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3. Factors That Impact the Immune System

Factors Affecting Immunity

Environmental and nutritional factors affect immunity. Studies show that nutritional deprivation at an early age is associated with developmental failure of the immune response.

In addition, human activity is having a major impact in the possible advance of new microbial infestations. Collectively, man is creating an environmental and chemical imbalance that is disturbing ecosystems.

Although the true causes of global warming are not absolutely known, (and to some people, do not exist) there are visible signs that can be seen and sometimes felt everywhere in the world. For example, icebergs are melting, the waters are becoming desalinated and the balance is shifting. Electronics such as cell phones, I-pods, computers, video cameras, digital cameras, etc. are morphing quickly creating new toxic possibilities (One can do the math of several billion people disposing of their electronics every few months and years, and can imagine the landfills rising with leaching.

Our environment contains plastics, synthetic chemicals, smog, polyester, pesticides, genetically modified foods, antibiotic gorged animals, intentional bioengineering for terror, genetic engineering for new pharmaceuticals, and experimental and accidental viral monsters created in some archaic labs. We have ingested Teflon for years as it too has infiltrated our every day, not just in cooking pans, but also in building materials, etc. And we wonder why so many new diseases are emerging.

For years tobacco was applauded in the USA. While now it is no longer trendy in the United States it is “fashionable and in style” in other countries. Studies have also shown that cigarette smoke might contain radioactive particles. It was reported in the New England Journal of Medicine that when tobacco is inhaled, two dangerous alpha-emitting radioisotopes enter the body and affect the lymph nodes. The radiochemistry of cigarette smoke is established — a step in the right direction for enhancing health.

Of course in retrospect, many things gain clarity. For example, in the 1950s, shoe departments used X-ray machines to show people how their shoes fit. They didn’t know then that X-rayed feet could be responsible for congenital problems.

Toxic waste that is improperly disposed of may end up in our water supply. It is known that 90% of the world’s toxic waste is disposed of improperly. The list of the potential body toxins is augmented by radiation, petrochemicals, industrial waste, medical drugs, street drugs, pesticides, herbicides and insecticides. Have you read the ingredients in your shampoo or toothpaste lately?

In the last 55 years more pollution has been introduced into the environment than has been contributed in the entire history of the world. Scientists have found that in the past 100 years the chemistry of the environment has changed through progressive poisoning of nature with our man made by-products.

More than 1,000,000,000 pounds of chemicals have been released into the ground threatening the earth’s water supply, and 2,400,000,000 pounds of air emissions have been pumped into the atmosphere.

Impact of Heavy Metals on the Immune System

Mercury, lead, cadmium, arsenic, nickel, and aluminum are considered to be heavy metals that are poisonous. Up to 25% of the US population alone suffers from heavy metal poisoning resulting from environmental contamination due to industrial pollution. As if that were not enough, lead from cooking utensils, cigarette smoke, mercury fillings, aluminum from antacids, and solder in tin cans adds “injury to insult,” as the saying goes.

Mercury is prevalent in our environment and is one of the oldest pollutants. A neurological side effect of mercury has been found to be decreased production of white blood cells, including T cells. Mercury is found in pesticides, cosmetics, dental substances, tuna, swordfish and pharmaceuticals. Aluminum is also considered a toxic heavy metal found in food additives, antacids, baking powder and some pots and pans. Aluminum toxicity has been implicated in Alzheimer’s, constipation and schizophrenia. The list continues.

Cadmium is pervasive in air, food and water and because it’s a cumulative poison it is a serious health problem. It is especially prevalent in cigarette smoke, coffee, and gasoline. Cadmium toxicity creates retarded immune responses due to effect on the kidneys, liver, and T cell production.

Stress and the Immune System

We all experience stress. Whether it is everyday hassles, such as being stuck in traffic, watching the daily news, or having disagreements with loved ones, stress is there. With more acute forms of stress, such as pain, traumatic experiences, or horrific events, stress bombardment cannot be avoided.

The immune system is suppressed during periods of stress to serve as a protective function in the evolution of our species (Carson, Butcher, & Mineka, 2002). Chronic stress induces an alteration of the function of thyroid axis that alters the immune response. (Life Science 2000 Nov 17; 67(26): 3171-9)

Stress Defined

Stress is defined as a feeling of emotional or physical tension. Emotional stress usually occurs when situations are considered difficult or unmanageable. Hans Selye, the pioneer in the study of stress, calls it “the rate ( of wear and tear within the body” a series of bodily changes. Factors that cause stress are called stressors.

