A11 - Immunology of Transplantation

What is an Autograft?

Transplant from one site to another in the same body.

What is an Isograft?

Transplant between genetically identical individuals

What is an Allograft?

Transplant between non-identical members of the same species

What is a Xenograft?

Transplant between different species

• E.g. Chemically treated pig heart valves

What is a reperfusion injury?

While on ice, toxic metabolites build up in the organ.

When the organ is transplanted, blood rushes in and Neutrophils begin to digest the tissue and damage the organ

What is EVLP?

Ex-vivo lung perfusion (EVLP)

A technique which uses a pump to inflate and deflate the lungs

Oxygenation is used to remove oxygen before its sent back into the lungs

What is Hyperacute rejection?

Rejection of a transplanted organ which occurs rapidly (minutes after transplantation)

Rarely occurs as cross-matching organ and recipient can help prevent it

What mediates Hyperacute rejection and what can it result in?

Pre-formed antibodies and complement

Results in vascular damage and thrombosis

What is Acute rejection?

Rejection of a transplanted organ which occurs during the first 3 months

Usually managed successfully by immunosuppression

What mediates Acute rejection?

T-cell mediated immune response.

• Response is targeted at histocompatibility antigens

What is Chronic rejection?

Rejection of a transplanted organ which occurs months or years after transplantation.

Most common type of graft failure and cause is largely unknown with no good treatment

What are the two classes of MHC molecules in humans?

Class I - HLA-A, HLA-B and HLA-C

Class II - HLA-DR, HLA-DQ, HLA-DP

What percent of T-cells are estimated to be able to react with transplanted tissue before it’s even been transplanted?

5% of T-cells before transplantation

What is Direct donor antigen presentation of MHC molecules?

Recognition of intact donor peptide/MHC complexes on donor cells

• Major route of acute rejection

What is Indirect donor antigen presentation?

Recognition of donor proteins after processing and presentation by recipient APCs

• Mainly recipient dendritic cells

What are the pros and cons of immunosuppression treatment following organ transplantation?

Pros

• Hopefully prevents graft failure

Cons

• Toxicity

• Cancer

• Infections

• Lower quality of life

  • Hair loss

  • Tremors

  • Gum overgrowth

What are the two types of drugs used for transplants?

• Maintenance drugs

• Rescue drugs

What are examples of maintenance drugs following transplant?

Azathioprine

Cyclosporin A and Tacrolimus

What does Azathioprine do?

Inhibits DNA synthesis in all cells

What do Cyclosporin A and Tacrolimus do?

Inhibit T-cell activation by blocking IL-2 binding

• Doesn’t affect pre-activated T-cells

What are examples of rescue drugs following transplant?

• High dose steroids

• Mycophenolate mofetil

• Anti-T-cell antibodies

• Highly specific ‘humanized’ chimeric antibodies

What is Graft specific immune tolerance?

Graft survival without the use of immunosuppressive drugs.

Several strategies are known to induce tolerance in model systems but nothing reliable yet

What is an example of a tissue which can evade rejection?

Cornea as it’s immune privileged

What is an example of an organ which can induce (partial) tolerance?

Liver is sometimes tolerogenic

Allows for an individual to slowly withdraw from immunosuppressive drugs