to fibrosis.

Question 24

What tests are performed prior to transplant?

Answer 24

HLA type of recipient and donor.
Screen recipient for presence of pre-formed HLA antibodies (every 3 months when patient is on transplant list).
Crossmatch patient and donor prior to transplant to ensure negative result (i.e. no reactions).

Question 25

Describe the order of transplant allocation for kidneys?

Answer 25

All kidneys from deceased heartbeating donors are allocated through a nation scheme:

1. Paediatric patients (HLA match), highly sensitised (to HLA so small pool of possible kidneys, priority given on waiting time.
2. Other paediatric patients (HLA match - priority given on waiting time)..
3. Adult patients, highly sensitised (HLA match).
4. All other adults (HLA match and favourable).
5. All other eligible patients.