A stressor is any stimuli that cause a nonspecific response in an individual, otherwise known as stress (Elliott and Eisdorfer, 1982). There are two main categories of stress: acute and chronic

Acute. Acute stressors include unexpected or uncontrollable noise, under or over stimulation, work overload, prestige or status loss, electric shock, uncontrollable situations, physical illness, surgery, threats to self-esteem, and traumatic experiences.

Chronic. Chronic stressors include sleep deprivation, daily “hassles,” 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.

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.

Stress is thus sometimes considered to be a vague and ambiguous term. However, it causes specific and documented changes to the immune system, for example to Helper T cells (also known as CD4 cells), and suppressor T cells (known as CD8 cells) (Glaser, Anderson & Anderson, 1992).

Individual differences in responding to challenge are products of genetics, developmental and environmental influences. Life experience also plays a role. Some people may cope well with stress, rising to the challenge and meeting their goals. Whereas others may be adversely affected by stressors, which can lead to fatigue or even mental disorders.

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.

High and Low Reactors

High reactors are people who are significantly affected by stress, as shown by a significant increase in heart rate, blood pressure, catecholamine, and CD8 cells. Low reactors show little or no change in those areas (Manuck, et al, 1991).

Catecholamines are chemicals that work in nerve transmission. The three main catecholamines include dopamine, epinephrine, and norepinephrine. These increase under stress.

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).

Increases such as these can suppress aspects of immune function, including natural killer cell (cells that attack antigens without having recognized them first) activity. 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.


Psychoneuroimmunology attempts to understand the interactions between the nervous system, immune system, and psyche. This is a rich area of research in which much work has been done testing many different theories. There is a highly active area of research n which psychologists have been studying the effects of stress and psychopathology on the immune system.

This research has found correlations between stress, depression, and the immune system. For example, depression influences the health of a person either by having a direct relationship on the immune system, or by indirectly influencing self care.

In a large study involving parents of children with cancer and parents with children who were relatively healthy, the results showed that chronic psychological stress might reduce the immune system’s reactions to hormonal secretions that were normally used to fight the inflammatory response (Miller, Cohen, & Ritchey, 2002).

We know that when we are stressed, more adrenaline and cortisol are produced and there is a finite amount of resources. When the resources allotted to stress are increased, they must correspondingly be decreased someplace else, and the someplace else is the immune system.

As the output of adrenaline and cortisol are increased, the body compensates for the energy expenditure by decreasing the amount of energy available for the immune system. Consequently, the numbers of antibodies drop and strength of lymphocytes also diminish.

The brain is connected to organs of the immune system (the spleen, thymus, lymph nodes, and bone marrow); stress and depression affect their performance. But most interesting of all is the connection between the neuropeptides produced by brain cells and the rest of the body. In much the same way that the immune system uses the interleukins to communicate with itself, the brain uses the hormone-like neuropeptides to communicate with itself and the rest of the body, including the immune system.

For example, the brain produces one kind of neuropeptide. The cells of the immune system have specific receptor sites for these “up” chemicals. Once received and locked into the receptor sites, these neuropeptides literally cause the cells of the immune system to strengthen and build.

Correspondingly, when we are depressed, we produce a different set of neuropeptides. Immune cells also have specific receptors for these “down” communicators, whose net effect on the immune system is to shut it down.

The brain cells have receptor sites for the interleukins and interferon produced by the lymphocytes of the immune system. Some macrophages and activated lymphocytes actually are capable of producing their own neuropeptides to communicate directly back to the brain in its own language. The communication is bi-directional, constant, and total.

A group of medical researchers in Montreal tracked 222 post heart attack male and female victims. The January 1995 issue of the American Journal of Medicine reported a study of patients with a history of heart disease. It was found that those who were depressed were eight times more likely to develop potentially deadly heart rhythms than those who were not depressed.

Ten-Year Study

A ten-year study was conducted to follow the mortality rates of people who experienced a stroke. Those who had been diagnosed with either major or minor depression were 3.4 times more likely to have died within the follow-up period than those who had not been diagnosed. In another study looking at 194 heart attack patients, those who reported lower amounts of emotional support were nearly 3 times more likely to die within 6 months than those with higher levels of emotional support.

Statistically, it turns out that people are more likely to die on Monday morning before going to work than at any other time of the week. There has been much speculation as to why this happens but, in general, most people agree it’s something along the lines of: “Most people have heart attacks on Monday morning, because they are stressed that they are heading back to jobs they can’t stand after a weekend off.”

