ATREPSY (Latin immunitas release, disposal of something) — a complex of the reactions of immune system of an organism directed against a tumor cell, determined by activity of immune lymphocytes, macrophages and antibodies.
The factors of natural immunity which are taking part in Nominative are almost not studied. Distinctions in the frequency of emergence at animals of different type of spontaneous tumors or to induction of certain tumors include in their resistance, undoubtedly, both factors of not immunological nature, and factors of virus-induced immunity. Experimentally established resistance of certain lines of mice and hens to reproduction of sarkomo-leukemic viruses has neimmunol. nature. It is possible that antibodies to oncogenic viruses, napr, to a virus of a polioma at healthy mice or to Epstayn's virus — Burra at people, are factors of natural resistance to these tumors. Apparently, plays a part in Nominative interferon (see), having overwhelming effect on oncogenic viruses and tumor cells. Assume that in the course of evolution of this species of animals gene pattern, defining an effective immune response in relation to the oncogenous viruses circulating in this look and to the antigens induced by these viruses forms. By such way various sensitivity of certain animal species to different oncogenic viruses can be created.
The main condition for development of artificial immunity is existence in structure of tumor cells specific to a tumor antigens (see), perceived by immunological system of an organism as alien. These antigens can be either intracellular, or included in an outer membrane of cells, or the waste products of cells getting then in a blood channel. Tumoral antigens stimulate education antibodies (see) and immune lymphocytes which can interact with tumor cells if the corresponding antigen is on a cell membrane. As a result of such interaction the tumor can disappear, slow down the growth or gain immunoresistance. The net result of growth of a tumor in the conditions of Nominative is defined by quantity and dynamics of antibody formation and immune lymphocytes with a growth of a tumor, amount of specific tumoral antigens on surfaces of cells, type of a tumor, its immunoresistance etc.
The main method of definition of Nominative in vivo is the transplant test; existence and tension of Nominative come to light on increase in the minimum oncogenous dose of tumor cells at their transplantation by an immunizirovanny animal in comparison with control. The transplant test is feasible only in strictly singenny system i.e. when the donor of a tumor and recipients are genetically identical and do not differ on antigens of histocompatibility.
In certain cases Nominative can be revealed by the so-called skin test on reaction of hypersensitivity of the slowed-down type in an injection site of tumoral antigen.
Very widely Nominative is studied by in the vitro methods. Interaction of antibodies with a membrane of tumor cells in the presence of a complement can give cytotoxic effect. The antibodies connected with a membrane can come to light also so-called fluorescent or marked 1251 antibodies against immunoglobulins.
Nominative caused by action of immune lymphocytes can be revealed in culture of tumor cells at addition of lymphocytes of the immunizirovanny donor to it or the organism affected with a tumor.
Emergence of the acquired Nominative is caused by existence of specific tumoral antigens which belong to five basic groups. The first group combines specific antigens of viral tumors, controlled genome (see) a virus. These antigens significantly differ on structure and the nature in different classes oncogenous viruses (see) — Papova viruses and adenoviruses, oncornaviruses and viruses of group of herpes. The tumor cells transformed papova-and adenoviruses, have the virusindutsirovanny antigens which are localized in a kernel and on a cellular membrane. Some of membrane specific tumoral antigens are capable to induce the strong Nominative which is not allowing a tumor to take root on singenny immunizirovanny recipients and even suppressing developing of tumors at the animals infected with the same virus.
In the cells transformed by oncornaviruses, specific tumoral antigens are generally presented by structural components of a virus — proteins or glycoproteins — which are synthesized usually and in those tumors in which there are no products of full virus particles. Except structural components of a virus, the tumors induced by oncornaviruses may contain the antigens which are not a part of virus particles localized on a surface of a cell. Essential feature of virusindutsirovanny antigens is their identity in all those tumors which are caused by one certain type of a virus, irrespective of gistol, structures of a tumor or a species of an animal.
