Four Factors That Sabotage a Healthy Immune System
by Nieske Zabriskie, ND
Many factors play important roles in how our body will respond when faced with immune challenges. When our body is overwhelmed from dealing with excessive alcohol intake, secondhand smoke, lack of sunlight, stress or deficient sleep, antioxidant defenses become overwhelmed. When white blood cells are weakened by the oxidative stress occurring from these factors, they are less able to fend off viruses and bacteria.
A good example of the way oxidative stress affects immunity is intense exercise. Although non-strenuous exercise is good for immunity, strenuous exercise increases oxidative stress and therefore lowers immunity.1 In fact, due to increased oxidative stress, moderate and high-intensity cycling and running have been found to decrease the concentration of antioxidant carotenoids in the skin.2
The Immune System 101
Understanding the basics of the immune system is necessary to appreciate how these external factors alter immune function. Innate immunity includes non-specific mechanisms such as fever, stomach acid, skin and mucous membranes, and chemical mediators that cause inflammation. This part of the immune system also includes white blood cells (leukocytes) such as natural killer cells, mast cells, eosinophils, basophils, neutrophils, macrophages and dendritic cells that function to identify and engulf (phagocytize) pathogens.
The complement system is also part of the non-specific response. This is a cascade of protein activation resulting in various immune responses such as opsonization, in which a pathogen is marked for ingestion and destruction by a phagocyte; chemotaxis, in which macrophages and neutrophils are recruited to a site of injury or inflammation; and destruction of susceptible cell membranes or foreign cells.
The acquired immune response is more complex and allows for the formation of an immunological memory. This response includes immunoglobulins (antibodies) including IgA, IgD, IgE, IgM and IgG made by B-lymphocytes and functions by recognition and binding of foreign antigens. T-lymphocytes are also part of the acquired response. T-cells bind to antigens and release various chemical mediators known as cytokines. These chemical mediators include numerous interleukins (IL), tumor necrosis factor (TNF) and interferon (IFN)-gamma. They activate other white blood cells, induce inflammation, destroy weakened and susceptible cells and regulate the immune response.
Factors Affecting The Immune System
Many factors can alter the outcome of the battle between the host immune response and an invading pathogen. The aging process weakens the immune system and predisposes older individuals to a higher rate of immune insults that are often more severe than in younger people. Additionally, secondhand cigarette smoke, alcohol or environmental pollutants can negatively influence the effectiveness of the immune system’s response to a foreign invader. The immune response suppression is frequently attributed to dysregulated cytokine production, the loss of migratory ability of the immune cells or the inability to phagocytize pathogens.3 Lack of sunlight, resulting in vitamin D deficiency, is also an important factor affecting the immune system.
Let’s look at some of these factors in more detail.
Researchers have long known that aging affects the immune system. But a recent study has discovered a new mechanism controlling aging in white blood cells. Each time you recover from an immune insult a percentage of your white blood cells are deactivated. As these deactivated cells accumulate over time, your defenses are weakened.
Until now, aging in immune cells was thought to be largely determined by the length of special caps—called telomeres—on the ends of DNA. Telomeres get shorter each time a white blood cell multiplies. When a telomere becomes too short, the cell is permanently deactivated. This means that immune cells can only be effective for so long and immune protection into old age declines.
However, after studying blood samples, researchers determined that some of the white blood cells in the sample were inactive and yet still had long telomeres. This indicated that another mechanism in the immune system independent of telomere length must be responsible for the cells becoming deactivated. It also indicated that perhaps immune cells thought “dead” could actually be brought temporarily back to life. When the researchers blocked the newly found pathway responsible for the immune cell’s demise, the white blood cells were reactivated.4
Alcohol intake can impact the immune system, depending on the amount and duration. Research suggests that light-to-moderate intake of alcohol high in antioxidants such as red wine enhances immune function. Moderate amounts of beer also have been shown to enhance immunity. In one study, researchers demonstrated that daily moderate consumption of beer (about one, 12-ounce beer for women and two, 12-ounce beers for men) after 30 days of abstinence enhanced non-specific immunity, showing an increase in the absolute values of leukocytes, neutrophils, lymphocytes and basophils in women, and an increase in basophils in men.5
Extensive alcohol intake, however, has the opposite effect and can directly suppress a wide range of immune responses.6 Investigators suggest that excessive alcohol exposure weakens host defenses by impairing function of T and B lymphocytes, natural killer cells and monocytes and macrophages, decreasing the inflammatory response, altering cytokine production and causing abnormal reactive oxygen intermediate generation.7
Binge drinking also has been shown to inhibit immune system activation via toll-like receptors. This results in the inhibition of the release of pro-inflammatory cytokines, which are necessary to combat foreign invaders.8 In fact, the immune system inhibition lasted for at least 24 hours after the alcohol ingestion.8 Furthermore, chronic alcohol ingestion has been shown to activate the complement cascade, resulting in changes to the structure and function of cells in the liver.9
One study investigated the immune response to acute, moderate alcohol consumption in nonalcoholic subjects. The subjects were given 2 mL of vodka per kg body weight and were evaluated for blood levels of cytokines. The results of the study showed that after a bacterial challenge, the cytokines including IFN-gamma were increased after four hours, but were decreased at 16 hours after alcohol ingestion. Additionally, monocytes release of IL-1-beta was decreased at 16 hours after alcohol ingestion upon bacterial stimulation, indicating decreased ability to fight off immune insults.10
