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Yagmur Idil Ozdemir, January 21 2021

How does stress affect our immune system?

Chronic stress causes far reaching deleterious effects in our immunity. According to the American Psychological Association, chronic stress impairs the communication between our immunity and systems involved in regulating our stress response. (American Psychological Association et al., 2018; Morey et al., 2015; Segerstrom & Miller, 2004).

In a healthy response to stress, anything our body perceives as a stressor acts on sympathetic fibers all around our body that communicate with our lymphoid tissues, which regulate immunity. Depending on the level of stress fibers can release a range of substances that bind to the white cells situated in the lymphoid tissue, which modulate the responsiveness of these cells. Hormones such as epinephrine, norepinephrine and cortisol that get released from the  first responders to stress (brain structures such as hypothalamic pituitary adrenal axis and sympathetic norepinephrine medullary axis) also directly act on these white blood cells for similar effects (Mariotti, 2015; Segerstrom & Miller, 2004).

A generalised immune function is called natural immunity, and in a healthy immune system, white blood cells such as neutrophils and macrophages create an inflammatory response at the site of damage, and communicate with proteins called cytokines to promote wound healing. Natural immunity gets accidentally activated in the case of allergies or auto-immune diseases (Segerstrom & Miller, 2004). Chronic stress dysregulates the activation of natural immunity by affecting these cells and proteins. 

The highly accepted theory in the field that defines how stress affects immunity was proposed by Dhabar and McEwen in 1997, called the biphasic model of stress. The theory states that acute stress is helpful by increasing natural immunity, but sustained stress that gets chronic is unhelpful as it suppresses natural immunity through altering cytokine production (Dhabhar & Mcewen, 1997). This increases vulnerability to certain infectious and autoimmune diseases which can be even more problematic with age and immunocompromised systems, for example by making individuals less responsive to vaccinations (Segerstrom & Miller, 2004).

 The chart illustrates the overall effects of stress on periphery networks, from Mariotti, 2015.

Bae and colleagues (2019) state that chronic stress exposure results in, besides autoimmune diseases, cancers and chronic infection through its effects in the immune signaling networks (Bae et al., 2019). Some support for these findings come from Di Rosso and colleagues showing chronic stress leads to lessened protection to tumor (Di Rosso et al., 2018). Terry and colleagues similarly show that stress leads to resistance to cell-mediated cytotoxicity which creates a general immune suppression (Terry et al., 2017)

A metaanalysis conducted by Segerstrom and Miller shows mounting evidence in line with the stress model that acute stress enhances natural immunity, with changes in the amount and functionality of white cells which increase natural immunity, and that these effects do not change for the type or duration of the stressor applied, meaning our natural immunity will be enhanced when we experience any transient stress (Segerstrom & Miller, 2004). This is why it is important to keep in mind that stress, where it develops naturally in reaction to a situation and can be mitigated naturally, can be a helpful tool to deal with the demands of the environment. For chronic stress, they show that exposure to sustained stress creates adverse effects on almost all functional measures of the immune cells.

Holzer and his team shows that lesser immune function caused by stress in turn reinforces more stress, thus damaging our immunity even more (Holzer et al., 2017). They identify gastrointestinal tract as a site in which this lessened immunity affects stress coping and resilience systems in the brain, by inflammation in the intestinal tract leading to distinct signaling in the gut-brain axis. These results show that stress creates a vicious cycle of damaging our immune system, which must be broken with interventions.


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Yagmur Idil Ozdemir

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