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

2. 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

3. Two-loop model

4. 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

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

6. 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

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

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