Robust model matching control of immune systems under environmental disturbances: dynamic game approach

J Theor Biol. 2008 Aug 21;253(4):824-37. doi: 10.1016/j.jtbi.2008.04.024. Epub 2008 Apr 29.


A robust model matching control of immune response is proposed for therapeutic enhancement to match a prescribed immune response under uncertain initial states and environmental disturbances, including continuous intrusion of exogenous pathogens. The worst-case effect of all possible environmental disturbances and uncertain initial states on the matching for a desired immune response is minimized for the enhanced immune system, i.e. a robust control is designed to track a prescribed immune model response from the minimax matching perspective. This minimax matching problem could herein be transformed to an equivalent dynamic game problem. The exogenous pathogens and environmental disturbances are considered as a player to maximize (worsen) the matching error when the therapeutic control agents are considered as another player to minimize the matching error. Since the innate immune system is highly nonlinear, it is not easy to solve the robust model matching control problem by the nonlinear dynamic game method directly. A fuzzy model is proposed to interpolate several linearized immune systems at different operating points to approximate the innate immune system via smooth fuzzy membership functions. With the help of fuzzy approximation method, the minimax matching control problem of immune systems could be easily solved by the proposed fuzzy dynamic game method via the linear matrix inequality (LMI) technique with the help of Robust Control Toolbox in Matlab. Finally, in silico examples are given to illustrate the design procedure and to confirm the efficiency and efficacy of the proposed method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computer Simulation*
  • Fuzzy Logic
  • Game Theory*
  • Humans
  • Immune System / physiology*
  • Immunity, Innate
  • Infections / immunology*
  • Matched-Pair Analysis
  • Models, Immunological*