Transplantation immunology
Author(s): Tim Kendall and David Dorward
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
Mechanism of recognition Part 3 of 7
Antibody-mediated
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.
Mechanism
- 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
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