Effects of viral and cytokine delays on dynamics of autoimmunity

TL;DR

This paper develops a mathematical model to study how delays in viral infection response and cytokine signaling influence the development of autoimmunity, highlighting the importance of initial conditions and parameter values.

Contribution

It introduces a new delay differential equation model incorporating T cells, Tregs, and cytokines to analyze autoimmune disease dynamics.

Findings

Delays can lead to different immune outcomes, including autoimmunity or clearance.

Initial infection levels significantly influence disease progression.

Parameter regions associated with autoimmune behavior are identified.

Abstract

A major contribution to the onset and development of autoimmune disease is known to come from infections. An important practical problem is identifying the precise mechanism by which the breakdown of immune tolerance as a result of immune response to infection leads to autoimmunity. In this paper, we develop a mathematical model of immune response to a viral infection, which includes T cells with different activation thresholds, regulatory T cells (Tregs), and~a cytokine mediating immune dynamics. Particular emphasis is made on the role of time delays associated with the processes of infection and mounting the immune response. Stability analysis of various steady states of the model allows us to identify parameter regions associated with different types of immune behaviour, such as, normal clearance of infection, chronic infection, and autoimmune dynamics. Numerical simulations are used to illustrate different dynamical regimes, and to identify basins of attraction of different dynamical states. An important result of the analysis is that not only the parameters of the system, but also the initial level of infection and the initial state of the immune system determine the progress and outcome of the dynamics.