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.
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 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.
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.
A. KH. KANCHURIN and N. V. MEDUNITSYN