CYTOTOXINS

From Big Medical Encyclopedia

TsITOTOKSYNY (Greek kytos a receptacle, here — a cell + toxins) — the antibodies causing damage of cells. Sometimes as a synonym of the concept «cytotoxins» use the term «cytolysins», to-ry has wider value since it is applicable to any substances capable to dissolve cellular elements. The antibodies destroying erythrocytes usually call hemolysins (see Hemolysis), the destroying leukocytes — a leykolysis, the inactivating spermatozoa — spermatolysins. K Ts. carry also bacteriolysins — antibodies to bacterial antigens, capable in the presence of a complement to cause a bacteriolysis (see).

C. are formed at immunization of an animal by antigens of a cellular origin, to-rye can belong to fabrics of animal other look (heterocytotoxins), the same type, but other genetic line (gomotsitotoksina), to tissues of an animal of the same line, as immuniziruyemy (isocytotoxins), and to own tissues of an immuniziruyemy animal (autocytotoxins). The more antigens of the donor differ from antigens of the recipient, the antibodies are formed easier. Therefore on the practician Ts. receive, immunizing an animal a cellular suspension or antigenic material of bodies of animal other look. The immune serums received at the same time contain different types of anti-cellular antibodies (anti-cellular serums) or the anti-organ antibodies (anti-body-nye of serum) which both are promoting, and not promoting emergence of cytotoxic action. In this regard the terms «An-titsellyulyarnaya serum» and «An-tiorgannaya serum» are wider, than the term «cytotoxic serum» applied to those serums, cytotoxic action to-rykh is confirmed.

It is established that at allotransplantation of fabrics in blood of the recipient gomotsitotoksina appear, to-rye, obviously, play a part in the mechanism of rejection of allotransplant. At isotransplantation probably the insignificant number of C is formed., their value in the mechanism of graft rejection is insignificant, and isotransplants, as a rule, beget (see Transplantation).

In 1898 Zh. Borde in I. I. Mechnikov's laboratory showed that immunization by heterogeneous erythrocytes is followed by formation of specific antibodies — hemolysins. The possibility of receiving antibodies not only against microorganisms, but also against cellular elements of a macroorganism was proved to these that formed the basis of the doctrine

about cytotoxins. In 1900, immunizing Guinea pigs fabrics of a rabbit seed plant, I. I. Mechnikov received I spermotsitotoksiche-will hold down the serum immobilizing spermatozoa of a Guinea pig. I. I. Mechnikov and A. M. Bezredka made leykotoksichesky and hemolitic serums. Leykotoksichesky serum was received at immunization of a Guinea pig by cells of lymphoid bodies of a rabbit, hemolitic serum — at immunization by erythrocytes. Both serums showed the specific action which is selectively directed in the first case to leukocytes (an immobilization and their disintegration) in the second — on erythrocytes (hemolysis). Administration of these serums in high doses reduced respectively number of leukocytes and erythrocytes, injections of small doses, on the contrary, led to increase in their number in blood. Thus, in P. P. Mechnikov's laboratory was not only the doctrine about C is put., but also basic distinction in operation of high and small doses of cytotoxic serums is shown: high doses showed toxic action, small doses worked as activators.

After I. I. Mechnikov spermatoxins were received by S. I. Me-taljnikov (1900), E. S. London (1901), M. P. Tushnov (1911), etc. Further a number of researchers received testikulo-cytotoxins, ovariotsitotoksina and pl atsentotsitotoksina, use to-rykh in high doses were led to dystrophic processes respectively in seed plants, ovaries and a placenta. The gepato-cytotoxins causing fatty dystrophy, development of cirrhosis and necrotic changes in a liver were received; a nave-rotsitotoksiny, at introduction to-rykh heavy changes in kidneys developed. The neurotoxins entered in high doses caused severe damages of a brain and peripheral nerves. Similar changes in tissues of an eye arose under the influence of the oftalmotsitotoksin prepared by S. S. Golovin (1904), etc. C Were received., the hearts operating on fabric, a stomach, a spleen, skin, hemadens and other bodies.

In 1909. A. A. Bogomolets proved a possibility of stimulation of function of adrenal glands small doses of suprarenotsitotoksin. With the help morfol. and fiziol. methods of a research he established that introduction to a cat of small doses of suprarenotsitotok-sichesky serum causes increase in the ABP, increase of pulse and breath. Microscopic changes in adrenal glands demonstrated strengthening under the influence of C. their hormonal activity. This work of A. A. Bogomolts should be considered the beginning fiziol. the period in studying of C. unlike preceding, preferential morphological. In 1925. L. A. Var-shamov and I. A. Leontyev in laboratory A. A. Bogomoltsa the cytotoxic serum to active elements of connecting fabric called

by A. A. Bogomolts antireticular cytotoxic serum

(see) was for the first time received.

V. K. Lingdemang, H. N. Nefedyev

and P. A. Herzen showed that at damage of one of kidneys to an organism of an experimental animal there are autocytotoxins having the damaging effect on a healthy kidney. Autocytotoxins in bigger or smaller quantity are produced at disintegration of any fabric in an organism as a result of a disease or exogenous damage (beam influence, a burn, etc.); at the same time autoantigens come to blood of the patient. The autoimmunization leading to emergence of autocytotoxins (autoantibodies) plays an essential role in the mechanism of further development patol. process. At inflammatory, dystrophic and other diseases of a thyroid gland existence in blood of autothyrocytotoxins is established.

