immunity (redirected from granting immunity)

immunity, ability of an organism to resist disease by identifying and destroying foreign substances or organisms. Although all animals have some immune capabilities, little is known about nonmammalian immunity. Mammals are protected by a variety of preventive mechanisms, some of them nonspecific (e.g., barriers, such as the skin), others highly specific (e.g., the response of antibodies).

Nonspecific Defenses

Nonspecific defenses include physical and chemical barriers, the inflammatory response, and interferons. Physical barriers include the intact skin and mucous membranes. These barriers are aided by various antimicrobial chemicals in tissue and fluids. An example of such a substance is lysozyme, an enzyme present in tears that destroys the cell membranes of certain bacteria.

Inflammatory Response

Another line of defense is the inflammatory response, in which white blood cells called monocytes and granulocytes (e.g., basophils and neutrophils) reach an injured area. Basophils release histamine, which results in increased local blood flow and increased permeability of the capillaries and allows phagocytizing cells, such as neutrophils and monocytes (macrophages), into the area. The same response sometimes results in fever. Leakage of the clotting protein fibrinogen and other substances into the injured area results in blockage of tissue by clots, which wall off the injured area to retard the spread of bacteria or their toxins.

Interferons

Interferons are proteins released by a virus-invaded cell that prompt surrounding cells to produce enzymes that interfere with viral replication. They are the reason that, in most instances, infection with one virus precludes infection by a second virus.

Nonsusceptibility

Nonsusceptibility is the inability of certain disease-carrying organisms to grow in a particular host species. Nonsusceptibility may be caused by such conditions as lack of availability of particular growth substances needed by the infecting microorganism or body temperature unsuitable for the invading microorganism. For example, chickens are nonsusceptible to anthrax because the bacteria cannot grow at the body temperature normal for that animal.

The Immune Response

The principal parts of the immune system are the bone marrow, thymus, lymphatic system, tonsils, and spleen. The lymph nodes, tonsils, and spleen act to trap and destroy antigens from the lymph, air, and blood, respectively. Antigens are molecules that the body reacts to by producing antibodies, highly specific proteins also known as immunoglobulins. Antigens include bacteria and their toxins, viruses, malignant cells, foreign tissues, and the like. Their destruction is accomplished by white blood cells (lymphocytes and the granulocytes and monocytes mentioned above), which are produced and constantly replenished by the stem cells of the bone marrow. The two types of lymphocytes are called B lymphocytes (B cells) and T lymphocytes (T cells). B cells are responsible for production of antibodies in what is called "humoral" immunity after the ancient medical concept of the body humors.

B Lymphocytes

The presence of antigens in contact with receptor sites on the surface of a B lymphocyte stimulates the lymphocyte to divide and become a clone (a line of descendant cells), with each cell of the clone specific for the same antigen. Some cells of the clone, called plasma cells, secrete large quantities of antibody; others, called memory cells, enter a resting state, remaining prepared to respond to any later invasions by the same antigen. Antibody secretion by lymphocytes can be stimulated or suppressed by such variables as the concentration of antigens, the way the antigen fits the lymphocyte's receptor regions, the age of the lymphocyte, and the effect of other lymphocytes.

According to the modified clonal selection theory originally postulated by the Australian immunologist Sir Macfarlane Burnet (for which he was awarded the 1960 Nobel Prize for Physiology or Medicine), a lymphocyte is potentially able to secrete one particular, specific humoral, or free-circulating, antibody molecule. It is believed that early in life lymphocytes are formed to recognize thousands of different antigens, including a group of autoimmune lymphocytes, i.e., cells recognizing antigens of the organism's own body. The immune system is self-tolerant; i.e., it does not normally attack molecules and cells of the organism's own body, because those lymphocytes that are autoimmune are inactivated or destroyed early in life, and the cells that remain, the majority, recognize only foreign antigens. Burnet's theory was confirmed with the development of monoclonal antibodies.

