The Immune System

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THE IMMUNE SYSTEM

CONCEPT

The immune system is a network of organs, glands, and tissues that protects the body from foreign substances. These substances include bacteria, viruses, and other infection-causing parasites and pathogens. Usually, the immune system is extremely effective in performing its work of defending the body, but sometimes an error occurs in this highly complex system, and it can lead to terrible mistakes. The result can be an allergic reaction, which can be as simple as a case of the sniffles and as serious as a fatal condition. Or the error can manifest as an autoimmune disorder, such as lupus, in which the body rejects its own constituents as foreign invaders.

HOW IT WORKS

The Immune System in General

The human body is under near constant attack from pathogens, or disease-carrying parasites, of the type discussed in Infection, Infectious Diseases, and Parasites and Parasitology. No human would live very long without the immune system, which includes two levels or layers of protection, the nonspecific and the specific defenses. The nonspecific defenses, including the skin and mucous membranes, serve as a first defensive line for preventing pathogens from entering the body. The specific defenses are activated when these microorganisms get past the nonspecific defenses and invade the body.

For the immune system to work properly, two things must happen: first, the body must recognize that it has been invaded, either by pathogens or toxins or by some other outside threat. Second, the immune response must be activated quickly, before the invaders destroy many body tissue cells. For the immune system to respond effectively, several conditions must be in place, including the proper interaction of non-specific and specific defenses. The nonspecific defenses on the skin do not identify the antigen (a substance capable of stimulating an immune response or reaction) that is attacking or potentially attacking the body; instead, these defenses simply react to the presence of what it identifies as something foreign. Often, the nonspecific defenses effectively destroy microorganisms, but if these defenses prove ineffective and the microorganisms manage to infect tissues, the specific defenses go into action. The specific defenses function by detecting the antigen in question and mounting a response that targets it for destruction.

THE MAJOR HISTOCOMPATIBILITY COMPLEX.

How does the specific system "know" what is foreign and what is part of the body? The cell membrane of every cell is studded with various proteins, which together are known as the major histocompatibility complex, or MHC. The MHC is a kind of pass code, since all cells in the body must possess an identical pattern so that the body will identify those cells as belonging to the "self." An invading microorganism, such as a bacterium, does not have the same MHC, and when the immune system encounters it, it alerts the body that it has been invaded by a foreign cell.

Every person has his or her nearly unique MHC, and the response of the immune system to foreign MHC can pose a problem where organ transplants are concerned. Because the immune system interprets the transplanted organ, with its foreign MHC, as an invader, the body may reject the transplant, and therefore organ recipients usually take immunosuppressant drugs to quell the immune response. Furthermore, doctors often attempt transplants only between close relatives, who are likely to have genetically similar MHCs, or try to find organs that match in the major histocompatibility antigens.

Parts of the Immune System

The organs of the immune system include the lymphatic vessels, lymph nodes, tonsils, thymus, Peyer's patch, and spleen. Each of these organs either produces the cells that participate in the immune response or serves as a site for immune function. Lymphocytes, a type of white blood cell, are concentrated in the lymph nodes, which are masses of tissue that act as filters for blood at various places throughout the body-most notably the neck, under the arms, and in the groin. As the lymph (white blood cells plus plasma) filters through the lymph nodes, foreign cells are detected and overpowered.

The tonsils, located at the back of the throat and under the tongue, contain large numbers of lymphocytes and filter out potentially harmful bacteria that might enter the body via the nose and mouth. Peyer's patches, scattered throughout the small intestine and appendix, are lymphatic tissues that perform this same function in the digestive system. The thymus gland, located within the upper chest region, is another site of lymphocyte production, though it is most active during childhood. The thymus gland continues to grow until puberty, protecting a child through the critical years of early development, but in adulthood it shrinks almost to the point of vanishing.

