Transplant Immunology L9

Question 1

Define Isograft.

Answer 1

Transplantation between genetically identical individuals.

Question 2

Define Xenograft.

Answer 2

Graft between different species:

• Chemically treated pig heart valves
• Organs from transgenic pigs

Question 3

Define Allograft.

Answer 3

Graft between non-identical members of the same species

- Conventional transplant surgery

Question 4

Describe Hyperacute rejection.

Answer 4

• Occurs rapidly (maybe minutes after transplantation)
• Mediated by pre-formed antibodies and complement
• Results in vascular damage and thrombosis
• Generally easy to prevent by cross-matching
• Rarely encountered (big problem in xenografting)

Question 5

Describe Acute rejection.

Answer 5

• Episodes occur in most patients during the first 3 months after transplantation
• T-cell mediated response; CD4 and CD8 T cells
• Targeted at histocompatibility antigens (MHC)
• Can be managed successfully in most cases by immunosuppression

Question 6

Describe Chronic rejection.

Answer 6

• Occurs months and years after transplantation
• Now the most common cause of graft failure
• Generally observed as a fibro-proliferative disease
• Cause largely unknown
• Variable organ sensitivity
  - lung is very susceptible to obliterative bronchiolitis
• No good treatment

Question 7

Name the class 1 MHC HLA’s.

Answer 7

• HLA-A
• HLA-B
• HLA-C

Question 8

Name the class 2 MHC HLA’s.

Answer 8

• HLA-DR
• HLA-DP
• HLA-DQ

Question 9

Why are there so many allospecific cells?

Answer 9

These cells have never been excluded by negative thymic selection.

Question 10

Describe Renal Allograft Rejection.

Answer 10

1. Donor dendritic cells from the kidney activate allospecific T-cells in the spleen.
2. Activated allospecific cells infiltrate the donor kidney (peak ~3-5 days).

Question 11

Describe Bone marrow transplantation.

Answer 11

• Similar to solid organ transplantation
  - But the other way around
• Transplantation of the immune system
• There is a potential for transplanted T cells to respond to the recipient patient’s entire body
• Termed “Graft versus Host Disease” or GvHD
• Reduced by very accurate tissue matching

Question 12

Describe immunosuppression in transplantation.

Answer 12

• This is almost always necessary despite tissue typing
• Present strategies block T cell-mediated immune responses
• Almost all patients receive drug therapy for the life of the graft

Question 13

Name and describe the commonly used immunosuppressive ‘maintenance’ drugs.

Answer 13

Azathioprine
- anti-metabolite; inhibits DNA synthesis (proliferation) in all cells

Cyclosporin A and Tacrolimus
- Inhibit T cell activation; calcineurin inhibitors; primarily block the production of T-Cell growth factor (IL-2)

Question 14

Name and describe the commonly used immunosuppressive ‘rescue’ drugs.

Answer 14

High-dose steroids

Mycophenolate mofetil
- block T cell proliferation (similar to anti-cancer drugs)

Anti T-Cell antibodies
- include polyclonal preparations (eg ATG) and monoclonal antibodies (eg OKT-3)

Highly specific ‘humanised’ chimeric antibodies
- including antagonistic antibodies targeted at the IL-2 receptor (eg basiliximab)

Question 15

Describe Graft-specific immune tolerance.

Answer 15

Would allow graft survival without drugs

Several strategies can induce tolerance in model systems

But, nothing is reliable in the clinic

Some tissues can evade rejection after transplantation
- the cornea is ‘immune privileged’ (as are the testis)

Some organs can induce (partial) tolerance
- the liver is sometimes tolerogenic, allowing gradual withdrawal of all immunosuppression