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Interlocked feedback loops balance the adaptive immune response.

Lingli Zhou1,2, Fengqing Fu3,4, Yao Wang1,2

  • 1School of Mathematical Sciences, Soochow University, Suzhou 215006, China.

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|March 28, 2022
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Summary

This study models adaptive immune responses, revealing how feedback loops create distinct states like cytokine storms or normal immunity. Understanding these dynamics, particularly bistability, is key to preventing pathological immune responses and guiding treatments.

Keywords:
bistablecytokine stormfeedback loopsimmune escapeimmune responsemathematical model

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Area of Science:

  • Immunology
  • Mathematical Biology
  • Systems Biology

Background:

  • Adaptive immune responses are crucial for pathogen defense but can dysregulate, causing conditions like cytokine storms and immune escape.
  • T cell proliferation, differentiation, and apoptosis are key to maintaining immune homeostasis, but disruptions lead to pathology.

Purpose of the Study:

  • To develop a qualitative mathematical model of immune system feedback loops.
  • To investigate the dynamics of normal and pathological immune responses, including cytokine storms and immune escape.
  • To understand the role of feedback loop interactions in immune system behavior.

Main Methods:

  • Development of a qualitative mathematical model representing key immune feedback loops.
  • Simulation of the model to reproduce known immune response behaviors.
  • Stability analysis to characterize different dynamic states (monostable, bistable).

Main Results:

  • Model simulations accurately reflected various immune response processes, especially pathological ones.
  • The interaction of positive and negative feedback loops was shown to generate irreversible bistable, reversible bistable, and monostable states.
  • These states correspond to distinct immune phenomena: cytokine storm (irreversible bistable), normal immune response (reversible bistable), and immune escape (monostable).

Conclusions:

  • Switch-like immune system activation is based on bistable mechanisms.
  • A balance between positive and negative regulatory feedback loops is essential for preventing pathological immune responses.
  • The identified bistable mechanisms provide insights into immune response dynamics and potential therapeutic strategies for restoring healthy states.