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Stress and Immune Response

What is the definition of stress and how is it related to the immune response?

Stress is a physical, chemical or emotional factor that causes bodily or mental tension and may be a factor in disease causation. Stress can be divided by time of exposure (chronic stress), effects it has upon the person (eustress) or according to the origin of the stress (workplace). Chronic stress is a persistent stress which can lead to illness and mental disorder. Eustress is a positive stress that can lead to improved long-term functioning. Workplace stress is a sub-type of chronic stress that is induced by employment. Stress can manifest itself in both physiological and psychological ways. Stress can either boost or suppress the immune response and system. It terms of sympathetic response, stress can prompt the immune system to ready itself in response to insults such as: Injuries, scrapes, infection, bites or attacks. Chronic stress may suppress the immune system via the cellular level and later the broader immune function. The longer and more severe the stress, the more skewed the immune system diverges from status quo and the more susceptible the body is to infection and disease. (1) Specific examples of stress and the different responses they induce: There are different categories of stress according to Sergerstrom and Miller who published a paper on the subject in 2004. Some are based on time while others are based on the effects it has on a person. These are: •	Acute, time limited stressors: 	Public speaking or mental math. These stressors prepare the body for the fight or flight response which prompts the immune system to be ready for bites, scrapes and other types of injuries. •	Brief naturalistic stressors: 	Taking an exam for example, enhances quick, energy efficient natural immunity. •	Stressful event sequences: 	Losing a spouse or a natural disaster. There seems to be a weak correlation with these and the immune response and further study is recommended. •	Chronic stressors: 	Injury resulting in permanent disability or caring for a disabled spouse. •	Distant stressors: 	Traumatic experiences that occurred in the past like combat trauma or being a prisoner of war. The authors of the paper found that the most chronic stressors or those that have a long lasting effect on the person have the most global suppression of immunity. In other words the longer the stress the more the immune system is shifted from adaptive to detrimental. At first the cellular immunity is affected then after a certain amount of time the whole system is affected. The authors are satisfied that their meta-analysis confirms the value of looking at stressors and immunity in greater detail to learn the mechanisms underlying the body’s response to stress. In this case, defining stressor types and examining natural versus specific and cellular versus humoral immune responses turned up useful information. (7)

Specific role that stress induces in the immune response Chronic stressors have been proven to affect the immune response, making the person under stress prone to medical illness especially viral infections. Unfortunately the mechanisms of how stress affects the immune system are yet to be elucidated. Several approaches have been proposed and tested over the years, and even though a final conclusion has not yet been reached, there is one hypothesis which may explain how stress affects the immune system. This hypothesis works with the hypothalamic-pituitary-adrenocortical (HPA) axis, and the release of cortisol induce by stress. It Is known that in leukocytes, cortisol ligates cytosolic glucorticoid receptors (GR), and these complexes translocate to the nucleus, where they inhibit activity of several immunoregulatory transcription control pathways, including nuclear-factor kappa-B (NF-κB), activator-protein 1 (AP-1), and JAK-STAT factors (2). These transcriptions factors are involved in the regulation of immune response and inflammation. So the actions of cortisol should ameliorate or inhibit inflammatory response, this seems paradoxical since inflammation is a key pathogenic mechanism in many infectious, autoimmune, cardiovascular, and psychiatric diseases (3–5). However it has been found that this is true in the presence of acute stress, this response is beneficial to the person, but in presence of chronic stress is have been observe that an inflammatory state governs even though cortisol is being release more continuously. According to Webster et all, chronic stressors elicit sustained elevations in cortisol that, over time, prompt immune cells to undergo a compensatory downregulation of glucorticoid receptors activity. This adaptively limits cortisol’s ability to further dampen immune responses. However, in cells such as monocytes that are tightly regulated by cortisol, this dynamic also diminishes the potency of an important hormonal constraint, which acts to tonically inhibit NF-κB, AP-1, and other pro-inflammatory transcriptional control pathways (2). The long-term result of this process is mild, low-grade inflammation, fostered by monocytes that have acquired resistance to cortisol. The resulting persistent inflammation is hypothesized to contribute to the infectious, autoimmune, and cardiac diseases to which stress is linked.(5) This means that what is causing the inflammatory state is the down regulation of the glucocorticoids receptor, which after a long chronic exposition to cortisol due to elevated stress become unresponsive to the anti-inflammatory message of cortisol. Recent work done by Gregory E. Miller et all supports that stress induces an immune response by suggesting that even in the absence of excess adrenocortical output, stress brings about functional resistance to glucocorticoids in monocytes, which enables activation of pro-inflammatory transcription control pathways. This persistent activation of inflammatory mechanisms may contribute to stress-related morbidity and mortality. (5)	In conclusion, whether the immune response induce by stress works via the HPA pathway or if is a direct response in immune cells, chronic stress induces a inflammation state which makes the patients more prone to infections, and many other health problems.

References 1. About.com. 2005. How Stress affects the immune system. http://mentalhealth.about.com/od/stress/a/stressimmune604_2.htm 2. Webster JI, Tonelli L, Sternberg EM (2002): Neuroendocrine regulation of immunity. Annu Rev Immunol 20:125–163. 3. Libby P, Theroux P (2005): Pathophysiology of coronary artery disease. Circulation 111:3481–3488. 4. Papanicoloaou DA, Wilder RL, Manolagas SC, Chrousos GP (1998): The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 128:127–137. 5. Charo IF, Ransohoff RM (2006): The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621. 6. Gregory E. Miller, Edith Chen, Jasmen Sze, Teresa Marin, Jesusa M.G. Arevalo, Richard Doll, Roy Ma, and Steve W. Cole (2008): A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB Signaling. BIOL PSYCHIATRY 2008;64:266–272 7. Sergerstrom and Miller. Psychological Stress and the Human Immune System: A Meta Analytic Study of 30 years of Injury. 2004. Available at http://www.apa.org/journals/releases/bul1304601.pdf 8. Herbert, Tracy Bennett, Cohen, Sheldon. Stress and Immunity in Humans: A Meta-Analytic Review. 1993. http://www.psychosomaticmedicine.org/cgi/reprint/55/4/364 9. Ronald Glaser, PhD Janice Keicolt-Galiser Pd.D, Stress Damages Immune System and Health Discover Medicine, Volume 5 #26 p.165 April 2005 10. Keicolt-Glasier JK,Preacher KJ, MacCallum RC, Atkinson C, Marlerkey WB, Calser R. Chronic stress and age-related increases in proimflammatory cytokine IL-6. Proceedings of the National Academy of Science USA 100:9090-9095.2003 11. www.Expert-reviews.com Identifying the stress-susceptible patient at risk for inflammatory diseases: an interdisciplinary approach Clin. Immunol. 5 (2), 119-121 (2009) 12. Rowe, William, MD. Inflammatory Bowel Disease. eMedicine Health Practice Guide to Health. WebMD, LLC, 2009. http://www.emedicinehealth.com/script/main/art.asp?articlekey=59121&pf=3&page=1