Effects of Stress on the Immune System - Research Paper Example

? Effects of Stress on the Immune System Stress does have a profound effect on the immune system. Though stress was initially considered to exert a physiological effect in the human body, later studies have revealed that it also affects the immune system by changing the immune response to infectious agents and environmental pollutants. Further studies have shown that depending on the nature and duration of the stressful event the immune system can either be enhanced or depressed. These immune changes however, have minimal clinical consequences in healthy individuals, but the weakening of the immune system in response to aging and disease results in prominent changes in the immunity of the individual to stress. Stress has also been linked to the progression of various diseases such as tumors and autoimmune diseases. The changes in immune response are mediated by signals from the endocrine and nervous system which are the initially responders to the environmental stresses. Various stress hormones released in response to stress play a role in the activation or suppression of the immune cells. While in majority of the cases stress has a detrimental effect on the functioning of the immune system, in some cases acute limited stress have been shown to up regulate natural immunity parameters that are useful in protection against a possible injury or infection (Segerstrom & Miller, 2004; Hussain, 2010). Stress has for long been linked to changes in the physiology of humans such an increased delivery of oxygen and glucose to the heart muscles. However, researchers have shown that apart from these physiological changes stress also affects the immune response of an individual. The immune system was largely considered to function autonomously but this was also disproved by studies that showed that signals from the endocrine and nervous system were passed to the immune cells in response to stress. In response to stress sympathetic fibers from the brain are passed on to primary and secondary lymphoid tissues where the fibers release several substances that bind to specific receptors on the white blood cells and regulate their function and distribution (Segerstrom & Miller, 2004; Hawkley & Cacioppo, 2004). The hypothalamus of the brain is the integrative center that responds to environmental stimuli to which it reacts via the nervous and hormonal systems. The hypothalamus controls the secretion of hormones from the pituitary, adrenal cortex and medulla. When this hypothalamus- pituitary- adrenal cortex axes is subjected to chronic activation it can have a pronounced effect on the health through continued secretion of hormones. When the receptors for glucocorticoid (GC) hormones present on the immune cells are bound by GC hormones they interfere with the activity of NF-kB which in turn suppresses the secretion of cytokines by these cells. The activation of the HPA axis also causes the secretion of catecholamine’s from the adrenal medulla which also binds to adrenergic receptors on the immune cells and increases the production of cytokines and antibody which is the body’s immediate response to stress. However, when subject to chronic activation these hormones can have a similar effect like the GC on the immune cells (Padgett & Glaser, 2003). While these stress hormones make us resistant to the effects of stressors by increasing heart rate, blood pressure and sugar levels to combat the perceived threat, they however have a deleterious effect on the immune system when produced chronically (Psychological Stress and Cancer, 2012). For example, the release of cortisol under conditions of stress has been found to have an inhibitory effect on the synthesis and activity of white blood cells. In addition it has also been found to interfere with communication of immune cells thus preventing them from providing the necessary protection to the body (Hussain, 2010). The effect of stress hormones on the immune system has been studied in great detail during the past decade. Hormones released by various glands in response to stress namely cortisol, epinephrine and norepinephrine by the adrenal glands, prolactin and growth hormone secreted by the pituitary and the brain peptides namely melatonin, beta-endorphin and encephalin also bind to receptors on the lymphocytes and regulate their function (Segerstrom & Miller, 2004; Reiche, Nunes & Morimoto, 2004). Firdaus Dhabhar has been working for nearly a decade to understand the effects of stress hormones on the immune system. His studies have shown that when both animals and humans are exposed to short-term stress a redistribution of immune cells occur within the bloodstream and also to other tissues such as the skin. These cells help in protecting against infections and also in the process of wound healing. His research has also shown that short-term stress is actually beneficial in patients who are scheduled for surgery as it could be beneficial during the post-operative recovery process. Through his studies with rats Dhabhar and his colleagues showed that in response to mild stressors the body produces three major stress hormones namely, epinephrine, norepinephrine and cortisol which are released by the adrenal glands in response to signals from the brain. These hormones in turn caused the release of specific