Excerpt from a Physiology News feature by Natalie Riddell, School of Biosciences and Medicine, University of Surrey, UK, @N_Riddell_Immun
Stress can get under our skin. It can influence each and every physiological system, and all of the major contemporary diseases in the UK, including cardiovascular disease, inflammatory disorders, metabolic syndrome, infectious diseases and cancer, have been associated with stress. Stress affects everyone, and levels of anxiety and mental health disorders are increasing with work-related stress now being the second most commonly reported illness in the UK workforce. Over the last four decades, research in the area of Psychoneuroimmunology (PNI) has identified stress induced immune alterations as a potential mediator between chronic stress and ill-health.
In the 1970s, Holmes and Rahe developed a scale to subjectively grade stress, [which inspired our recent survey of stress in modern Britain]. They ranked over 40 different types of life stressors, such as the death of someone close to you, changes in relationship status, work-related stress, even Christmas, and they assigned each stressor a score. The total tally of stress scores that a person had experienced in the last year could accurately predict the likeliness of future illness. This demonstrated that stress and illness were closely related. In the 1990’s, Cohen et al., eloquently demonstrated that psychological stress increased the rates of respiratory infections and clinical symptoms in participants inoculated with the common cold (Cohen, Tyrrell et al. 1993). Subsequent studies revealed that every organ, tissue and cell of the immune system could be altered by psychological stress. The involvement of immune alterations in stress induced diseases was recognised and the field of PNI was born.
Defining stress
Stress is highly subjective. Something that I may class as stressful (watching Arsenal this season), may not be stressful to other people (Tottenham supporters). So how can we define stress? In the 1960s, the psychologist Richard Lazarus introduced the concept that stress is a process consisting of three distinct steps. First, a stimulus (i.e., the stressor) has to be present and perceived. Second, the stimulus initiates a conscious or sub-conscious process whereby the stressor is evaluated in relation to available coping options. If the demands of the situation exceed the ability to cope, then the situation is perceived as stressful. Thirdly, this results in a stress response involving emotional (e.g., anxiety, embarrassment) and biological (e.g., autonomic-endocrine) adaptations. Put simply; stress is a situation or event that exceeds, or is perceived to exceed, the individual’s ability to cope, that then triggers an emotional and biological response.

The stress adaptation response and immunity
The biological adaptation to stress is activation of the sympathetic nervous system. The same biological response is induced whether the stressor is psychological, such as anxiety or embarrassment, or physical, for example, exercise, trauma or fever. In the case of psychological stress, the individual perceives an inability to cope and this results in the amygdala, a part of the brain that contributes to emotion processing, sending a distress signal to the nearby hypothalamus. The hypothalamus can communicate with the rest of the body via either of two arms of the involuntary nervous system: “rest and digest” (parasympathetic) or “fight or flight” (sympathetic). During stress, this “fight or flight” system is triggered and various physiological changes occur, including an increase in heart rate, respiration and energy production. This promotes survival of the individual by maximising physical capacity to cope with the stressor.
During stress, signalling from the “fight or flight” sympathetic nervous system causes the adrenal gland to secrete the two main stress hormones; adrenaline and cortisol. These hormones can spread and act throughout the body via the circulation. The sympathetic nervous system innervates all of the organs of the immune system, and individual immune cells can directly respond to changes in circulating levels of adrenaline and cortisol. Stress is therefore able to alter every process of immunity, from the initial development of stem cells into early immune cells in the bone marrow, through to the triggering of immune responses to specific antigens in the lymph nodes. Even when in the peripheral tissues, such as the skin or gut, where mature immune cells are most likely to encounter infections, the cells can be regulated by stress hormones. It is therefore unsurprising that the immune system is a modifiable target of stress.
Read Natalie’s full article in our magazine Physiology News to find out how acute stress changes the composition of the blood, and why our Stone Age brain can’t cope with the constant stress of modern life. Her feature takes a more detailed dive into the effects of stress on the immune system’s day-night (circadian) rhythm, and points to stress management as an easy and affordable way to make us healthier.
Reference
Cohen, S., D. A. Tyrrell and A. P. Smith (1993). Negative life events, perceived stress, negative affect, and susceptibility to the common cold. J Pers Soc Psychol 64(1): 131-140.