CHIMERAS

From Big Medical Encyclopedia

CHIMERAS (Greek Chimaira a fire-spitting monster with the head of a lion, a trunk of a goat and a tail of a dragon) — metaphytes, a body to-rykh consists of the genetically different cells which were initially belonging to different individuals. Artificial creation and studying of chimeras is used in immunological, genetic and other researches.

Distinguish primary himerizm, at Krom genetically different cells (or groups of cells) combine in one germ in the earliest stage of an embryogenesis or already from the moment of fertilization, and a secondary himerizm, at Krom fabrics from two or more adult individuals or germs after the beginning of the period of an organogenesis are combined. Chimeras usually receive experimentally, but occasionally they can arise in also natural way as a result of aggregation of two separate zygotes or disperse fertilization when one spermatozoon merges with an ovum, and another — with a polar little body. On a genetic raznokachestvennost of cells mosaics — the individuals who developed each of one zygote, but gained heterogeneity of cellular structure during ontogenesis are close to chimeras (see Mosaicism).

In experimental conditions of primary chimeras receive by aggregation of blastomeres of two or more genetically different germs (an aggregation method) or introduction of cells of internal cellular mass of a blastocyste of the donor (or totipotent cells of other origin, in particular stem cells of a teratocarcinoma) in blastotsel a re-tsipiyentny germ (an injection method). Usually use the germs which are on 8 — a 12-cellular stage of development. They are washed away from oviducts and for dissolution of an egg cover process in vitro fermental drug of pronazy. The blastomeres of two germs exempted from an egg cover aggregate with each other, cultivate such mixed unit of blastomeres within 24 — 48 hour. After achievement by himerny germs of a stage of a blastocyste they are implanted into a uterus of a female of the recipient. At an injection method of receiving chimeras use the micromanipulator: a special

sucker hold a blastocyste recipient and by means of a micropipet enter a cell or several cells of a donor embryo in blastotsel near cellular weight or directly into it. Then the blastocyste, as well as at an aggregation method, is replaced in a uterus of an animal.

At primary chimeras any signs immunol are not revealed. incompatibility of cell populations of a different genotype. Their tolerance carries rather inborn, than acquired character. As a result of aggregation of blastomeres himerny germs with sets of gonosomes turn out: XX/XX (25%), XY/XY (25%) and XX/XY (50%). Three quarters of such chimeras become males and one quarter — females; the hermaphroditism is rare (1 — 2%). XY of a cell XX/XY of a himerny gonad is obvious allocate a gormonopodobny factor, capable to diffusion, to-ry induces a testicular organogenesis in surrounding XX cells (see Paule).

On aggregation chimeras of a mouse with use of various markers it is established that cells of a germ at a stage of a morula have totipotency (i.e. each blastomere is capable to give development to any cellular type). By means of an injection method it is shown that cells of internal cellular weight, from a cut there is an embryo, keep totipotency and at a stage of a blastocyste. Each of about 15 cells of internal cellular weight can give rise to any of 3 germinal leaves: to an ectoderm, mesoderm and

entoderm. Many new data on features of an expression of genes and cellular interactions in ontogenesis of mammals are obtained. It was established that from more or less certain number of clones of cells there are rudiments of separate fabrics and bodies that allowed to formulate the theory of clonal development of the higher organisms. By experiences with introduction in blastotsel stem cells of a teratocarcinoma it is shown that if tumor cells in the developing embryo are in close contact with normal cells, then they lose the oncogenous properties, are normally differentiated and give rise to normal cellular systems of a himerny organism. These data indicate that tumors can result from disturbance of an expression of a normal genome in ontogenesis.

Secondary chimeras create experimentally by transplantation of fabrics, hemotransfusions, or they arise at mammals as a result of spontaneous transfer of blood cells between mother and a fruit or between fruits.

At vegetable organisms of chimeras receive by an inoculation of a plant of one view of another (e.g., chimeras between a black nightshade and a tomato yellow Michurina, between a medlar and a hawthorn etc.). In this way chimeras were received also at the lowest animals, napr, during the merging of hydras of different types. At cold-bloodeds (fish, a frog, a lizard) fabric chimeras it is possible to receive as a result of transplantation and the subsequent keeping of animals at the lowered temperature (apprx. 10 °); at temperature increase of the environment to 20 ° the replaced fabrics are exposed to destruction. At more high-organized animals to receive the phenomenon of a cellular himerizm much more difficultly as it is in direct dependence on an immune responsiveness of an organism of the owner (see Incompatibility immunological). At birds of chimeras receive by an union of germs and the subsequent change of fabrics between parabionts (see).

