Modelling and Simulation of the Dynamics of the Antigen-Specific T Cell Response Using Variable Structure Control Theory

PLoS One. 2016 Nov 18;11(11):e0166163. doi: 10.1371/journal.pone.0166163. eCollection 2016.

Abstract

Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. This paper hypothesizes strong synergies between this existing work and the dynamical behaviour of engineering systems with a variable structure control (VSC) law. These findings motivate the interpretation of the immune system as a variable structure control system. It is shown that dynamical properties as well as conditions to analytically assess the transition from health to disease can be developed for the specific T cell response from the theory of variable structure control. In particular, it is shown that the robustness properties of the specific T cell response as observed in experiments can be explained analytically using a VSC perspective. Further, the predictive capacity of the VSC framework to determine the T cell help required to overcome chronic Lymphocytic Choriomeningitis Virus (LCMV) infection is demonstrated. The findings demonstrate that studying the immune system using variable structure control theory provides a new framework for evaluating immunological dynamics and experimental observations. A modelling and simulation tool results with predictive capacity to determine how to modify the immune response to achieve healthy outcomes which may have application in drug development and vaccine design.

MeSH terms

  • Algorithms
  • Animals
  • Antigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Computer Simulation
  • Epitopes, T-Lymphocyte / immunology*
  • Host-Pathogen Interactions / immunology
  • Immunologic Memory
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Models, Immunological*
  • T-Lymphocytes / immunology*

Substances

  • Antigens
  • Epitopes, T-Lymphocyte

Grants and funding

AJNA was funded by a scholarship from The Ministry of Higher Education and Scientific Research of the Republic of Cote d’Ivoire. This grant contributed to the payment of his PhD tuition fees and living expenses to work on the immune system and this work will be returned as an output of his doctoral research. SKS was funded by an EPSRC (https://www.epsrc.ac.uk/) Research Grant reference number EP/J018295/1 entitled Finite time orbitally stabilizing synthesis of complex dynamic systems with bifurcations with application to biological systems. This grant contributed to the payment of her salary to work on the immune system and this work will be returned as an output of the project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.