Antibodies

The antibodies produced by B cells are a type of globulin protein called immunoglobulins. There are five classes of immunoglobulins designated IgA, IgD, IgE, IgG, and IgM; gamma globulin (IgG) predominates. Antibody molecules are able to chemically recognize surface portions, or epitopes, of large molecules that act as antigens, such as nucleic acids, proteins, and polysaccharides. About 10 amino acid subunits of a protein may compose a single epitope recognizable to a specific antibody. The fit of an epitope to a specific antibody is analogous to the way a key fits a specific lock. The amino acid sequence and configuration of an antibody were determined in the 1960s by the biochemists Gerald Edelman, an American, and R. R. Porter, an Englishman; for this achievement they shared the 1972 Nobel Prize for Physiology or Medicine.

The antibody molecule consists of four polypeptide chains, two identical heavy (i.e., long) chains and two identical light (i.e., short) chains. All antibody molecules are alike except for certain small segments that, varying in amino acid sequence, account for the specificity of the molecules for particular antigens. In order to recognize and neutralize a specific antigen, the body produces millions of antibodies, each differing slightly in the amino acid sequence of the variable regions; some of these molecules will chemically fit the invading antigen.

Antibodies act in several ways. For example, they combine with some antigens, such as bacterial toxins, and neutralize their effect; they remove other substances from circulation in body fluids; and they bind certain bacteria or foreign cells together, a process known as agglutination. Antibodies attached to antigens on the surfaces of invading cells activate a group of at least 11 blood serum proteins called complement, which cause the breakdown of the invading cells in a complex series of enzymatic reactions. Complement proteins are believed to cause swelling and eventual rupture of cells by making holes in the lipid portion of the cell's membrane.

T Lymphocytes

After their production in the bone marrow, some lymphocytes (called T lymphocytes or T cells) travel to the thymus, where they differentiate and mature. The T cells interact with the body's own cells, regulating the immune response and acting against foreign cells that are not susceptible to antibodies in what is termed "cell-mediated immunity." Three classes of T lymphocytes have been identified: helper T cells, suppressor T cells, and cytotoxic T cells. Each T cell has certain membrane glycoproteins on its surface that determine the cell's function and its specificity for antigens.

One type of function-determining membrane glycoprotein exists in two forms called T4 or T8 (CD4 or CD8 in another system of nomenclature); T4 molecules are on helper T cells, T8 molecules are on suppressor and cytotoxic T cells. Another type of membrane glycoprotein is the receptor that helps the T cell recognize the body's own cells and any foreign antigens on those cells. These receptors are associated with another group of proteins, T3 (CD3), whose function is not clearly understood. T cells distinguish self from nonself with the help of antigens naturally occurring on the surface of the body's cells. These antigens are, in part, coded by a group of genes called the major histocompatibility complex (MCH). Each person's MCH is as individual as a fingerprint.

When a cytotoxic T lymphocyte recognizes foreign antigens on the surface of a cell, it again differentiates, this time into active cells that attack the infected cells directly or into memory cells that continue to circulate. The active cytotoxic T cells can also release chemicals called lymphokines that draw macrophages. Some (the "killer T cells") release cell-killing toxins of their own; some release interferon. Helper T cells bind to active macrophages and B lymphocytes and produce proteins called interleukins, which stimulate production of B cells and cytotoxic T cells. Although poorly understood, suppressor T cells appear to help dampen the activity of the immune system when an infection has been controlled.

Active and Passive Immunity

Naturally acquired active immunity occurs when the person is exposed to a live pathogen, develops the disease, and becomes immune as a result of the primary immune response. Artificially acquired active immunity can be induced by a vaccine, a substance that contains the antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease (see vaccination).

Artificially acquired passive immunity is a short-term immunization by the injection of antibodies, such as gamma globulin, that are not produced by the recipient's cells. Naturally acquired passive immunity occurs during pregnancy, in which certain antibodies are passed from the maternal into the fetal bloodstream. Immunologic tolerance for foreign antigens can be induced experimentally by creating conditions of high-zone tolerance, i.e., by injecting large amounts of a foreign antigen into the host organism, or low-zone tolerance, i.e., injecting small amounts of foreign antigen over long periods of time.