immune cells from the spleen and bone marrow in to the bloodstream and to their destinations such as the skin and other tissues. The study also found that among the three hormones norepinephrine and epinephrine was released early in response to stress and they mobilized the major cells of the immune system in to the blood. Cortisol, which was released later, channeled the release of all types of immune cells into the bloodstream. When similar responses to short-term stressors were observed in patients who had undergone surgery, the immune cell redistribution was found to be helpful in the wound healing process as these patients recovered slightly quicker compared to those who had less redistribution of immune cells owing to less stressors. This finding could have potential medical applications for administering low doses of stress hormones prior to surgery (Stanford University, 2012). The immunosuppressive effect of stress was first reported by Hans Selye in the year 1975. In his model he proposed three stages through which the body reacts to a stressful situation. In the first alarm stage the body prepares itself to respond to the stress. When the stress persists the body begins to resist the stress by secreting more hormones and increased energy. However when the stressful condition prolongs for a long time the body goes into the exhaustion phase wherein all its resources and energy gets depleted, the immune system is severely compromised and it succumbs to opportunistic illnesses (Hussain, 2010). Following Seyle’s initial model, Dhabar and McEwen proposed the biphasic model using mice. They found that during acute stressful periods a redistribution of T cells occurred in the skin which in fact contributed to increased immunity. However, these cells failed to accumulate in the skin during periods of chronic stress that resulted in a lower immune response (Segerstrom & Miller, 2004; Hussain, 2010). A further modification of this model proposed that stress causes an activation of natural immune response while at the same time diminishing the specific immune responses as the former requires less energy and are have a more rapid onset. In order to further explain the effect of chronic stress on causing suppression and increased activation of the immune system that could result in an autoimmune response, researchers have proposed that alteration in the secretion of cytokines during chronic stress is responsible for this enhancement or suppression of the immune system. During periods of chronic stress the Th1 cytokines that activate cellular immune response against an infection or neoplastic disease are suppressed. This in turn causes an increased production of Th2 cytokines which has the potential to activate the humoral immune response which plays a role in aggravating the allergic response and initiating an autoimmune response within the body. All these effects are mediated via the secretion of cortisol by the adrenal glands (Segerstrom & Miller, 2004; Hawkley & Cacioppo, 2004; Reiche, Nunes & Morimoto, 2004). A meta-analytical study, which included results from several independent studies, has categorized the immune effects of specific stressors. In the case of acute time-limited stressors, which included events like public speaking and performing arithmetic calculations, there was an up-regulation of natural immunity through increased production and cytotoxicity of natural killer cells, high number of neutrophils in blood and an increased secretion of pro-inflammatory cytokines. However, it down-regulated the specific immune response as characterized by a diminished mitogen-stimulated proliferative response. The next category of stressors included brief-naturalistic stressors that included students who were facing examinations. Though this type of stressors did not increase the number of immune cells in circulation, it however, affected the functioning of these cells by causing a shift from cellular immunity by suppressing the Th1 cells to humoral or antibody mediated immunity by increasing the proliferation of Th2 class of cells. A stressful event sequence includes witnessing a natural disaster or losing a spouse. This type of stressor lacked a consistent pattern of immune changes. The changes varied depending on the nature of the stressor. In the case of loss of a spouse a decline in the natural immune response through a decrease in the NK cell cytotoxicity was noted. For natural disasters, owing to the lower sample number, only less significant increases in natural and specific immune response was observed. In cases involving breast biopsy there was no significant immune changes observed (Segerstrom & Miller, 2004; Hussain, 2010). The chronic stressors or long-term stressors which included living with handicaps, lack of employment, and providing nursing care for persons affected by dementia showed significant negative effects on the overall immune system including the natural and specific mechanisms. In an experiment conducted by psychologist Janice Kiecolt-Glaser, caregivers of chronically ill patients were administered with flu vaccine. A majority of the caregivers were unable to elicit adequate antibody responses to the vaccine suggesting that their immune system was not functioning optimally which in turn increased their risk of infections. In addition to delaying wound