Inhalation of smoke, whether from tobacco or wood, also influences our immune function. Cigarette smoke promotes the production of numerous pro-inflammatory cytokines such as TNF-alpha, IL-1, IL-6 and IL-8 and decreases the levels of anti-inflammatory cytokines such as IL-10. Tobacco smoke also activates macrophage and dendritic cells and results in elevated levels of IgE, which is associated with immune hypersensitivity reactions.11 Cigarette smoke weakens innate defenses against pathogens, alters antigen presentation and promotes autoimmunity.12
Research indicates that cigarette smoke alters the immune response toward bacteria. Cells exposed to cigarette smoke and challenged with common bacteria showed various immune alterations including inhibition of bacteria-stimulated production of the cytokines IL-6 and IL-8, and NF-kappaB activation. This study also showed that the addition of antioxidants mitigated the effect of cigarette smoke on IL-8.13
Cigarette smokers are seven-times more likely to contract common viral infections in the lungs compared to nonsmokers. Researchers have shown that cigarette smoke alters anti-viral defenses in the lungs, including reducing the production of anti-viral cytokines and decreasing expression of retinoic-acid-inducible gene (RIG)-I. RIG-I detects viruses and triggers an IFN-mediated response that protects the host against viral infection.14
Similarly, another study evaluated the immune response in the nasal cavity to a common virus in smokers, non-smokers and subjects exposed to secondhand smoke. The study showed that in smokers, nasal fluid had decreased levels of the cytokine IL-6 and increased virus RNA compared to non-smokers. The subjects exposed to secondhand smoke had intermediate values between controls and smokers. Additionally, the study showed that as the nicotine-metabolite cotinine increased, there was a proportional decrease in IL-6 and proportional increase in viral RNA.15
Another interesting study evaluated children exposed to secondhand smoke with repeated upper respiratory symptoms. The cytokine profile of lymphocytes in the adenoids were evaluated and compared to children not exposed to smoke. The study found that the children exposed to secondhand smoke had a lower percentage of IFN-gamma-producing CD8+ T-cells (killer T-cells) in the adenoids than non-exposed children.16
Animal models have demonstrated that exposure to wood smoke also impacts immune function. Macrophages from the lungs in wood-smoke-exposed animals showed decreased adherence to bacteria and phagocytosis compared to animals not exposed to smoke.17
Sunlight and Vitamin D
Vitamin D is a steroid hormone most well known for its role in calcium and bone metabolism. Vitamin D is produced in the skin after exposure to sunlight UVB radiation, hydroxylated in the liver to form 25-hydroxyvitamin D then further metabolized in the kidney to 1,25-dihydroxyvitamin D, the most active form of the hormone. In wintertime in northern countries, sunlight exposure is inadequate for vitamin D production and the main sources are diet and supplementation.
Vitamin D insufficiency is a global issue with widespread health consequences. In particular, research is uncovering the critical role that vitamin D plays in our immune response. Studies indicate that vitamin D influences both innate and acquired immunity. In innate immunity, vitamin D modulates the cytokine response and the production of the peptides cathelicidin and defensins following Toll-like receptor stimulation by foreign lipopeptides. Vitamin D also influences T and B lymphocyte activation, and boosts the activity of monocytes and macrophages.18-19 In addition, vitamin D influences the development of suppressor regulatory T-cells and the maturation of antigen-presenting dendritic cells.20-21 Furthermore, sufficient levels of vitamin D may be associated with enhanced respiratory health.22
A vitamin D blood test can help you find out how much you should be taking. A healthy adult should have vitamin D levels greater than 30 ng/mL and many doctors recommend their patients bring their levels up to 55 ng/mL. If your levels are less than 55 ng/mL, consider taking 1,000 to 5,000 IU per day to bring your levels up to where they need to be, and then retest in 6 to 8 weeks, with the guidance of your healthcare provider.
As mentioned above, moderate exercise supports immune function. If you want to give your immune system a boost, exercising for a little while each day can be helpful. Research indicates that moderate exercise in sedentary individuals stimulates the phagocytic capacity of neutrophils, and the stimulation lasts for at least 24 hours.23 Other studies suggest that exercise training may boost monocyte and T-cell-mediated immunity in elderly individuals.24
Additionally, as the research has shown, antioxidants mitigate many of the changes in immune function caused by external factors. Antioxidants allow for optimal immune function and support host defenses against various invaders. For example, N-acetyl cysteine has prevented the senescence (aging) of immune cells25 while tocotrienols improved lymphocytes ability to resist damage caused by oxidative stress in both younger and older individuals.26
Supplementation with antioxidants may support your immune function, as many studies indicate that immune modulation is, at least in part, controlled by oxidative mechanisms. Vitamins A, C and E, N-acetyl cysteine (NAC), lipoic acid, tocotrienols and astaxanthin, as well as the botanicals Rhodiola rosea, rosemary leaf, and the flavonol myricetin are antioxidants that function throughout your body to combat free radicals and oxidative damage. This combination provides significant synergistic antioxidant activity.
The immune system is highly sensitive to external factors such as smoke inhalation, alcohol intake and low vitamin D levels. Optimizing immune function can mitigate these influences, resulting in enhanced immune function. Antioxidant and vitamin D supplementation, moderate consumption of red wine and beer, and healthy amounts of exercise are simple ways to enhance immune function and support overall health.
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