Immune response

BACKGROUND

The immune response is a defensive reaction against harmful substances, such as viruses or bacteria, which enter the body. The immune response helps protect the body from disease, infection, and cancer.

The immune system is a complex network of cells, proteins, tissues, and organs in the body that work together to fight off harmful substances and disease-causing microorganisms, called pathogens.

The immune system is also responsible for allergic reactions. An allergic reaction occurs when the body overreacts to substances called allergens, which are normally harmless in healthy individuals. For instance, if the immune system mistakes substances, such as pollen, fungus spores, parasites, or animal dander, for a harmful invader, the body will launch an attack. This reaction causes allergy symptoms such as sneezing, runny nose, and hives.

If the immune system is not functioning properly, individuals are more susceptible to diseases, infections, and cancers. This is because the immune system is the body's first line of defense against these conditions. Some patients may be born with immune disorders, such as Nijmegen breakage syndrome. Others may acquire immune disorders, such as HIV, later in life.

Some individuals may develop autoimmune system disorders, which cause the immune system to be overactive. Autoimmune disorders occur when the immune system attacks the body's cells because they are mistaken for harmful invaders, such as bacteria. These disorders can destroy body tissues, cause abnormal organ growth, and/or impair organ function.

The immune response can be broken down into two major parts: the humoral immune response and cell-mediated response. The humoral immune system involves proteins called immunoglobulin antibodies that help signal immune cells to destroy harmful substances that enter the body. The second part of the immune system, called cell-mediated immunity, involves white blood cells that destroy foreign invaders in the body. There are several different types of white blood cells that have important roles in the immune response, including B-cells and T-cells.

IMMUNE SYSTEM ORGANS

Bone marrow: Bone marrow is the soft, spongy tissue found inside bones. All of the cells of the immune system initially come from the bone marrow during a process called hematopoiesis. During this process, stem cells in the bone marrow either develop into mature immune cells or immature immune cells. The immature immune cells leave the bone marrow and mature in other areas of the body, such as the thymus gland.

Lymph nodes: The lymph nodes are small glands found throughout the body. The lymph nodes filter a type of bodily fluid called lymph fluid. The immune cells inside the lymph nodes capture foreign substances that are present in this fluid, preventing them from causing an infection.

Spleen: The spleen, which is a dark red oval organ on the left side of the body, filters the blood. The immune cells in this organ destroy foreign invaders that are present in a person's blood.

Thymus gland: The thymus gland, which is located in the front of the chest area, produces white blood cells called T-cells that help the body fight against disease and infection. This gland is most prominent early in life. Once an individual reaches puberty, the gland gradually decreases in size throughout adulthood.

IMMUNE RESPONSES

Humoral response: The humoral immune system involves proteins called immunoglobulin antibodies that fight against disease and infection. These antibodies, which are secreted by white blood cells called B-cells, detect and bind to foreign substances that enter the body. Once the antibody detects a foreign substance in the body, the antibody attaches to it. This action signals other immune cells to destroy it.

There are five classes of immunoglobulin antibodies: immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE), immunoglobulin G (IgG), and immunoglobulin M (IgM). Each antibody is specific for a certain invader.

IgA antibodies are primarily found in the nose, airway passages, digestive tract, ears, eyes, saliva, tears, and vagina. These antibodies protect body surfaces that are frequently exposed to foreign organisms and substances from outside of the body. The IgA antibodies make up about 10-15% of the antibodies found in the body.

IgG antibodies are the smallest, but most abundant antibodies in the body, making up 75-80% of all of the antibodies in the body. They are present in all body fluids. In addition, they are the only antibodies that can cross the placenta during pregnancy. Therefore, the IgG antibodies of a pregnant woman help protect her fetus. IgG antibodies are considered to be the most important antibodies for fighting against bacterial and viral infections.

IgM antibodies are the largest type of antibody. They are found in the bloodstream and lymph fluid. The IgM antibodies are the first antibodies that are produced in response to an infection. They also stimulate other immune system cells, including macrophages, to produce compounds that can destroy invading cells. IgM antibodies normally make up about 5-10% of all of the antibodies in the body.

IgD antibodies are found in small quantities in the tissues that line the abdominal and chest cavity of the body. The function of IgD antibodies is not well understood. Researchers believe they play a role in allergic reactions to some substances, such as milk, medications, and poisons. IgD and IgE are present in very small amounts in normal human serum.

