Information flow within the multi-scale model.

(a) Active migration of agents and passive transport (carried by blood and lymph) of cytokines between compartments representing different organs. See Methods for details of how the intercompartmental flow rates affect the cytokine concentrations. The target organ varies depending on the infection being modeled. The cells depicted in each compartment are only for illustrative purposes. See Methods for more information on the distribution of cells in each compartment. (b) The flow of information between the models during simulations. The intracellular events described by the logical model and the metabolic models are assumed to occur instantaneously. The cytokine concentrations described by the ordinary differential equations are updated every hour, which is the antigen load’s time-resolution. The agent attributes are also updated every hour, but some agent-associated events take multiple hours to complete, such as cell cycling. Red numbers indicate the sequential steps of a complete update at the systemic/cellular time scale. Labels on the arrows list the variables exchanged between models.