healing and increasing vulnerability to infections chronic stress also increases the risk of developing heart diseases, osteoporosis and autoimmune diseases such as type 2 diabetes (Wenner, 2008). Kiecolt-Glaser also analyzed the effect of stress on medical students and found that during the three-day exam period the students had lower number of natural killer cells and T cells that defend against infections (Stress Weakens the Immune System, 2006). Another category included distant stressors in which the individuals tested had undergone stress or trauma during their younger years. In this type, the only significant change was in the cytotoxicity of the NK cells (Segerstrom & Miller, 2004; Hussain, 2010). With regard to individuals who are more vulnerable to stress-related immune changes, studies have shown that in case of healthy individuals even large stresses would only result in small clinical consequences on the individual mainly owing to the fact that the immune cells are usually redundant at a young age. However, when the stress becomes chronic it does cause significant changes to the immune system which could increase the susceptibility to diseases due to exhaustion of the resources and the inability of the body to meet the demands of chronic stress. In addition, the immune system can also be compromised under stressful conditions in older individuals and those who are already affected by a disease. In the case of autoimmune diseases the self-regulation mechanism suffers a set-back and as a result the immune cells attacks self-tissues which results in disease pathogenesis. The self-regulating mechanisms can also be lost during asthma and other allergic conditions and all the above conditions increases the vulnerability of the individual to stress related changes in immunity (Segerstrom & Miller, 2004; Hawkley & Cacioppo, 2004). In a study conducted by health psychologists Sarah Pressman and Sheldon Cohen, first-year students who experienced feelings of loneliness and who had fewer friend circles exhibited a diminished immune response to flu vaccinations given to them as part of the study (Stress Weakens the Immune System, 2006). In addition, long-term stress will cause a person to get addicted to smoking, alcohol and other substance abuse which in turn could have an effect on their immunity and also increase the risk of developing cancer (Psychological Stress and Cancer, 2012). Stress has also been found to play a role in progression of tumors by increasing the expression of interleukin 1 and 6, TNF-alpha and decreasing the expression of interleukin 2, interferon-gamma and class II MHC molecules. The ability of malignant cells to bypass immune surveillance is facilitated by increased secretion of TNF-alpha (Reiche, Nunes & Morimoto, 2004). In conclusion, stress has been found to have both beneficial as well as deleterious effects on the human body depending on the nature and duration of the stressor. In most cases, however, the harmful effects outweigh the benefits of stress on the immune system which is especially the case in chronic stressful conditions. While the effects of acute temporary stressors on healthy individuals are beneficial, chronic stressors often lead to deleterious conditions by increasing the vulnerability of individuals to various pathogens. This is further exacerbated in older individuals and those who are already affected by some disease. In addition, stress also plays a role in accelerating disease progression such as cancers and autoimmune conditions. References Hawkley, L. C., & Cacioppo, J. T. (2004). Stress and the aging immune system. Brain, Behavior and Immunity, 18: 114-119. Retrieved April 7, 2013, from, http://psychology.uchicago.edu/people/faculty/cacioppo/jtcreprints/hc04.pdf Hussain, D. (2010). Stress, Immunity, and Health: Research Findings and Implications. International Journal of Psychosocial Rehabilitation, 15(1): 94-100. Retrieved April 7, 2013, from, http://www.psychosocial.com/IJPR_15/Stress_Immunity_Health_Hussain.html Padgett, D. A., & Glaser, R. (2003). How stress influences the immune response. TRENDS in Immunology, 24(8): 444-448. Retrieved April 7, 2013, from, http://www.direct-ms.org/sites/default/files/Stress%20and%20immunity.pdf Psychological Stress and Cancer. (2012). National Cancer Institute. Retrieved April 7, 2013, from, http://www.cancer.gov/cancertopics/factsheet/Risk/stress Reiche, E. M. V., Nunes, S. O. V., & Morimoto, H. K. (2004). Stress, depression, the immune system and cancer, Lancet Oncology, 5: 617-625. Retrieved 7 Apr. 2013, from, http://bmb.pharma.hr/lauc/NI/303.pdf Segerstrom, S. C., & Miller, G. E. (2004). Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 years of Inquiry. Psychological Bulletin, 130(4): 601-630. Retrieved April 7, 2013, from, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361287/ Stanford University Medical Center (2012). How stress can boost immune system. ScienceDaily. Retrieved April 7, 2013, from, http://www.sciencedaily.com/releases/2012/06/120621223525.htm Stress Weakens the Immune System. (2006). American Psychological Association. Retrieved April 7, 2013, from, http://www.apa.org/research/action/immune.aspx Wenner, M. (2008). The Danger of Stress. Scientific American. Retrieved April 7, 2013, from, http://www.scientificamerican.com/article.cfm?id=stress-dangers . Read More