The second group of tumoral antigens is made by antigens of the tumors induced 'by chemical carcinogens. Antigens of the tumors caused by the same chemical carcinogen at animals, identical on a genotype, and in identical conditions differ in the immunological specificity. In certain cases in the tumors caused by carcinogens it is possible to find the cross reacting antigens, however in these cases they are less characteristic and meet along with individual specific antigens. The nature and origins of antigens of the second group are not studied. These antigens can induce transplant immunity, however only to that tumor, cells a cut were used for immunization.
The third group of antigens combines the specific tumoral antigens which are the usual isoantigens which are available for normal animal some closed lines or for a certain percent of individuals in heterogeneous population. Antigens of this group prove as specific tumoral in those lines (or individuals) at which they are not synthesized in normal conditions, and appear in tumor cells only as a result of carcinogenesis. These antigens meet in virus, induced by carcinogens, and spontaneous tumors. An example of formation of specific tumoral antigens of the third group is synthesis of antigen, serological similar to blood-group antigens And, in tumor cells of patients with a blood group of B or 0. TL (thymus — leukemia) - antigen of mouse leukoses which is normal organospetsifichesky of antigen of thymocytes at some lines of mice can be other example, but it is found in mice of other lines only at the spontaneous or induced leukosis.
Tumoral embryonic antigens enter into the fourth group of antigens. Idiosyncrasy of these antigens — their presence at normal fabrics at an embryonal stage of development or in the early post-natal period. In an adult organism their synthesis sharply decreases, but at formation of a tumor increases again. In view of absence or very low level of tumoral embryonic antigens in an adult organism immunol, tolerance to them is absent or is easily surmountable. At emergence of embryonic antigens in tumor cells in quantities, sufficient for an immunogenesis, they can induce antibody formation or immune lymphocytes and, therefore, act as specific tumoral antigens. Embryonic antigens were found in virus, caused by chemical carcinogens, and spontaneous tumors.
The specific tumoral antigens characterizing spontaneous tumors of an unknown etiology make the most extensive — the fifth group of tumoral antigens. Specific antigens of tumors of the person generally concern to them. These antigens come to light and studied by means of cytotoxic reaction of the immune lymphocytes taken from the patient with a tumor to the cells of his own or similar tumor cultivated by in vitro. The specific tumoral antigens revealed in these conditions are similar or identical in tumors of a certain histogenesis. It is possible that a part of antigens of this group belongs to tumoral embryonic antigens. Spontaneous tumors cause only very weak Nominative in animals
Thus, in the majority of tumors there are specific antigens of this or that type capable to induce immunol, the answer of an organism. Some of them can not only cause an immune response of an organism, but also it is essential to increase resistance both to induction of a tumor, and to its transplantation. Antigens of the first and second groups are especially effective in this respect. Cases of a spontaneous rassasyvaniye of a tumor are followed strong immunol, the answer to specific antigens that also indicates a significant role of immune system in destruction of a tumor. However Nominative has no absolute character; at introduction it is even high - the immune animal of high doses of tumor cells at most of them forms the tumors leading of an organism to death. The main mechanisms allowing cells of a tumor to overcome the conflict with immunol, system of an organism are experimentally studied. Treats them insufficient immunol, competence of an adult organism, edge can be the cause of free growth of tumor cells. Artificial suppression of immune system of an organism by radiation, thymectomies, actions of immunodepressants or anti-lymphocytic serum significantly promotes emergence of spontaneous tumors (in some systems), induction of tumors by means of oncogenous viruses or chemical carcinogens. Oncogenous viruses and many chemical carcinogens also possess an immunodepressive effect. The fact that the greatest percent onkol, diseases falls on advanced age when the immune system is weakened, and also sharp increase of percent of new growths at patients with inborn defects of immune system or systematically receiving immunodepressants will well be coordinated with this mechanism. Inspection onkol, patients showed that at many of them the system of a complement is broken, the lack of B-lymphocytes — predecessors of plasmocytes (antibody producers), and also T lymphocytes — predecessors of immune lymphocytes is felt, activity of macrophages and other elements of reticuloendothelial system is reduced (see. Immunity ).
