Stress and The Immune System

Learning Objectives

  • Describe how stress impacts the functioning of the immune system

Psychophysiological Disorders

If the reactions that compose the stress response are chronic or if they frequently exceed normal ranges, they can lead to cumulative wear and tear on the body, in much the same way that running your air conditioner on full blast all summer will eventually cause wear and tear on it. For example, the high blood pressure that a person under considerable job strain experiences might eventually take a toll on his heart and set the stage for a heart attack or heart failure. Also, someone exposed to high levels of the stress hormone cortisol might become vulnerable to infection or disease because of weakened immune system functioning (McEwen, 1998).

Link to Learning

Robert Sapolsky, a noted Stanford University neurobiologist and professor, has for over 30 years conducted extensive research on stress, its impact on our bodies, and how psychological tumult can escalate stress—even in baboons. This video shows Dr. Sapolsky in an in-depth documentary from National Geographic.

Physical disorders or diseases whose symptoms are brought about or worsened by stress and emotional factors are called psychophysiological disorders. The physical symptoms of psychophysiological disorders are real and they can be produced or exacerbated by psychological factors (hence the psycho and physiological in psychophysiological). A list of frequently encountered psychophysiological disorders is provided in Table 1.

Table 1. Types of Psychophysiological Disorders (adapted from Everly & Lating, 2002)
Type of Psychophysiological Disorder Examples
Cardiovascular hypertension, coronary heart disease
Gastrointestinal irritable bowel syndrome
Respiratory asthma, allergy
Musculoskeletal low back pain, tension headaches
Skin acne, eczema, psoriasis

In addition to stress itself, emotional upset and certain stressful personality traits have been proposed as potential contributors to ill health. Franz Alexander (1950), an early-20th-century psychoanalyst and physician, once postulated that various diseases are caused by specific unconscious conflicts. For example, he linked hypertension to repressed anger, asthma to separation anxiety, and ulcers to an unconscious desire to “remain in the dependent infantile situation—to be loved and cared for” (Alexander, 1950, p. 102). Although hypertension does appear to be linked to anger (as you will learn below), Alexander’s assertions have not been supported by research. Years later, Friedman and Booth-Kewley (1987), after statistically reviewing 101 studies examining the link between personality and illness, proposed the existence of disease-prone personality characteristics, including depression, anger/hostility, and anxiety. Indeed, a study of over 61,000 Norwegians identified depression as a risk factor for all major disease-related causes of death (Mykletun et al., 2007). In addition, neuroticism—a personality trait that reflects how anxious, moody, and sad one is—has been identified as a risk factor for chronic health problems and mortality (Ploubidis & Grundy, 2009).

Before we discuss two kinds of psychophysiological disorders about which a great deal is known: cardiovascular disorders and asthma, it is necessary to turn our attention to a discussion of the immune system—one of the major pathways through which stress and emotional factors can lead to illness and disease.

Immune System

In a sense, the immune system is the body’s surveillance system. It consists of a variety of structures, cells, and mechanisms that serve to protect the body from invading toxins and microorganisms that can harm or damage the body’s tissues and organs. When the immune system is working as it should, it keeps us healthy and disease free by eliminating bacteria, viruses, and other foreign substances that have entered the body (Everly & Lating, 2002).

Immune System Errors

Sometimes, the immune system will function erroneously. For example, sometimes it can go awry by mistaking your body’s own healthy cells for invaders and repeatedly attacking them. When this happens, the person is said to have an autoimmune disease, which can affect almost any part of the body. How an autoimmune disease affects a person depends on what part of the body is targeted. For instance, rheumatoid arthritis, an autoimmune disease that affects the joints, results in joint pain, stiffness, and loss of function. Systemic lupus erythematosus, an autoimmune disease that affects tissue in many parts of the body, can result in rashes and swelling of joints and skin among other symptoms. Grave’s disease, an autoimmune disease that affects the thyroid gland, can result in fatigue, weight gain, and muscle aches (National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS], 2012).

