[The disturbances of the relationship between oxidative homeostasis and the immune status of lymphocytes in liquidators of the consequences of the Chernobyl accident].

We investigated into the relations between the immune status of individuals who took part in liquidating the consequences of the Chernobyl accident (liquidators) and the level of active oxygen forms in peripheral blood lymphocytes, as well as the level of the genome damage in lymphocytes (frequency of cells with micronuclei). The results show that the immune status changes as the level of the genome damage increases: the content of some markers increases and others decreases. It has also been shown that a) active oxygen forms participate in forming some indexes of the immunological lymphocyte status and b) the exposure of liquidators to irradiation many years ago almost completely changes the characteristics of the relation between the concentration of active oxygen forms and immunological status indexes. It has been shown that there are many more immunological indexes that experienced changes in their relation with the concentration of active oxygen forms than the amount of indexes associated with the genome damage. It has been found that a) there is little difference in the concentration of active oxygen forms in donors and liquidators and b) the concentration is not associated with the level of the genome damage. Taking this into account, the authors speculate that the changes in the relation between the concentration of active oxygen forms and the immunological indexes are reflection of how irradiation influences the level of the immune status formation based on the relation between the concentration of active oxygen forms and the appearance of a marker in the immune status. The obtained results point to the new, previously unknown aspects of how the primary injuries which are the result of the low dose irradiation influence the health of irradiated individuals. The changes in relations that can be seen in liquidators in comparison with donors lead to a different set of immunological indexes as well as to different immune status, and may become the reason for the deterioration in their health. The authors suppose that the above results could be a substantial contribution to the research into the fundamental mechanisms of the human immune status formation and human health.

[The epidemiological analysis of monitoring of the immune status in liquidators of consequences of the Chernobyl accident for early identification of risk groups and diagnostics of oncological diseases. Report 2. Dependence of frequency and changes in the immune status on risk factors of radiation accident].

Malignant neoplasms (MN) have been found to develop most frequently in the liquidators of entry into the ChNPP zones in 1986 (43.75%), as well as among the liquidators who worked for long, one quarter of whom participated in liquidation of the consequences of failure (LCF) in 1986. Specific features of the immune status depending on the timing of participation in LCF and the year of entry into the ChN PP zone have been established. Changes in the immune system in the persons with a confirmed diagnosis of MN who took both a non-permanent and permanent part in liquidating the consequences of the ChNPP failure in 1986 had the same character of deviations and differed in the magnitudes of deviations of immunological parameters. Continuous participation in the period of extreme conditions and a greater exposure to the radiation factor led to the increased content of CD8(+)-T-cells, CD16(+)-lymphocytes and activated T-lymphocytes, as well as to the reduced index of immune regulation, decreased content ofCD3-16/56+(NK)-cells (%) and the total IgE and to a greater deficiency of B-lymphocytes. Distinctions in the groups of liquidators who participated in LCF in 1986 and 1987 have been revealed. The greatest deviations in the IS indicators were found in liquidators-87. A similar effect came to light in case of a continuance in the ChNPP zones in 1986 and 1987; however, the degree of deviation of the content of CD4(+)-T-lymphocytes (41), CD8(+)-T-lymphocytes (1) and the immune regulation index (41) were remarkably higher in liquidators-87. A continuous stay in the ChNPP zones in 1987 led to the deficiency of CD4(+)-T-lymphocytes, increased values of CD8(+)-T-lymphocytes, a decreased index of CD4+/CD8+, as well as to the change in the ratio between NK-T and NK cells, increased numbers of CD95+, HLA-DR+ and activated T-lymphocytes, and a lower level of the total IgE. Long-term participation in LCF didn't cause any enhanced expression of cellular activation markers in liquidators-86. Specific features of changes in IS depending on a dose of external gamma-irradiation have been established. Increase in the frequency of MN among liquidators, in relation to the number of examinees in each age group, with age has been revealed. Distinctions in the age dynamics of IS in liquidators in the presence and in the absence of MN manifested themselves in a stable level of values of CD3+, CD4+, CD8(+)-T-lymphocytes, immune regulation index, CD95+, serum IgA at the age between 40 and 70 years old with a subsequent reduction in indicators and increase in the content of CD8(+)-T-lymphocytes with age in the absence of MN; continuous increase of CD3-16/56(+)-NK-cells in the presence of MN and decrease in the values after 70 in the absence of MN. Also revealed in IS of the both age groups of liquidators over 70 with and without MN was the deficiency of the T-cell component (CD3+, CD4(+)-T-lymphocytes, CD4+/CD8+ index) and the increase in absolute values of CD8(+)-T-lymphocytes. The growing deficiency of CD4(+)-T-lymphocytes during monitoring against the background of ever rising values of CD8(+)-T-lymphocytes leading to the weakening of the immune regulation due to progressing disorders of the T-lymphocyte regulatory subpopulation distribution can serve an indicator for the adverse prognosis of the life expectancy in the presence of MN.

