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immune system


n.

The integrated body system of organs, tissues, cells, and cell products such as antibodies that differentiates self from nonself and neutralizes potentially pathogenic organisms or substances.


 
 
Science of Everyday Things: 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.


 
World of the Body: immune system

Have you ever wondered why you are resistant to the colds that plague your friends, even though you have been exposed to the same environment? This is because you have an efficient immune system which is working overtime to identify and mount a reaction to ‘invaders’, including microorganisms capable of causing disease and foreign macromolecules like polysaccharides and proteins — a phenomenon known as immunity.

Historically, immunity referred to protection from infectious diseases, and the term was derived from the Latin word immunitas, meaning the exemption from civic duties and prosecution extended to Roman senators. However the concept of immunity existed long before, especially in the Chinese custom of making children inhale powders of crust of skin lesions of patients recovering from small pox. The first scientifically documented evidence of inducing immunity was the landmark work of Dr Edward Jenner, an English physician. He noticed that milkmaids who had recovered from cowpox were resistant to contracting small pox. When he injected the material from a cowpox pustule into a young boy, the boy did not develop small pox even when intentionally inoculated. Jenner published his findings in 1798 and laid the foundation for the future development of ‘vaccination’ (the Latin word vacinus means of or from cows) and other forms of immunization.

Two basic levels of immunity exist in healthy individuals to confer protection against microbes and other foreign bodies; the less perfect natural immunity and the more specific acquired immunity.

Natural immunity

Those defence mechanisms that exist prior to exposure to foreign substances, that are not enhanced by subsequent exposures, and that cannot discriminate between most foreign molecules, are categorized as natural or innate immunity. This includes the first line of defence — the protective barriers like the skin and the mucous membranes lining the body tracts, which secrete acids and enzymes capable of digesting bacterial cell walls. Often a failure at this level may lead to fatal complications (such as in cystic fibrosis, where the mucus formed is not protective).

If this protective barrier is breached, the next lines of defence involve two components of natural immunity — the humoral (mediated by substances free in the body fluids) and the cellular (mediated by cells). A number of humoral agents are rapidly produced or activated to exert non-specific effects: that is, they are equally effective against multiple microbes. They include acute phase proteins, serum complements, and interferons. Interferons are vital mainly in controlling viral infections. At this time the cellular component also comes into play. Two types of phagocytic cells ‘eat up’ and destroy the foreign molecules. The first of these are the polymorphonuclear neutrophil leucocytes (white blood cells), which circulate in blood and migrate to sites of microbial invasion; the second are called monocytes in the blood and macrophages in the tissues (they migrate between the two) — collectively, the macrophage-monocyte system. Humoral and cellular mechanisms interact: serum complements bind to the surface of the foreign molecule and increase the efficiency of phagocytosis by the cells.

Acquired immunity

By the time the components of natural immunity perform their act, more specific defence mechanisms are also mounted. These mechanisms are induced by exposure to the foreign molecules which are known as antigens. Besides amplifying the protective mechanisms of innate immunity, the specific immune system also ‘memorizes’ each encounter with a particular antigen such that subsequent exposure to that antigen leads to the development of ‘active immunity’. Specific immunity can also be induced in an individual by transferring cells or serum (depending on the type of immune response, see later) from a specifically immunized individual, so that the recipient becomes immune to the particular antigen without getting an actual exposure to it. This form of immunity is called ‘passive immunity’, and often is a useful method for rapid conferring of immunity. This technique has helped in saving lives following potentially lethal snake bites, by the administration of antibodies from immunized individuals. Much more commonly, anti-tetanus serum has been widely used to confer passive immunity after potentially contaminated minor injuries.

Lymphocytes are the primary players in specific immunity. These are cells that are present throughout the body, circulating in the blood and lymph and organized in lymphoid tissues. They are produced in primary lymphoid organs — the liver in the fetus, the thymus, and the bone marrow. Some lymphocytes pass through the thymus after release from the bone marrow, re-enter the circulation and then settle in secondary lymphoid organs like the spleen and the lymph nodes. During passage through the thymus these lymphocytes acquire antigen specificity, properties which equip them to act against a particular invader, and are thereafter known as T-cells. Other lymphocytes do not pass through the thymus, but settle directly in the secondary lymphoid organs where they mature and develop antigen specificity. These cells are called B-lymphocytes or B-cells; they carry on their surface a ‘recognition molecule’ or antibody, which acts as a receptor for an antigen.

