Although the concept of stress has earned a bad reputation, it is important to recognize that the adaptive purpose of a physiological stress response is to promote survival during fight or flight. While long-term stress is generally harmful, short-term stress can be protective as it prepares the organism to deal with challenges. This review discusses the immune effects of biological stress responses that can be induced by psychological, physiological, or physical (including exercise) stressors. We have proposed that short-term stress is one of the nature’s fundamental but under-appreciated survival mechanisms that could be clinically harnessed to enhance immunoprotection. Short-term (i.e., lasting for minutes to hours) stress experienced during immune activation enhances innate/primary and adaptive/secondary immune responses. Mechanisms of immuno-enhancement include changes in dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and function as well as local and systemic production of cytokines. In contrast, long-term stress suppresses or dysregulates innate and adaptive immune responses by altering the Type 1–Type 2 cytokine balance, inducing low-grade chronic inflammation, and suppressing numbers, trafficking, and function of immunoprotective cells. Chronic stress may also increase susceptibility to some types of cancer by suppressing Type 1 cytokines and protective T cells and increasing regulatory/suppressor T cell function. Here, we classify immune responses as being protective, pathological, or regulatory, and discuss “good” versus “bad” effects of stress on health. Thus, short-term stress can enhance the acquisition and/or expression of immunoprotective (wound healing, vaccination, anti-infectious agent, anti-tumor) or immuno-pathological (pro-inflammatory, autoimmune) responses. In contrast, chronic stress can suppress protective immune responses and/or exacerbate pathological immune responses. Studies such as the ones discussed here could provide mechanistic targets and conceptual frameworks for pharmacological and/or biobehavioral interventions designed to enhance the effects of “good” stress, minimize the effects of “bad” stress, and maximally promote health and healing.
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I thank current and previous members of my laboratory, particularly, Dr. Kavitha Viswanathan, Dr. Alison Saul, Christine Daugherty, Jean Tillie, and Nicole Taylor, whose work and publications are among those discussed in this manuscript. I also thank my mentors, colleagues, and collaborators for their significant contributions. I am grateful for all the studies that we have done together and the fun that we have had doing them. I am deeply grateful to the following institutions that have been critical for enabling us to conduct our research: The NIH (AI48995, AR46299, CA107498), startup funds from the Carl and Elizabeth Naumann Fund, The Office of Naval Research, The Dana Foundation, and The John D. and Catherine T. MacArthur Foundation.
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Dhabhar, F.S. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res 58, 193–210 (2014). https://doi.org/10.1007/s12026-014-8517-0