Unit 2 - Transplants

Question 1

What is transplantation?

Answer 1

Process of moving cells, tissues or organs from one site to another for the purpose of replacing or repairing damaged or diseased organs and tissues

Question 2

How are transplant donor and recipient matched?

Answer 2

Blood group
Tissue typing
Recipient’s blood serum reaction to donor cells

Question 3

Why are transplant donor and recipients matched?

Answer 3

To minimise the risk of rejection

Question 4

What causes transplant rejection?

Answer 4

The immune systems identifies the transplant as foreign, triggering a response that will ultimately destroy the transplanted organ or tissue

Question 5

What type of drugs are given to prevent and to treat transplant rejection by dampening the overall immune response?

Answer 5

Immunosuppressive drugs

Question 6

What are the problems with using immunosuppressive drugs?

Answer 6

Patients are more susceptible to disease as well as being associated with numerous unwanted side effects

Question 7

Which tissues and organs can be transplanted?

Answer 7

Heart
Kidneys
Thymus
Liver
Lungs
Pancreas
Intestine

Question 8

What are the four types of transplant?

Answer 8

• autografts/autologous grafts
• syngeneic/isografts
• allogeneic grafts
• xenogeneic grafts

Question 9

What is an autograft transplant?

Answer 9

Transplant between sites within the same individual

• skin grafting
• bone marrow

Question 10

What is an isograft transplant?

Answer 10

Transplant between two genetically identical individuals

- monozygotic twins

Question 11

What is an allogeneic graft?

Answer 11

Transplant between two genetically different individuals of the same species

• heart
• lung
• kidney
• liver graft

Question 12

What is an xenogeneic graft?

Answer 12

Transplant between individuals of different species?

Question 13

What is a stem cell transplant?

Answer 13

Stem cells are cells that have the capacity to develop into a range of different types of cells in the body
- blood stem cells (haematopoietic stem cells) can develop into all the different cells found in the blood and are donated to replace damaged or destroyed blood cells

Question 14

What are haematopoietic stem cells used to treat?

Answer 14

Certain types of cancer
- leukaemia
Blood diseases where the bone marrow has become damaged, preventing the production of healthy blood cells

Question 15

How are haematopoietic stem cells harvested?

Answer 15

• directly from the bone marrow

- from umbilical cord blood from consenting mothers following childbirth

Question 16

What are the two major alloantigens?

Answer 16

ABO antigens
- routine to cross match donor with recipient blood serum
MHC proteins that are co-dominantly expressed on the surface of our cells
- donor MHC being recognised by the recipients immune system as foreign

Question 17

What encodes for MHC?

Answer 17

Human Leukocyte Antigen (HLA)

Question 18

Which cells are MHC class I found on the surface of?

Answer 18

All nucleated cells

- act as ‘self-markers’ telling the immune system not to trigger a response

Question 19

What is histocompatibility?

Answer 19

Degree of similarity between the HLA genes of the donor and recipient

Question 20

What are the two types of compatibility test that are carried out for transplants?

Answer 20

• tissue typing

- cross matching

Question 21

How is tissue typing carried out?

Answer 21

• a blood sample is taken from the recipient to identify the HLA antigens present on the surface of their cells to help find a histone compatible donor
• the more alike the HLA types of the donor and recipient are, the more likely a transplant will be successful
• family members, in particular siblings, are often the best HLA matches due to their genetic similarity

Question 22

How is cross matching carried out?

Answer 22

• blood samples are taken from both the recipient and donor and the cells of the donor are mixed with the blood serum of the recipient
• if the recipient’s antibodies attack the donor cells, they are considered a positive match and transplantation will not be suitable due to increased risk of hyper-acute rejection

Question 23

What are the 6 HLA antigens that are studied for tissue typing?

Answer 23

Two each at

• HLA-A
• HLA-B
• HLA-DR

Question 24

What is alloreactivity?

Answer 24

MHC molecules invoke powerful immune response from allogenic T-cells

Question 25

What will allogenic T-cells will cross react against?

Answer 25

1. Foreign (donor) allogenic MHC - ‘abundant’
2. Foreign peptide in foreign MHC
3. Foreign peptide in self-MHC
4. Self-peptide in foreign MHC

Question 26

Which type of white blood cells are central to rejection?

Answer 26

Lymphocytes

Question 27

What is a major barrier to transplantation?

Answer 27

Immune response

• T cells play a primary role
• B cells can/do play a role

Question 28

What are the three types of rejection reactions involved in transplantation?

Answer 28

• hyperacute
• acute
• chronic

Question 29

What is a hyperacute rejection reaction?

Answer 29

Antibody mediated

• widespread arteriolitis
• arteritis
• thrombosis
• ischemic necrosis

Question 30

What is an acute rejection reaction?

Answer 30

Antibody and cell mediated

• lymphocytic infiltraion
• vasculitis
• tubulitis
• edema

Question 31

What is a chronic rejection reaction?

Answer 31

Vascular changes

• sclerosis
• intimal fibrosis

Question 32

What is given to prevent organ rejection in induction therapy?

Answer 32

• basiliximab

- rabbit anti-human thymocyte immunoglobulin

Question 33

What is given to prevent organ rejection in initial and long-term maintenance therapy?

Answer 33

• mycophenolate mofetil
• mycopehnolate sodium
• sirolumus
• prolonged-release tacrolimus
• immediate-release tacrolimus
• everolimus
• belatacept

Question 34

What are the limitations to immunosuppressive drugs?

Answer 34

Immunodeficiency
Susceptible to opportunistic infection
Adverse side effects
- high blood pressure
- impaired renal function
- diabetes mellitus and increased risk of cancer

Question 35

What is induction immunosuppression?

Answer 35

Prophylatic therapy used at the time of transplant based on more powerful immunosuppression is required to prevent acute rejection early

Question 36

Where is induction immunosuppression carried out?

Answer 36

Specialist transplant centres

Question 37

What is the target of induction immunosuppression?

Answer 37

T-lymphocyte - non-depleting

Question 38

What drugs are used to target lymphocytes in induction immunosuppression?

Answer 38

Basiliximab
Calcineurin inhibitor
Corticosteroid