[The epidemiological analysis of monitoring of the immune status in liquidators of consequences of the Chernobyl accident for early identification of risk groups and diagnostics of oncological diseases. Report 1].

Ionizing radiation is one of major factors of risk of oncological diseases. A question about the frequency of malignant neoplasms (MN) and their early identification in the liquidators of consequences of the Chernobyl accident remains opened. In the present work, the results of long-term immunological monitoring of the liquidators of consequences of the failure at the Chernobyl Nuclear Power Plant (ChN PP) living in the Northwest region of Russia are analyzed; we also heve made an attempt to reveal the predictors of oncological diseases in this group of individuals. The frequency of the newly revealed MN cases in a cohort of the persons who took part in liquidation of consequences of the ChNPP failure and were followed-up in 1999-2009, has made up 89 cases per 1005 persons (8.856%), which somewhat exceeds general population indicators. Regarding the frequency of separate MN localizations, lung cancer, cancer of stomach and cancer of prostate gland predominated, which corresponds to the world's tendency of MN prevalence. It has been established that as early as 1-3 years before diagnosis of MN is confirmed in liquidators, a number of changes in the immune status comes to light: drop in percentage of CD3+ and CD4(+)-T-lymphocytes, B-lymphocytes to a lesser extent, decrease in the CD4+/CD8+ index, increase of the relative and absolute content of CD16(+)-lymphocytes, increase of absolute content of CD8(+)-T-lymphocytes, prevalence of CD3+16/56+(NK-T) cell over CD3-16/56+(NK) cells, rise of the activity of phagocytes. Patients with the presence of one or several of the above-mentioned signs should be attributed to the MN risk group for determination of tumor markers, thorough examination and dynamic observation.

[The connection between molecular-cellular parameters and immune status of liquidators after Chernobyl accident].

The genome damage (the frequencies of cells with micronuclei (MN), chromosome aberrations, the level of DNA double-strand breaks (DSB DNA), the concentration of reactive oxygen species (ROS) and 28 immunological parameters have been studied on the blood lymphocytes of Chernobyl accident liquidators. The purpose of this article was the investigation of cytogenetic, molecular changes of blood lymphocytes of irradiated individuals 24 years after accident, examination it there are correlation between genome damage and immunological parameters. It was shown that in lymphocytes of liquidators the frequencies of cells with MN and with all type of chromosome aberrations didn't differ from the lymphocytes of nonirradiated individuals, but the frequency of chromosome aberration type was increased, the level of DSB DNA was increased too. The concentration of ROS is decreased. The percent of cytotoxic CD8(+)-T-lymphocytes, natural killer cells (CD16(+)-lymphocytes), CD3+ CD16+ CD56+ (NK-T-cells), that posses antivirus and antitumor activity--HLA-DR+, regulatory T-lymphocytes (CD4+ CD25+high) in liquidators significantly increases. The level of serum immunoglobulin (Ig A) significantly increases too. The index of immune regulation, meaning of phagocyte neutrophil (FAN) and macrophage activity decreases. In liquidators there are significant correlation between the frequencies of cells with MN and the content of regulatory T-lymphocytes (p < 0.05), between the concentrations of ROS and activated T-lymphocytes. More connection is on the tendency level (p < 0.10): the frequency of chromosome aberrations, the DSB DNA level with natural killer cells and regulatory T-lymphocytes; the frequency of cells with MN and DSB DNA and FAM. We can suppose that genomic instability induced by the liquidators of Chernobyl accident consequences 24 years ago manifests now as increased genome damage and oxidative status decrease that can result in imbalance of cells and humoral immune status, disturbancies of health.

[Dynamics of immune status indices of liquidators in the remote period after the accident at the Chernobyl NPP].

