title: Modelling and Simulation of the Dynamics of the Antigen-Specific T Cell Response Using Variable Structure Control Theory.
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.
authors.affiliation: School of Engineering and Digital Arts, University of Kent, Canterbury, Kent, United Kingdom, CT2 7NT, United Kingdom.
authors.forename: Anet J N
authors.initials: AJ
authors.lastname: Anelone
authors.affiliation: School of Engineering and Digital Arts, University of Kent, Canterbury, Kent, United Kingdom, CT2 7NT, United Kingdom.
authors.forename: Sarah K
authors.identifier: http://orcid.org/0000-0003-3451-0650
authors.initials: SK
authors.lastname: Spurgeon
mesh_terms: D000465:Algorithms; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003198:Computer Simulation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D007156:Immunologic Memory; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000941:Antigens; D018984:Epitopes, T-Lymphocyte