Marrow, the soft tissue at the core of bones, is a key producer both of lymphocytes and of another component of blood, the hemoglobin-containing red blood cells. Because of its critical role in the immune system, it is a very serious decision to allow marrow to be extracted (itself an extremely serious operation, of course) for use in a cancer treatment, as described in Noninfectious Diseases. The spleen, in addition to containing lymphatic tissue and producing lymphocytes, acts as a reservoir for blood and destroys worn-out red blood cells.

ANTIBODIES, B CELLS, AND T CELLS.

The functioning of the immune system also calls into play a wide array of substances, most notably antibodies and the two significant varieties of lymphocyte: B cells and T cells. Antibodies, the most well known of the three, are proteins in the human immune system that help fight foreign invaders. B cells (B lymphocytes) are a type of white blood cell that gives rise to antibodies, whereas T cells (T lymphocytes), are a type of white blood cell that plays an important role in the immune response. T cells are a key component in the cell-mediated response, the specific immune response that utilizes T cells to neutralize cells that have been infected with viruses and certain bacteria. There are three types of T cells: cytotoxic, helper, and suppressor T cells. Cytotoxic T cells destroy virus-infected cells in the cell-mediated immune response, whereas helper T cells play a part in activating both the antibody and the cell-mediated immune responses. Suppressor T cells deactivate T cells and B cells when needed, and thus prevent the immune response from becoming too intense.

The intricacies of the immune system's functioning are far beyond the scope of this essay. The reader interested in a more in-depth review of the substances, organs, glands, and processes is encouraged to seek clarification from a textbook. On the other hand, a very basic and nontechnical example of how the body resists infection can help clarify, in general terms, how the immune system does its work.

REAL-LIFE APPLICATIONS

Protecting the Body

As discussed in Infection, not all bacteria are bad; in fact, many are helpful or even essential to humans. When the word bacteria is mentioned, however, most of us think of the "bad" bacteria, which is understandable, since there are so many of them and their effects can be so dramatic. Suppose such a bacterium enters the body, which is an easy situation to imagine—it happens all the time. Indeed, even as you are reading these words, literally trillions of bacteria the world over are attempting to invade human bodies, including your own. Their chances of success are determined by the immune system and response.

Most of the time, the skin provides us with sufficient protection from invaders, but if the skin is broken, it creates a pathway for invasion. Even a minor cut on a finger can serve as an opening for a microorganism that, once inside the body, will flourish in the body's warm, blood-washed interior. When it is established, the bacterium begins to divide rapidly, but already the specific immune system has begun to mount its resistance, and sometimes evidence of the battle can be seen on the outside—for example, in the form of a red, pus-exuding welt. In the bloodstream, lymphocytes engulf bacteria and carry them toward the lymph nodes. For this reason, when the body is under attack, it begins producing white blood cells at an accelerated rate, and for this reason doctors sometimes measure a patient's white blood cell count. If the number is high, the physician knows that an infection is active somewhere in the patient's body.

Killer blood cells, known by the generic name phagocyte, engulf the bacteria and digest-them, but even as this is occurring, the rapid reproduction of the bacterium provides a challenge to the immune system. If the infectious agent reproduces at a rate beyond the control of the immune system, the physician may provide help in the form of an antibiotic. Alternatively, he or she may lance (cut open) a superficial infection to allow it to drain and to provide access for an antiseptic agent. If the bacterial invasion is minor, the immune system soon dispatches the invader, and the system returns to normal.

Often, some of the white blood cells form antibodies against such invading bacteria, so that the immune system will be better armed to combat any future invasions by the same microorganism. The white blood cell count returns to its normal level, but still with the capability of mobilizing the immune defense on short notice. It is this response that is the basis for inoculations against certain infections, a topic discussed in Immunity. Sometimes, however, something goes wrong in the production of antibodies, and instead of properly protecting the body against invaders, the immune system creates an allergy.