Receiving a cellular himerizm at mammals is connected with induction in an organism of the owner of a state immunol. meeknesses in relation to alien cellular material (see unresponsiveness). Himerizm is characterized by existence in an organism of an animal or the person of cells of tissues of the owner, antigenically different from cells, and emergence of chimeras is connected with decrease immunol. reactivity of the owner, induction of a state immunol. tolerances to certain allogenic (xenogenic) antigens of genetically alien cells. Under natural conditions the phenomenon of a cellular himerizm is revealed at the twin calfs having antigenically affine erythrocytes in a blood channel. It is found out that the himerizm on blood cells results from exchange between twins through placental vessels of parent hemopoietic cells. In the similar way the himerizm of blood can arise also at twins of the person. In literature there are descriptions apprx. 20 cases of a himerizm at the person identified on isoantigens of the AB0 systems, a Rhesus factor Kel, Daffi, Kidd, etc. Himerizm arises at the person and at transplantation of donor organs. Compatibility of allogenic cells demands suppression from chimeras immunol. the reactions of an organism of the recipient directed in usual conditions against antigenically alien cells and causing death of the replaced fabric. Chimeras are received at mice, rabbits, dogs and other animals by transplantation allogenic (is more rare than xenogenic) hemopoietic fabric — marrow, a spleen, limf, nodes or other fabrics (see Organ and tissue transplantation). Animals are previously subjected to impact of x-ray emission, use immunodepressive drugs: imuran (aza-

tioprin), Mercaptopurinum, cyclophosphamide, anti-lymphocytic serum (AJI C), corticosteroid hormones, etc. In these conditions there is a reproduction of cells of the transplanted fabric and substitution of the hemopoietic tissue of the recipient by it. At the person the cellular himerizm can be observed after transplantation of marrow, identical on HLA antigens, by the patient who underwent before transplantation

of immunodepressive therapy (beam, hormonal, cytostatic). Such changes make the patient with acute forms of leukoses, aplastic anemia and others zabolevaniyakhm. The short-term cellular himerizm takes place at massive transfusion of erythrocytes of the donor 0(1) blood groups to the patient with a blood group of A(P), V (Sh), AB (IV). At chimeras between an organism of the recipient and genetically alien immunol. cells of a transplant develop difficult immunol. the relations as transplant immunity and immunol. tolerances (see Immunity transplant, unresponsiveness, Immunology radiation). Often at chimeras development immunol is observed. the reaction proceeding from immunocompetent cells of a transplant, alien for an organism of the recipient (see. Immunocompetent cells). This reaction received names — reactions of a transplant against the owner, a secondary disease, a homologous disease, a transplant disease (see the Welt disease). The immunological reaction proceeding from genetically alien cells of a transplant

(see) is the main obstacle in a way wide a wedge, uses of allotransplantation of marrow (see Transplantation

of marrow). At the heart of formation of the conflict relations between an organism of the recipient and genetically alien cells of a transplant patterns

of immunology {see) and immunogenet

ki lie (see).

Bibliography: 3 about t and to about in E. A. Antigenic systems of the person and homeostasis, M., 1982; Kindyakov B. N., Grooms B. V. and Malinin N. And, Studying of an expression of mutant genes at aggregation chimeras of a mouse, I. Gene of white, Ontogenesis, t. 15, No. 2,

page 153, 1984; P. N Jambs. Isoantigens and isoantibodies of the person it is normal also of pathology, M., 1974; Kupriyanov S. D. and B. V. Grooms. Studying of an expression of mutant genes at aggregation chimeras of a mouse, 2. Gene of dominant cataract-Fr, Ontogenesis, t. 15, No. 4, page 348, 1984; IAC-JI and p e N E. Chimeras of mammals, the lane with English, M., 1979; Mayansky DN. and To and at l e D. R N. Transplant disease, Novosibirsk, 1978; Petrov R. V. Immunology and immunogenetics, M., 1976; Snell D., Dosse Zh. and Netenson S. Sovmestimost of fabrics, the lane with English, M., 1979; Fon-talin L. N. and e in N and c to and y L. A., Unresponsiveness, M., 1978; Fehilly C. B., W i 1 1 a d-s e n S. M of a. Tucker E. M of Interspecific chimaerism between sheep and goat. Nature (Lond.), v. 307, p. 634, 1984; Meinecke-Tillmann S. a., Meinecke B. Experimental chimae-ras-removal of reproductive barrier between sheep and goat, ibid., p. 637; Owen R.D, Immunogenetic conseguences of vascular anastomoses between bovine twins, Science, v. 102, p. 400, 1945; it, Erythrocyte mosaics among bovine twins and quadruplets, Genetics, v. 31, p. 227, 1946.

E. A. Zotikov, B. V. Konyukhov.

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