Stress and the Immune System
Everyone experiences stress. Whether it is everyday hassles, such as being stuck in traffic, or more acute forms of stress, such as pain or traumatic experiences, stress plays a part in everyone's lives. In this paper I will discuss the various forms of stress, how stress affects the immune system, and how that affectation influences diseases.
Before diving right into the technical aspects of stressors and the immune system, I need to define several terms. A stressor is any stimuli that causes a nonspecific response in an indidual, otherwise known as stress (Elliott and Eisdorfer, 1982).
There are two main catagories of stress: acute and chronic. Acute stressors include unpleasant films, understimulation/work underload, overstimulation/work overload, unexpected or uncontrollable noise, prestige or status loss, electric shock, uncontrollable situations, physical illness, surgery, threats to self-esteem, and traumatic experiences. Chronic stressors include sleep deprivation, daily "hassles", work overload or underload, role strains, or social isolation. There are, of course, many more things that can cause stress, but these are the stressors most commonly used in experimental research and most commonly seen in the general population (Elliott and Eisdorfer, 1982).
While there is no way to predict conclusively how an individual will respond to different stressors, stress does cause some common changes. Emotionally, stress can lead to feelings of depression, anxiety, and anger (McEwen & Stellar, 1993). But even these seemingly simple reactions have high degrees of expressivity, and different individuals are affected in different ways.
Individual differences in responding to challenge are products of genetics, developmental and environmental influences, and experience (McEwen & Stellar, 1993). Some people may cope well with stress, rising to the challenge and meeting their goals. Others may be more adversely affected by stressors, leading to mental as well as physical fatigue.
But under what mechanism does this occur? How does stress, a vague and ambiguous term, cause specific and documented changes in the body?
In order to understand these changes, I must first introduce you to the immune system. The immune system protects the body from disease organisms and other foreign bodies, known as antigens. The first line of defense is local barriers such as the skin, peritoneum, etc, and inflammation due to immunoglobulins, or antibodies. If those fail to block or destroy the antigens, the cell-mediated immune response and the humoral immune response kick in. The cell-mediated response uses sensitized T cells (white blood cells derived in the thymus) to recognize, attach to, and render antigens inactive. Other types of T cells, helper T cells, which aid in production of antibodies by B (bone marrow) cells, and suppressor/cytotoxic T cells, which inhibit that production, are also essential for proper immune system function. Helper T cells are also known as CD4 cells, and suppressor T cells are known as CD8 cells (Glaser, Anderson & Anderson, 1992).
Studies by Manuck, et al in 1991 showed that psychological stressors induced cell division among CD8 cells, thereby increasing the number of CD8 cells and suppressing immune function. However, this response was only seen in those subjects who also showed high heart rate change and catecholamine change during the stressors. This was consistent with the theory that there are two groups of people ?those who are "high reactors", and those who are "low reactors". High reactors are significantly affected by stress, as shown by a significant increase in heart rate, blood pressure, catecholamines, and CD8 cells. Low reactors show little or no change in those areas (Manuck, et al, 1991).
Catecholamines are chemicals produced by the body that work in nerve transmission. The three main catecholamines include dopamine, epinephrine, and norepinephrine. Dopamine raises the heart rate and blood pressure, epinephrine raises heart rate and opens blood vessels (lowering blood pressure), and norepinephrine closes blood vessels (raising blood pressure) (Glaser, Anderson & Anderson, 1992). Epinephrine and norepinephrine are the catecholamines most commonly measured in stress experiments, and both increase under stress. Increases such as these can suppress aspects of immune function, including natural killer cell (cells that attack antigens without having recognized them first) activity. Increases in catacholemines may also rapidly alter cell numbers via redistribution (Naliboff, et al, 1991). In fact, changes in epinephrine levels are thought to reflect lymphocyte migration from bone marrow, the extremities, and the thymus (Kiecolt-Glaser, et al, 1992) to other areas of the body.
How do these chemical changes influence disease? It is well known that asthma, diabetes, various gastro-intestinal disorders, heart disease and viral infections are influenced by stress, but to what extent? When the immune system is suppressed, as it is under stress, latent viruses can obviously stage a comeback, but how does stress affect non-viral diseases?
In asthma, a disease which involves both external and internal factors, it is the internal factor that is most affected by acute effects of psychological stressors. Studies have shown that children with chronic asthma inprove considerably when away from their parents. The changes may have resulted from removal of an interaction that produced frequent stressful situations. In 1974, Liebman et al successfully used family therapy to treat severe and chronic asthma in seven out of seven children. Additionally, asthmatics exposed to a harmless substance that they thought they were allergic to illicited a severe attack (Elliott & Eisdorfer, 1982). Even more importantly, interactions between antigens and immunoglobulin E antibodies lead to the release of histamine, which blocks airways, and other mediating agents (Elliot & Eisdorfer, 1982). When antigens have an easier time invading the body, as they do under stress, the number of such interactions increases considerably.