Allergies

An allergy is a change in bodily reactivity to an antigen as a result of a first exposure. Allergies bring about an exaggerated reaction to substances or physical states that would normally have little significant effect on a healthy person. Although the immune system behaves as if it is fighting off a pathogen, in fact, it is launching a complex series of reactions against an irritant. The irritant, or allergen, may well be an otherwise innocuous substance that hardly bothers a person without the allergy. It could even be something that other people enjoy—for example, peanuts or bananas—or at least something, such as animal hair, that does not typically cause people undue discomfort. Allergies also may involve a substance, such as venom from a bee sting, that most people consider far from pleasant but which does not pose a serious threat to someone who is not allergic to it.

In extreme cases of allergic reaction, the situation that follows exposure to an allergen truly is one of life and death. The immune response may be accompanied by a number of stressful symptoms, ranging from mild reactions, such as hives (the formation of red, swollen areas on the surface of the skin) to a life-threatening situation known as anaphylactic shock. The latter, a condition characterized by a sudden drop in blood pressure and difficulty in breathing, can be accompanied by acute skin irritation in the form of angry red boils all over the body. Collapse or coma can ensue and may result in death.

CAUSES OF ALLERGY.

Pollens from grasses, trees, and weeds produce such allergic reactions as sneezing, runny nose, swollen nasal tissues, headaches, blocked sinuses, and watery, irritated eyes. Of the 46 million allergy sufferers in the United States, about 25 million have this form of allergy, known to scientists as rhinitis but to the populace as hay fever. Other common allergens are dust and dust mites, pet hair and fur, insect bites, certain foods or drugs, and skin contact with specific chemical substances. About 12 million Americans are allergic to a variety of chemicals.

Some people are allergic to a wide range of substances, while others are affected by only a few or none. Why the difference? The reasons can be found in the makeup of an individual's immune system, which may produce several chemical agents that cause allergic reactions. The main immune system substances responsible for the symptoms of allergy are the histamines that are produced after exposure to an allergen. When an allergen first enters the body, the lymphocytes make what are known as E antibodies. These antibodies attach to mast cells, large cells that are found in connective tissue and contain histamines. The histamines are chemicals released by basophils, a type of lymphocyte, during the inflammatory response.

The second time a given allergen enters the body of a person who has an allergy, it becomes attached to the E antibodies. They stimulate the mast cells to discharge their histamines and other anti-allergen substances. One type of histamine travels to various receptor sites in the nasal passages, respiratory system, and skin, dilating smaller blood vessels and constricting airways. The results include some of the reactions associated with allergies, for instance, sneezing or the formation of hives. Another type of histamine constricts the larger blood vessels and travels to the receptor sites found in the salivary and tear glands and in the stomach's mucosal lining. These histamines stimulate the release of stomach acid, thus creating a stomach ulcer condition.

TREATMENTS.

There are many treatments for allergy, including (obviously) avoidance of the substance to which the patient is allergic. Among these treatments are the administration of antihistamines, which either inhibit the production of histamine or block histamines at receptor sites. After the administration of anti-histamines, E antibody receptor sites on the mast cells are blocked, thereby preventing the release of the histamines that cause the allergic reactions. The allergens are still there, but the body's allergic reactions are suspended for the period of time that the antihistamines are active. Antihistamines, sold both in prescription and over-the-counter forms, also constrict the smaller blood vessels and capillaries, thereby removing excess fluids. Decongestants can bring relief as well, but they can be used for only a short time, since their continued use can irritate and intensify the allergic reaction.

In cases of extreme allergic reaction leading to anaphylactic shock, the patient may require an injection of epinephrine (also sometimes called adrenaline ), a hormone that the body produces for responding to situations of fear and danger. In the case of anaphylactic shock, which involves such severe constriction of the breathing passages that the patient runs a risk of suffocation, epinephrine causes the passages to open, making it possible to breathe again. It also constricts the blood vessels, increasing the pressure and making the blood move more rapidly throughout the body. The body's own supply of epinephrine is not enough to counteract anaphylactic shock, however, and therefore a person experiencing that condition must receive an emergency injection containing many times the amount of the hormone naturally supplied by the body. It may be administered at a hospital, though doctors usually advise people with severe allergies to keep an emergency supply on hand.

