Lec 5 - transplantation

Question 1

Define auto/ iso/ allo and xenografting.

Illustrate major antigenic differences between donor and recipient in humans.

Define the concept of privileged sites.

Illustrate complications of transplantation.

Describe measures taken to prevent graft rejection.

Answer 1

Describe mechanisms of graft rejection.

Illustrate the classification of graft rejection involved in hyperacute, acute and chronic rejection.

Define and explain Graft Versus Host Disease.

Illustrate the current clinical spectrum of transplantation.

Illustrate, broadly, measures for treatment of graft rejection.

Question 2

Define auto/ iso/ allo and xenografting

Answer 2

AUTOGRAFT - transfer of tissue between different sites within the same organism (e.g. skin graft)

ISOGRAFT - transfer between genetically identical individuals, ie. identical twins, also known as syngeneic

ALLOGRAFT - transfer between genetically non-identical members of the same species

XENOGRAFT - transfer between species (HIGHEST RISK OF REJECTION; RARELY USED)

Question 3

What is an autologous transplant

Answer 3

Refers to tissue returning to the same individual after a period outside the body, usually in a frozen state

Question 4

What is a syngeneic transplant

Answer 4

Refers to transplant between identical twins; there is usually no problem with graft rejection

AKA ISOGRAFT!

Question 5

Allogeneic transplant aka

Answer 5

Allograft

Question 6

An example of autograft

Answer 6

Skin graft

Question 7

When talking about recipient receiving organ from a stranger, what kind of transplant is that (commonest type)

Answer 7

Allograft

Question 8

Examples of transplantable organs

Answer 8

Kidney, heart, lung, skin, bone, pancreas/ islets of Langerhans, small bowel, bone marrow, cornea, uterus

Question 9

Main problem with all solid organ transplants is the risk for

Answer 9

REJECTION

Question 10

Measures taken to prevent graft rejection (4)

Answer 10

Donor and recipient must be ABO compatible.

Recipient must not have anti-donor human leukocyte antigen (HLA) antibodies

Donor should be selected with as close as possible HLA match to the recipient

Patient must take immunosuppressants (before + after)

Question 11

2 major antigens which donor and recipient must share in order for a graft to survive (2)

Answer 11

1. ABO blood group antigens

2. Major Histocompatability Antigens (HLA)

Question 12

Minor histocompatability antigens are less well defined and mismatch does not tend to be a major clinical problem. However, in what rare cases of may they be responsible for major rejection problems?

Answer 12

When donor and recipient are well matched for ABO and HLA antigens but rejection still occurs

Question 13

Complications of transplantation.

Answer 13

1) Graft rejection
2) Graft versus host disease (GVHD)
3) Infection (as a result of immunosuppressive therapy or of transfer of infectious agent in graft)
4) Neoplasia (lymphoma, skin tumours)
5) Drug side effects
6) Recurrence of original disease

Question 14

Graft rejection is usually caused by

Answer 14

Histocompatibility differences between donor and recipient

ABO blood group mismatch is rare

Question 15

4 types of graft rejection

Answer 15

Hyperacute
Accelerated
Acute
Chronic

Question 16

Describe hyperacute graft rejection

• how long after op
• mechanism
• triggers which type hypersensitivity
• common or rare

Answer 16

Minutes to hours

Pre-formed host antibody
against donor HLA or ABO antigens –> triggers type 2 hypersensitivity reaction and destroys graft by vascular thrombosis

RARE - as good cross matching prevents this

Question 17

Describe acute graft rejection

• how long after op
• mechanism
• triggers which type hypersensitivity

Answer 17

1-3 weeks

Donor dendritic cells stimulate an allogeneic response in a local lymph node and T cells proliferate and migrate to the donor graft –> type 4 hypersensitivity reaction

Question 18

Describe acute graft rejection

• how long after op
• mechanism
• triggers which type hypersensitivity

Answer 18

1-3 weeks

Donor dendritic cells stimulate an allogeneic response in a local lymph node and T cells proliferate and migrate to the donor graft –> type 4 hypersensitivity reaction

Question 19

Immunopathology of graft rejection

• afferent phase
• effector phase

Answer 19

Afferent phase
-donor MHC molecules within the graft are recognised by the recipient’s CD4+ T cells (allorecognition)

Effector phase
-CD4+ T cells recruit effector cells responsible for the tissue damage of rejection, e.g. macrophages, CD8+ T cells, NK cells and B lymphocytes

Question 20

Is autologous or allogenic SCT safer?

Is allogenic SCT or allogenic solid organ transplant safer?

Answer 20

Autologous SCT obviously as it’s their own cells

Allogenic SCT MUCH RISKIER than solid organ transplant, even with good cross matching

Question 21

Name a disease principally associated with allogenic SCT but can also occur with organ or tissue grafts

Answer 21

Grast versus host disease (GVHD)

Question 22

Sources of stem cells

Answer 22

Bone marrow
Peripheral blood
Umbilical cord blood

Question 23

What is Grast versus host disease (GVHD)

• mechanism
• causes

Answer 23

When donor T cells respond to allogeneic recipient antigens

Causes

• presence of functioning immunocompetent donor T cells in the graft
• defective immunity (especially T cell immunity) in graft recipient
• HLA differences between donor & recipient

Question 24

Grast versus host disease (GVHD) affects what organs

Answer 24

Skin, gut, liver, and lungs

Question 25

Treatment of graft rejection = IMMUNOSUPPRESSANTS

Name some

Answer 25

Corticosteroids

T-cell signalling blockers, e.g. cyclosporine (block cytokine production)

IL-2 blockers

• monoclonal antibodies against IL-2, e.g. basiliximab
• rapamycin

Antiproliferatives
-inhibit DNA production

Question 26

Cyclosporine, a T-cell signalling blockers, specifically blockers the production of which cytokine which is key for T cell proliferation and effector function

Answer 26

IL-2