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Immune System

The body's defenses against the microorganisms that cause disease.

The immune system provides the human body with protection from the microorganisms that cause disease. Traditionally scientists viewed the immune system as a defensive network that protected the "self from infectious "non-self invaders. In the mid-1990s, some immunologists modified this view of the immune system, creating a new model of the body's immune system that is able to discriminate between beneficial "non-self invaders (food or helpful bacteria) and threatening invaders. One of the leading scientists investigating the functioning of the immune system in the 1990s was Polly Matzinger of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. Matzinger proposed a model of the immune system that responds to invaders only when cells of the body are injured or damaged.

No matter what model is used, immunologists generally agree that the immune systems consists of three lines of defense. The first line is made up of the physical barriers—the skin and mucous membranes—that prevent microorganisms from entering the body. The next line of defense, the innate or non-specific immunity, features responses from cells that surround and digest invaders, and from chemicals like histamine and serum proteins that help to destroy bacteria. The final defense is slower acting but more specific to the invader. This specific immunity calls into action the lymphocytes or white blood cells produced by the thymus and bone marrow.

The human body is constantly bombarded with microorganisms, including viruses (such as those that cause colds and influenza), bacteria (such as those that cause pneumonia and food poisoning), parasites, and fungi. The immune system efficiently wages a daily battle to rid the body of harmful organisms. When the immune system is unable to function because of injury or damage, the consequences are severe. For instance, Acquired Immune Deficiency Syndrome (AIDS) is caused by a virus—human immunodeficiency virus (HIV)—that attacks a key immune system cell, the helper T-cell lymphocyte. Without these cells, the immune system cannot fight off the harmful microorganisms. Eventually, the person succumbs to infections that a healthy immune system would effortlessly neutralize.

Organs of the immune system

The organs of the immune system either make the cells that participate in the immune response or act as sites for immune function. These organs include the lymphatic vessels, lymph nodes, tonsils, thymus, Peyer's patches, and spleen. Lymphatic fluid (or lymph) circulates through the lymph nodes via the lymphatic vessels. The lymph nodes are small aggregations of tissues located throughout the lymphatic system. White blood cells (lymphocytes) that function in the immune response are concentrated in the lymph nodes where foreign cells of microorganisms are detected and overpowered.

The tonsils and Peyer's patches contain large numbers of lymphocytes. Located at the back of the throat and under the tongue (tonsils) and in the small intestine and appendix (Peyer's patches), these organs filter out potentially harmful bacteria that may enter the body via the nose, mouth, and digestive system.

The thymus gland, located within the upper chest region, weighs about 15 grams or one-half ounce at birth. It continues to grow until, by the time the child has reached age 12, the thymus has roughly doubled in size. During childhood, the thymus makes large numbers of the lymphocytes known as T-lymphocytes or T-cells. Around puberty, T-cell production is taken over by the lymph nodes and spleen, and the thymus begins to shrink. By adulthood, it is sometimes impossible to detect in χ rays. Prior to puberty, removal of the thymus due to disease or injury in a child may have a negative effect on both physical growth and the development of immunity to certain organisms.

Bone marrow, found within the interior of bones, also produces lymphocytes that migrate out of the bone marrow to other sites in the body. Because bone marrow is an integral part of the immune system, certain bone cancer treatments that require the destruction of bone marrow are extremely risky, because without bone marrow, a person cannot make lymphocytes. People undergoing bone marrow replacement must be kept in strict isolation to prevent exposure to viruses or bacteria.

The spleen destroys worn-out red blood cells and acts as a reservoir for blood. Any rupture to the spleen can cause dangerous internal bleeding, a potentially fatal condition. The spleen also contains lymphatic tissue and produces lymphocytes.

Overview of the immune system

For the immune system to work properly, two things must happen: first, the body must recognize that it is being threatened by foreign microorganisms. Second, the immune response must be quickly activated before many body tissue cells are destroyed by the invaders.

