Transplant immunology

Question 1

Hyperacute

Answer 1

Within minutes
Antibody mediated, type II
Because of the presence of preformed anti donor antibodies in the transplant recipient

Features: occludes graft vessels, causing ischemia and necrosis

Question 2

Acute

Answer 2

Weeks later

Cell-mediated due to CTLs reacting against foreign MHCs
Reversible with immunosuppressants (cyclosporin, muromonab -CD3)

Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate

Question 3

Chronic

Answer 3

Months to years

Class I MHC nonself is perceived by CTL as class I MHC self presenting non self antigen

Irreversible, T cell and antibody mediated vascular damage (Obliterative vascular necrosis); fibrosis of graft tissue and blood vessels

Question 4

GVH

Answer 4

Grafted immunocompetent T cells proliferate in the irradiated immunocompromised disease host and reject cells with foreign proteins, resulting in severe organ dysfunction.

Maculopapular rash, jaundice, HSM, and diarrhea

Usually in bone marrow and liver transplant (organs rich in lymphocytes), potentially beneficial in bone marrow transplant.

Question 5

Cyclosporin

Answer 5

Binds cyclophilin and blocks the differentiation and activation of T cells by inhibiting calcineurin, thus preventing the production of IL2 and its receptor

Suppresses organ rejection after transplant, selected autoimmune disorders

Toxicity: renal, HTN, hyperlipidemia, hyperglycemia, tremer, gingival hyperplasia, hirsutism

Question 6

Tracrolimus

Answer 6

Similar to cyclosporin, binds to FK-binding protein, inhibiting calcineurin and secretion of IL2 and other cytokines

Potent immunosuppressive used in organ transplant recipient.

Toxicity: similar to cyclosporine except no gingival hyperplasia and hirsutism

Question 7

Azathioprine

Answer 7

Antimetabolite precursor of 6-mercaptopurine that interferes with the metabolism and synthesis of nucleic acid. Toxic to proliferating lymphocytes.

Kidney transplant, autoimmune disorders (including glomerulonephritis and hemolytic anemia)

Toxicity: bone marrow suppression, active metabolite mercaptopurine is metabolized by XO; thus toxicity effect may be increased by allopurinol

Question 8

Muromonab-CD3 (OKT3)

Answer 8

Antibody that binds to CD3 (epsilon chain) on the surface of the T cells. Blocks cellular interaction with CD3 protein responsible for T cell transduction

Immunosuppression after kidney transplant

Toxicity: cytokine release syndrome, hypersensitivity reaction.