Interlocked feedback loops balance the adaptive immune response

Lingli Zhou; Fengqing Fu; Yao Wang; Ling Yang; Lingli Zhou; Fengqing Fu; Yao Wang; Ling Yang

doi:10.3934/mbe.2022188

Mathematical Biosciences and Engineering

2022, Volume 19, Issue 4: 4084-4100. doi: 10.3934/mbe.2022188

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Interlocked feedback loops balance the adaptive immune response

1.
School of Mathematical Sciences, Soochow University, Suzhou 215006, China
2.
Center for Systems Biology, Soochow University, Suzhou 215006, China
3.
Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215000, China
4.
State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China

Academic Editor:Evans K. Afenya

Received: 12 November 2021 Revised: 10 January 2022 Accepted: 08 February 2022 Published: 15 February 2022

Adaptive immune responses can be activated by harmful stimuli. Upon activation, a cascade of biochemical events ensues the proliferation and the differentiation of T cells, which can remove the stimuli and undergo cell death to maintain immune cell homeostasis. However, normal immune processes can be disrupted by certain dysregulations, leading to pathological responses, such as cytokine storms and immune escape. In this paper, a qualitative mathematical model, composed of key feedback loops within the immune system, was developed to study the dynamics of various response behaviors. First, simulation results of the model well reproduce the results of several immune response processes, particularly pathological immune responses. Next, we demonstrated how the interaction of positive and negative feedback loops leads to irreversible bistable, reversible bistable and monostable, which characterize different immune response processes: cytokine storm, normal immune response, immune escape. The stability analyses suggest that the switch-like behavior is the basis of rapid activation of the immune system, and a balance between positive and negative regulation loops is necessary to prevent pathological responses. Furthermore, we have shown how the treatment moves the system back to a healthy state from the pathological immune response. The bistable mechanism that revealed in this work is helpful to understand the dynamics of different immune response processes.
- immune response,
- cytokine storm,
- immune escape,
- mathematical model,
- bistable,
- feedback loops
Citation: Lingli Zhou, Fengqing Fu, Yao Wang, Ling Yang. Interlocked feedback loops balance the adaptive immune response[J]. Mathematical Biosciences and Engineering, 2022, 19(4): 4084-4100. doi: 10.3934/mbe.2022188

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Abstract

Adaptive immune responses can be activated by harmful stimuli. Upon activation, a cascade of biochemical events ensues the proliferation and the differentiation of T cells, which can remove the stimuli and undergo cell death to maintain immune cell homeostasis. However, normal immune processes can be disrupted by certain dysregulations, leading to pathological responses, such as cytokine storms and immune escape. In this paper, a qualitative mathematical model, composed of key feedback loops within the immune system, was developed to study the dynamics of various response behaviors. First, simulation results of the model well reproduce the results of several immune response processes, particularly pathological immune responses. Next, we demonstrated how the interaction of positive and negative feedback loops leads to irreversible bistable, reversible bistable and monostable, which characterize different immune response processes: cytokine storm, normal immune response, immune escape. The stability analyses suggest that the switch-like behavior is the basis of rapid activation of the immune system, and a balance between positive and negative regulation loops is necessary to prevent pathological responses. Furthermore, we have shown how the treatment moves the system back to a healthy state from the pathological immune response. The bistable mechanism that revealed in this work is helpful to understand the dynamics of different immune response processes.

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