Transplantation And Immunosupressive Drugs

Question 1

What is transplantation?

Answer 1

Introduction of biological material into an organism

Question 2

What are the types of donor?

Answer 2

Autologous
Syngeneic
Allogenic
Xenogenic

Question 3

What is an autologous donor/patient relationship?

Answer 3

Transplant from one part of a patient to another

Question 4

What is an syngeneic donor/patient relationship?

Answer 4

Transplant from a donor to a recipient that are genetically identical and therefore do not create immunogenic problems (identical twins)

Question 5

What is an allogenic donor/patient relationship?

Answer 5

Donor and recipient are the same species but genetically different

Question 6

What is an xenogenic donor/patient relationship?

Answer 6

Donor and recipient are different species

Question 7

What are immune responses to transplant caused by?

Answer 7

MHC differences between donor and recipient

Question 8

What is NGS used for?

Answer 8

To see differences between donor and recipient HLAs

Question 9

What is another word for T-cell activation?

Answer 9

Allorecognition

Question 10

What are the examples of indirect allorecognition?

Answer 10

Self HLA + self peptide

Self HLA + non-self peptide

Question 11

What are the examples of direct allorecognition?

Answer 11

Matched HLA + peptide

Unmatched HLA + peptide

Question 12

Which allorecognition will lead to no T cell activation?

Answer 12

Self HLA + self peptide

Matched HLA + peptide

Question 13

Which allorecognition will lead to T cell activation?

Answer 13

Self HLA + non-self peptide

Unmatched HLA + peptide

Question 14

What is increased with more HLA mismatches?

Answer 14

Chance of rejection

Question 15

Why are dead donors bad?

Answer 15

Likely to be inflamed due to ischaemia, so more likely to be rejected as the inflammation will flag it up to the immune system

Question 16

What are the types of rejection?

Answer 16

Hyperacute
Acute
Chronic

Question 17

How quickly does hyperacute rejection happen?

Answer 17

Within a few hours of transplant

Question 18

What is the method of hyperacute rejection?

Answer 18

Antibodies fix to endothelial cells
Complement fixation
Accumulation of innate immune cells
Endothelial damage, platelets accumulate and thrombi develop

Question 19

What does hyperacute rejection require?

Answer 19

Pre-existing antibodies

Question 20

What generally happens in acute rejection?

Answer 20

Inflammation results in activation of organ resident dendritic cells

Question 21

What happens in acute rejection?

Answer 21

Inflammation results in activation of organ resident dendritic cells
Dendritic cells move to secondary lymphoid tissue where they encounter circulating effector T cells
Macrophages and CTL increase inflammation and destroy transplant

Question 22

When does chronic rejection occur?

Answer 22

Months or years after transplant

Question 23

What is the method of chronic rejection?

Answer 23

Alloantibodies recruit inflammatory cells to the blood vessel wall of the transplanted organ
Increased damage enables immune effectors to enter and damage tissue of the blood vessel wall
Blood vessel wall thickened and lumen narrowed -> loss of blood supply
-> donor derived cells die
Membrane fragments containing donor MHC are taken up by host DC
Donor MHC is processed into peptides which are presented by host MHC

Question 24

How do antibodies cause damage to transplanted tissue?

Answer 24

Recognition of Fc region leading to:

• complement activation
• Antibody dependant cellular cytotoxicity (Fc receptors on NK cells)
• Phagocytosis (Fc receptors on macrophages)

Question 25

What happens in haematopoietic stem cell transfer?

Answer 25

Transplanted HSCs can find their way to bone marrow after infusion and regenerate

Question 26

What is graft versus host disease?

Answer 26

When transplanted tissue is immune cells themselves, there is risk of the donor immune cells attacking the host

Question 27

What is the best approach to graft vs host disease treatment?

Answer 27

Prevention

Question 28

What reduces the chance of GVHD?

Answer 28

Removing T cells from transplant or suppressing their function

Question 29

When can GVHD be beneficial?

Answer 29

Removing original leukaemia may prevent disease relapse

Question 30

What are the phases of immunosupression?

Answer 30

Induction, maintenance and rescue phases of treatment

Question 31

What are the types of immunosuppressants?

Answer 31

General immune inhibitors
Cytotoxic
Inhibit T cell activation

Question 32

What are examples of general immune inhibitors?

Answer 32

Corticosteroids

Question 33

What are examples of cytotoxic immunosuppressants?

Answer 33

Methotrexate

Question 34

What are examples of immunosuppressants that inhibit T cell activation?

Answer 34

Cyclosporine

Question 35

How does cyclosporin work?

Answer 35

Blocks T cell proliferation and differentiation

Question 36

What are the two types of immunosuppressive induction?

Answer 36

Antibody induction therapy

Triple drug regimen

Question 37

What antibodies are used in antibody induction therapy?

Answer 37

Lymphocyte depleting rabbit anti-thymocyte globulins

Question 38

What are the types of drugs used in the triple drug regimen?

Answer 38

Calcineurin inhibitor
Antiproliferative agent
Corticosteroid

Question 39

What is the maintenance bit of the immunosuppressive regime?

Answer 39

Triple drug regimen at lower doses

Question 40

What is T cell mediated rejection treated with?

Answer 40

Anti-thymocyte globulin (ATG) and steroids

Question 41

What is B-cell mediated rejection treated with?

Answer 41

IVIg or anti-CD20 antibody and steroids

Question 42

What can immunosuppressive drug toxicity lead to?

Answer 42

Organ failure

Question 43

What are transplant patients more susceptible to?

Answer 43

Infection and malignancy