Barriers: skin and mucous membranes

The skin and mucous membranes act as effective barriers against harmful invaders. The surface of the skin is slightly acidic which makes it difficult for many microorganisms to survive. In addition, the enzyme lysozyme, present in sweat, tears, and saliva, kills many bacteria. Mucous membranes line many of the body's entrances, such as those that open into the respiratory, digestive, and uro-genital tract. Bacteria become trapped in the thick mucous layers and are thus prevented from entering the body.

In the upper respiratory tract, the hairs that line the nose also trap bacteria. Any bacteria that are inhaled deeper into the respiratory tract are swept back out again by the cilia—tiny hairs—that line the trachea and bronchii. One reason why smokers are more susceptible to respiratory infections is that hot cigarette smoke disables the cilia, slowing the movement of mucus and bacteria out of the respiratory tract.

Non-specific immune defenses

Non-specific lymphocytes carry out "search and destroy" missions within the body. If these cells encounter a foreign microorganism, they will either engulf the foreign invader or destroy the invader with enzymes. The following are non-specific lymphocytes:

Macrophages are large lymphocytes that engulf foreign cells. Because macrophages ingest other cells, they are also called phagocytes (phagein, to eat + kytos, cell).

Neutrophils are cells that migrate to areas where bacteria have invaded, such as entrances created by cuts in the skin. Neutrophils digest microorganisms and release microorganism-killing enzymes. Neutrophils die quickly; pus is an accumulation of dead neutrophils.

Natural killer cells kill body cells infected with viruses by punching a hole in the cell membrane, causing the cell to lyse, or break apart.

Fever response is a non-specific response to bacterial or viral invasion. The body responds by increasing its internal temperature, creating conditions that are hostile to the growth of the virus or bacteria.

The inflammatory response is an immune response confined to a small area. When a fìnger is cut, the area becomes inflamed—red, swollen, and warm. These signs are evidence of the inflammatory response. Injured tissues send out signals to immune system cells, which quickly migrate to the injured area. These immune cells perform different functions: some engulf bacteria, others release bacteria-killing chemicals. Other immune cells release a substance called histamine, which causes blood vessels to become wider (dilate), thus increasing blood flow to the area. All of these activities promote healing in the injured tissue.

When the body's immune system reacts to pollen (a harmless substance) as if it were a bacterium, an immune response is prompted. Histamine is released which dilates blood vessels, causes large amounts of mucus to be produced, and stimulates the release of tears. To combat these reactions, many people take antihistamines, drugs that deactivate histamine.

Specific immune defenses

The specific immune response is activated when microorganisms survive or get past the non-specific defenses. Two types of specific defenses destroy microorganisms in the human body: the cell-mediated response and the antibody response. The cell-mediated response attacks cells which have been infected by viruses. The antibody response attacks both "free" viruses that haven't yet penetrated cells and bacteria. Most bacteria do not infect cells, although some do, such as the Mycobacteria that cause tuberculosis. The specific immune response depends on the ability of the immune lymphocytes to identify the invader and create immune cells that specifically mark the invader for destruction. Bone marrow produces an amazing array of lymphocytes, each of which is capable of recognizing one specific molecular shape called an antigen.

Two kinds of lymphocytes operate in the specific immune response: T lymphocytes and B lymphocytes, (T lymphocytes are made in the thymus gland, while B lymphocytes are made in bone marrow). B and T lymphocytes are individually configured to attack a specific antigen. For example, the blood and lymph of humans have T-cell lymphocytes that specifically target the chicken pox virus, T-cell lymphocytes that target the diphtheria virus, and so on. When T-cell lymphocytes specific for the chicken pox virus encounter a body cell infected with this virus, the T-cell multiplies rapidly and destroys the invading virus.

After the invader has been neutralized, some T cells remain behind. These cells, called memory cells, impart immunity to future attacks by the virus. Once a person has had chicken pox, memory cells quickly stave off subsequent infections. This secondary immune response, involving memory cells, is much faster than the primary immune response. When a human is immunized against a disease, the vaccination injects whole or parts of killed viruses or bacteria into the bloodstream, prompting memory cells to be made without a person developing the disease.

