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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 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.
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 histaminehistamine
, organic compound derived in the body from the amino acid histidine by the removal of a carboxyl group (COOH). Although found in many plant and animal tissues, histamine is specifically important in human physiology because it is one of the chemicals released from
..... Click the link for more information. , 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 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 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 systemlymphatic system
, network of vessels carrying lymph, or tissue-cleansing fluid, from the tissues into the veins of the circulatory system. The lymphatic system functions along with the circulatory system in absorbing nutrients from the small intestines.
..... Click the link for more information. , tonsilstonsils,
name commonly referring to the palatine tonsils, two ovoid masses of lymphoid tissue situated on either side of the throat at the back of the tongue. The pharyngeal tonsils, or adenoids, are masses of similar tissue located in the nasopharynx, and the lingual tonsils
..... Click the link for more information. , and spleenspleen,
soft, purplish-red organ that lies under the diaphragm on the left side of the abdominal cavity. The spleen acts as a filter against foreign organisms that infect the bloodstream, and also filters out old red blood cells from the bloodstream and decomposes them.
..... Click the link for more information. . 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 humorshumor,
according to ancient theory, any of four bodily fluids that determined human health and temperament. Hippocrates postulated that an imbalance among the humors (blood, phlegm, yellow bile, and black bile) resulted in pain and disease, and that good health was achieved
..... Click the link for more information. .
The presence of antigens in contact with receptor sites on the surface of a B lymphocyte stimulates the lymphocyte to divide and become a cloneclone,
group of organisms, all of which are descended from a single individual through asexual reproduction, as in a pure cell culture of bacteria. Except for changes in the hereditary material that come about by mutation, all members of a clone are genetically identical.
..... Click the link for more information. (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 BurnetBurnet, Sir Macfarlane,
1899–1985, Australian virologist and physician. He was resident pathologist (1923–24) at the Royal Melbourne Hospital and a Beit fellow (1926–27) at the Lister Institute, London.
..... Click the link for more information. (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 antibodiesmonoclonal antibody,
an antibody that is mass produced in the laboratory from a single clone and that recognizes only one antigen. Monoclonal antibodies are typically made by fusing a normally short-lived, antibody-producing B cell (see immunity) to a fast-growing cell, such as
..... Click the link for more information. .
The antibodies produced by B cells are a type of globulinglobulin,
any of a large family of proteins of a spherical or globular shape that are widely distributed throughout the plant and animal kingdoms. Many of them have been prepared in pure crystalline form.
..... Click the link for more information. 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 toxinstoxin,
poison produced by living organisms. Toxins are classified as either exotoxins or endotoxins. Exotoxins are a diverse group of soluble proteins released into the surrounding tissue by living bacterial cells. Exotoxins have specific reaction sites in the host; e.g.
..... Click the link for more information. , 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.
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 vaccinationvaccination,
means of producing immunity against pathogens, such as viruses and bacteria, by the introduction of live, killed, or altered antigens that stimulate the body to produce antibodies against more dangerous forms.
..... Click the link for more information. ).
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 transplantationtransplantation, medical,
surgical procedure by which a tissue or organ is removed and replaced by a corresponding part, usually from another part of the body or from another individual.
..... Click the link for more information. 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 groupsblood groups,
differentiation of blood by type, classified according to immunological (antigenic) properties, which are determined by specific substances on the surface of red blood cells.
..... Click the link for more information. ). An immune reaction can also occur between a mother and baby (see Rh factorRh factor,
protein substance present in the red blood cells of most people, capable of inducing intense antigenic reactions. The Rh, or rhesus, factor was discovered in 1940 by K. Landsteiner and A. S.
..... Click the link for more information. ). Allergyallergy,
hypersensitive reaction of the body tissues of certain individuals to certain substances that, in similar amounts and circumstances, are innocuous to other persons. Allergens, or allergy-causing substances, can be airborne substances (e.g.
