Computational Modelling of Circuits Homework assignment, group 2

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Computational Modelling of Circuits Homework assignment, group 2 Elisa Alasuvanto, Ida Ruuth

Naive T lymphocytes are differentiated into type I T helper (Th1) cells. IFN-γ and IL-12 affect the expression of the Th1 transcription factor T- bet  simulation of how they effect it The process is modelled with MATLAB and the script run_two_loop_model.m

Two-loop model

1. Simulation for with both IL-12 and IFN-γ (wild type cells) The antigen activates the IFN-γ loop  IFN- γ spike in the beginning spike in the Tbet expression At about 20h antigen stimulation ends IL-12 starts to be expressed Expression of Tbet is maintained through the positive control loop

2. Simulation without IFN-γ No IFN-γ No spike in the Tbet expression  Expression of IL-12 starts slower

3. Simulation without IL-12 No IL-12 No IFN-γ The second wave of Tbet doesn’t start so the expression of Tbet must be controlled by IL-12

4. Simulation without IFN-γ or IL-12 The antigen slightly stimulates Tbet Low expression levels Not enough IL-12 to stimulate IFN-γ

References Sequential Polarization and Imprinting of Type 1 T Helper Lymphocytes by Interferon-γ and Interleukin-12, Schulz et al. Immunity, 2009.