Diabetes mellitus, the most common form of diabetes, is significantly affected by stress. Physical or psychological stressors can alter insulin needs; stressors may often be responsible for episodes of loss of control, especially in diabetic children. Type II diabetes is most often affected by stress, as it tends to occur in overweight adults and is a less severe form of diabetes (Elliot & Eisdorfer, 1982). Additionally, children who had stressful life events stemming from actual or threatened losses within the family and occuring between ages 5 and 9 had a significantly higher risk of Type I diabetes (McEwen & Stellar, 1993).
Gastrointestinal diseases such as peptic ulcers and ulcerative colitis are known to be greatly influenced by stress. Peptic ulcers occur twice as often in air traffic controllers as in civilian copilots, and occured more frequently among air traffic controllers at high-stress control centers (Chicago O'Hare, La Guardia, JFK, and Los Angeles International Airport) than at low-stress control centers (airports in less-populated cities in Virginia, Ohio, Texas, and Michigan). Although stress is a major risk factor in peptic ulcers, more than 20 other factors are thought to be associated as well; blood type, sex, HLA antigen type, alcoholic cirrhosis, hypertension, chronic obstructive pulmonary disease, cigarette smoking, and even consumption of coffee, carbonated beverages or milk during college (Elliott & Eisdorfer, 1982).
Ulcers are caused by excessive stomach acid, and studies of patients with gastric fistulas (openings leading from the stomach to the outside of the body) have shown that anger and hostility increase stomach acidity, while depression and withdrawal decrease it. Stress ulcers frequently occur in patients who experience severe trauma, extensive surgery, major burns or infections, brain injury or surgery, or other catastrophic events. Stress ulcers are quite different from peptic ulcers; they are acute, hemorrhagic (bleeding), and are usually preceeded by shock (Ballieux, 1984).
Myocardial infarction (MI, or heart attack) is the best-known example of an acute health problem that is usually precipitated by both acute and chronic physical or psychological stress. Interactions between diet and stress lead to a condition that promotes endocrine imbalances that alter body fat distributions, as well as increase atherosclerosis (plaque buildup in the arteries). Studies have shown that people with Type A behavior (unusually aggressive, competitive, work-oriented, and urgent behavior) have a much higher incidence of heart attacks than do Type B people, who exhibit fewer of these traits. In addition, Type A behavior is associated with high cholesterol, triglycerides, glucocorticoids; a greater insulin response to glucose; increased severity of coronary artery lesions; and greater range and magnitude of blood pressure and catecholamine responses to timed tests (Elliott & Eisdorfer, 1982). As stated earlier, stress increases catecholamines, and the increase of plasma catecholamines enhances platelet aggregation, lowers the threshold to cardiac arrythmias, induces narrowing of the blood vessels, and suppresses insulin secretion (McEwen & Stellar, 1993). All of these combined can lead to a very high risk of heart attack or angina.
Psychological stress has also been shown to increase susceptibility to viral infection. Subjects exposed to stress showed increases in infection rates from 74% to 90%, and clinical colds rose from 27% to 47%. Earlier studies have shown that medical students have an increased risk of mononucleosis during examination periods (McEwen & Stellar, 1993). This is not surprising, as stress does suppress the immune system; latent viruses then have an easier time resurging, since the body cannot defend itself as well (Brosschot, et al, 1994). This is supported by studies showing that colds and other infections manifest themselves on weekends after busy and stressful work weeks. Additionally, studies on monkeys have shown that ulceration showed up most severely during the rest and recovery periods, rather than during the stress period itself (McEwen & Stellar, 1993).
In conclusion, psychological stress does have a significant affect on the immune system. It raises catecholamine and CD8 levels, which suppresses the immune system. This suppression, in turn, raises the risk of viral infection. Stress also leads to the release of histamines, which can trigger severe broncoconstriction in asthmatics. Stress increases the risk for diabetes mellitus, especially in overweight individuals, since psychological stress alters insulin needs. Psychological stress also alters the acid concentration in the stomach, which can lead to peptic ulcers, stress ulcers, or ulcerative colitis. Chronic stress can also lead to plaque buildup in the arteries, especially if combined with a high-fat diet. This buildup is called atherosclerosis, and is often responsible for angina or heart attacks, which are usually brought on by acute stress themselves. These diseases are by no means the only ones connected with psychological stress, although they are the most common. Further research is needed to clarify exactly how stressors contribute to each of these problems, so that treatment can be given to protect the body from these diseases.