..... Click the link for more information. , anaphylaxisanaphylaxis
, hypersensitive state that may develop after introduction of a foreign protein or other antigen into the body tissues. When an anaphylactic state exists, a second dose of the same protein (commonly an antibiotic such as penicillin, or certain insect venoms) will
..... Click the link for more information. , and serum sicknessserum sickness,
hypersensitive response that occurs after injection of a large amount of foreign protein. The condition is named for the serum taken from horses or other animals immunized against a particular disease, e.g., tetanus or diphtheria.
..... Click the link for more information. are all manifestations of undesirable immune responses.
Many degenerative disorders of aging, e.g., arthritisarthritis,
painful inflammation of a joint or joints of the body, usually producing heat and redness. There are many kinds of arthritis. In its various forms, arthritis disables more people than any other chronic disorder.
..... Click the link for more information. , are thought to be disorders of the immune system. In autoimmune diseasesautoimmune disease,
any of a number of abnormal conditions caused when the body produces antibodies to its own substances. In rheumatoid arthritis, a group of antibody molecules called collectively RF, or rheumatoid factor, is complexed to the individual's own gamma globulin
..... Click the link for more information. , such as rheumatoid arthritis and lupuslupus
, noninfectious chronic disease in which antibodies in an individual's immune system attack the body's own substances. In lupus, known medically as lupus erythematosus, antibodies are produced against the individual's own cells, causing tissue inflammation and cell damage.
..... Click the link for more information. , 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 nephritisnephritis
, inflammation of the kidney. The earliest finding is within the renal capillaries (glomeruli); interstitial edema is typically followed by interstitial infiltration of lymphocytes, plasma cells, eosinophils, and a small number of polymorphonuclear leukocytes.
..... Click the link for more information. ) 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. AIDSAIDS
or acquired immunodeficiency syndrome,
fatal disease caused by a rapidly mutating retrovirus that attacks the immune system and leaves the victim vulnerable to infections, malignancies, and neurological disorders. It was first recognized as a disease in 1981.
..... Click the link for more information. (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.
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)
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
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
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
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.
(in history) in medieval Europe, privileges of large landowners, consisting of the possession of rights of political power over the population of an estate.
Immunity took shape through royal grants, which gave magnates the rights to conduct justice (as a rule, within the scope of the lowest jurisdiction), collect taxes and other requisitions, and exercise police and military-administrative functions within the boundaries of their possessions (and sometimes over a more extensive area as well), while barring state officials from the immune territory. Immunity became widespread as early as the time of the Frankish state (the first deeds of immunity that have come down to us date to the mid-seventh century). The institution of immunity fell into decay in the process of political centralization.
The specific character of feudal relations in various countries influenced the nature of immunity. Thus, in Germany, where immunity reached full bloom during the reign of the Saxon dynasty (tenth and 11th centuries), the development of immunity led in a number of instances to the formation of compact immune holdings, and this was highly significant in the formation of territorial principalities. In England, where it was chiefly the legislative immunity that developed during the Anglo-Saxon period, immunity as a whole was not strongly expressed. In Byzantium, excussia, which was close to the Frankish immunity, was in the nature of tax exemptions.
Immunity played a large role in the development of feudal property. In realizing the rights granted to them, the holders of immune estates brought under their power peasants who still retained their freedom. In appropriating taxes and other requisitions (which had been collected previously for the benefit of the state), feudal lords—the possessors of the rights of immunity— increased the magnitude of feudal exploitation. An attribute of large-scale feudal landed property, immunity was a factor of the greatest importance in the process of the formation of the system of extraeconomic constraint.
REFERENCESDanilov, A. I. “Osnovnye cherty immuniteta i fogtstva na tserkovnykh zemliakh v Germanii X-XII vv.” In the collection Doklady i soob-shcheniia istoricheskogo f-ta MGU, issue 7. Moscow, 1948.
Gutnova, E. V. “K voprosu ob immunitete v Anglii XIII v.” In the collection Srednie veka, issue 3. Moscow, 1951.
Gramenitskii, D. S. “K voprosu o proiskhozhdenii i soderzhanii frankskogo immuniteta.” Ibid., issue 2. Moscow, 1946.
IA. D. SEROVAISKII
insusceptibility to infectious agents and foreign substances of antigenic nature (substances bearing foreign genetic information). Insusceptibility to infectious diseases is the most frequent manifestation of immunity.
