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The Effects of Stress on the Immune System

November 18, 2020 • 3 min read

Homeostasis is the state of maintaining one’s internal environment to be constant in the face of a changing environment.1 Stress is anything that disrupts that. Those disruptions can come from physical, psychological, or emotional disturbances, but they all evoke a physiological response. Stress is an important adaptive mechanism when short-lived and managed, but stress that is severe or on-going can disrupt proper immune function and lead to higher incidence of illness and disease.

The Immune System

The immune system is a complex association of cells, enzymes, tissues, and organs that work together to protect the body from injury, infection, and disease. There are non-specific components (innate) that serve as immediate protection and specific components (adaptive) that proliferate and become active over the course of days. The adaptive response involves both cellular immunity (active against intracellular invaders) and humoral immunity (active in extracellular spaces and responsible for antibody production).

The Stress Response

When presented with a stressor, the body induces an adaptive response in an attempt to promote survival. The stress response is mainly controlled by two related but independent axes:  the sympatho-adreno-medullary (SAM) axis and the hypothalamus-pituitary-adrenal (HPA) axis. In the initial stages of a stress response, the SAM axis signals the release of catecholamines, norepinephrine and epinephrine (also known as noradrenaline and adrenaline). These catecholamines are released within seconds and are responsible for effects associated with the fight of flight response, including preparing the immune system for protection from possible wound or injury. In this regard, acute stress is pro-inflammatory, standing ready to fight against pathogens or other foreign invaders through increased activity of immune cells in the bloodstream.

At the same time as the SAM axis initiates a response, the HPA axis is activated, resulting in an increase in cortisol production. Cortisol generally increases approximately 15 minutes after the onset of stress and remains elevated for several hours.2 In the initial stages of the stress response, cortisol is generally recognized as anti-inflammatory and may ameliorate the pro-inflammatory effects of the catecholamines so as to prevent overactivation that could cause damage to the body’s own tissues.

The total effect of stress on the immune system depends on the length and severity of the stressor. A meta-analysis of more than 300 articles on the relationship between psychological stress and the immune system showed that acute stressors (lasting minutes) were associated with an upregulation of innate immunity and partial down-regulation of specific immunity. Real-life short-term challenges (such as exams) tended to suppress cellular immunity while preserving humoral immunity, and chronic stressors tended to suppress both cellular and humoral measures.3

The upregulation of innate immunity during acute stress makes sense for the protection of the body from injury or infection in the context of being in immediate danger. A rapid recruitment of immune cells to the site of injury could be important for survival. However, chronic stress is associated with a drop in almost all measures of immune function and leads to an increased risk of chronic infections, autoimmune challenges, and cancers.3

Caregiving has been used as a model for studying the stress response, and several studies have shown an association between caregivers and dysregulated immune function.  In one study of those caring for family members with dementia there was a significant decrease in the ability to produce antibodies to the influenza vaccine after six weeks, with only 38 percent of caregivers able to mount an antibody response as compared to 60 percent of the control group.4

Chronic stress is also associated with impaired control of latent viruses such as herpes simplex virus -1 and -2 (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). A latent virus is one that remains dormant after initial infection but is never fully cleared from the host. It has been shown that times of stress can reactivate these viruses.5 In one cross-sectional study of older family dementia caregivers, there were higher antibody titers to CMV and HSV-1 as compared to non-caregiving controls.6 Antibody titers provide approximations of virus reactivation. Another longitudinal study of older adults caring for a spouse with dementia had larger increases in EBV-VCA immunoglobulin G (IgG) – which appears during the acute phase of infection – over a 13-month period compared to non-caregiving older adults.7

As in all of physiology, the susceptibility of stress related immune effects varies from person to person and can depend on differences in genetics, coping strategies, social support, and personality. The good news is that adaptive strategies may function to reduce the impact of stress on the immune system. Several studies have reported that mindfulness techniques and even one’s attitude toward a situation can diminish the adverse immune effects caused by stress. A non-randomized study of recently diagnosed breast cancer patients showed that those who engaged in a mindfulness-based stress reduction program experienced beneficial effects on immune function.8  And a study of 40 HIV-infected men residing in South Florida that were hit hard by Hurricane Andrew found that higher levels of optimism were related to lower EBV titers and greater cellular immunologic control over herpes virus-6 and EBV.9

Stress is an unavoidable part of life, but controlling the length and severity can help manage the impact on immune health. Mindfulness techniques and other coping strategies can play a role in maintaining proper immune function and may be important for optimal immune protection.

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  1. Schneiderman N, Ironson G, Siegel SD. Stress and health: psychological, behavioral, and biological determinants. Annu Rev Clin Psychol. 2005;1:607-628. doi:10.1146/annurev.clinpsy.1.102803.144141
  2. Hannibal KE, Bishop MD. Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation. Phys Ther. 2014;94(12):1816-1825. doi:10.2522/ptj.20130597
  3. Segerstrom SC, Miller GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull. 2004;130(4):601-630. doi:10.1037/0033-2909.130.4.601
  4. Gouin JP, Hantsoo L, Kiecolt-Glaser JK. Immune dysregulation and chronic stress among older adults: a review. Neuroimmunomodulation. 2008;15(4-6):251-259. doi:10.1159/000156468
  5. Avgousti DC, Weitzman MD. Stress Flips a Chromatin Switch to Wake Up Latent Virus. Cell Host Microbe. 2015;18(6):639-641. doi:10.1016/j.chom.2015.11.011
  6. Kiecolt-Glaser JK, Dura JR, Speicher CE, Trask OJ, Glaser R. Spousal caregivers of dementia victims: longitudinal changes in immunity and health. Psychosom Med. 1991 Jul-Aug;53(4):345-62. doi: 10.1097/00006842-199107000-00001. PMID: 1656478.
  7. Glaser R, Kiecolt-Glaser JK. Chronic stress modulates the virus-specific immune response to latent herpes simplex virus type 1. Ann Behav Med. 1997 Spring;19(2):78-82. doi: 10.1007/BF02883323. PMID: 9603681
  8. Witek-Janusek L, Albuquerque K, Chroniak KR, Chroniak C, Durazo-Arvizu R, Mathews HL. Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer. Brain Behav Immun. 2008;22(6):969-981. doi:10.1016/j.bbi.2008.01.012
  9. Cruess, S., Antoni, M., Kilbourn, K. et al. Optimism, distress, and immunologic status in HIV-infected gay men following hurricane andrew. Int. J. Behav. Med 7, 160–182 (2000). https://doi.org/10.1207/S15327558IJBM0702_5

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