IgE antibodies reside in the lungs, skin, and mucous membranes. They induce allergic reactions against foreign substances like pollen, fungus spores, parasites, and animal dander. IgE antibody levels are often high in people who have allergies. When IgE is active, the antibody triggers an allergic reaction called a hypersensitive reaction.

An allergic response occurs when the immune system overreacts to substances called allergens, which are normally harmless in healthy individuals. The immunoglobulin antibodies detect and bind to the allergens. These antibodies also trigger the release of chemicals, including histamine, which cause allergic symptoms such as runny nose, sneezing, and hives.

Cell-mediated immune response: The second part of the immune system, called cell-mediated immunity, involves white blood cells that help destroy harmful invaders that enter the body. This response helps prevent disease and infection.

Cytotoxic T-cells destroy cells infected with viruses and cancers. When a cell is infected with a virus or it is cancerous, the molecules on the cell's surface are changed. Cytotoxic T-cells identify these specific molecules as harmful substances and destroy the infected cells. Cytotoxic T-cells contain pouches, called granules, which are filled with chemicals that kill infected cells on contact. These cells are also involved in organ transplant rejection. The cytotoxic T-cells attack the donated organ because it is perceived as an infected body cell.

Natural killer (NK) T-cells are similar to cytotoxic T-cells because they recognize and destroy body cells that have become infected with viruses or cancer. They also have granules that are filled with chemicals that destroy infected cells on contact. Unlike cytotoxic cells, the NK T-cells do not need to recognize a specific molecule on the surface of other immune cells in order to become activated. Instead, they attack cells that do not have external molecules that label them as body cells.

Macrophages, another type of white blood cell, are found inside the tissues of humans. Macrophages are phagocytes, which means they are able to engulf foreign substances that enter the body. Macrophages are in a resting state until chemicals that are released during an immune response activate them. Upon activation, these cells travel toward the site of injury and they engulf disease-causing organisms, called pathogens. Once a macrophage ingests a pathogen, the pathogen is trapped inside the cell's food vacuole. Enzymes and toxic substances inside the cell start to ingest the foreign substance. The cells then secrete chemicals called interferons, lysozyme, and other factors that stimulate other immune cells to respond to the foreign invaders and destroy them.

TYPES OF IMMUNITY

Innate immunity: All humans are born with innate (natural) immunity. Innate immune responses are both immediate and nonspecific. In other words, immune cells involved in innate immunity are not specific to just one type of foreign substance. Instead, the immune cells engulf substances that are identified as foreign. This response primarily occurs on the external barriers of the body, including the skin, nose, throat, and gastrointestinal tract. It is the body's first line of defense to prevent disease-causing organisms from entering the body.

Adaptive immunity: Adaptive immunity is a type of protection that develops over the course of an individual's life. Adaptive immunity involves the development of immunoglobulin antibodies that respond to specific foreign substances that enter the body. When individuals are exposed to certain foreign invaders, the body develops antibodies against the pathogens. Then, if the same substance enters the body in the future, the body is now prepared to respond quickly because the antibodies are already developed.

Passive immunity: Passive immunity describes the immune system of babies who are less than six months old. Because a fetus' immune system is not fully developed, pregnant mothers pass immunoglobulin antibodies from their bloodstream, through the placenta, and to the fetus. These antibodies are an essential part of the immune system. They identify and bind to harmful substances that enter the body. When this happens, other immune cells are triggered to destroy the foreign substance. As a result, antibodies help prevent disease and infection. This provides the fetus with passive immunity.

Immunoglobulin G (IgG) is the only antibody that crosses the placenta to the fetus during pregnancy. IgG antibodies are the smallest, but most abundant antibodies, making up for 75-80% of all the antibodies in the body. They are present in all body fluids, and they are considered to be the most important antibodies for fighting against bacterial and viral infections. These antibodies help protect the fetus from developing an infection inside the womb.

Immediately after birth, the newborn has high levels of the mother's antibodies. Babies who are breastfed continue to receive antibodies via breast milk. Breast milk contains all five types of antibodies, including immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE), IgG, and immunoglobulin M (IgM). This is called passive immunity because the mother is "passing" her antibodies to her child.

INTEGRATIVE THERAPIES

Good scientific evidence :

Ginseng : For more than 2,000 years, the roots of this slow-growing plant have been valued in Chinese medicine. Several studies suggest that ginseng can effectively enhance immune system function.

Avoid ginseng with a known allergy to plants in the Araliaceae family. There has been a report of a serious life-threatening skin reaction, possibly caused by contaminants in the ginseng formulation.