Congenital (nonspecific, constitutional, species) immunity is insusceptibility caused by the innate biological (hereditarily fixed) characteristics of the organism—for example, man’s immunity to canine or cattle plague or the immunity of animals to gonorrhea and leprosy. The various individuals within a single species may also differ in degree of resistance to the same disease (individual immunity characteristics).
Acquired (specific) immunity is the insusceptibility to infectious diseases that develops during the life of the organism. Natural and artificial acquired immunity are distinguished. Both forms may be active (the organism itself manufactures antibodies after having had a disease or after active immunization) and passive (caused by preformed antibodies artificially introduced by passive immunization, such as in the injection of anti-diphtheritic serum or in the penetration by the antibodies to the fetus from the mother through the placenta or to the infant through the mother’s milk). Active immunity is more stable and longer lasting. In some diseases, such as smallpox, it lasts a lifetime; in others, such as measles and scarlet fever, the immunity lasts many years but is not transmitted by heredity. Passive immunity begins to develop several hours after the injection of antibodies and lasts from two or three weeks to several months.
Immunity is subdivided into antimicrobial (the body’s defenses are directed against the causative agent itself) and antitoxic (the defenses are directed against the toxins manufactured by the causative agent), sterile (existing even after the causative agent disappears from the body) and nonsterile. Nonsterile immunity develops and exists only in the presence of the infectious principle in the body. This form of immunity is seen in tuberculosis. Acquired immunity in all its forms is generally relative. It can be overcome by a massive infection, although the course of the disease is milder in such cases. The characteristics of the immunological reactivity of individual tissues and organs to a given infection were the basis for establishing the concept of local immunity (A. M. Bezredka, 1925). The development of such immunity is invariably accompanied by the appearance of some degree of general immunity.
An example of immunity to a principle other than infection is the immunity that develops after grafting tissue, or so-called transplantation immunity, in which immune lymphocytes are the main factor.
Mechanisms of immunity. Intact skin and mucous membranes, which possess bactericidal properties, act as a barrier to most microbes. These bactericidal properties are believed to be due chiefly to lactic and fatty acids secreted by the sweat and sebaceous glands. These acids kill most pathogenic bacteria. For example, the causative agents of typhoid die after 15 minutes of contact with healthy human skin. Equally destructive of bacteria and pathogenic fungi are discharges of the external auditory meatus; smegma; lysozyme, present in the discharges of many mucous membranes; mucin, which covers the mucous membranes; hydrochloric acid; enzymes; and bile in the digestive tract. The mucous membranes of some organs are capable of mechanically removing particles that come into contact with them. For example, the movements of the cilia of mucosal epithelium help to remove bacteria and dust particles from the respiratory passages. The internal environment of mammals is sterile under normal conditions.
Any agent that increases the permeability of skin or mucosa lowers the resistance to infections. If an infection is massive and the microbes are highly virulent, the cutaneous and mucous barriers are inadequate and the microbes penetrate to the deeper tissues. In most cases this leads to inflammation, which prevents the microbes from spreading beyond the site of penetration. Normal and immune antibodies and phagocytosis play an important role in fixing and destroying microorganisms at the focus of inflammation. Cells of local mesenchymal tissue and cells from the blood vessels participate in phagocytosis. Causative agents that are not destroyed at the focus of inflammation are phagocytized by cells of the reticuloendothelial system in the lymph nodes. The fixing function of the lymph nodes increases in the process of immunization.
Microbes and foreign substances that penetrate the barriers are subjected to the properdin system, which is present in blood plasma and tissue fluids and consists of complement, or alexin, properdin, and magnesium salts. Lysozyme and certain peptides (spermine) and lipids liberated from leukocytes are also capable of killing bacteria. Neuraminic acid and mucoproteins of erythrocytes and bronchial epithelial cells play a special role in nonspecific antiviral immunity. When a virus or microbe penetrates the body the cells secrete a protective protein called interferon. The acid reaction of the tissue medium, caused by the presence of organic acids, also inhibits the reproduction of microbes. A high oxygen content in the tissues inhibits the reproduction of anaerobic microorganisms. This group of factors is nonspecific; it exerts a bactericidal effect on many bacterial species.