The defining role in rejection by an organism of tumor cells belongs to immune T lymphocytes. However specific tumoral antigens, as a rule, induce both formation of immune lymphocytes, and antibodies, and their ratio can be important at development of a tumor. Antibodies to antigens of a cellular membrane, having reacted with them in the presence of a complement, can render cytotoxic effect on a tumor cell. Antibodies can interfere with rejection of a tumor; in this case they block those determinants of antigens against which specific receptors of immune lymphocytes are directed (so-called effect of acceleration of growth of a tumor antibodies). The effect of acceleration is accurately shown for graft-specific antigens of tumors in allogenic system. It is undoubted that it can play a role and in specific Nominative. As the blocking factors for action of immune lymphocytes also tumoral antigens can act if they, being components of a cellular membrane, circulate also in a soluble form in blood. Assume that soluble tumoral antigens, being present at a complex with the corresponding antibodies, render the blocking effect on immune lymphocytes, connecting to their specific receptors on an outer cellular membrane. Thus, humoral immunity to tumoral antigens can help a tumor to overcome Nominative. Under other conditions of an antibody are capable to suppress growth of tumor cells as it takes place at experimental leukoses.
Specific tumoral antigens of spontaneous tumors and some virusindutsirovanny antigens cause weak immunol, the answer of an organism or do not induce it absolutely. The weak immunogenicity of such antigens can be connected with full or partial tolerance of an organism to them — the carrier of a tumor. E.g., natural carcinogenesis at mice and hens is closely connected with presence at their organisms of oncornaviruses leukemic sarkomatoznogo a complex and family of viruses of cancer of mammary glands (at mice). The genome of these viruses is integrated with a genome of cells and is transmitted in the vertical way, i.e. from parents to posterity through gametes. In the spontaneous or induced tumors the virus genome is present at an active form, controlling synthesis of virusindutsirovanny antigens. In normal fabrics during the embryonal period of development activation of some virus genes and synthesis of the corresponding antigens is observed. Thereof the organism does not distinguish virusindutsirovanny antigens as alien and becomes to them in whole or in part tolerant. Under these conditions immunity to specific antigens cannot be rather intense and does not suppress growth of tumor cells. The similar picture is observed by transfer of a virus of cancer of mammary glands of mice with milk.
In the presence of Nominative the tumor can become immuiorezistentny and not react to presence of antibodies or immune lymphocytes. Mechanisms of such resistance are very various. One of them is immunoselection, thanking a cut there is a selection of the tumor cells containing the smallest quantity of specific antigens that allows them to develop contrary to an immune response of an organism. Other mechanism is connected with disappearance of tumoral antigens of a cellular membrane after their contact with antibodies. This phenomenon received the name of antigenic modulation and is observed not with all membrane antigens.
Tumoral antigens of a cellular membrane can be present at the latent form, forming a complex with the cellular components closing antigenic determinants and interfering their interaction with antibodies or immune lymphocytes. Thus immunoresistance of tumor cells is created, edges it can be eliminated with processing of cells of in vitro a neuraminidase, trypsin, etc.
Mechanisms and features of Nominative are studied by hl. obr. on pilot models, however many of them carry, apparently, obshchebiol. character can also take place not only at animals, but also at the person. Specific antigens of this or that group are found in some tumors of the person; ability of some of these antigens to induce emergence in an organism — the carrier of a tumor of antibodies and immune lymphocytes is shown; the blocking factors for immune lymphocytes are found; various disturbances immunol, competence at onkol, patients are found. At Berkitt's lymphoma, emergence a cut is closely connected with presence at cells of a virus of Epstayn — Barre belonging to group of herpes at patients the answer to viral and virusindutsirovanny antigens is observed typical immunol. Accurately expressed Nominative in this case, perhaps, promotes successful chemotherapy of this tumor. Not all specific antigens found in tumors of the person cause Nominative: so, the lipopolisakharidny antigens, specific to them, found in tumors of the person do not conduct to antibody formation in an organism of patients.