Zinc : Zinc formulations have been used since ancient Egyptian times to enhance wound healing. Zinc appears to be an essential trace element for the immune system, but there is little research on the effect of zinc supplementation on immune function and most studies focus on patients with specific diseases. Zinc gluconate appears to exert beneficial effects on immune cells, improving CD3 and CD4 counts and increasing CD4/CD8 ratios in children. There are relatively few studies that examine zinc levels and the effects of zinc supplementation on the health of the elderly population. Further research is needed before a firm conclusion can be made.

Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride, since studies have not been done on its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used because studies cannot rule out the possibility of harm to the fetus.

Unclear or conflicting scientific evidence :

Arginine (L-arginine) : L-arginine helps maintain the body's fluid balance, fights infection, and aids in wound healing, hair growth, sperm production, and blood vessel relaxation. Preliminary research results suggest that arginine supplementation may enhance the immune response elicited by the pneumococcal vaccine in older people. More studies are needed to confirm these results.

Avoid if allergic to arginine. Avoid with history of stroke, liver disease, or kidney disease. Avoid if pregnant or breastfeeding. Use cautiously if taking blood-thinning drugs (like warfarin) and blood pressure drugs, herbs, or supplements with similar effects. Check blood potassium levels.

Astragalus : In traditional Chinese medicine (TCM), astragalus is commonly found in mixtures with other herbs. Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. High quality human research is necessary before a firm conclusion can be drawn.

Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research and in traditional accounts. There are published reports from China of white blood cell counts increasing during the use of astragalus preparations, although details are limited. Reliable scientific study has not been conducted in this area. High-quality human research is necessary before a firm conclusion can be drawn.

Avoid if allergic to astragalus, peas, or any related plants or with a history of Quillaja bark-induced asthma. Avoid with aspirin, aspirin products, or herbs or supplements with similar effects. Avoid with inflammation (swelling), fever, stroke, transplant, or autoimmune diseases (such as HIV/AIDS). Stop use two weeks before surgery/dental/diagnostic procedures with a risk of bleeding and avoid use immediately after these procedures. Use cautiously with bleeding disorders, diabetes, high blood pressure, lipid disorders, or kidney disorders. Use cautiously with blood-thinners, blood sugar drugs, diuretics, or herbs and supplements with similar effects. Avoid if pregnant or breastfeeding.

Beta-carotene : Beta-carotene is a member of the carotenoids. They are naturally found in many fruits, grains, oil, and vegetables (such as green plants, carrots, sweet potatoes, squash, spinach, apricots, and green peppers). Preliminary research of beta-carotene for immune system maintenance or stimulation shows mixed results. Further research is needed before a conclusion can be drawn.

Avoid if sensitive to beta-carotene, vitamin A, or any other ingredients in beta-carotene products.

Cat's claw : Cat's claw is widely used in the United States and Europe, and it is one of the top herbal remedies sold, despite a lack of high-quality human evidence. In Germany and Austria, cat's claw is only available by prescription. A few early studies suggest that cat's claw may boost the immune system. However, results from different studies have not agreed with each other. Further research is needed before a firm conclusion can be made.

Avoid if allergic to Cat's claw or Uncaria plants or plants in the Rubiaceae family such as gardenia, coffee, or quinine. Avoid with a history of conditions affecting the immune system (such as AIDS, HIV, some types of cancer, multiple sclerosis, tuberculosis, rheumatoid arthritis, or lupus). Use cautiously with bleeding disorders or history of stroke, or if taking drugs that may increase the risk of bleeding. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding. Cat's claw may be contaminated with other Uncaria species. Reports exist of the potentially toxic Texan grown plant Acacia gregii being substituted for cat's claw.

Copper : Copper is a mineral that occurs naturally in many foods including vegetables, legumes, nuts, grains, and fruits, as well as shellfish, avocado, beef, and animal organs such as the liver and kidney. Copper is involved in the development of immune cells and immune function in the body. Severe copper deficiency appears to have side effects on immune function, although the exact mechanism is unclear.

Avoid if allergic/hypersensitive to copper. Avoid use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia, occasionally observed in disease states including cutaneous leishmaniasis, sickle-cell disease, unipolar depression, breast cancer, epilepsy, measles, Down's syndrome, and controlled fibrocalculous pancreatic diabetes (a unique form of secondary diabetes mellitus). Avoid with genetic disorders affecting copper metabolism, such as Wilson's disease, Indian childhood cirrhosis, or idiopathic copper toxicosis. Avoid with HIV/AIDS. Use cautiously with water containing copper concentrations greater than 6mg/L. Use cautiously with anemia, arthralgia, and myalgia. Use cautiously if taking oral contraceptives (birth control pills). Use cautiously if at risk for selenium deficiency. The recommended dietary allowance (RDA) is 1,000µg (micrograms) for pregnant women. The RDA is 1,300µg for breastfeeding women.

