Question

Please write and/or draw the calineurin pathway in T-cells AND also the mechanism of calcineurin inhibitors.

You can choose to use both words and pictures.

Answer 1

Cytoplasm NFAT Calcium-Calmodulin dependent pathway dephosphorylation FK506 Calcineurin FK binding protein Dephosphorylated NFAT CSA Nucleus Cyclophylin Gene (e.g. IL-2) T lymphocyte

When the antigen presenting cell interact with T cell there is an increase in cytoplasmic level of calcium. Tjis will then activates Calcineurin by binding to a regulatory subunit and activating calmodulin binding. The transcription factor NFATS that are induced by Calcineurin and that will transcripts IL-2 genes. IL-2 will activate T helper lymphocytes and induces the production of cytokines.

Antigen Helper T-cell Ca²+ Calcineurin Tacrolimus FKBP-12 NF-ATC NF-ATc/n IL-2 transcription Immunosuppression

Calcineurin inhibitors exert their immunosuppressive action by reducing IL-2 production and IL-2 receptor suppression. This will lead to reduction in T cell activation.

Tacrolimus is an inhibitor of Calcineurin. Above figure shows the mechanism of Calcineurin inhibitor.