Immunology 5

Question 1

Define rejection with regards to transplant

Answer 1

Damage done by the immune system to a transplanted organ

Question 2

Define autologous transplant

Answer 2

Tissue returning to the same individual after a periods outside the body

Question 3

Define syngeneic transplant/ isograft

Answer 3

Transplant between identical twins

Normally no problem with graft reflection

Question 4

Define allogeneic transplant

Answer 4

Between genetically non identical members of the same species

Question 5

Define cadaveric transplant

Answer 5

Use organs from dead donors

Question 6

Define xenogeneic transplant

Answer 6

Takes place between different species and carriers the highest risk of rejection

Question 7

Solid organ transplant criteria

Answer 7

Good evidence damage is irreversible
That alternative treatments are not applicable
Disease must not recur

Question 8

How to minimise the rejection chances of transplant

Answer 8

Donor and recipient must be ABO compatible
Recipient must not have anti-donor human leukocyte antigen antibodies
Close as possible HLA match to recipient
Patient must take immunosuppressive treatment

Question 9

What is a hyperacute rejection

Answer 9

Within hours 
Preformed antibodies binding to either ABO blood groups or HLA class I antigens on graft 

Antibody binding triggers a type II hypersensitivity reaction and the graft is destroyed by vascular thrombosis

Question 10

Type of hypersensitivity reaction of hyperacute rejection

Answer 10

Type 2

Question 11

Type of hypersensitivity reaction of acute rejection

Answer 11

4

Question 12

Describe acute rejection

Answer 12

Delayed
Takes place within days or weeks of transplant

Donor dendritic cells stimulate an allogeneic response in a local lymph node and T cells proliferate and migrate into donor kidney

HLA incompatibility is the main cause

Question 13

What is a chronic rejection with regards to transplant

Answer 13

Takes months or years
An element of allogeneic reaction is often mediated by T cells, which can result in repeated acute rejection

May be caused by recurrence of pre-existing autoimmune disease

Question 14

Describe immunosuppressive drugs

Answer 14

Prevent rejection until stopped

Also lack specificity of true tolerance and thus prevent immune response to infectious agents

Question 15

Immunopathology of graft rejection

Answer 15

Afferent phase:
MHC molecules recognised by CD4+ T cells (allorecognition)

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

Question 16

Tissue typing techniques

Answer 16

HLA typing

HLA cross matching

Question 17

What is stem cell transplantation

Answer 17

Hematopoietic stem cells are used to restore myeloid and lymphoid cels

Question 18

Describe the different types of stem cell transplantation

Answer 18

Autologous SCT
-marrow remove, frozen and reinfused, normally after chemotherapy

Allogenic SCT

• much riskier than solid organ donation
• due to Graft vs Host disease

Question 19

When are allogenic SCT carried out

Answer 19

In:
Hematologic malignancy
Myeloid cell production is reduced
SCID

Question 20

Sources of stem cells

Answer 20

Bone marrow,
Peripheral blood
Cord blood

Question 21

What is conditioning

Answer 21

High dose chemotherapy
High dose radiotherapy

Destroy recipient’s stem cells and allow the engraftment of donor cells

Question 22

What is Graft vs Host disease

Answer 22

Occurs when donor T cells respond to allogeneic recipient antigens

Mismatches in major or minor histocompatibility antigens

All patients given SCT are given immunosuppressive drugs to avoid

Acute GVHD occurs up to 4 weeks after SCT
-involves skin, gut, liver and lungs

Chronic GVHD occurs later
-affects skin and liver

Question 23

Immunosuppressive drugs used

Answer 23

Corticosteroids,

T cell signalling blockade (cyclosporin (!!), tacrolimus)

IL-2 blockade (basiliximab and daclizumab (monoclonal antibodies against IL-2) and rapamycin)

Antiproliferatives (azathioprine, mycophenolate, mofetil, methotrexate) (inihibit DNA production preventing lymphocyte proliferation)

Question 24

When are IL-2 blockade drugs used

Answer 24

Monoclonal antibodies against IL-2 receptor
-acute graft rejection

Rapamycin
-prevent graft rejection

Question 25

Main side effect of antiproliferatives

Answer 25

Myelotoxicity

Bone marrow suppression

Question 26

Xenotransplanation problems

Answer 26

Primates assemble different sugar side chains from other species

Antibodies against gal-α1,3-gal bind onto xenotransplanted organs, activate complement, and trigger hyperacute rejection.

Acute rejection may occur because pig proteins elicit T-cell responses.
Even pigs reared in microbe-free conditions are infected with endogenous retroviruses; these have never been known to infect humans, but there is a risk as pig viruses are more likely to infect recipients taking immunosuppressive drugs.