In addition, the immune system may sometimes break down and be unable to do its job. This situation is referred to as immunosuppression, the decreased effectiveness of the immune system. When people experience immunosuppression, they become susceptible to any number of infections, illness, and diseases. For example, acquired immune deficiency syndrome (AIDS) is a serious and lethal disease that is caused by human immunodeficiency virus (HIV), which greatly weakens the immune system by infecting and destroying antibody-producing cells, thus rendering a person vulnerable to any of a number of opportunistic infections (Powell, 1996).

Stressors and Immune Function

The question of whether stress and negative emotional states can influence immune function has captivated researchers for over three decades, and discoveries made over that time have dramatically changed the face of health psychology (Kiecolt-Glaser, 2009). Psychoneuroimmunology is the field that studies how psychological factors such as stress influence the immune system and immune functioning. The term psychoneuroimmunology was first coined in 1981, when it appeared as the title of a book that reviewed available evidence for associations between the brain, endocrine system, and immune system (Zacharie, 2009). To a large extent, this field evolved from the discovery that there is a connection between the central nervous system and the immune system.

Some of the most compelling evidence for a connection between the brain and the immune system comes from studies in which researchers demonstrated that immune responses in animals could be classically conditioned (Everly & Lating, 2002). For example, Ader and Cohen (1975) paired flavored water (the conditioned stimulus) with the presentation of an immunosuppressive drug (the unconditioned stimulus), causing sickness (an unconditioned response). Not surprisingly, rats exposed to this pairing developed a conditioned aversion to the flavored water. However, the taste of the water itself later produced immunosuppression (a conditioned response), indicating that the immune system itself had been conditioned. Many subsequent studies over the years have further demonstrated that immune responses can be classically conditioned in both animals and humans (Ader & Cohen, 2001). Thus, if classical conditioning can alter immunity, other psychological factors should be capable of altering it as well.

Hundreds of studies involving tens of thousands of participants have tested many kinds of brief and chronic stressors and their effect on the immune system (e.g., public speaking, medical school examinations, unemployment, marital discord, divorce, death of spouse, burnout and job strain, caring for a relative with Alzheimer’s disease, and exposure to the harsh climate of Antarctica). It has been repeatedly demonstrated that many kinds of stressors are associated with poor or weakened immune functioning (Glaser & Kiecolt-Glaser, 2005; Kiecolt-Glaser, McGuire, Robles, & Glaser, 2002; Segerstrom & Miller, 2004).

When evaluating these findings, it is important to remember that there is a tangible physiological connection between the brain and the immune system. For example, the sympathetic nervous system innervates immune organs such as the thymus, bone marrow, spleen, and even lymph nodes (Maier, Watkins, & Fleshner, 1994). Also, we noted earlier that stress hormones released during hypothalamic-pituitary-adrenal (HPA) axis activation can adversely impact immune function. One way they do this is by inhibiting the production of lymphocytes, white blood cells that circulate in the body’s fluids that are important in the immune response (Everly & Lating, 2002).

Some of the more dramatic examples demonstrating the link between stress and impaired immune function involve studies in which volunteers were exposed to viruses. The rationale behind this research is that because stress weakens the immune system, people with high stress levels should be more likely to develop an illness compared to those under little stress. In one memorable experiment using this method, researchers interviewed 276 healthy volunteers about recent stressful experiences (Cohen et al., 1998). Following the interview, these participants were given nasal drops containing the cold virus (in case you are wondering why anybody would ever want to participate in a study in which they are subjected to such treatment, the participants were paid $800 for their trouble). When examined later, participants who reported experiencing chronic stressors for more than one month—especially enduring difficulties involving work or relationships—were considerably more likely to have developed colds than were participants who reported no chronic stressors (Figure 1).

A bar graph shows the relationship between chronic stressors and the percentage of people who developed colds after receiving the cold virus. About 50% of people with chronic stressors for at least one month developed a cold compared to about 35% without chronic stressors. About 52% of people with chronic stressors for at least three months developed a cold compared to about 35% without chronic stressors. About 51% of people with chronic stressors for at least six months developed a cold compared to about 35% without chronic stressors.

Figure 1. This graph shows the percentages of participants who developed colds (after receiving the cold virus) after reporting having experienced chronic stressors lasting at least one month, three months, and six months (adapted from Cohen et al., 1998).