Echinacea : The roots and herb of Echinacea species have attracted recent scientific interest because they may have immune stimulant properties. Echinacea has been studied alone and in combination with other herbs or supplements for immune system stimulation (including in patients receiving cancer chemotherapy). It remains unclear if there are clinically significant benefits. Additional studies are needed in this area before conclusions can be drawn regarding safety or effectiveness.

Avoid if allergic to plants in the Asteraceae or Compositae family (ragweed, chrysanthemums, marigolds, and daisies). Avoid Echinacea injections. Avoid if history of liver disease or if taking amoxicillin. Avoid in transplant patients. Use cautiously if driving or operating heavy machinery or if history of asthma, diabetes, conditions affecting the immune systems (like lupus, TB, AIDS-HIV), or rheumatologic conditions (rheumatoid arthritis). Avoid if pregnant or breastfeeding. Tinctures may contain large amounts of alcohol.

Gamma linolenic acid (GLA) : Gamma linolenic acid (GLA) is a dietary fatty acid. It is found in many plant oil extracts. A limited amount of GLA is found naturally in human breast milk, cold-water fish, and organ meats (such as liver). GLA is commonly sold as a dietary supplement either in the form of capsules or oil. Few clinical trials have investigated the effects of GLA on immune responses in healthy human subjects. Results from one randomized, clinical trial suggest that GLA, as blackcurrant seed oil, may offer some benefits. Further, well-designed clinical trials are required before definite conclusions can be made.

Use cautiously with drugs that increase the risk of bleeding, such as anticoagulants and anti-platelet drugs (blood thinners). Avoid if pregnant or breastfeeding.

Goldenseal : Goldenseal is one of the five top-selling herbal products in the United States. However, there is little scientific evidence about its safety or effectiveness. Goldenseal can be found in dietary supplements, eardrops, feminine cleansing products, cold/flu remedies, allergy remedies, laxatives, and digestive aids. Goldenseal is sometimes suggested to be an immune system stimulant. However, there is little human or laboratory evidence in this area. More research is needed before a firm conclusion can be drawn.

Avoid if allergic or hypersensitive to goldenseal or any of its constituents, such as berberine and hydrastine. Use cautiously with bleeding disorders, diabetes, or low blood sugar. Avoid if pregnant or breastfeeding.

Maitake mushroom : Maitake mushrooms (Grifola frondosa) are fungi that can be eaten. Maitake has been used both as a food and for medical conditions. Animal and laboratory studies suggest that beta-glucan extracts from maitake may alter the immune system. However, no reliable studies in humans are available.

Maitake has not been studied thoroughly in humans and its effects are not well known. Because it has been used historically as a food, it is thought that low doses may be safe. Avoid if allergic or hypersensitive to Grifola frondosa (maitake). Use cautiously with a history of low blood pressure, diabetes, or with drugs, herbs, or supplements that treat such conditions. Avoid if pregnant or breastfeeding.

Massage : Various forms of massage have been practiced to promote well-being, relaxation, pain-reduction, stress-relief, musculoskeletal injury healing, sleep enhancement, and quality-of-life. Preliminary evidence suggests that massage therapy may preserve immune function. Further research is needed before a firm conclusion can be made.

Avoid with bleeding disorders, low platelet counts, or if taking blood-thinning medications (such as heparin or warfarin). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously with a history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.

Meditation : A common goal of meditation is to attain a state of thoughtless awareness of sensations and mental activities occurring at the present moment. Preliminary research reports increased antibody response after meditation. Further study is needed to confirm these findings.

Use cautiously with underlying mental illnesses. People with psychiatric disorders should consult with their primary mental healthcare professional(s) before starting a program of meditation and should explore how meditation may or may not fit in with their current treatment plan. Avoid with risk of seizures. The practice of meditation should not delay the time to diagnosis or treatment with more proven techniques or therapies and should not be used as the sole approach to illnesses.

Mistletoe : Once considered a sacred herb in Celtic tradition, mistletoe has been used for centuries for high blood pressure, epilepsy, exhaustion, anxiety, arthritis, vertigo (dizziness), and degenerative inflammation of the joints. A few small trials found mistletoe to be promising as an immunostimulant in individuals with the common cold. Further research is needed to confirm these results.