The described features of Nominative allow to plan various approaches to an immunotherapy of tumors. In view of a variety of the ways leading to strengthening of Nominative in the organism affected with a tumor, the immunotherapy is subdivided into four main types: active, passive, adoptive and nonspecific.
The active immunotherapy is directed generally to creation of such conditions under which own immune system of an organism becomes capable to distinguish specific tumoral antigens and to fight actively against tumor cells. Usual schemes of an active immunotherapy consist of repeated injections auto-or the allogenic irradiated or killed tumor cells, extract or homogenate from them or the purified tumoral antigen. In experimental oncology methods of an active immunotherapy yield good results for virusindutsirovanny tumors and many tumors caused by chemical carcinogens. These methods as the preventive measures interfering emergence of tumors or their growth at transplantation are especially effective. In a wedge, oncology the methods of an active immunotherapy causing intense and durable immunity in patients to tumor cells are not found yet; the improvement of a condition of patients observed sometimes is temporary.
The passive immunotherapy includes ways of increase in humoral immunity by introduction of cytotoxic antibodies to tumoral antigens. Allogenic or heterogeneous antiserums to specific tumoral antigens can be a source of such antibodies. Efficiency of their use is limited generally to the tumors possessing a large amount and high density of antigens on a cellular membrane. The most interesting in a passive immunotherapy methods of increase in cytotoxic effect of antibodies are represented. For this purpose the purified immunoglobulins, antibody-containing to tumoral antigens, are conjugated with substances, toxic for cells (radioisotopes, bacterial toxins, chemical inhibitors of metabolism etc.). In this case antibodies which in itself are not capable to lyse a cell destroy it by means of the conjugated agents. In a wedge, oncology the passive immunotherapy is practically not used.
The adoptive (apprehended) immunotherapy, unlike passive, allows to increase immunity of cellular type by introduction to an organism of the lymphocytes, immune to tumoral antigens, taken from the donor, immunizirovanny by tumoral material of the recipient. In view of the fact that cellular immunity plays the main role in Nominative, the positive effect gained at an adoptive immunotherapy is much higher, than at passive. However hallo - or heterogeneous sensibilized lymphocytes induce an immune response of the recipient on antigens of histocompatibility (see. Incompatibility immunological ) and, therefore, cannot be used for long treatment. Besides, among donor lymphocytes there can be cells which through a nek-swarm time after introduction to the recipient will begin to react to normal antigens of his fabrics and will cause reaction, pernicious for an organism, «a transplant against the owner». To avoid similar complications, immune lymphocytes subject previously to radiation, and to the recipient enter the immuno-depressants suppressing his own immune system. In clinic the adoptive immunotherapy is used extremely seldom due to the lack of a constant source of immune lymphocytes, free of strong antigens of histocompatibility. Considerable interest is attracted by studying of induction of cellular immunity the factor allocated from acellular material of immune lymphocytes («transfer factor»). This factor has no antigenic properties, but can induce cellular immunity in a healthy organism to those antigens, to the Crimea immune lymphocytes — donors of «transfer factor» were received.
In clinic the nonspecific immunotherapy is rather often used. Methods of this type of therapy are diverse; most of them is directed to creation of conditions under which there is a nonspecific activation of all immunol, systems of an organism. The most widespread is stimulation of resistance by injections of the killed or attenuirovanny bacilli of Kalmett — Gerena. These bacilli, possessing a strong immunogenicity, activate all mechanisms of immunity, but hl. obr. cellular. The clinical effect of a nonspecific immunotherapy is studied.
See also Tumours, immunology .
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G. I. Abelev.