Stress alters immunity

Psychologists have long known that stress affects our ability to fight infection, but a major new “meta-analysis” – a study of studies – has elucidated intriguing patterns of how stress affects human immunity, strengthening it in the short term but wearing it down over time.

The report appears in the July issue of Psychological Bulletin, which is published by the American Psychological Association.

Major findings are three-fold. First, the overlapping findings of 293 independent studies reported in peer-reviewed scientific journals between 1960 and 2001 – with some 18,941 individuals taking part in all -- powerfully confirm the core fact that stress alters immunity. Second, the authors of the meta-analysis observed a distinctive pattern: Short-term stress actually “revs up” the immune system, an adaptive response preparing for injury or infection, but long-term or chronic stress causes too much wear and tear, and the system breaks down. Third, the immune systems of people who are older or already sick are more prone to stress-related change.

Psychologists Suzanne Segerstrom, PhD, of the University of Kentucky, and Gregory Miller, PhD, of the University of British Columbia, analyzed the results of the nearly 300 studies by sorting them into different categories and statistically evaluating relationships. For example, the five stressor categories included:

• Acute time-limited stressors: lab challenges such as public speaking or mental math.
• Brief naturalistic stressors: real-world challenges such as academic tests.
• Stressful event sequences: a focal event such as loss of a spouse or major natural disaster gives rise to a series of related challenges that people know at some point will end.
• Chronic stressors: pervasive demands that force people to restructure their identity or social roles, without any clear end point – such as injury resulting in permanent disability, caring for a spouse with severe dementia, or being a refugee forced from one’s native country by war.
• Distant stressors: traumatic experiences that occurred in the distant past yet can continue modifying the immune system because of their long-lasting emotional and cognitive consequences, such as child abuse, combat trauma or having been a prisoner of war.

The psychologists also looked at the effects of the various stressors on different immune responses, such as natural and specific immunity. Natural immunity produces quick-acting, all-purpose cells that can attack many pathogens; they bring fever and inflammation. While they fight on the front line, the body takes a few days to mount a more efficient attack on specific invaders via the lymphocytes (T-cells and B cells) of specific immunity. Specific immunity has both cellular responses, which fight pathogens that get inside cells (such as viruses), and humoral responses, which fight pathogens that stay outside cells, such as bacteria and parasites. Scientists have identified the blood markers of these different immune responses; stress studies measure them to indicate stress response. As a result, Segerstrom and Miller were able to assess how different types of immune response correlated with different types of stress.

Write the authors, “Stressful events reliably associate with changes in the immune system and…characteristics of those events are important in determining the kind of change that occurs.”

Acute time-limited stressors, the type that produce a “fight or flight” response, prompted the immune system to ready itself for infections resulting from bites, punctures, scrapes or other challenges to the integrity of the skin and blood. In evolution, this response would be selected as adaptive. Brief stressors enhanced quick, energy-efficient natural immunity, to help the body meet the challenge prompting fight or flight. At the same time, certain aspects of specific immunity that consume time and energy were suppressed.

Stressful event sequences seemed to be weakly associated with different immune consequences, depending on the type of event. The data suggested different patterns for bereavement (loss) and trauma, but the authors didn't see associations strong enough to make new claims. In this regard, further study is needed.

The most chronic stressors – which change people’s identities or social roles, are more beyond their control and seem endless -- were associated with the most global suppression of immunity; almost all measures of immune function dropped across the board. Duration of stress came into play: The longer the stress, the more the immune system shifted from potentially adaptive changes (such as those in the acute “fight or flight” response) to potentially detrimental changes, at first in cellular immunity and then in broader immune function. Thus, stressors that turn a person’s world upside down and appear to offer no “light at the end of the tunnel” could have the greatest psychological and physiological impact.

Finally, Segerstrom and Miller found that age and disease status affected a person’s vulnerability to stress-related decreases in immune function. They attribute this to how illness and age make it harder for the body to regulate itself.

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 vs. specific and cellular vs. humoral immune responses turned up useful information. Says Miller, “A meta-analysis lets you ask questions that are too big for any one study to answer. You see if things are consistent over the gamut of labs, methods and people.”

Future studies, the authors hope, will look at the role of behavior in the stress-immunity pathway. For example, optimism and coping are known to mitigate the immune response to stress. Further, they write that the most pressing question facing researchers is, “the extent to which stressor-induced changes in the immune system have meaningful implications for disease susceptibility in otherwise healthy humans.” The field of psychoneuroimmunology has yet to tie together the various threads of research to determine whether immune system changes are the reason that stress makes people more likely to get sick.

Article: “Psychological Stress and the Human Immune System: A Meta-Analytic Study of 30 Years of Inquiry,” Suzanne C. Segerstrom, Ph.D., University of Kentucky, and Gregory E. Miller, Ph.D., University of British Columbia; Psychological Bulletin, Vol. 130, No. 4.

Full text of the article is available from the APA Public Affairs Office and at http://www.apa.org/journals/bul/press_releases/july_2004/bul1304601.html