[Immunologic aspects of cellular therapy].
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Biomedical subjects
Publications and source records attributed to V V Malaĭtsev.
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The model of T-dependent dopamine-protein conjugates prepared by the glutaraldehyde method was used to study the influence of hapten valence and molecular weight on the immunogenicity of these conjugates. The immunogenicity of dopamine-protein conjugates increased in the range of DA4-BSA--DA5,8-BSA--DA14-BSA and decreased with further increase of hapten density. It was assumed that partial tolerogenic properties of DA18-22-BSA were due to nonspecific mechanisms associated with changes in the physical molecular characteristics of the antigen during the procedure of conjugation, rather than to specific mechanisms. The latter are more typical for low substituted conjugates.
Constitutive and lipopolysaccharide (LPS)--induced production of interleukin (IL)-1 and IL-6 have been investigated in peripheral blood (PB) and bone marrow (BM) of patients with multiple myeloma (MM) and PB of health donors. The level of these cytokines has been higher in MM in comparison with norm. Monocytes of PB of patients with MM have been more stimulated by LPS than those of health people. When adherent and nonadherent cells have been cultured apart, there not have not been any differences in constitutive IL-6 production between compared groups. The important role of cell-cell interactions in regulation of IL-6 production is proposed. High level of IL-6 in BM of patients with MM is conditioned by mutual stimulation of adherent and nonadherent cells.
The change of 11-1, IL-3, CSA concentrations in adherent and nonadherent bone marrow cells condition medium at stress were investigated. The activation of bone marrow hemopoiesis was registered at mice after immobilization stress. The number of CFU-GM increased on 1, 4 and 5 day after stress. Maximum of CSA in adherent and nonadherent cells conditioned medium was observed on day 4, 6 or 2, 5 respectively. The increasing of 11-3 activity in culture of nonadherent bone marrow cells was registered from day 1 and mount to maximum at 4-5 days. The increasing of 11-1 level in culture of adherent bone marrow cells was found at 1 and 4 days.
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The effect of the in vivo treatment with synthetic interferon inducer B-58 on natural killer (NK) and cytostatic cell activity was studied in CBA and A/Sn mice. A marked increase in NK cell activity against target cells YAC-1 was observed in the spleen of CBA mice within 4 days after treatment. On the other hand, NK activity in A/Sn mice was not affected by B-58. However, B-58 was shown to enhance cytostatic cell activity both in CBA and A/Sn mice, when tested against target cells P 815.
The immune competence of C57Bl/6 mice implanted with EL-4 lymphoma of Lewis Lung carcinoma 3LL was investigated during 3 weeks after implantation. Splenic lymphocyte responses to mitogens (Con A, PHA, LPS, PWM) cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2) production were assessed. A dramatic reduction in mitogenic responses to Con A and PHA was observed during tumour progression. LPS and PWM responses were less depressed. Con A-induced IL-2 production correlated with Con A and PHA responses. Allospecific CTL response to mastocytoma P 815 was not decreased in syngeneic tumour-bearing mice.
Interleukin 2 used in vitro and in vivo induces effectively the recovery of cytotoxic activity of natural killers and lectin-dependent cellular cytotoxicity effectors in stress-immobilized CBA mice. This lymphokin can be used for correction of stressor depression in the cells of the natural anti-tumor resistance system.
Con A-induced production of interleukin 2 was studied in peripheral blood lymphocytes obtained from 15 normal subjects and 42 patients with different thyroid diseases. It was found that thyroid diseases are accompanied by changes in IL 2 production. The level of IL 2 production by T lymphocytes is determined by the functional status of thyroid glands, their anatomy, stages of the disease and mode of treatment.
Mice exposed to immobilization stress manifested a dramatic lowering of the activity of normal killers against YAC-1 tumor as well as against the lectin-induced cellular cytotoxicity mediated by Helix pomatia agglutinin and detected by the cytolytic test against xenogeneic tumor cells K 562. Exposure to stress did not provoke any change in the production of cytotoxic factor of normal killers, whereas dexamethasone (5 X 10(-7) M) in vitro inhibited the production of this factor.
Muramyl dipeptide and its synthetic derivative N-acetyl-glucosaminyl-N-acetyl-muramyl-alanyl - D-isoglutamine induce mitogenic factor production for Con A activated blasts (Con A-blasts) in splenocytes. The maximal factor production was revealed 24 h after stimulation with muramyl dipeptide or its derivative. Addition of the inducers to the culture of Con A-blasts led but to the negligible proliferative response. Therefore, the mitogenic action of muramyl dipeptide on target cells is mediated by the growth factor, evidently by interleukin-2. It has been also shown that muramyl dipeptide and its derivative with Con A exerted a synergic action in interleukin-2 induction.
Natural cytotoxic activity of cells from human fetal spleen, liver, bone marrow, appendix, tonsilar glands and thymus was investigated in 14-26-week-old embryos. The spleen and liver expressed powerful NK activity against K-562 target cells from a 22 week-old embryo. Thymocytes and cells from the appendix and tonsilar glands displayed but negligible cytotoxic activity.
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The main function of lymphocyte is the immunological supervision which is brought about via receptor structures of the cell surface. An antigen is recognized by surface immunoglobulin of B-lymphocytes as well as by antigen-recognizing receptors of T-lymphocytes and natural killers. The regulation of lymphocyte functions if brought about via another class of receptors (Fc, C3-receptors). In immunopathological processes certain characteristics of lymphocytes surface change. These changes are manifested at the level of cell populations and clones of antigen-specific lymphocytes.