Undesirable Immune Responses and Conditions

Immunity has taken on increased medical importance since the mid-20th cent. For instance, the ability of the body to reject foreign matter is the main obstacle to the successful transplantation of certain tissues and organs. In blood transfusions the immune response is the cause of severe cell agglutination or rupture (lysis) when the blood donor and recipient are not matched for immunological compatibility (see blood groups). An immune reaction can also occur between a mother and baby (see Rh factor). Allergy, anaphylaxis, and serum sickness are all manifestations of undesirable immune responses.

Many degenerative disorders of aging, e.g., arthritis, are thought to be disorders of the immune system. In autoimmune diseases, such as rheumatoid arthritis and lupus, individuals produce antibodies against their own proteins and cell components. Combinations of foreign proteins and their antibodies, called immune complexes, circulating through the body may cause glomerulonephritis (see nephritis) and Bright's disease (a kidney disease). Circulating immune complexes following infection by the hepatitis virus may cause arthritis.

At an extreme end of the spectrum of undesirable conditions is the lack of immunity itself. As a childhood condition, this absence can result from a congenital inability to produce antibodies or from severe disorders of the immune system, which leave individuals unprotected from disease. Such children usually die before adulthood. AIDS (Acquired Immune Deficiency Syndrome), which ultimately destroys the immune system, is caused by a retrovirus called the human immunodeficiency virus (HIV), which was identified in 1981. It infects the helper T cells, thereby disabling the immune system and leaving the person subject to a vast number of progressive complications and death.

Bibliography

See I. Cohen et al., ed., Auto-Immunity (1986); S. Sell, Immunology, Immunopathology, and Immunity (1987); R. Langman, The Immune System (1989); E. Sercarz, ed., Antigenic Determinants and Immune Regulation (1989); J. Kreier, Infection, Resistence, and Immunity (1990)

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immunity

Acquired immunity depends on the activities of T and B lymphocytes (T and B cells). One part of …

(credit: © Merriam-Webster Inc.)

Ability to resist attack or overcome infection by invading microbes or larger parasites. Immunity is based on the proper functioning of the body's immune system. In natural or innate immunity, immune mechanisms present at birth work against a wide variety of microbes whether or not they have been encountered before. Acquired immune responses, tailored to act against a specific microbe or its products, are stimulated by the prior presence of that microbe. Previous infection with a particular pathogen, as well as vaccines, produce this type of immunity. The mechanisms of innate immunity include physical barriers (including the skin) and chemical barriers (such as bactericidal enzymes present in saliva). Microbes that penetrate the body's natural barriers encounter substances (such as interferon) that inhibit their growth or reproduction. Phagocytes (particle-engulfing cells) surround and destroy invading microbes, and natural killer cells pierce the microbe's outer membrane. Innate immunity does not confer lasting resistance, or immunity, to the body. Acquired immunity is based on the recognition of antigen by B cells and T cells and is activated when innate mechanisms are insufficient to stem further invasion by pathogens. Killer or cytotoxic T cells destroy infected and foreign cells. Helper T cells induce B cells stimulated by the presence of antigen to proliferate into antibody-secreting cells, or plasma cells. Antibodies produced by plasma cells bind to antigen-bearing cells, marking them for destruction. Acquired immunity relies on the long-term survival of sensitized T and B memory cells, which can proliferate quickly upon reinfection by the same pathogen. See also immunodeficiency; immunology; leukocyte; reticuloendothelial system.

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immunity

In law, exemption or freedom from liability. Under international treaty, a diplomatic representative is exempt from local laws, both civil and criminal. In many countries, judges, legislators, and government officials, including the heads of state, enjoy limited or absolute immunity at home to protect them from personal liability for wrongful acts or omissions that arise from the performance of their duties. A public prosecutor may grant immunity from prosecution to a witness who is suspected of criminal activity in return for testimony against other suspected criminals.

