Transplant and Immunosuppressive Drugs

Question 1

Describe the different donor-recipient relationships.

Answer 1

• Autologous and syngeneic - donors and recipients genetically identical, no immunological problems - e.g. skin graft using patient’s own skin.
• Allogeneic - same species but genetically different.
• Xenogeneic - different species.

Question 2

What is human leukocyte antigen (HLA)?

Answer 2

The name given by the WHO to the human MHC proteins.

Question 3

Compare and contrast the roles of MHC I and II.

Answer 3

• MHC I - presents fragments of intracellular proteins - T cell receptor on cytotoxic T cells via CD8+.
• MHC II - presents fragments of proteins taken up by endocytosis - T cell receptor on helper T cells via CD4+.

Question 4

Explain the different classifications of graft rejection.

Answer 4

Hyperacute rejection:

• Within hours of transplant, usually in highly vascularised organs e.g. kidney.
• Pre-existing antibodies to MHC-I or ABO antigens.
• Antibodies to MHC can arise from prengancy, blood transfusion or previous transplants.

Acute rejection:

• Inflammation results in activation of organ’s resident dendritic cells.
• T cell response develops due to MHC mismatch.

Chronic rejection:

• Months/years after transplant.
• Blood vessel walls thickened, lumina narrowed, loss of blood supply.
• Correlates with presence of antibodies to MHC-I.

Question 5

What is graft versus host disease (GVHD)?

Answer 5

• Donor immune cells - e.g. from haematopoeitic stem cell transfer - attack the host.
• Can be lethal - best approach is prevention.
• Removing T cells from transplant reduces GVHD.

Question 6

Describe 3 types of immunosuppressants.

Answer 6

1. General immune inhibitors - e.g. corticosteroids.
2. Cytotoxic - kill proliferating lymphocytes - e.g. methotrexate.
3. Inhibit T cell activation - e.g. cyclosporin.