Now take a deep breath and calm your immune system.

Throughout the COVID-19 outbreak we witnessed the good (rapid vaccine development and production, alongside the amazing work done by our healthcare workers), the bad (misinformation spreading) and the ugly (higher mortality rates due to COVID-19 infection and post-infection COVID-19 syndrome). While, during the peak of crisis researchers prioritized the treatments and side effects, now we can also focus on the psychological side. Apart from the horrid experience of disease and deaths, stress was also a by-product of the implementation of lockdown by several countries.

What is stress?

It is difficult to exactly define stress as each one of us perceives situations differently. The process remains the same: a trigger initiates a reaction in the brain that in turn activates a physiological or biological stress response to allow the organism to deal with the stress trigger.

Stress can activate one of the two neurological pathways: 1. SNS (sympathetic nervous system) and 2. HPA axis (hypothalamic-pituitary-adrenal) and most of our immune cells have receptors for stress hormones resulting from these pathways. Our SNS is activated and induces higher secretions of adrenaline and noradrenaline, which increase levels of proinflammatory cytokines IL-1, IL-6 and TNF-alpha causing inflammation. On the other hand, stress induced arginine vasopressin and corticotropin-releasing hormone synergistically activates HPA axis into secreting adrenocorticotropic hormone, followed by secretions of glucocorticoids, especially cortisol. Cortisol, in the end, will have a direct effect on the immune system by: 1. reducing the number and activity of circulating immune cells, 2. inhibiting the production of pro-inflammatory mediators and cytokines, 3. inhibiting antigen presentation, and 4. reducing the proliferation of lymphocytes. All of this “fight or flight” maneuver will prepare our body for possible damage (like getting cut), but these reactions are not always necessary, like the time when you are on the stage for a public speech.

Stress can impair our immune system and leave us more vulnerable. However, the implication that stress can induce diseases is not news, in fact, 200 AD Galen connected melancholic women with higher cancer incidence.

Stress can be divided into acute and chronic. Acute stress has been mainly associated with enhancing immune and inflammatory conditions, while chronic has mostly been immunosuppressive. A study involving students during their examination time detected higher antibody titers to dormant viruses like Epstein-Bar virus, Herpes Simplex virus and Cytomegalovirus prior to the exam, but the levels returned to normal after the exam was over. Such acute stress-induced enhanced immunity could be harmful if it exacerbates preexisting inflammatory and/or autoimmune diseases. Contrary to this, in chronic stress, one study reported increased susceptibility to the common cold. Reasons behind this could be that continuous stress exhausts the adrenal gland or that immune cells receptors become “immune” to cortisol. Such responses can sometimes be beneficial, e.g. in preventing systemic inflammatory response syndrome (SIRS).

Further, stress can also be divided on whether it involves intrapersonal or interpersonal relationships:

People often pondering about negative situations from the past had increased inflammation due to high CRP-c reactive protein levels and immune cells. Emotional regulation significantly influences immune system as people who could adapt to situations had lower inflammation contrary to people suppressing their emotions. Optimistic people are also prone to have less inflammation and a better response to vaccination.

Interpersonal relationships can modulate our immune system responses as well. Couples who had more conflict during their marriage had higher levels of inflammation markers such as IL-6 and TNF-alpha. On the other hand, supportive relationships offer higher immunoprotection. An interesting study demonstrated that people who had an hour-long warm physical contact, such as hugging or kissing, had lower levels of IFN-gamma compared it to a control group that was reading in separate rooms. On the opposite spectrum, loneliness, one of the dominant mental consequences of pandemic, tend to lower immunity as shown by a study measuring antibody responses to an influenza vaccine. One doesn’t need to be in a relationship to enhance their immunity, when we know that there is nothing else like a mother’s love. On birth, mother’s antibodies transferred to us confer the first protection that we have from the world. However, children devoid of motherly love can contain high levels of CRP even 20 years after the initial maltreating experience. An interesting study in the Phillippines found that high levels of CRP induced by childhood trauma can be reversed if the children were exposed to a microbial-rich environment early in their life. Guess, the good bacteria will always be there for you.

In summary, stress can impair our body’s ability to protect us. Unfortunately, stress is not always easy to avoid, especially in today’s busy, competitive, pandemic ridden world. Often, we don’t know the previous stressors some people experienced, and we all don’t perceive stress in the same way. Now that we know that supportive relationships can reduce the negative impact of stress and bring balance to our immune system, go take time out with your loved ones, call that friend whom you have been meaning to talk to for days, and don’t forget to be kind to one another.

Sources:

Dhabhar FS. Acute stress enhances while chronic stress suppresses skin immunity. The role of stress hormones and leukocyte trafficking. Ann N Y Acad Sci. 2000;917:876-93. doi: 10.1111/j.1749-6632.2000.tb05454.x.

Khansari DN, Murgo AJ, Faith RE. Effects of stress on the immune system. Immunology Today. 1990 May;11(5):170-175. DOI: 10.1016/0167-5699(90)90069-l.

Dantzer R, Kelley KW. Stress and immunity: an integrated view of relationships between the brain and the immune system. Life Sci. 1989;44(26):1995-2008. doi: 10.1016/0024-3205(89)90345-7.

Pruett SB. Stress and the immune system. Pathophysiology. 2003 May;9(3):133-153. doi: 10.1016/s0928-4680(03)00003-8.

Leonard B. Stress, depression and the activation of the immune system. World J Biol Psychiatry. 2000 Jan;1(1):17-25. doi: 10.3109/15622970009150562.

Reed RG, Raison CL. Stress and the immune system. Env Influences on the Immune System. 2016;97-126. DOI: 10.1007/978-3-7091-1890-0_5

Article author: Ines Poljak. Ines is a MSc student at University of Copenhangen and works on multiple myeloma bone disease. She worked in several clinical laboratories before committing herself completely to research.

Editor: Sutonuka Bhar. Sutonuka is a PhD candidate at the University of Florida. Her work focuses on host immune responses against viruses and bacterial membrane vesicles.

Check out Antibuddies’ blog post “Now take a deep breath and calm your immune system.”

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