Having a positive attitude seems to correlate with an increased ability of the immune system in fighting diseases. In cases where patients have exhibited fear before a surgery, they have had a longer healing time afterwards. Correlations were observed in the number of lymphocyte cells and the person’s level of optimism.

Chronic psychological stress, such as dealing with a terminal illness in the self or loved ones, has been shown to reduce immune effectiveness. Positive attitude correlates strongly with increased ability of the immune system to fight pathogens.

Performance stress, such as that of students during an examination period, seems to correlate with a decrease in disease-fighting cells and the response of the immune system. Persons with an effective social support structure have been shown to have stronger immune abilities. Thus, other things being equal, psychosocial environment has a very powerful effect on the immune system.

Cardiovascular diseases are another area where stress could have a negative effect. The natural response of the “fight or flight” activation mechanism could have a decidedly negative impact on the cardiovascular system. Since the activation of the fight or flight system involves an increase in the heart rate, a frequent activation could increase the possibility of a heart attack or other negative aspect of the disease. Specifically, a study was done in an industrial work environment in which a much higher frequency of cardiovascular mortality was found to correlate with an environment in which there was very little reward incentive (Kivimaki et al., 2002).

Mood and Immunity

Mood can have an effect on immunity. A study with the common cold and emotions showed that participants with happy emotions exhibited a greater ability to fight off the cold when given a squirt of the rhinovirus (Jones, 2003). Inhibition of emotions could be another stress factor negatively affecting health. The ability to cry is healthier than not having the ability to do so.

Bottling up negative emotions seems to tie up resources of the immune system. Individuals who disclosed a tragic event seemed to have an elevated immune response and generally were healthier than those who inhibited expression of these emotions. There is considerable evidence that talking about problems and using mental health services decreases the number of sick days, and lowers health costs for these individuals (O’Leary, 1990).

One study of stress indicated that depression has its roots in the brain’s mood and pleasure pathways. The stress exposure can cause the glucocorticoid hormone to be overly active which causes a depletion of norepinephrine levels in locus coeruleus neurons. This has an effect of slowing the attentiveness within the individual. They become emotionless and inactive (Salzano, 2003).

The conclusion of another study was that schizophrenic patients had a reduced ability for cytokine to fight inflammations. The reason for the findings could be explained by a schizophrenic’s hypothalamus-pituitary-adrenal dysfunction. The endocrine system has close interactions with the immune system (Kudoh, Sakai, Ishiria, & Matsuki, 2001).

A report in the Archives of General Psychiatry finds that marital discord can slow the body’s ability to heal from trauma or surgical wounds. This was demonstrated by a team at Ohio State University, led by Jan Kiecolt-Glaser, a professor of psychiatry and psychology, and her husband, Ronald Glaser, an immunology professor. They found that married couples that showed high levels of hostility to each other needed two days longer to heal from wounds compared with couples whose hostility levels were low. Even typical married couples that argue for just a half hour slow their ability to heal from wounds by about one day (Bowman, Lee, Science, December 7, 2005.)

Type A and Type B Personalities and Stress

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 persons showing Type B behavior. 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. As stated earlier, stress increases catecholamines; the increase of plasma catecholamines enhances platelet aggregation, lowers the threshold to cardiac arrhythmias, and inducing the narrowing of the blood vessels, while suppressing insulin secretion (McEwen & Stellar, 1993). All of these combined can lead to a very high risk of heart attack or angina. Type B people exhibit fewer of these traits.

Diseases Associated with Stress


It is known that asthma, diabetes, various gastrointestinal 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 improve considerably when away from their parents. The changes may have resulted from removal of an interaction that produced frequent stressful situations.

In 1974, research 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 elicited a severe attack (Elliott & Eisdorfer, 1982).

Even more importantly, interactions between antigens and immunoglobulin E antibodies lead to the release of histamine 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.

Post- traumatic Stress Disorder

People who survive natural disasters or severe violence are at high risk for suffering years of post-traumatic stress disorder. First widely recognized in veterans of the Vietnam War, post-traumatic stress disorder is now recognized to be a problem in the larger population. (American Journal of Psychiatry June 2000; 157:911-916).