Autoimmune Disorders

Allergies are one example of an immune system gone awry, and though they can be fatal, they typically are a reaction to only one or two substances. An autoimmune disorder, on the other hand, is an entirely different class of phenomenon: it a condition in which a person's body actually rejects itself. This condition comes about when the ability of the immune system to read MHCs becomes scrambled, such that it fails to recognize cells from within the body and instead rejects them as though they came from outside. As a result, the body sets in motion the same destructive operation against its own cells that it normally would carry out against bacteria, viruses, and other such harmful invaders.

The reasons why the immune system becomes dysfunctional are not well understood, but most researchers agree that a combination of genetic, environmental, and hormonal factors plays into autoimmunity. They also speculate that certain mechanisms may trigger it. First, a substance normally restricted to one part of the body, and therefore not usually exposed to the immune system, is released into other areas, where it is attacked. Second, the immune system may mistake a component of the body for a similar foreign component. Third, cells of the body may be altered in some way, by drugs, infection, or some other environmental factor, so that they are no longer recognizable as "self" to the immune system. Fourth, the immune system itself may be dysfunctional, for instance, because of a genetic mutation.

SOME AUTOIMMUNE DISEASES.

Examples of autoimmune disorders include lupus, rheumatoid arthritis, autoimmune hemolytic anemia, pernicious anemia, and type 1 diabetes mellitus. (The last of these diseases is discussed in Noninfectious Diseases.) Lupus, or systemic lupus erythematosus, is seen mainly in young and middle-aged women, and its symptoms include fever, chills, fatigue, weight loss, skin rashes (especially a "butterfly" rash on the face), patchy hair loss, sores in the mouth or nose, enlargement of the lymph nodes, stomach problems, and irregular menstrual cycles. Lupus also may induce problems in the cardiopulmonary, urinary, and central nervous systems and can cause seizures, depression, and psychosis.

Rheumatoid arthritis, as its name suggests, is a type of both rheumatism and arthritis, which are general names for diseases associated with inflammation of connective tissue. Rheumatoid arthritis occurs when the immune system attacks and destroys the tissues that line bone joints and cartilage. The disease can affect any part of the body, although some joints may be more susceptible than others are. As it progresses, joint function diminishes sharply, and deformities arise.

Like rheumatism and arthritis, anemia is a general term for several conditions. Forms of it are marked either by a lack of red blood cells (hemoglobin) or by a shortage in total blood volume, and these deficiencies can produce effects that range from lethargy or sluggishness to death. Autoimmune hemolytic anemia occurs when the body makes antibodies that coat red blood cells. Patients have been known to experience a variety of symptoms, including jaundice, characterized by a yellowish coloration, before dying—sometimes just a few weeks after showing the first signs of the disease.

Pernicious anemia was so named at a time when it, too, was almost always fatal (pernicious means "deadly"), though treatments developed in the twentieth century have changed that situation. A disorder in which the immune system attacks the lining of the stomach in such a way that the body cannot metabolize vitamin B₁₂ (see Vitamins), pernicious anemia manifests symptoms that include weakness, sore tongue, bleeding gums, and tingling in the extremities. Because the disease leads to a decrease in stomach acid, nausea, vomiting, loss of appetite, weight loss, diarrhea, and constipation are also possible. Furthermore, since B₁₂ is essential to the functioning of the nervous system, a deficiency can result in a host of neurological problems, including weakness, lack of coordination, blurred vision, loss of fine motor skills, impaired sense of taste, ringing in the ears, and loss of bladder control.

WHERE TO LEARN MORE

All About Allergies. About.com (Web site). <http://gened.emc.maricopa.edu/bio/bio181/BIOBK/BioBookIMMUN.html>.

Clark, William R. At War Within: The Double-Edged Sword of Immunity. New York: Oxford University Press, 1995.