Antibodies belong to a group of proteins called immunoglobulins. They are similar in their overall Y-shaped structure. The 2 arms form the part known as ‘Fab’, which binds with the antigen. Here the amino acid sequence varies widely; these regions determine the specificity of the antibody and also account for the diversity of immunity. In fact there are between 10 and 1000 million structurally different antibodies in an individual, each with unique amino acid sequences in the Fab region. The stem of the antibody determines its biological function, and its properties are used in classifying the immunoglobulins (IgG, IgM, IgA, IgD, and IgE.)

Humoral immunity is mediated by antibodies that are released into the circulation from B-lymphocytes, and can therefore be transferred to non-immunized individuals by cell-free components of blood. It is the principal defence mechanism against extra-cellular foreign molecules or their toxins because the antibodies bind to these and lead to their destruction. Intracellular antigens are handled by cell-mediated immunity, of which the main component is T-lymphocytes. This form of immunity can be transferred only through the cells of the blood. Humoral and cellular immunity are thus the two types of acquired or specific immunity.

Following exposure to an antigen, the specific immune response is brought about in a sequential manner, which can be divided into three phases: ‘cognitive’, ‘activation’ and ‘effector’. During the cognitive phase, the antigen binds to specific receptors on mature lymphocytes of both types. The antibody on B-lymphocytes recognizes and binds foreign proteins, polysaccharides, or lipids in soluble form. Receptors on T-lymphocytes, on the other hand, can recognize only short peptide sequences in protein antigens present on the surface of other cells. In the technical jargon of immunology, the portion of an antigen that is specifically recognized by the antibody is called an ‘epitope’.

Next, in the activation phase, the antigen-specific lymphocytes of both types proliferate by cloning, thus amplifying the immune response. Lymphocytes develop into cells whose primary function is to eliminate the antigen. All clonal B-cells secrete the same antibody, which combines with the antigen and initiates a sequence of events leading to destruction of that antigen. Subsets of the antigen-specific T-cell clones develop different functions; some activate phagocytes; others, called T-cytotoxic cells, directly break down cells that produce viral antigens; some regulate the production of antibody by B-cells. Those T-cells, which promote the immune response, are called T-helper cells, while others that inhibit it as part of the self-limiting capability of the immune response, are called T-suppressor cells. Another subset, the Tdth cells (delayed type hypersensitivity) produce factors that modulate the functions of lymphocytes and macrophages.

A set of membrane proteins that are products of genes determining (in) compatibility of tissues between individuals are known as HLA (called human lymphocyte antigens, because they were first recognized on these cells, but they occur on other cells also). They regulate the T-cell activity in such a way that T-cells recognize other antigens only when they are associated with the HLA molecules. This system is highly variable in the human population and it is rare for two individuals to have the same HLA products. This is often the reason for transplant rejection due to an immune response, when the donor's proteins serve as antigens in the recipient. HLA typing and matching is thus an essential step before any transplant surgery to minimize the chances of an immune response.

Once the lymphocytes have been activated and the antigen has been presented to them, the immune response enters the effector phase. Few antigens bind directly to antigen-reactive T- or B-cells but are presented to the lymphocytes bound to other ‘antigen presenting cells’ such as macrophages. The effector phase requires the participation also of other non-lymphoid ‘effector cells’ such as mast cells, eosinophils, or natural killer (NK) cells, which act also as components of natural immunity. Antibodies bind to the antigen, and this promotes phagocytosis by neutrophils or other phagocytes. Antibodies can also activate the ‘complement system’, generating proteins that cause inflammation, cell breakdown, and phagocytosis of the antigen. Some antibodies, like IgA released from mucous membranes, coat the antigen and prevent its docking on the epithelial lining of body tracts. T-cells also secrete chemicals called cytokines, which stimulate an inflammatory response and enhance the function of natural immunity. The antigen thus faces a barrage of defence mechanisms' which leads to its destruction.