Post-traumatic stress disorder, or PTSD, is one of the few anxiety disorders where a specific trigger or cause for the disorder can be found. PTSD may be caused by a physical assault, witnessing death, the death of a loved one, or traumatic events such as war or natural disasters. People living with post-traumatic stress disorder often relive the event that triggered the disorder, either through nightmares or flashbacks. They may go to great lengths to avoid places or circumstances that remind them of the traumatic event. Many sufferers develop an emotional ‘numbness’ as the mind attempts to protect itself from the PTSD. Stress has been shown to affect the immune system because of the biochemical changes that occur.

Psychological stress caused by the death of a spouse, a financial crisis or other life-altering event may increase the risk of developing diabetes in middle age. Studies found that these types of major life events were associated with Type I diabetes regardless of family history of the disease, exercise or alcohol use. Type II diabetes usually occurs later in life, and in many cases can be controlled with diet and exercise.

Migraine Headaches

Stress is the leading cause of migraine headaches. High stress events (such as holidays, work deadlines, etc.) often trigger migraine headaches. Studies also note that migraine headache sufferers report higher rates of stress and depression.

Alzheimer’s Disease

Stress may contribute to the development of Alzheimer’s disease by accelerating brain degeneration. Relaxation techniques are known to activate certain areas in the brain involved in attention, motivation and memory. Stimulating these areas is thought to have a protective effect against the neurodegenerative processes that are seen in Alzheimer’s Disease.


Diabetes mellitus 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 occurring between ages 5 and 9 had a significantly higher risk of Type I diabetes (McEwen & Stellar, 1993).

The researchers asked more than 2,000 white adults between 50 and 74 years of age about stressful life events in the past five years, such as the death of a loved one, the end of a relationship or long-lasting financial problems. Diabetes was diagnosed in 5% of people participating in the study and those with the highest number of stressful events (three or more) were 60% more likely to have diabetes as those with fewer stressful life events.

They found that stressful life events increase the diabetes risk by increasing levels of the hormone cortisol and decreasing levels of sex steroids such as testosterone, which have been shown to influence the action of insulin. (Diabetes Care February 2000; 23:197-201).


Psoriasis, eczema, and other inflammatory immune system disorders have been linked to stress. When inflammation occurs, once again cortisol and other glucocorticoid hormones trigger an anti-inflammatory reaction in the immune system. Stress interferes with the immune system’s ability to respond to these hormones. (Archives of Dermatology (July 2003).

Gastrointestinal Diseases

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 occurred 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).

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, and are usually preceded by shock (Ballieux, 1984).

Myocardial Infarction

Myocardial infarction (MI) 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.

Wound Healing

Researchers created skin wounds in mice that were exposed to stressful living conditions, according to Brain, Behavior, and Immunity online 2001; 10.1006. They then applied Streptococcus bacteria to the wounds, and compared the healing rates of the stressed mice with those of mice with skin wounds that were also exposed to the bacteria but did not undergo the same levels of stress.

Mice that had been stressed prior to wounding and infection showed a 30% delay in wound healing at 3 and 5 days compared with the mice that were not stressed, the report indicates.

In addition, the investigators found that after 5 days, the stressed mice had 100,000 times more opportunistic bacteria in their wounds than the non-stressed mice. Seven days after the bacteria exposure, about 85% of the wounds in the stressed mice were infected, versus about 27% of the wounds in the non-stressed mice.

Psychological Stress and Viral Infection

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 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 suppresses the immune system; latent viruses then have an easier time resurging, since the body cannot defend itself as well (Brosschot, et al, 1994).

Research in humans has found that psychological stress can take a toll on the immune system by reducing the concentration of cytokines, proteins that help to ward off infections. In one study, skin wounds on the arms of women who had higher levels of cortisol (stress hormone) had lower levels of key compounds released by the body to mediate healing. (Brain, Behavior, and Immunity 2001; 10.1006)

Increasing Demands to Sustain a Life Style

In today world of increasing demands (both monetary and social pressures), people are experiencing daily life with a new velocity, which appears to limit the time spent in healthy relationships. The intense amount of information that we are constantly and consistently bombarded with from the outside world comes through television, cable, satellite TV, radio, podcasts, blogs, and the internet. These take their toll just to process the information.

The economic pressure from the globalization of the economy and its demands for increased productivity in order to compete successfully is a major new source of stress. The drive to sustain or increase life styles limits the amount of time we can physically devote to human-to human interaction (family, friends, etc.). We are just too tired, too busy, too distracted, and this can create additional stress. There is only so much time and energy a person has per day, and stress is felt when that is exceeded.


Psychological stress does have a significant effect 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 bronchial constriction 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. These diseases are by no means the only ones connected with psychological stress, although they are the most common.