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immunity

1. the ability of an organism to resist disease, either through the activities of specialized blood cells or antibodies produced by them in response to natural exposure or inoculation (active immunity) or by the injection of antiserum or the transfer of antibodies from a mother to her baby via the placenta or breast milk (passive immunity)

3. the exemption of ecclesiastical persons or property from various civil obligations or liabilities

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immunity [i′myü·nəd·ē]

(immunology)

The condition of a living organism whereby it resists and overcomes an infection or a disease.

(metallurgy)

The ability of metal to resist corrosion as a result of thermodynamic stability.

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Immunity

A state of resistance to an agent, the pathogen, that normally produces an infection. Pathogens include microorganisms such as bacteria and viruses, as well as larger parasites. The immune response that generates immunity is also responsible in some situations for allergies, delayed hypersensitivity states, autoimmune disease, and transplant rejection. See Allergy, Autoimmunity, Transplantation biology

Immunity is engendered by the host immune system, reacting in very specific ways to foreign components (such as proteins) of particular parasites or infective agents. It is influenced by many factors, including the environment, inherited genes, and acquired characteristics. Reaction to a pathogen is through a nonadaptive or innate response as well as an adaptive immune response. The innate response is not improved by repeated encounters with the pathogen. An adaptive response is characterized by specificity and memory: if reinfection occurs, the host will mount an enhanced response.

The components of the pathogen that give rise to an immune response, to which antibodies are generated, are called antigens. There are two types of specific responses to an antigen, antibodies and the cellular response. Antibodies help to neutralize the infectious agent by specifically binding it. A series of proteins in the blood (called complement) act in conjunction with antibodies to destroy pathogenic bacteria. In the cellular response, cytotoxic T cells are recruited to kill cells infected with intracellular agents such as viruses. Helper T cells may also be generated, which influence B cells to produce appropriate antibodies. Inflammatory responses and activation of other kinds of cells, such as macrophages, in conjunction with lymphocytes, is another important aspect of the immune response, as in delayed hypersensitivity. This kind of response seems to be common in certain chronic infections. See Antibody, Antigen, Complement

Complex immune systems (antibody and specific cellular responses) have been demonstrated in mammals, birds, amphibians, and fish, and are probably restricted to vertebrates.

Natural or innate immunity

There are natural barriers to infection, both physical and physiological, which are known collectively as innate immunity, and include the effects of certain cells (macrophages, neutrophils and natural killer cells) and substances such as serum proteins, cytokines, complement, lectins, and lipid-binding proteins. The skin or mucous membranes of the respiratory tract are obvious barriers and may contain bacteriostatic or bactericidal agents (such as lysozyme and spermine) that delay widespread infection until other defenses can be mobilized.

If organisms manage to enter tissues, they are often recognized by molecules present in serum and by receptors on cells. Bacterial cell walls, for example, contain substances such as lipopolysaccharides that activate the complement pathway or trigger phagocytic cells. Host range is dramatic in its specificity. Animals and plants are generally not susceptible to each other's pathogens. Within each kingdom, infectious agents are usually adapted to affect a restricted range of species. For example, mice are not known to be susceptible to pneumococcal pneumonia under natural conditions. The health of the host and environmental conditions may also make a difference to susceptibility. This is readily apparent in fish that succumb to fungal infections if their environment deteriorates. Genetic factors have an influence on susceptibility. Some of these genes have been identified, in particular the genes of the major histocompatibility complex which are involved in susceptibility to autoimmune diseases as well as some infectious disorders. See Histocompatibility

Once parasites gain entry, phagocytic cells attack them. They may engulf and destroy organisms directly, or they may need other factors such as antibody, complement, or lymphokines, secreted by lymphocytes, which enhance the ability of the phagocytes to take up antigenic material. In many cases these cells are responsible for alerting cells involved in active immunity so there is two-way communication between the innate and adaptive responses. See Phagocytosis

Adaptive immune response

Adaptive immunity is effected in part by lymphocytes. Lymphocytes are of two types: B cells, which develop in the bone marrow or fetal liver and may mature into antibody-producing plasma cells, and T cells, which develop in the thymus. T cells have a number of functions, which include helping B cells to produce antibody, killing virus-infected cells, regulating the level of immune response, and controlling the activities of other effector cells such as macrophages.

