Stress and Immunity

We have all likely noticed that pesky relationship between stress and immune function. It’s finals week and you have a million things to do, with seemingly no time to do it…and of course when you would ideally like to be operating at your best, you start to notice that soreness in your throat escalating. I was aware of the link between stress and immunosuppression, but Sapolsky (2004) helped me to better understand the processes by which stress can contribute to making us sick. As Sapolsky discussed, the most common way stress influences immunity is through the actions of glucocorticoids. When a stress response is initiated the release of glucocorticoids, such as cortisol, influence cell-mediated immunity. For example, glucocorticoids can actually induce programmed cell death of lymphocytes, which are a family of white blood cells that include natural killer cells and T cells. These cells are important for recognizing and destroying infectious agents, like viruses or bacteria. However, stress makes us more vulnerable to these agent’s due to immunosuppression. So, as humans we have the ability to make ourselves more vulnerable these predatory agents merely by conjuring up stress in our heads, such as the belief that we can’t possibly complete all our final assignments by the semesters end. So, there is no coincidence that oftentimes when I finally arrive at home for the holidays, after weeks of stressing and studying, I usually feel myself coming down with a cold. Interestingly, research by Cohen and colleagues (2012) confirmed this relationship between prolonged stress and susceptibility to developing symptoms of the common cold. Importantly, they found that the effects of cortisol on cold risk were not simply due to elevated levels of cortisol, as previously believed, but rather due to glucocorticoid receptor resistance on target immune cells that are involved in termination of the inflammatory response. As such, those individuals who reported a major stressful life event AND had higher glucocorticoid receptor resistance prior to being exposed to rhinovirus, were the ones who ultimately developed a cold. This idea that it is not simply an inverse relationship between increased levels of stress hormones contributing to immunosuppression is also illustrated in the time course of the stress effect on immune function. Turns out, immune function is initially increased during the first few minutes after the onset of stressor and this enhancement is due to the actions of glucocorticoids. As the stress response continues, glucocorticoids then begin to elicit immunosuppression, with the goal of returning immune function back to baseline levels. However, it is only with chronic stress where immunosuppression persists that we are increasingly susceptible to disease.

This association between stress and disease has prompted researchers to explore the effects of stress on a wide variety of diseases and disorders that may be perpetuated by stress-induced immune dysfunction, such as cancer and depression. However, as Sapolsky (2004) notes, it is quite difficult to establish a causal link between stress and disease risk. The first step in making this link is to determine that the individual has been stressed, which is sometimes easier said than done. As a research assistant, I ran a study attempting to measure stress response recovery following the Trier Social Stress Test. The study was well-designed, with one slight unavoidable flaw…the Tufts undergrads didn’t seem to be very phased by being asked to give a mock job interview, or perform a difficult mental arithmetic task. This is a common difficulty in stress research. You want to study the effects of stress, but sometimes you might not even be effectivity eliciting such stress. However, when it comes to immunity and stress, even though you can rest assured that a devastating life event (i.e. loss of a parent/spouse) is likely to effectively cause stress, this stress still may not be ultimately linked to disease outcome. This lack of relationship between stress and immunity was evident in a recent study done by Shoemaker and colleagues (2016) examining the relationship between perceived psychological stress and breast cancer risk. The prospective study followed participants over 6 years, yet did not find any real significant relationship between psychological stress and increased cancer risk. Though these results surprised me, it really made me appreciate the complexities of how stress does and maybe does not affect our bodies. Furthermore, understanding these complexities of the human immune system has lead researchers to really dive into how stress could directly and indirectly be effecting our psychological health. As Hodes and colleagues (2015) explain in their review, pro and anti-inflammatory immune responses may either contribute to or be caused by depression. As they detail, there are complex interrelationships between the sympathetic nervous system, immune system and central nervous system. Thus, further understanding how inflammation and immune function functionally contribute to depression will lead to important insights that may help us to foster effective treatments for those suffering.

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One Response to Stress and Immunity

  1. Profile photo of kcarva02 kcarva02 says:

    This was a great summary of these articles! I agree with you that it is interesting and surprising that research does not support an even stronger link between stress and disease. It would be great to think that we have some semblance of control over whether or not we get become seriously ill, but then again, as so many of us are frequently in chronic stress mode, it might not be such a good thing. It seems like you have a good grasp on this content, and although I could not quite understand it from the articles, I’m wondering how you would describe the reasons why chronic stress (and perhaps as a result chronic colds) do not necessarily lead up to larger disease. There could be of course a biological reason relating to the way our bodies respond to different types of viruses, but I’m wondering if there are any other types of illnesses aside from colds and depression (although not necessarily directly tied to immune functioning) that you would want to consider based on the readings.

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