Davis, Joel. Defending the Body: Unraveling the Mysteries of Immunology. New York: Atheneum, 1989.

Deane, Peter M. G., and Robert H. Schwartz. Coping with Allergies. New York: Rosen Publishing Group, 1999.

Focus on Allergies (Web site). <http://www.focusonallergies.com/script/main/hp.asp>.

"Infection and Immunity." University of Leicester Microbiology and Immunology (Web site). <http://www-micro.msb.le.ac.uk/MBChB/MBChB.html>.

Joneja, Janice M. Vickerstaff, and Leonard Bielory. Understanding Allergy, Sensitivity, and Immunity: A Comprehensive Guide. New Brunswick, NJ: Rutgers University Press, 1990.

The Vaccine Page: Vaccine News and Database (Web site). <http://vaccines.org/>.

Vaccine Safety (Web site). <http://www.vaccines.net/>.

Young, Stuart H., Bruce S. Dobozin, and MargaretMiner. Allergies: The Complete Guide to Diagnosis, Treatment and Daily Management. New York: Plume, 1999.

KEY TERMS

ALLERGY:

A change in bodily reactivity to an antigen as a result of a first exposure. Allergies bring about an exaggerated reaction to substances or physical states that normally would have little significant effect on a healthy person.

ANTIBODIES:

Proteins in the human immune system that help fight foreigninvaders, especially pathogens and toxins.

ANTIGEN:

A substance capable of stimulating an immune response or reaction.

ANTISEPSIS:

The practice of inhibiting the growth and multiplication of microorganisms, usually by ensuring the cleanliness of the environment.

APC:

An antigen-presenting cell—a macrophage that has ingested a foreign cell and displays the antigen on its surface.

B CELL:

A type of white blood cell that gives rise to antibodies. Also known as a B lymphocyte.

CELL-MEDIATED RESPONSE:

The specific immune response that utilizes T cells to neutralize cells that have been infected with viruses and certain bacteria.

GLAND:

A cell or group of cells that filters material from the blood, processes that material, and secretes it either for use again in the body or to be eliminated as waste.

HEMOGLOBIN:

An iron-containing protein in red blood cells that is responsible for transporting oxygen to the tissues and removing carbon dioxide from them. Hemoglobin is known for its deep redcolor.

HUMORAL:

Of or relating to the antibodies secreted by B cells that circulate in bodily fluids.

IMMUNE SYSTEM:

A network of organs, glands, and tissues that protects the body from foreign substances.

IMMUNITY:

The condition of being able to resist a particular disease, particularly through means that prevent the growth and development or counteract the effects of pathogens.

IMMUNOLOGY:

The study of the immune system, immunity, and immune responses.

LYMPH:

That portion of the blood that includes white blood cells and plasma but not red blood cells.

LYMPH NODES:

Masses of tissue at certain places in the body that act as filters for blood.

LYMPHOCYTE:

A type of white bloodcell, varieties of which include B cells and Tcells, or B lymphocytes and T lymphocytes.

MACROPHAGE:

A type of phagocyticcell derived from monocytes.

MHC:

Major histocompatibility complex, a group of proteins found on the membrane of each cell in an organism's body. Since all cells in a particular body have the same MHC pattern, the MHC is a kind of pass code, identifying cells in the body as belonging to the "self."

MONOCYTE:

A type of white blood cell that phagocytizes (engulfs and digests) foreign microorganisms.

PATHOGEN:

A disease-carrying parasite, usually a microorganism.

PHAGOCYTE:

A cell that engulfs and digests another cell.

T CELL:

A type of white blood cell, also known as a T lymphocyte, that plays a key role in the immune response. T cells include cytotoxic T cells, which destroy virus-infected cells in the cell-mediated immune response; helper T cells, which are key participants in specific immune responses that bind to APCs, activating both the antibody and cell-mediated immune responses; and suppressor T cells, which deactivate T cells and B cells.