Stressed Out: The Impact of Stress on the Immune System

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Hello readers! Sorry for the delayed post, been a hectic last few days getting my life arranged for my jaw surgery on Friday. This week’s question comes to Desiree, who asks “I’ve noticed I get sick more often when I’m really stressed about school. What exactly is happening that causes this and how can I avoid it in the future?” Well Desiree, I think most of us have experienced this phenomenon at one point or another. For some people, it can cause nastier problems than just more frequent colds. But, you’re spot on in your assessment that stress plays tricks on the immune system. Before we get to your question, we should first explore the relevant physiology of stress.

This response, commonly referred to as “fight or flight,” is meant to save your life in the event of an imminent threat or direct attack. It involves many different body systems and is a truly systemic in its effect. The complex interconnectedness is beyond the scope of this article, but the following is the basic rundown. I highly encourage independent research of this topic for a more complete picture.

The stress response is generated in the brain based on sensory input (ie. you see something scary coming towards you). The relevant signals are collected, processed, and travel to one or both of two locations. One is the locus coeruleus, which is responsible largely for initiating the stress response via production of norepinephrine in the brain. The other is the collective Raphe nuclei, which are responsible for, among other things, anxiety and are major serotonin producers in the brain. The subsequent release of neurotransmitters from one or both of these areas of the brain produce the stress response cascade throughout the rest of the body.

The signal produced by the brain has two major parts. First, direct neurological stimulation of the adrenal glands produces adrenaline very quickly. Second, the neurological signal initiated in the locus coeruleus is translated into hormonal signal by the hypothalamus. This then affects the pituitary gland and causes the release of ACTH, or adrenocorticotropic releasing hormone. This hormone enters the blood stream and stimulates the production and release of cortisol into the blood. Together with norepinephrine, which is also released by the adrenal glands along with adrenaline, these molecules are the dominant effectors of the stress response across the body. These molecules also feedback with the brain structures that originate them, creating a very complex web of effects that are not yet fully understood (ex. cortisol has an effect on serotonin production in the Raphe nuclei).

Adrenaline and norepinephrine (collectively a part of a group of molecules known as catecholamines) affect the sympathetic nervous system. It is not important to know what this is for the purposes of this discussion, just know it as one half of the body’s automatic systems. These molecules have a number of functions, namely opening the air passages, altering blood flow throughout the body, slowing digestion, and increasing heart rate. Many of the immediate physical effects you feel during a stressful situation are due to these because their release is much quicker than cortisol. This is also why adrenaline is used during anaphylaxis (allergic reaction), as it can open the narrowed airways and control the potentially deadly swelling.

Cortisol’s role is much different. Like the catecholamines, its job is to keep you alive when fighting for your life, but by a vastly different mechanism. Instead of priming the body to fight or move, cortisol’s main function is to augment its ability to produce and release glucose into the blood stream. It does this by both encouraging the breakdown of more complex storage sugars as well as increasing the processes that convert other molecules, such as proteins and fats, into glucose (known as gluconeogenesis). In other words, it provides the fuel you need to do whatever is necessary to survive, via the slash and burn method if necessary. It also has some inhibitory effects on body systems unnecessary in the short term, such as bone formation. Unfortunately, another one of cortisol’s inhibitory effects makes it the focus of this discussion for the remainder: immune system depression.

While it may seem counterintuitive to curtail the immune system when stressed, the reason for this is fairly simple once we understand the different nature of stress responses. The body has two basic types of stress: acute and chronic. Acute stress, caused by immediate stressors like being attacked or frightened, causes the release all of these molecules in tolerable amounts that temporarily empower us without a tremendous long term downside. Suppressing immune function in acute stress is smart because it holds off inflammation. As anyone who has injured themselves under stress can attest, function can be maintained through the injury until the stressful situation resolves. If the immune system were not held at bay during that time, the injury would quickly become immobile and hinder survival efforts.

However, chronic stress, with which many in graduate school or in dangerous/busy professions are intimately familiar, tips this balance towards the negative. If cortisol levels remain elevated continuously, the effects on the body due to continued suppression can cause a myriad of problems, including more frequent infections.

The immune suppressing function of cortisol has been utilized in medications for decades. Steroids (not the work out kind) such as prednisone and dexamethasone are commonly used in medicine to reduce inflammation, swelling, and the negative effects of autoimmune diseases. However, long term use of these drugs can have similar side effects as chronic stress. Thus, just as long term steroid use is often avoided due to its negative effects on the body, so too should chronic stress be avoided to prevent the same.

Unfortunately, cortisol is a natural part of the body and to attack it pharmacologically could be disastrous. So, stress management techniques are key to controlling its release by controlling the stimuli presented to the brain. Exercising, meditation, massage, acupuncture  and other similar activities have been shown clinically to be beneficial for stress reduction. Given that they have minimal downside and often benefit quality of life, they are also the most advisable methods of stress control. If these prove ineffective, low doses of anti-depressant medications that affect the serotonin and/or norepinephrine in the brain may be helpful for this purpose (as it already is shown to be for people with severe anxiety).

Hope this helps, Desiree! Thank you for the question. As always, I encourage question submission via the link at the top of the page!

Till next time, que le vaya con Dios.

J

Sources:

David DJ, et al. “Neurogenesis-Dependent and -Independent Effects of Fluoxetine in an Animal Model of Anxiety/Depression.” Neuron. 62(4); 2009 May: 453-455.

Laaris L, et al. “Stress-induced alterations of somatodendritic 5-HT1A autoreceptor sensitivity in the rat dorsal raphe nucleus — in vitro electrophysiological evidence.” Fundamental and Clinical Pharmacology. 11(3): 1997 May: 206–214.

Tsigos C, et al. “Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress.” Journal of Psychosomatic Research. 53; 2002: 865 – 871.

Valentino RJ, et al. “The Locus Coeruleus as a Site for Integrating Corticotropin-Releasing Factor and Noradrenergic Mediation of Stress Responses.” Annals of the New York Academy of Sciences. 697; 1993 Oct: 173-188.

Welch WJ, et al. “Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease.” Physiology Review. 72(4); 1992 Oct: 1063-1081.

http://learn.genetics.utah.edu/content/begin/cells/fight_flight/

http://waterhouselab.com/?page_id=302

http://cmhc.utexas.edu/stressrecess/index.html

http://www.mayoclinic.com/health/stress/SR00001

http://dujs.dartmouth.edu/fall-2010/the-physiology-of-stress-cortisol-and-the-hypothalamic-pituitary-adrenal-axis#.Ua17HGTwLIg

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