Antibody formation is the principal form of specific immunological response to the introduction of foreign substances and infection. Depending on their action, antibodies are called agglutinins, precipitins, bacteriolysins, antitoxins, and opsonins. They induce the agglutination and lysis of microbes and the precipitation of antigen; they also neutralize toxins and prepare microbes for phagocytosis. Autoantibodies, antibodies directed at the body’s own tissues and cells and the cause of autoimmune diseases, may be formed in certain cases.
The body’s ability to synthesize antibodies of a particular specificity and to create specific immunity is determined by its genotype. Most antibodies are synthesized in the plasma cells and in the cells of the lymph nodes and spleen. Immunological reconstruction takes place after the introduction of antigen; this occurs in two phases. In the first, or latent, phase, which lasts several days, adaptive morphological and biochemical changes take place in the lymphoid organs. The antigen is treated in this phase by the reticuloendothelial cells, and fragments of it come into selective contact with the appropriate leukocytes. Specific antibodies are formed in the second, or productive, phase. The antibodies are manufactured in plasma cells formed from undifferentiated reticular cells and, to a lesser extent, in lymphocytes. “Long-lived” lymphocytes, carriers of the so-called immunological “memory,” appear in the second phase. The repeated introduction of a very small dose of antigen may cause these cells to reproduce and give rise to plasma cells that again form antibodies. Preservation of the immunological “memory” by the organism is the basis of potential immunity. Thus, after vaccination with diphtheria toxoid, an infant will remain resistant to the disease despite the disappearance of the corresponding antibodies from the bloodstream, since even very small doses of diphtheria toxin can stimulate intensive antibody formation. Such antibody formation is called the secondary, anamnestic, or revaccinal response. A very large dose of antigen, however, can kill the cells that carry the immunological “memory.” As a result, antibody formation will be prevented and the introduction of antigen will not be challenged—that is, a state of specific immunological tolerance will arise. Immunological tolerance is an especially important factor in organ and tissue transplantation.
Immunological reconstruction of the organism following the introduction of antigen or infection may result in increased cellular and tissue sensitivity to the corresponding antigens—that is, in allergy—in addition to the formation of protective antibodies. Immediate and delayed types of increased sensitivity are distinguished among the allergic reactions, depending on the time necessary for the appearance of the symptoms of injury after the repeated introduction of antigens (allergens). Increased sensitivity of the immediate type is caused by special antibodies (reagins) that are found either circulating in the blood or fixed in the tissues. Increased sensitivity of the delayed type is caused by the specific reactivity of the lymphocytes and macrophages carrying the so-called cellular antibodies. Many bacterial infections and several vaccines raise the level of sensitivity of the delayed type; this can be shown in the skin reaction to the corresponding antigen. Increased sensitivity of the delayed type is the basis of the body’s reaction to foreign cells and tissues, that is, the basis of transplantation immunity, antitumor immunity, and a number of autoimmune diseases. Specific cellular immunity may develop simultaneously with increased sensitivity of the delayed type. It is manifested by the inability of a given causative agent to reproduce in the cells of the immunized organism. Increased sensitivity of the delayed type and related cellular and transplantation immunities can be transferred to a nonim-munized animal by live lymphocytes from an immunized animal of the same line and thereby create adoptive immunity in the recipient.
REFERENCESPetrov, R. V. Vvedenie v neinfektsionnuiu immunologiiu. Novosibirsk, 1968.
Fontalin, L. N. Immunologicheskaia reaktivnost’ limfoidnykh organov i kletok. Leningrad, 1967.
Nezlin, R. S. Biokhimiia antitel. Moscow, 1966.
Zil’ber, L. A. Osnovy immunologii 3rd ed. Moscow, 1958.
Zdrodovskii, P. F. Problemy infektsii, immuniteta i allergii, 3rd ed. Moscow, 1969.
Burnet, F. M. Kletochnaia immunologiia. Moscow, 1971. (Translated from English.)
A. KH. KANCHURIN and N. V. MEDUNITSYN