Each lymphocyte carries a different surface receptor that can recognize a particular antigen. The antigen receptor expressed by B cells consists of membrane-bound antibody of the specificity that it will eventually secrete; B cells can recognize unmodified antigen. However, T cells recognize antigen only when parts of it are complexed with a molecule of the major histocompatibility complex. The principle of the adaptive immune response is clonal recognition: each lymphocyte recognizes only one antigenic structure, and only those cells stimulated by antigen respond. Initially, in the primary response, there are few lymphocytes with the appropriate receptor for an antigen, but these cells proliferate. If the antigen is encountered again, there will be a proportionally amplified and more rapid response. Primed lymphocytes either differentiate into immune effector cells or form an expanded pool of memory cells that respond to a secondary challenge with the same antigen.

The acquired or adaptive immune response is characterized by exquisite specificity such that even small pieces of foreign proteins can be recognized. This specificity is achieved by the receptors on T cells and B cells as well as antibodies that are secreted by activated B cells. The genes for the receptors are arranged in multiple small pieces that come together to make novel combinations, by somatic recombination. Each T or B cell makes receptors specific to a single antigen. Those cells with receptors that bind to the foreign protein and not to self tissues are selected out of a large pool of cells. For T cells, this process takes place in the thymus. The extreme diversity of T- and B-cell receptors means that an almost infinite number of antigens can be recognized. It has been calculated that potentially about 3 × 10²² different T-cell receptors are made in an individual. Even if 99% of these are eliminated because they bind to self tissues, 3 × 10²⁰ would still be available.

Inflammation takes place to activate immune mechanisms and to eliminate thoroughly the source of infection. Of prime importance is the complement system, which consists of tens of serum proteins. A variety of cells are activated, including mast cells and macrophages. Inflammation results in local attraction of immune cells, increased blood supply, and increased vascular permeability. See Cellular immunology

Autoimmunity

The immune system is primed to react against foreign antigens while avoiding responses to self tissue by immunological tolerance. Although most T cells which might activate against host proteins are deleted in the thymus, these self-reactive cells are not always destroyed. These exceptions to self tolerance are frequently associated with disease, the autoimmune diseases, which are widespread pathological conditions, including Addison's disease, celiac disease, Goodpasture's syndrome, Hashimoto's thyroiditis, juvenile-onset diabetes mellitus, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, rheumatoid arthritis, Sjögren's disease, and systemic lupus erythematosus. In these diseases, antibodies or T cells activate against self components. See Autoimmunity

Immunization

Adaptive immunity is characterized by the ability to respond more rapidly and more intensely when encountering a pathogen for a second time, a feature known as immunological memory. This permits successful vaccination and prevents reinfection with pathogens that have been successfully repelled by an adaptive immune response. Mass immunization programs have led to the virtual eradication of several very serious diseases, although not always on a worldwide scale. Living attenuated vaccines against a variety of agents, including poliomyelitis, tuberculosis, yellow fever, and bubonic plague, have been used effectively. Nonliving vaccines are commonly used for prevention of bacterial diseases such as pertussis, typhoid, and cholera as well as some viral diseases such as influenza and bacterial toxins such as diphtheria and tetanus. See Vaccination

Passive immunization

Protective levels of antibody are not formed until some time after birth, and to compensate for this there is passive transfer of antibody across the placenta. Alternatively, in some animals antibody is transferred in the first milk (colostrum). Antibody may also be passively transferred artificially, for example, with a concentrated preparation of human serum gamma globulin containing antibodies against hepatitis. Protection is temporary. Horse serum is used for passive protection against snake venom. Serum from the same (homologous) species is tolerated, but heterologous serum is rapidly eliminated and may produce serum sickness. On repeated administration, a sensitized individual may experience anaphylactic shock, which in some cases is fatal. Cellular immunity can also be transferred, particularly in experimental animal situations when graft and host reactions to foreign tissue invariably occur unless strain tissue types are identical.