[Natural killer cells and endogenous biological relay].
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Biomedical subjects
Publications and source records attributed to S B Cheknev.
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The cytotoxic activity of natural killer (NK) cells isolated from peripheral blood of 20 healthy donors and 34 patients with multiple sclerosis (MS) against labelled with H3-uridine target cells K-562 before and after their 1 hr treatment with reaferon (RF), T-activin (TA), myelopid (MP), opioid preparation dalargin (DL) as well as with combinations of TA, MP and DL with RF was studied in 14 hrs cytotoxic test. It has been shown that combination of RF with TA, MP and DL changed the regulatory action of these peptides on NK cell activity in healthy donors in vitro. The same combination of the preparations in patients with MS caused another changes in regulation of NK activity by them because NK cells in MS patients had had initially changed sensitivity to action of these regulatory polypeptides.
The cytotoxic activity of natural killer (NK) cells against labelled with 3H-uridine target cells of standard human erythromyeloblast line K562 in 63 healthy donors was studied in 14-hr cytotoxic test. The cytotoxic reaction was realized in complete medium supplemented with different types of serum such as foetal calf serum (FCS), autologous or homologous sera in different schemes of incubation. It has been shown that NK cell activity was augmented by 50 per cent (p < 0.05) in the presence of homologous serum added to mononuclear cell suspension for 1 hr at 37 degrees C in comparison with the effect of FCS presence. Thus, the serum of healthy donors contains some factors which not only reflect an individual genotypic information of a donor, but also can be recognized by NK cells and significantly change the cytotoxic NK cell activity. The data obtained exclude possibility of using a homologous serum when positive controls for natural cytotoxic reactions are planned.
A study was made of the cytotoxic activity of natural killers (NK) against 3H-uridine labeled K-562 cells and its variability. 56 patients suffering from multiple sclerosis (MS), 33 healthy donors of different age and 34 patients with remitting MS and MS of different standing were entered into the study. The most remarkable lowering of the NK activity was seen in patients aged 41 to 50 years. In patients aged 51 to 59 years, the NK activity was not different from that in a group of healthy donors. The most pronounced increase of the variability index (VI) was recorded in patients aged 41 to 50 years. In the senior age group (from 51 to 59 years), the VI of the NK activity was 1.7 to 2.8 times as reduced as compared to the healthy control. It has been revealed that the changes in the NK activity and its variability in the respective patients' groups are of concomitant nature and that the estimates undergo fluctuations in the counterphase. During studies of the NK activity as dependent on the disease standing, NK deficiency was found to be associated with the gravity of the patient's clinical status and long disease standing. A possible relation of the changes in the NK activity and its variability to the disease pathogenesis is under discussion as are the compensation mechanisms that get triggered during depletion of the system according to the secondary deficiency type.
The action of mouse serum interferon--alpha/beta (IFN) at the dose of 100 U/ml, of its inhibitor (I) at the dose of 8 U/ml as well as of their combination with the above doses on sensitivities of mouse target cells (TC) of sensitive to IFN line L 929 and resistant to the one line MCB in natural cytotoxic reaction was studied. Cytotoxic activity of human natural killer cells was detected in 14 hrs cytotoxic test using 3H-uridine for labelling of TC. IFN, I, and IFN+I were added to cell cultures for 24 hrs at 37 degrees C with following removing of preparations. It has been shown that I abolished protective effect of IFN on TC L 929 whereas the one possessed the protective action on TC MCB in natural cytotoxic reaction. These data confirmed a suggestion about immunoregulatory properties of I which displayed in abolition or realization of protective effect on TC in natural cytotoxic reaction in dependence on initial sensitivity of TC to antiviral IFN action.
The cytotoxic activity of peripheral blood natural killers (NK) against target cells (TC) J-96 and L-929 with high sensitivity to interferon (IFN) action, J-41 and MCB resistant to IFN action and line K-562 labelled by H3-uridine was studied in 14 hrs cytotoxic test. It has been shown that human TC J-96 didn't differ from the J-41 in their sensitivity to NK cytotoxicity and they are strongly resistant to NK than TC K-562. The murine TC L-929 as the human TC didn't differ from the MCB in their sensitivity to NK lysis and had also the same sensitivity to NK as the K-562 cells.
Studies of the function of cyclic nucleotide system in the lymphocytes of patients with focal scleroderma have revealed that this condition is characterized by growth of the intracellular cAMP/cGMP ratio, correlating with the process duration, severity, and dissemination. A correlation between lymphocyte regulatory function defect and the presence of immunodeficiency syndrome was demonstrated. Sensitivity of lymphocytic cyclic nucleotides in focal scleroderma patients to thymoptin, a thymic agent, was examined. Manifest clinical effect of this drug is based on stabilization of the function of lymphocytic cyclic nucleotides system and, consequently, on normalization of the immunologic parameters. Potentialities and prospects of thymic factors immunotherapy of focal scleroderma patients are discussed.
The cytotoxic activity of natural killer (NK) cells against target cells K-562 was studied in patients with multiple sclerosis (MS). NK activity was increased in patients with remitting course of the disease, its duration of 6 to 10 years and 1 to 3 degree of neurologic defect. The immunocorrective therapy reduced the NK activity in some patients of any group. The authors discuss the possible role of natural cytotoxic system in the pathogenesis of autoimmunization in MS, and the value of NK population assessment for singling out a group of patients that would beneficially respond to immunocorrective therapy.
Dynamic examination of 47 patients over the first three weeks after the development of ischemic stroke (IS) has revealed a significant decrease in the natural killer activity (NKA) and antibody-dependent cellular cytotoxicity (ADCC). A decrease in the NK activity in IS patients appears to be related to dyslipoproteinemia, which has been confirmed by the detection of a reverse correlation between the values of the NKA and the atherogenicity coefficient, while suppression of ADCC in the same patients is explained by the suppressive influence of the prostaglandin system, which has been investigated in vitro. The elucidation in IS patients of immunopathological phenomena related to impairments of the effector component of immunity and of activities of NK- and K-cells justifies the inclusion of immunocorrecting drugs into the comprehensive therapy of IS.
The study of the activity of natural killer cells in patients with chronic alcoholism, stage II, has revealed its essential decrease in comparison with that in healthy subjects, which is particularly pronounced with effector/target cell ratio equal to 100:1 and 50:1 respectively. Besides, two subgroups can be differentiated among the total population of alcoholic patients: subgroup 1 with the activity of killer cells remaining practically intact and subgroup 2 with profound defects in the functioning of these cells. The presence of essential defects in natural killer cells of patients with the severe form of alcoholism is suggested.
Examination of 22 patients with multiple sclerosis (MS) has revealed a decrease in the cytotoxic activity of natural killer cells (NKC), in the production of endogenic interferon (EI) in the system of NK--target cells, and in the production of alpha- and gamma-interferon by stimulated lymphocytes. Some patients showed dissociation of the cytotoxic and interferon-producing activity of NKCs. Possible mechanisms responsible for changes in NKC activity are discussed. The authors have concluded that disturbances in the NKC-EI system are manifestations of the total regulatory imbalance in the immune system.