In the report there are present the results of monitoring of the state of immune status in the remote period after the accident at the Chernobyl Nuclear Power Plant among three groups of liquidators, which were from Moscow and the Moscow district, the Northwestern region of Leningrad district and from Krasnoyarsk territory. During the monitoring of the liquidators from different regions there was found phenotype of immune status with regional characteristics. In the Moscow district the clinical displays of immune insufficiency prevail and in the North western region the modifications of immune status prevail among liquidators. In all the groups we could see quantitative and immunoregulatory disbalance with the increase of parameters of cellular activity such as CD95+, HLA-DR+, T-activated lymphocytes, fluctuation cytotoxic cells (CD8+, CD16+), persevering disimmunoglobulinemia with differently directed modification serum of immunoglobulins at decrease B-lymphocytes. By the end of the twenty-year period after the accident we can see a similar phenotype of immune status in all the groups with increasing of the marker of late activation (HLA-DR+) and apoptotic activity (CD95+) and it is potentially dangerous regarding cancerogenesis. According to the basis of long-term monitoring there has been discovered the immune characteristic of proliferative syndrome for the first time. The monitoring of 2004 has revealed a huge similarity immune status at non-malignant growth at significant decrease CD25+ in the Northwestern region and some differences in common IgE.

[A comparative evaluation of the content of T-lymphocyte subpopulations, alpha 1-thymosin and autoantibodies to epithelial thymic cells in the personnel in the 30-kilometer control zone of the accident at the Chernobyl Atomic Electric Power Station]. / Sravnitel'naia otsenka soderzhaniia subpopuliatsii T-limfotsitov, al'fa 1-timozina i autoantitel k épitelial'nym kletkam timusa u personala 30-kilometrovoi zony kontrolia avarii na Chernobyl'skoi AES.

A significant decrease in mean number of CD5+, CD8(+)-lymphocytes in persons, who worked in 30-km zone of Chernobyl nuclear power station was revealed. A significant increase in percent of CD5+, CD4(+)-cell percents was observed in workers, who worked for 1,2-2,5 years in zone, but absolute number, were decreased comparing a control and data received in people, who have just arrived to work in 30-km zone. The positive correlation exists between the percent of lymphocytes and years of service in 30-km zone. The lower level of alpha 1-thymosine was revealed in serum of the persons, who worked in zone for 4.5-5 years than data received in people, who worked for 0.5 year. Increase level of serum autoantibodies reacting with thymic epithelial cell was detected in men, who worked in zone for 3-3.5 years. In persons, who worked more 5 years and have just arrived in zone identical data were received.

[State of immune reactivity of persons having occupational contact with Pu-239]. / Sostoianie immunnoi reaktivnosti lits, professional'no kontaktiruiushchikh s 239Pu.

Clinical and immunological investigation with immune status evaluation of the group of people who had professionally contacts with Pu-239 in the quantity of 328 persons. The clinical characters of immune deficiency (ID) were defected in 75.3% of examined persons. There are showed that leading clinical syndromes of ID is appeared the infection syndromes (62.5%). The distribution of ID clinical infection characters are increased with increasing of radiation from internal 239Pu contains and seniority of professional contact with them. The particularity of immune status and dependence of the change its indices from the internal radiation dose, seniority of professional contact with Pu-239 and chronic diseases were revealed.

[Serum levels of thymus hormones and autoantibodies to the thymus epithelium in inhabitants of regions contaminated with radionuclides]. / Soderzhanie gormonov timusa i autoantitel k épiteliiu timusa v syvorotke krovi zhitelei raionov, zagriaznennykh radionuklidami.

Increased level of serum thymic activity and normal serum concentration of alpha-1-thymosin were revealed in inhabitants of region polluted by radionuclides after Chernobyl accident (settlement Vyshkov, Bryansk region). In the same population the serum level of autoantibodies, reacting with thymic epithelial cell line was elevated. Similar but less prominent alterations were found in population of radiologically pure region (settlement Potchep). Revealed autoantibodies had mainly IgM isotype. The negative correlation exists between levels of autoantibodies and serum thymic activity. Sera of persons from the control group and one half of Vyshkov inhabitants reacted with thymic epithelial cells of both human and mouse origin; in other half of Vyshkov inhabitants species-specific autoantibodies were revealed. We propose that correlated increase of antithymic autoantibody level and decrease of serum thymic activity are the consequence and indicators of unfavorable ecological conditions; however the contribution of radiation factor to their induction can not be estimated on the basis of presented data.

[Immune status of adult population of the Bryansk region living in territory polluted by radionuclides]. / Immunnyi status vzroslogo naseleniia Brianskoi oblasti, prozhivaiushchego na territoriiakh, zagriaznennykh radionuklidami.