Helper T cells are a subset of T-cell lymphocytes present in large numbers in the blood and lymphatic system, lymph nodes, and Peyer's patches. When one of the body's macrophage cells ingests a foreign invader, it displays the antigen on its membrane surface. These antigen-displaying-macrophages, or APCs, are the immune system's distress signal. When a helper T cell encounters an APC, it immediately binds to the antigen on the macrophage. This binding unleashes several powerful chemicals called cytokines. Some cytokines stimulate the growth and division of T cells, while others play a role in the fever response. Still another cytokine, called interleukin II, stimulates the division of cytotoxic T cells, key components of the cell-mediated response. The binding also "turns on" the antibody response. Any disease, such as HIV, that destroys helper T cells destroys the immune system.

Antibodies are made when a B cell specific for the invading antigen is stimulated to divide. The dividing B cells, called plasma cells, secrete antibodies composed of a special type of protein called immunoglobin (Ig).

T cells

T-cell lymphocytes are the primary players in the cell-mediated response. When an antigen-specific helper T cell is activated, the cell multiplies. The cells produced from this division are called cytotoxic T cells. Cytotoxic T cells target and kill cells that have been infected with a specific microorganism. After the infection has subsided, a few memory T cells persist, so conferring immunity.

Chemical signals activate the immune response; likewise, chemical signals must turn it off. When all the invading microorganisms have been neutralized, special T cells (called suppressor T cells) release cytokines that deactivate the cytotoxic T cells and the plasma cells, and the cells of the body return to normal functioning.

Immune system disorders

Sudden Infant Death Syndrome

In 1994, researchers reported in the medical journal The Lancet that abnormal immune response in the respiratory system may contribute to sudden infant death syndrome (SIDS). Two to three times as many T-lymphocytes were found in lungs of children who died from SIDS that in those who died from other causes. In addition, the number of B-lymphocytes appears to be higher in SIDS infants than in others.

The World Resources Institute in Washington, DC, issued a report in 1996 linking the increased exposure to chemical pesticides in the environment and immune system disorders. Developing nations are at the greatest risk, since they often do not regulate pesticide use. The Institute cited the former Soviet republic of Moldova, where, from 1960 to the late 1980s, pesticides were used in concentrations nearly 20 times the average used elsewhere in the world. Eighty percent of children known to have been exposed to the pesticides appear to have irregularities in their immune systems. Because the interpretation of the study results is difficult, more research is needed.

For Further Study

Books

Almonte, Paul. The Immune System. Crest wood House; Maxwell Macmillan Canada; Macmillan International, 1991.

Cook, Allan R. Immune System Disorders Sourcebook: Basic Information for the Layperson. Detroit, MI: Omnigraphics, 1996.

Edelson, Edward. The Immune System. New York: Chelsea House, 1989.

Schindler, Lydia Woods. The Immune System: How It Works. Bethesda, MD: U. S. National Institutes of Health, 1993.

Periodicals

Engelhard, Victor H. "How Cells Process Antigens." Scientific American 271, August 1994, p. 54.

Kedzierski, Marie. "Vaccines and Immunisation (sic)." New Scientist 133, February 8, 1992, p. S1.

Kisielow, Pavelrod. "Self-Nonself Discrimination by T Cells." Science 248, June 15, 1990, p. 1369.

Miller, Jacques. "The Thymus: Maestro of the Immune System." BioEssays 16, July 1994, p. 509.

Radesky, Peter. "Of Parasites and Pollens." Discover 14, September 1993, p. 54.

"Special Issue: Life, Death, and the Immune System." Scientific American 269, September 1993.

Strange, Carolyn. "Rethinking Immunity." BioScience 45, November 1995, pp. 663+.

Travis, John. "Tracing the Immune System's Evolutionary History."Science 261, July 9, 1993, p. 164.