Once the antigenic stimulation is removed, lymphocytes become quiescent and only some remain viable as memory cells. On a subsequent exposure to the same antigen these become rapidly activated and can mount a faster response than the first time, called the secondary immune response. A series of feedback controls also come into play, which makes the immune response self limiting.

One of the distinguishing and essential features of the immune system is its ability to discriminate between foreign and ‘self-antigens’. Immunity is unresponsive to molecules present in the individual that would be antigenic in another. This arises due to an acquired process called self-tolerance. Thus during the early stages of development, functionally immature ‘self-recognizing’ lymphocytes come in contact with self-antigens and are prevented from developing to a stage where they can respond to self-antigens. However, in certain unfortunate conditions, abnormalities in induction or maintenance of self-tolerance may occur, which leads to the immune system acting against a normal component of the same body. This leads to the development of autoimmune diseases.

— Shiladitya Sengupta, Tai-Ping Fan

See also allergy; autoimmune diseases.

 
Food and Nutrition: immune system

Series of defence mechanisms of the body. There are two major parts: humoral, mediated through antibodies secreted into the circulation (immunoglobulins); and cell-mediated. Lymphocytes produce antibodies against, and bind to, the antigens of foreign cells, leading to death of the invading organisms; other white blood cells are phagocytic and engulf the invading organisms.

 
Food and Fitness: immune system

The system of internal defence mechanisms which enables the body to resist disease. The body's first line of defence is the skin and lining of the cavities (especially the gut and lungs). They act as a barrier to the entry of unwanted substances and foreign cells. If foreign bodies penetrate through these defences, the immune system is activated. Cells and proteins within the blood and lymph attack, disarm, destroy, and remove the foreign bodies. Special white blood cells (B-cell lymphocytes) are able to recognize the chemicals (called antigens) associated with foreign bodies and produce antibodies, proteins which attack them. The immune system seems to be able to remember previous encounters with a specific foreign substance, so that if confronted again with the same substance it can mount a prompt and effective defence. This is the basis of immunity.

People with allergies may have an overzealous immune system that attacks harmless substances or fails to attack harmful ones. Sometimes the immune system breaks down and starts to attack the body's own cells. This condition is called autoimmunity and is implicated in the development of a number of diseases, including rheumatoid arthritis.

The immune system can function efficiently only if it is supplied with adequate nutrients. Energy from carbohydrates and fat is needed to mobilize the army of white cells that fight off attacks. Vitamins and minerals are essential components of many chemicals produced to defend the body (see antioxidant). A deficiency or an overdose of any nutrient is likely to harm the immune system.

The immune system is also affected by the physiological and psychological stress of exercise. Although the results of scientific investigations are not clear, it appears that low to moderate levels of exercise are generally beneficial, activating the immune system and improving its ability to defend the body against disease. Exercise may boost the production of natural killer cells. One of their main duties is to destroy cancer cells before they can develop into full-blown tumours. However, there seems to be a critical level of exercise, specific to each individual, above which the immune system becomes increasingly compromised (see also general adaptation syndrome). Many athletes preparing for a major competition push themselves to their mental and physical limits, exceed their critical level, and succumb to illness. Elite athletes walk a tightrope between supreme physical condition and a breakdown of health. A new test that uses saliva samples is being devised for monitoring the competence of the immune system. This should help athletes and others know when they should take particular care to avoid overtraining.

 
Dental Dictionary: immune system

n

A biochemical complex that protects the body against pathogenic organisms and other foreign bodies. The system incorporates the humoral immune response, which produces antibodies to react with specific antigents, and the cell-mediated response, which uses T cells to mobilize tissue macrophages in the presence of a foreign body. The immune system also protects the body from invasion by creating local barriers and inflammation. The principal organs of the immune response system include the bone marrow, the thymus, and the lymphoid tissues.