Clinical and immunological investigation with immune status evaluation of three groups of adult population of Bryansk Region was performed. The first group included 165 persons living in Vyshkov (settlement of town type in Bryansk Region) contaminated with radionuclides as a result of Chernobyl accident. The second group included 68 persons living in Vyshkov, immunological monitoring of those was performed. The third group consisted of 114 persons living on the "clean" area of Pochep (Bryansk Region). On both areas (contaminated Vyshkov and "clean" Pochep) the large percent of persons (three quarters of all investigated ones) had clinical manifestations of immune deficiency. The immune status of Vyshkov inhabitants was characterized by T-helper/inductor activation. That was expressed in significant increase of CD4+, CD4+/CD8+ in comparison of control group of primary donors and to "clean" Pochep inhabitants and in stable decrease of average values of serum IgG in comparison to control group, IgG and IgM in comparison to Pochep group. Maximum high values of T-helpers under lowest T-suppressor/killer values were observed at clinical symptoms which may be stipulated by radiation factor (loss of hair and teeth, surplus weight, predisposition to bleedings) and in persons working in cattle-breeding.

[Clinico-immunological and allergological characteristics of population of the Middle ural]. / Kliniko-immunologicheskaia i allergologicheskaia kharakteristika zhitelei Srednego Urala.

Clinical investigation of immune and allergic state of 633 adult dwellers of the Middle Ural region was carried out. The first (occupational) group consisted of 479 workers of the industrial plant, most of which exposed to negative factors such as radiation, harmful chemical substances and stress. The second (control) group consisted of 154 town-dwellers, who did not work at the industrial plant. Immune state was assessed in 714 people. Clinical symptoms of immune deficiency were found in 67% of the occupational group and in 76% of the control group. Allergic condition and allergic-infection syndrome were common for both groups, the rate of infection syndrome being relatively low. The immune state of the occupational group showed in comparison to control reliable increase in absolute and relative amount of T-lymphocytes, in the ratio CD4+/CD8+ and in the level of serum IgG. It was found also the decrease in the concentration of T-killers, the amount of NK cells and B-lymphocytes, phagocyte activity and the level of serum IgA. It was suggested that regional and ecological peculiarities influence the immune state rather than induce clinical symptoms of immune deficiency.

[Clinico-immunological characteristics of people who worked within the 30-kilometer zone of the accident at the Chernobyl Atomic Power Plant 4 years after the accident]. / Kliniko-immunologicheskaia kharakteristika kontingenta lits, rabotavshikh v 30-kilometrovoi zone avarii na Chernobyl'skoi AES cherez 4 goda posle radiatsionnoi avarii.

Clinical examination with immune status assessment of more than 300 healthy persons, who worked in 30-km Chernobyl NPP zone four years after the accident was carried out. The clinical characters of immune deficiency were detected in 6.67% of examined persons and appeared as repeated respiratory diseases. Significant increase in mean level of leukocytes and lymphocytes was revealed. Activation of T-helper link of cell immunity was determined by increase of CD4+ cells in 35.2% of examined persons, that were lower than in people who took part in Chernobyl accident amelioration in 1986. Decrease in content of T-cells and B-cells was observed in 1/4 and 3/4 of persons correspondingly by rosette assays. No changes in serum immunoglobulins level was observed.

[Epidemiologic evaluation of immune deficiency and other chronic pathology among the adult population of Bryansk region, living in radionuclide-contaminated territory]. / Epidemiologicheskaia otsenka immunologicheskoi nedostatochnosti i drugoi khronicheskoi patologii sredi vzroslogo naseleniia Brianskoi oblasti, prozhivaiushchego na territorii, zagriaznennoi radionuklidami.

Immune deficiency epidemiological survey covered adult population of the town of Vyshkov in the Bryansk region of Russia referred to the zone of radionuclide contamination hazard after the Chernobyl accident. A total of 3892 subjects were examined for the leading immunopathological syndromes (infectious, allergic atopic, autoimmune, lymphoproliferative) according to a specially devised technique developed in the Research Institute of Immunology in Moscow. Immune deficiency risk group made up 10.25% which is much higher than relevant value for control rural population of the southern Urals exposed to low-dose radiation and of polluted region in the East Siberia. The quantitative analysis indicated more frequent occurrence of infectious and lymphoproliferative syndromes of immune deficiency in the absence of radiation-related allergic diseases in the town of Vyshkov.

[Incidence of immune deficiency in children population from industrial city]. / Rasprostranennost' immunologicheskoi nedostatochnosti sredi detskogo naseleniia promyshlennogo goroda.

The authors relate the data on the incidence of different forms of immune deficiency (ID). The studies were carried out within the framework of the All-Union program of mass immunoepidemiological screenings, among the childhood population of industrial city numbering 59,178 persons. The primary group at ID risk amounting to 2.2% was distinguished. Based on the clinico-anamnestic data a group at higher ID risk was made up (n-421). 450 children were examined by the level I tests. The children were characterized clinicoimmunologically according to different immunopathological syndromes. All the children with the identified forms of ID and those without well-defined forms of immunodeficiency conditions but with steady alterations of the immunologic parameters and the clinical signs need prophylactic medical examinations.