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 also Allergy; Autoimmunity; Hypersensitivity; 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 also 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 also 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 also 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 also 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 also 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 also Cancer (medicine); 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.
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