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The immune system represents a complex sophisticated network based on specialized immune cells coordinated by fine tuned signaling pathways. The presence of T-lymphocytes, in particular T-helper-cells, is in this context of great importance, but in some medical issues their immunological implication must be repressed. For example, the appearance of graft rejection is a major problem in transplantation medicine. In order to suppress the causative immunological reaction, the pharmaceuticals cyclosporin A (CsA) and tacrolimus (FK506) are in use as standard drugs. Blocking the relevant signaling cascade in activated T-cells and in this way also modulating the calcium influx passing through the calcium-release activated channel (CRAC) in the plasma membrane of T-lymphocytes, both immunomodulators affect electrophysiological processes.With regard to the significance of electrophysiology in coherence with immunological interactions and pharmacological issues, a mathematical modeling approach is demanded in order to understand the associated ion dynamics in T-lymphocytes, embedded in a systems immunological context. Building on the results from experimental data out of electrophysiological measurements, the intended T-cell model will include single transmembrane protein characteristics in order to represent ion dynamics pattern with the focus on calcium levels on the origin of the CRAC channel under different circumstances. Technically, the background of the projected in silico investigation of T-cell electrophysiology is based on mathematical modeling of the electrophysiology of the pancreatic beta-cell [1]. Starting the simulation with a resting T-cell, the model will then be extended regarding the electrophysiological changes following T-cell activation. Further, the modeling approach will finally provide a starting point for in silico studies relating to the therapeutic immune modulation of ion-conducting proteins in T-lymphocytes.[1] Meyer-Hermann, Michael E. The Electrophysiology of the s-Cell Based on Single Transmembrane Protein Characteristics. Biophysical Journal 93, 2007: 2952-2968 |