In another study, older volunteers were given an influenza virus vaccination. Compared to controls, those who were caring for a spouse with Alzheimer’s disease (and thus were under chronic stress) showed poorer antibody response following the vaccination (Kiecolt-Glaser, Glaser, Gravenstein, Malarkey, & Sheridan, 1996).

Other studies have demonstrated that stress slows down wound healing by impairing immune responses important to wound repair (Glaser & Kiecolt-Glaser, 2005). In one study, for example, skin blisters were induced on the forearm. Subjects who reported higher levels of stress produced lower levels of immune proteins necessary for wound healing (Glaser et al., 1999). Stress, then, is not so much the sword that kills the knight, so to speak; rather, it’s the sword that breaks the knight’s shield, and your immune system is that shield.

Stress and Aging: A Tale of Telomeres

Have you ever wondered why people who are stressed often seem to have a haggard look about them? A pioneering study from 2004 suggests that the reason is because stress can actually accelerate the cell biology of aging.

Stress, it seems, can shorten telomeres, which are segments of DNA that protect the ends of chromosomes. Shortened telomeres can inhibit or block cell division, which includes growth and proliferation of new cells, thereby leading to more rapid aging (Sapolsky, 2004). In the study, researchers compared telomere lengths in the white blood cells in mothers of chronically ill children to those of mothers of healthy children (Epel et al., 2004). Mothers of chronically ill children would be expected to experience more stress than would mothers of healthy children. The longer a mother had spent caring for her ill child, the shorter her telomeres (the correlation between years of caregiving and telomere length was r = -.40). In addition, higher levels of perceived stress were negatively correlated with telomere size (r = -.31). These researchers also found that the average telomere length of the most stressed mothers, compared to the least stressed, was similar to what you would find in people who were 9–17 years older than they were on average.

Numerous other studies since have continued to find associations between stress and eroded telomeres (Blackburn & Epel, 2012). Some studies have even demonstrated that stress can begin to erode telomeres in childhood and perhaps even before children are born. For example, childhood exposure to violence (e.g., maternal domestic violence, bullying victimization, and physical maltreatment) was found in one study to accelerate telomere erosion from ages 5 to 10 (Shalev et al., 2013). Another study reported that young adults whose mothers had experienced severe stress during their pregnancy had shorter telomeres than did those whose mothers had stress-free and uneventful pregnancies (Entringer et al., 2011). Further, the corrosive effects of childhood stress on telomeres can extend into young adulthood. In an investigation of over 4,000 U.K. women ages 41–80, adverse experiences during childhood (e.g., physical abuse, being sent away from home, and parent divorce) were associated with shortened telomere length (Surtees et al., 2010), and telomere size decreased as the amount of experienced adversity increased (Figure 2).

A bar graph shows the relationship between telomere length in kilobase pairs and the number of adversities people experienced. Those who experienced zero adversities had about 6.6 kilobase pairs for telomere size. Those who experienced one adversity had about 6.4 kilobase pairs for telomere size. Those who experienced more than one adversity had about 5.9 kilobase pairs for telomere size.

Figure 2. Telomeres are shorter in adults who experienced more trauma as children (adapted from Blackburn & Epel, 2012).

Efforts to dissect the precise cellular and physiological mechanisms linking short telomeres to stress and disease are currently underway. For the time being, telomeres provide us with yet another reminder that stress, especially during early life, can be just as harmful to our health as smoking or fast food (Blackburn & Epel, 2012).

Try It

Glossary

cardiovascular disorders: disorders that involve the heart and blood circulation system
hypertension: high blood pressure
immune system: various structures, cells, and mechanisms that protect the body from foreign substances that can damage the body’s tissues and organs
immunosuppression: decreased effectiveness of the immune system
lymphocytes: white blood cells that circulate in the body’s fluids and are especially important in the body’s immune response
psychoneuroimmunology: field that studies how psychological factors (such as stress) influence the immune system and immune functioning
psychophysiological disorders: physical disorders or diseases in which symptoms are brought about or worsened by stress and emotional factors

Contribute!

Did you have an idea for improving this content? We’d love your input.

Improve this pageLearn More