Transplantation

Question 1

Definition of transplant

Answer 1

The replacement of tissues or organs that have undergone an irreversible pathological process which threatens the patients life or to a significant degree, considerably hampers their QoL

Question 2

Types of graft

Answer 2

Xenograft
Allograft
Isograft
Autograft

Question 3

What is a xenograft?

Answer 3

A transplantation from a donor of a different species from the recipient

Question 4

What is an allograft?

Answer 4

A transplant from one person to another

Question 5

What is an isograft?

Answer 5

A transplant between two individuals who are genetically identical i.e. monozygotic twins

Question 6

What is an autograft?

Answer 6

A transplant from one point to another of the same individuals body

Question 7

What is immune tolerance?

Answer 7

A state of unresponsiveness of the immune system to SELF

Question 8

Two types of immune tolerance

Answer 8

Central control (thymus) 
Peripheral control

Question 9

What is involved in central control?

Answer 9

Inactivation of cells required for initiation of an immune response

Question 10

What is involved in peripheral control?

Answer 10

Inhibition of expression of the immune response

Question 11

Two classes of HLA

Answer 11

Class 1
- HLA- A,B,C
Class 2
- HLA- DR, DP, DQ

Question 12

Where is class 1 of HLA found?

Answer 12

On all nucleated cells

Question 13

What class of HLA is most important in rejection?

Answer 13

Class 2

Question 14

What recognises class 1 HLA?

Answer 14

CD8 + / Tc cells

Question 15

What recognises class 2 HLA?

Answer 15

CD4 + / Th cells

Question 16

The major histocompatibility complex consists of…..

Answer 16

Human leukocyte antigen (HLA)

Chromosome 6

Question 17

Features of privileged sites

Answer 17

No sensitisation / no tolerance
No requirement for tissue matching
No immunosuppression

Question 18

Blood flow and immunity

Answer 18

If there is blood flow = immunity exposed

Question 19

What is graft rejection?

Answer 19

Occurs when transplanted tissue is rejected by the recipients immune system, which destroys the transplanted tissue

Question 20

Causes of transplant / graft rejection

Answer 20

ABO or HLA incompatible
Pre formed immunity (sensitisation)
Failed immunosuppression (including non compliance)
Infections / environmental triggers

Question 21

When can immediate rejection happen?

Answer 21

Within minutes

Question 22

Classes of rejection

Answer 22

Immediate
Acute
Chronic

Question 23

Pathology of immediate rejection

Answer 23

ABO/HLA antibodies
Complement activation damages blood vessels
Inflammation and thrombosis

Question 24

When does acute rejection happen?

Answer 24

Usually in 1st 6 months

Question 25

Pathology of acute rejection

Answer 25

Sensitisation phase 1. recognition 2. APC reaction 3. co stimulation Pre sensitised T cells hasten the process Can be a mix of cell and antibody mediated Cellular infiltration of graft by Tc cells, B cells, NK cells and macrophages Endothelial inflammation and parenchymal cell damage

Question 26

What is the commonest cause of graft failure?

Answer 26

Chronic graft failure

Question 27

When does chronic graft failure occur?

Answer 27

> 6 months

Question 28

Pathology of chronic graft failure

Answer 28

Antibody mediated with other innate components | Myointimal proliferation in arteries

Question 29

Treatment of rejection

Answer 29

Corticosteriods Anti-thymocyte globulin Plasma exchange

Question 30

Complications of transplantation

Answer 30

``` Rejection Infection (including zoonotic) Drug side effects Recurrence of original disease Surgical problems Ethical problems ```

Question 31

Prevention of graft rejection

Answer 31

ABO matching Tissue typing (Class I and II HLA) Prophylactic immunosuppression Humanised or silenced xenografts

Question 32

What is used for immunosuppression?

Answer 32

``` Corticosteriods (prednisolone) - wide spread anti inflammatory Calcineurin inhibitors (tacrolimus) - block IL-2 gene transcription Anti proliferatives (MMF) - prevent lymphocyte proliferation ```

Question 33

What is graft vs host disease principally a problem of?

Answer 33

Bone marrow transplant

Question 34

Requirements for graft vs host disease

Answer 34

Immunocompetent cells in graft Deficient recipient immunity HLA differences between donor and recipient

Question 35

Prevention of graft vs host disease

Answer 35

Donor / recipient matching | Donor marrow T cell depletion

Question 36

Types of donors

Answer 36

``` Living - related / unrelated - altruistic Deceased donor - brain death (DBD) - cadaveric death (DCD) ```

Question 37

Which types of donors have less rejection, are quicker, last longer and healthier and are easier to manage?

Answer 37

Living donors