Avoid if allergic or hypersensitive to mistletoe or to any of its constituents. Anaphylactic reactions (life threatening, shock) have been described after injections of mistletoe. Avoid with acute, highly febrile, inflammatory disease, thyroid disorders, seizure disorders, or heart disease. Use cautiously with diabetes, glaucoma, or with cholinergics.

Probiotics : Probiotics are beneficial bacteria and are sometimes called "friendly germs." They help maintain a healthy intestine and aid in digestion. They also help keep harmful bacteria and yeasts in the gut under control. Most probiotics come from food sources, especially cultured milk products. Probiotics can be taken as capsules, tablets, beverages, powders, yogurts, and other foods. Lactobacillus in fermented milk, low-fat milk, or lactose-hydrolyzed low-fat milk may enhance immune function. Bifidobacterium may as well, including in the elderly. However, commercially produced yogurt may not yield similar benefits. There is some evidence that probiotics added during food preparation (e.g., waffles with Enterococcus faecium M-74 added) can enhance immune functioning. More studies are needed, particularly with yogurt, before a firm conclusion can be made.

Probiotics are generally considered safe and well tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.

Vitamin A (retinol) : Vitamin A is a fat-soluble vitamin that is derived from two sources: retinoids and carotenoids. Retinoids are found in animal products (such as the liver, kidney, eggs, and dairy products). Carotenoids are found in plants, such as dark or yellow vegetables and carrots. Vitamin A deficiency may compromise immunity, but there is no clear evidence that additional vitamin A supplementation is beneficial for immune function in patients who are not vitamin A deficient.

Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity can occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.

Vitamin B6 (pyridoxine) : Major sources of vitamin B6 include cereal grains, legumes (beans), vegetables (such as carrots, spinach, peas), potatoes, milk, cheese, eggs, fish, liver, meat, and flour. Vitamin B6 is important for immune system function in older individuals. One study found that the amount of vitamin B6 required to reverse immune system impairments in elderly people was more than the current recommended dietary allowance (RDA). Well-designed clinical trials on vitamin B6 supplementation for this indication are needed before a recommendation can be made.

Some individuals seem to be particularly sensitive to vitamin B6 and may have problems at lower doses. Avoid excessive dosing. Vitamin B6 is likely safe when used orally in doses not exceeding the recommended dietary allowance (RDA). The RDA for pregnant women is 1.9mg per day. There is some concern that high-dose pyridoxine taken by a pregnant mother may cause seizures in a newborn. The RDA in breastfeeding women is 2mg per day.

Vitamin E : Vitamin E exists in eight different forms: alpha, beta, gamma and delta tocopherol; and alpha, beta, gamma and delta tocotrienol. Alpha-tocopherol is the most active form in humans. Studies of the effects of vitamin E supplementation on immune system function have yielded mixed results. Further research is needed before a clear conclusion can be drawn.

Avoid if allergic or hypersensitive to vitamin E. For short periods of time, vitamin E supplementation is generally considered safe at doses up to 1,000mg per day. Avoid doses higher than 1,000mg a day. Avoid with retinitis pigmentosa (loss of peripheral vision). Use cautiously with bleeding disorders. The recommended dose of vitamin E for pregnant women of any age is 15mg and the recommended dose for breastfeeding women of any age is 19mg. Use beyond this level in pregnant women is not recommended.

Fair negative scientific evidence :

DHEA (dehydroepiandrosterone) : DHEA (dehydroepiandrosterone) is a naturally occurring hormone that is produced by the adrenal glands. Some authors of textbooks and review articles have suggested that DHEA can stimulate the immune system. However, current scientific evidence does not support this claim.

Avoid if allergic to DHEA. Avoid with a history of seizures. Use cautiously with adrenal or thyroid disorders or if taking anticoagulants or drugs, herbs, or supplements for diabetes, heart disease, seizure, or stroke. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.

Lycopene : Lycopene is a carotenoid found in tomatoes that is present in human serum, liver, adrenal glands, lungs, prostate, colon, and skin. It has been proposed that lycopene and other carotenoids, such as beta-carotene, may stimulate the immune system. However, several studies of lycopene supplements and tomato juice intake in humans report no effects on the immune system.

Avoid if allergic to tomatoes or to lycopene. Due to a lack of conclusive data, avoid if pregnant or breastfeeding.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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