 

Cells, cell products, organs, and structures of the body involved in the detection and destruction of foreign invaders, such as bacteria, viruses, and cancer cells. Immunity is based on the system's ability to launch a defense against such invaders. For the system to function properly, it must be able to distinguish between the material of its own body (self) and material that originates outside of it (nonself). Failure to make this distinction can result in autoimmune diseases. An exaggerated or inappropriate response by the immune system to nonharmful substances (e.g., pollen, animal dander) can result in allergies. The system's principal cells include lymphocytes that recognize antigens and related accessory cells (such as phagocytic macrophages, which engulf and destroy foreign material). Lymphocytes arise in the bone marrow from stem cells, with T lymphocytes (T cells) migrating to the thymus to mature and B lymphocytes (B cells) maturing in the bone marrow. Mature lymphocytes enter the bloodstream, and many become lodged, along with accessory cells, in various body tissues, including the spleen, lymph nodes, tonsils, and intestinal lining. Organs or tissues containing such concentrations are termed lymphoid. Within these organs and tissues the lymphocytes are confined within a delicate network of connective tissue that channels them so they come into contact with antigens. T cells and B cells can mature and multiply further in lymphoid tissue when suitably stimulated. Fluid (lymph) draining from lymphoid tissues is conveyed to the blood through lymphatic vessels. Lymph nodes distributed along these vessels filter the lymph, exposing macrophages and lymphocytes contained within to any antigen present. The spleen plays a similar role, sampling the blood for the presence of antigens. The capability of lymphocytes to pass between lymphoid tissue, the blood, and lymph is an important element in the system's functioning. See also immunodeficiency; immunology.

For more information on immune system, visit Britannica.com.

 

A complex body system consisting of interacting hormones, cells, and other adaptive mechanisms that defends the body against diseases caused by micro-organisms and abnormal malignant cell growth. If an infection occurs, an effective immune system reduces its severity and accelerates recovery.

 
Health Dictionary: immune system

The system in the body that works to ward off infection and disease. Central to this system are the white blood cells. Some white blood cells produce antibodies in response to specific antigens that may invade the body; others function as scavengers to fight infection by destroying bacteria and removing dead cells.

 
Wikipedia: immune system
A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange).
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A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange).

An immune system is a collection of mechanisms within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in order to function properly. Detection is complicated as pathogens adapt and evolve new ways to successfully infect the host organism.

To survive this challenge, several mechanisms have evolved that recognize and neutralize pathogens. Even simple unicellular organisms such as bacteria possess enzyme systems that protect against viral infections. Other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants, fish, reptiles, and insects. These mechanisms include antimicrobial peptides called defensins, pattern recognition receptors, and the complement system. More sophisticated mechanisms, however, developed relatively recently, with the evolution of vertebrates.[1] The immune systems of vertebrates such as humans consist of many types of proteins, cells, organs, and tissues, which interact in an elaborate and dynamic network. As part of this more complex immune response, the vertebrate system adapts over time to recognize particular pathogens more efficiently. The adaptation process creates immunological memories and allows even more effective protection during future encounters with these pathogens. This process of acquired immunity is the basis of vaccination.

Disorders in the immune system can cause disease. Immunodeficiency diseases occur when the immune system is less active than normal, resulting in recurring and life-threatening infections. Immunodeficiency can either be the result of a genetic disease, such as severe combined immunodeficiency, or be produced by pharmaceuticals or an infection, such as the acquired immune deficiency syndrome (AIDS) that is caused by the retrovirus HIV. In contrast, autoimmune diseases result from a hyperactive immune system attacking normal tissues as if they were foreign organisms. Common autoimmune diseases include rheumatoid arthritis, diabetes mellitus type 1 and lupus erythematosus. These critical roles of immunology in health and disease are areas of intense scientific study.

Layered defense in immunity

The immune system protects organisms from infection with layered defenses of increasing specificity. Most simply, physical barriers prevent pathogens such as bacteria and viruses from entering the body. If a pathogen breaches these barriers, the innate immune system provides an immediate, but non-specific response. Innate immune systems are found in all plants and animals.[2] However, if pathogens successfully evade the innate response, vertebrates possess a third layer of protection, the adaptive immune system. Here, the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered.[3]

Components of the immune system
Innate immune system Adaptive immune system
Response is non-specific Pathogen and antigen specific response
Exposure leads to immediate maximal response Lag time between exposure and maximal response
Cell-mediated and humoral components Cell-mediated and humoral components
No immunological memory Exposure leads to immunological memory
Found in nearly all forms of life Found only in jawed vertebrates

