title: Understanding the roles of activation threshold and infections in the dynamics of autoimmune disease.
abstract: Onset and development of autoimmunity have been attributed to a number of factors, including genetic predisposition, age and different environmental factors. In this paper we discuss mathematical models of autoimmunity with an emphasis on two particular aspects of immune dynamics: breakdown of immune tolerance in response to an infection with a pathogen, and interactions between T cells with different activation thresholds. We illustrate how the explicit account of T cells with different activation thresholds provides a viable model of immune dynamics able to reproduce several types of immune behaviour, including normal clearance of infection, emergence of a chronic state, and development of a recurrent infection with autoimmunity. We discuss a number of open research problems that can be addressed within the same modelling framework.
authors.affiliation: Department of Mathematics, University of Sussex, Falmer, Brighton BN1 9QH, UK. Electronic address: k.blyuss@sussex.ac.uk.
authors.forename: K B
authors.initials: KB
authors.lastname: Blyuss
authors.affiliation: School of Cellular and Molecular Medicine & School of Clinical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK. Electronic address: l.nicholson@bristol.ac.uk.
authors.forename: L B
authors.initials: LB
authors.lastname: Nicholson
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D015551:Autoimmunity; D002908:Chronic Disease; D020022:Genetic Predisposition to Disease; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D013269:Stochastic Processes; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
keywords: Autoimmunity; Mathematical model; Virus