Transplantation immunology

Learning outcomes

By the end of this CAL you will be able to:

  • Described the different types of rejection, and their mechanisms, that can affect transplants
  • Understand graft-versus-host disease
  • Describe the mechanisms of immunosuppressive drugs used in transplantation medicine

Introduction Part 1 of 7

Transplantation is the introduction of biological material (organs or tissues) into an organism.

The immune system functions to identify and reject non-self material, requiring therapeutic intervention.

Genetic variation between donor and recipient is identified at:

  • The MHC
  • ‘Minor’ antigens

Types of transplantation Part 2 of 7

©David Dorward, University of Edinburgh 2017 CC BY-SA
Types of transplantation.

Mechanism of recognition Part 3 of 7


Recognition of foreign antigens by host antibody.

T cell-mediated

  • Recognition of foreign MHC by T cells (direct recognition)
  • Recognition of foreign antigens presented by self MHC (indirect recognition)

Acute graft rejection Part 4 of 7

The main barrier to allotransplantation. Occurs to some extent in all transplants.

Develops over weeks – months.


  • Due to T-cell recognition of the transplanted tissue
  • Two main ways in which this is thought to occur –
    • Direct recognition of allo-MHC molecules
    • Indirect recognition of minor transplantation antigen
©David Dorward, University of Edinburgh 2017 CC BY-SA
Direct recognition of donor MHC molecules.
©David Dorward, University of Edinburgh 2017 CC BY-SA
Indirect recognition of minor ‘H’ antigens or allo-MHC.

©Calicut Medical College [CC BY-SA 4.0 (], via Wikimedia Commons
Acute cellular rejection in a transplanted kidney showing lymphocytic tubulitis.

Chronic rejection Part 5 of 7

Occurs months or years after transplant. Characterised by a gradual reduction of blood supply (ischaemia).

No improvement in the incidence of chronic rejection in the past 30 years.

Recent evidence:

  • Type III hypersensitivity
  • Anti-HLA IgG deposition of immune complexes in blood vessels
  • Inflammation

Graft-versus-host disease Part 6 of 7

Graft-versus-host disease (GVHD) is a T cell-mediated process.

Immunocompetent donor cells are transferred into the immunodeficient recipient. Transferred T cells recognise host alloantigens and attack host tissue (e.g. gut, skin, liver).

GVHD occurs in the following:

  • Allogeneic bone marrow transplant
  • Lymphoid-rich solid organ transplant (liver)
  • Blood transfusion if not irradiated to kill the immune cells

It can be minimised by HLA matching.

Immunosuppression Part 7 of 7

Immunosuppression is essential to the success of clinical transplantation.

Agents include:

  • Corticosteroids e.g. prednisone – anti-inflammatory action similar to natural hormones
  • Cytotoxic drugs e.g. azathioprine – kill dividing cells e.g. T cells
  • Immunosuppressive e.g. cyclosporin, tacrolimus – block signal transduction for activation of T cells