Both innate and adaptive immunity depend on the ability of the immune system to distinguish between self and non-self molecules. In immunology, self molecules are those components of an organism's body that can be distinguished from foreign substances by the immune system.[4] Conversely, non-self molecules are those recognized as foreign molecules. One class of non-self molecules are called antigens (short for antibody generators) and are defined as substances that bind to specific immune receptors and elicit an immune response.[5]

Surface barriers

Several barriers protect organisms from infection, including mechanical, chemical and biological barriers. The waxy cuticle of many leaves, the exoskeleton of insects, the shells and membranes of externally deposited eggs, and skin are examples of the mechanical barriers that are the first line of defense against infection.[5] However, as organisms cannot be completely sealed against their environments, other systems act to protect body openings such as the lungs, intestines, and the genitourinary tract. In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from the respiratory tract. The flushing action of tears and urine also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms.[6]

Chemical barriers also protect against infection. The skin and respiratory tract secrete antimicrobial peptides such as the β-defensins.[7] Enzymes such as lysozyme and phospholipase A2 in saliva, tears, and breast milk are also antibacterials.[8][9] Vaginal secretions serve as a chemical barrier following menarche, when they become slightly acidic, while semen contains defensins and zinc to kill pathogens.[10][11] In the stomach, gastric acid and proteases serve as powerful chemical defenses against ingested pathogens.

Within the genitourinary and gastrointestinal tracts, commensal flora serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, by changing the conditions in their environment, such as pH or available iron.[12] This reduces the probability that pathogens will be able to reach sufficient numbers to cause illness. However, since most antibiotics non-specifically target bacteria and do not affect fungi, oral antibiotics can lead to an “overgrowth” of fungi and cause conditions such as a vaginal candidiasis (yeast infection).[13] There is good evidence that re-introduction of probiotic flora, such as pure cultures of the lactobacilli normally found in yoghurt, helps restore a healthy balance of microbial populations in intestinal infections in children and encouraging preliminary data in studies on bacterial gastroenteritis, inflammatory bowel diseases, urinary tract infection and post-surgical infections.[14][15][16]

Innate immunity

For more details on this topic, see Innate immune system.

Microorganisms that successfully enter an organism will encounter the cells and mechanisms of the innate immune system. Innate immune defenses are non-specific, meaning these systems recognize and respond to pathogens in a generic way.[5] This system does not confer long-lasting immunity against a pathogen. The innate immune system is the dominant system of host defense in most organisms.[2]

Humoral and chemical barriers

Inflammation

For more details on this topic, see Inflammation.

Inflammation is one of the first responses of the immune system to infection.[17] The symptoms of inflammation are redness and swelling, which are caused by increased blood flow into a tissue. Inflammation is produced by eicosanoids and cytokines, which are released by injured or infected cells. Eicosanoids include prostaglandins that produce fever and the dilation of blood vessels associated with inflammation, and leukotrienes that attract certain white blood cells (leukocytes).[18][19] Common cytokines include interleukins that are responsible for communication between white blood cells; chemokines that promote chemotaxis; and interferons that have anti-viral effects, such as shutting down protein synthesis in the host cell.[20] Growth factors and cytotoxic factors may also be released. These cytokines and other chemicals recruit immune cells to the site of infection and promote healing of any damaged tissue following the removal of pathogens.[21]

Complement system

For more details on this topic, see Complement system.

The complement system is a biochemical cascade that attacks the surfaces of foreign cells. It contains over 20 different proteins and is named for its ability to “complement” the killing of pathogens by antibodies. Complement is the major humoral component of the innate immune response.[22][23] Many species have complement systems, including non-mammals like plants, fish, and some invertebrates.[24]

In humans, this response is activated by complement binding to antibodies that have attached to these microbes or the binding of complement proteins to carbohydrates on the surfaces of microbes. This recognition signal triggers a rapid killing response.[25] The speed of the response is a result of signal amplification that occurs following sequential proteolytic activation of complement molecules, which are also proteases. After complement proteins initially bind to the microbe, they activate their protease activity, which in turn activates other complement proteases, and so on. This produces a catalytic cascade that amplifies the initial signal by controlled positive feedback.[26] The cascade results in the production of peptides that attract immune cells, increase vascular permeability, and opsonize (coat) the surface of a pathogen, marking it for destruction. This deposition of complement can also kill cells directly by disrupting their plasma membrane.[22]

Cellular barriers of the innate system

A scanning electron microscope image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including lymphocytes, a monocyte, a neutrophil, and many small disc-shaped platelets.
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A scanning electron microscope image of normal circulating human blood. One can see red blood cells, several knobby white blood cells including lymphocytes, a monocyte, a neutrophil, and many small disc-shaped platelets.