C. receive as well as other highly active and specific drugs of antibodies. Specificity of C. it is reached by immunization of animals the organ-specific purified antigens or careful adsorption of immune serum the organ-specific antigens which were present at the material used for immunization. Problem of receiving uzkospetsifichesky C., as well as other high-specific antibodies, decides in a crust, time on the basis of the gibridomny equipment (see the Hybridoma, t. 20, additional

materials) allowing to receive monoclones.

Extent of dysfunction of body depends on a dose, biological activity of cytotoxin and functional lability of cellular substrate. A part of cells perishes under the influence of C.; at the remained cells function is broken.

Mechanism of action of small doses of C., stimulating function of body it is more difficult. Due to the education on a cell membrane of a complex antigen — an antibody function of the corresponding cells of body is broken, a part of fabric elements, obviously, the least resistant, perishes, but at the same time there is a process of recovery which is followed by the expressed functional activation of body. Such explanation of action of small doses of C., in particular antireticular cytotoxic serum,

A. A. Bogomolets gave. In a crust, time it is standard.

Mechanism of action of C. antigen — an antibody consists in activation of system of a complement (see) the formed complex (see. And ntigen — an antibody reaction). Cytotoxic action the antibodies belonging to immunoglobulins (see) with the expressed complement-linked ability possess. C. belong preferential to immunoglobulin of a class G. Change of spatial structure of a molecule of an antibody as a result of linkng with antigen leads to an exposure on an antibody of the sites connecting a complement. The stages of consecutive activation of components of a complement conducting to a cytolysis are fullestly studied on erythrocytes on the example of immune hemolysis (see) also are confirmed on other cells. Destruction of cellular membranes at action of C. and a complement it is established by means of a submicroscopy. The damages arising in membranes of erythrocytes represent round openings to dia. 8 — 10 nanometers. In yadrosoderzhashchy cells there is invagination of cellular membranes, swelling of mitochondrions and membranes of endoplasmic) a reticulum. Increase in permeability of a cellular membrane is shown by loss of intracellular potassium ions, amino acids and ribonucleotides. Cells bulk up, and as a result of an osmotic lysis from them proteins and nucleinic to - you are released. Actually a lysis of a cellular membrane is carried out at the last stage of activation of system of a complement by a decamolecular complex with involvement of components of a complement of C5 — C9. The decamolecular complex (on one molecule S5, S6, S7, S8 and 6 molecules C9) has a pier. the weight (weight) apprx. 995 Ltd companies. It is possible that damage results from interactions of this complex with lipids of a cellular membrane. Morfol. signs of damage of a cellular membrane become noticeable after fixing of C5 owing to detergentny action of the activated form of this component (S5), to-ry shows sharply expressed hydrophobic properties in relation to phospholipids of a membrane. Interaction of other components of a complement strengthens detergentny action of S5 that leads to fusion of sites of a cellular membrane.

C. apply in pilot studies to studying of function of separate bodies and systems. Methods of cytotoxic stimulation and cytotoxic suppression of function of various bodies and fiziol. systems entered into arsenal patofiziol. methods. Similar action of C. render in vitro at addition them in a medium. So, small doses of C. strengthen proliferation of the corresponding cellular elements, high doses suppress reproduction of cells.

C., specific to surface antigens of certain cells, apply to identification of these cells in cytotoxic in vitro test in the presence of a complement. Use of immune serums and monoclones for identification of populations and subpopulations of lymphoid cells can be an example.

In a wedge, practice apply in small doses antireticular cytotoxic serum for the purpose of increase in protective functions of an organism at infectious and tumoral processes. For strengthening of an erythrocytopoiesis, a leykotsitopoez or a thrombocytopoiesis enter the cytotoxic serums received at immunization of an animal respectively by erythrocytes, leukocytes or thrombocytes. For acceleration of recovery of normal composition of blood at donors, and also at hyporegenerative anemia (see) use miyelotsitotoksichesky serum.

See also Anti-lymphocytic serum, Antibodies, Hemotoxins, Nephrite cyto toxic y experimental.

Bibliography: And d about A. D. General allergology, M., 1978; B about about m about l e A. A c.

The methodological value of cytotoxins, as specific stimulators, Medical - Ziol. zhurn., century 3, page 35, 1926; about N e, the Chosen works, t. 3, page 138, Kiev, 1958; M e h N and to about in I. I. Cellular poisons (cytotoxins), Russian arkh. patol., t. 11, century 2, page 101, 1901; P e t r about in R. V. Immunologiya, M., 1982; F e d about r about in N. A., etc. Experimental and clinical materials on a research of new cytotoxic serums, M., 1956; In i e of O. G. and. lake of Fundamentals of immunology, p. Ill, N. Y. a. o., 1981; Handbuch der Biochemie des Men-schen und der Tiere, hrsg. v. C. Oppenheimer, Bd 2, Hft 1, S. 542, Jena, 1910; Humph-@ e at J. N of a. D about and of m a s h k i n H. R. The lesions in cell membranes caused by complement, Advanc. Immunol., v. 11, p. 75, 1969; Immunology in medicine, ed. byE. J. Holborowa. W. G. Reeves, L. a. o., 198,3; Miiller-EberhardH.J. Complement, Ann. Rev. Biochem., v. 44, p. 697, 1975; Muller-EberhardH. J. a. o. A molecular concept of immune cytolysis, Arch. Path., v. 82, p. 205, 1966.

260 CYTOTOXIC ANTIRETICULAR SERUM


I. M. Neumann, I. S. Gushchin.

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