Leukocytes (white blood cells) act like independent, single-celled organisms and are the second arm of the innate immune system.[5] The innate leukocytes include the phagocytes (macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells. These cells identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms.[24] Innate cells are also important mediators in the activation of the adaptive immune system.[3]

Phagocytosis is an important feature of cellular innate immunity performed by cells called 'phagocytes' that engulf, or eat, pathogens or particles. Phagocytes generally patrol the body searching for pathogens, but can be called to specific locations by cytokines.[5] Once a pathogen has been engulfed by a phagocyte, it becomes trapped in an intracellular vesicle called a phagosome, which subsequently fuses with another vesicle called a lysosome to form a phagolysosome. The pathogen is killed by the activity of digestive enzymes or following a respiratory burst that releases free radicals into the phagolysosome.[27][28] Phagocytosis evolved as a means of acquiring nutrients, but this role was extended in phagocytes to include engulfment of pathogens as a defense mechanism.[29] Phagocytosis probably represents the oldest form of host defense, as phagocytes have been identified in both vertebrate and invertebrate animals.[30]

Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of invading pathogens.[31] Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, normally representing 50% to 60% of the total circulating leukocytes.[32] During the acute phase of inflammation, particularly as a result of bacterial infection, neutrophils migrate toward the site of inflammation in a process called chemotaxis, and are usually the first cells to arrive at the scene of infection. Macrophages are versatile cells that reside within tissues and produce a wide array of chemicals including enzymes, complement proteins, and regulatory factors such as interleukin 1.[33] Macrophages also act as scavengers, ridding the body of worn-out cells and other debris, and as antigen-presenting cells that activate the adaptive immune system.[3]

Dendritic cells (DC) are phagocytes in tissues that are in contact with the external environment; therefore, they are located mainly in the skin, nose, lungs, stomach, and intestines.[34] They are named for their resemblance to neuronal dendrites, as both have many spine-like projections, but dendritic cells are in no way connected to the nervous system. Dendritic cells serve as a link between the innate and adaptive immune systems, as they present antigen to T cells, one of the key cell types of the adaptive immune system.[34]

Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory response.[35] They are most often associated with allergy and anaphylaxis.[32] Basophils and eosinophils are related to neutrophils. They secrete chemical mediators that are involved in defending against parasites and play a role in allergic reactions, such as asthma.[36] Natural killer (NK cells) cells are leukocytes that attack and destroy tumor cells, or cells that have been infected by viruses.[37]

Adaptive immunity

For more details on this topic, see Adaptive immune system.

The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as well as immunological memory, where each pathogen is "remembered" by a signature antigen.[38] The adaptive immune response is antigen-specific and requires the recognition of specific “non-self” antigens during a process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are used to quickly eliminate it.

Lymphocytes

The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T cells are the major types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow.[24] B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response.

Association of a T cell with MHC class I or MHC class II, and antigen (in red)
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Association of a T cell with MHC class I or MHC class II, and antigen (in red)

Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a “non-self” target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a “self” receptor called a major histocompatibility complex (MHC) molecule. There are two major subtypes of T cells: the killer T cell and the helper T cell. Killer T cells only recognize antigens coupled to Class I MHC molecules, while helper T cells only recognize antigens coupled to Class II MHC molecules. These two mechanisms of antigen presentation reflect the different roles of the two types of T cell. A third, minor subtype are the γδ T cells that recognize intact antigens that are not bound to MHC receptors.[39]

In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface, and recognizes whole pathogens without any need for antigen processing. Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture.[24]

Killer T cells

Killer T cells directly attack other cells carrying foreign or abnormal antigens on their surfaces.[40]
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Killer T cells directly attack other cells carrying foreign or abnormal antigens on their surfaces.[40]

Killer T cell are a sub-group of T cells that kill cells infected with viruses (a