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Biomedical subjects

M M Averbakh

Publications and source records attributed to M M Averbakh.

At least 19 recordsLinked to original sources

[Anti-tuberculous IgE antibodies. I. Immunodominant antigens].

It is widely accepted that protection against tuberculosis is provided by the formation of type 1 immune response, which is characterized by the production of IFN-gamma and IL-2. However, type 2 antimycobacterial immune response is also present: specific IgE antibodies that are IL-4 dependent, are usually found in tuberculosis patients. There is elevated production of type 2 cytokines in some cases. Thus, both types of an immune response can simultaneously develop, probably counteracting with each other. It is unknown which of mycobacterial antigens are capable of inducing a preferential type 2 response. To detect these antigens, the authors studied tuberculosis IgE antibodies in the sera of 500 tuberculosis patients by using the ELISA assay with ultrasonic disintegrated M. Tuberculosis H37Rv (sonicate). Antigens recognized by IgE antibodies were found to be localized in the cell wall of mycobacteria. The IgE-response was specific since the sera did not react with the antigens of atypical mycobacteria and other bacterial species.

Blotting, Western↗

[Tuberculous IgE antibodies. Part II. Study of its concentrations in different forms of tuberculosis].

Tuberculosis-afflicted lung are infiltrated by two functionally types of lymphocytes, which presumably counteract with each other by producing proinflammatory (type 1) and anti-inflammatory (type 2) cytokines. It is held that irregular sequestration of antigen into different compartments of the lung may lead to preferential activation of T-helper 1 or T-helper 2 lymphocytes. Unlike IgE antibodies, specific tuberculosis IgE antibodies are seen only in tuberculosis infection. The mean values of IgE antibodies in tuberculosis (7.661 +/- 0.849 IU/ml) are significantly greater than those in other pulmonary diseases (1.768 +/- 0.116 IU/ml). Low concentrations of tuberculosis IgE antibodies in persons with a marked hyperergic response to tuberculin (1.808 +/- 0.097 IU/ml) are of importance. Significant concentrations of mycobacterial IgE antibodies are mainly detected in fibrocavernous (14.56 +/- 1.11 IU/ml), infiltrative (10.10 +/- 1.08 IU/ml), peripheral lymph nodal (10.53 +/- 1.09 IU/ml) tuberculosis rather than intrathoracic lymph nodal tuberculosis (4.555 +/- 0.340 IU/ml). There is a particularly considerable increase in specific IgE antibodies in a phase of decay (15.98 +/- 1.64 IU/ml) and infiltration (12.66 +/- 1.08 IU/ml). These groups also show a concurrent rise in tuberculosis IgG antibodies, which nevertheless disagree with the increase of IgE (the correlation coefficient is 0.599).

Humans↗

Comparative analysis of mycobacterial infections in susceptible I/St and resistant A/Sn inbred mice.

SETTING: The availability and appropriate use of animal models is of significant importance for a better and more detailed understanding of the genetic, immunological and pathological mechanisms underlying the development of mycobacterial disease in humans. OBJECTIVE: To define a mouse model for tuberculosis severity that can be easily adapted to genetic and immunological analysis of host response to Mycobacterium tuberculosis infection. DESIGN: We describe here two inbred strains of mice, I/St and A/Sn (both Nramp1'), that differ vastly in commonly used parameters of susceptibility to infection with virulent and attenuated strains of M. tuberculosis. RESULTS: Following infection with a high dose of virulent H37Rv. M. tuberculosis and compared to their resistant A/Sn counterparts, I/St mice displayed more than a 2-fold shorter mean survival time and a more rapid onset and progression of severe body weight loss (cachexia). Moreover, I/St mice supported 20-100-fold higher multiplication of M. tuberculosis following challenge with H37Rv over a large range of infectious inocula. The high susceptibility of I/St mice was also reflected by more severe lung histopathology as evidenced by larger and more numerous lung granuloma and macrophage dominated cellular infiltrates. Finally, we determined that I/St are also unable to control infection with attenuated H37Ra M. tuberculosis and two strains of M. bovis (BCG and Ravenel) indicating hyper-susceptibility of the I/St mouse strain to mycobacterial infections. CONCLUSIONS: The results of our experiments suggest that comparative analysis of resistant A/Sn and susceptible I/St mice provides an ideal way to study host dependent aspects of tuberculosis susceptibility under the controlled conditions provided by an animal model.

Animals↗

[Cytokines in tuberculosis].

The paper presents the data available in the literature and the authors' own findings concerning the production of cytokines, such as interleukins 1, 2, 4, 6, and 8, interferons and tumor necrosis factor, in patients with different stages of tuberculosis. A relationship between the production rate of some cytokines and the stage of the disease, the extent of the process, chemotherapeutical efficiency and other clinically important factors is discussed. The prospects of further investigations in this area are dealt with.

Antitubercular Agents↗

[Immunity and resistance in experimental tuberculosis in mice exposed to various environmental factors].

CBA mice maintained on the chow and water with either normal or deficient in particular trace elements were infected with M. tuberculosis H37Rv. Mice with deficiency of silicon showed a tendency for decreased survival, had less active DTH response to tuberculin and proliferation in vitro upon stimulation by mycobacterial antigens and nonspecific mytogens than mice on balanced diet, higher levels of specific IgG. Addition of silicon to the diet of silicon-deficient mice corrected antituberculosis immunity.

Animals↗

[Development of laboratory investigation methods in phthisio-pulmonology (summary of activities of the Central Research Institute of Tuberculosis, USSR Ministry of Health, during the twelfth 5-year plan of the laboratory section of the All-Union program 0.69.08)].

Comprehensive laboratory studies were performed to develop and introduce new techniques for examining patients with respiratory tuberculosis and some other pulmonary diseases. The techniques should improve and develop the immunologic and bacteriological diagnosis of tuberculosis, sarcoidosis, various exogenous allergic alveolitis and nonspecific inflammatory (microbial and mycotic) pulmonary diseases. Some of the methods were elaborated for morphological verification of sarcoidosis, alveolitis and rare pulmonary diseases. Radioimmuno-, enzyme immuno-, and other assays for the activity of various enzymes, as well as biochemical methods for assessing the superficial properties of individual cellular elements have found application in performing biochemical studies in pulmonary tuberculosis and non-specific diseases. Immunologic, bacteriological, cytologic and biochemical methods of study have been adjusted to examine the amount of bronchoalveolar washings in patients with different pulmonary diseases.

Alveolitis, Extrinsic Allergic↗

[The course of experimental staphylococcal sepsis in opposite mouse strains and first-generation hybrids].

The survival time and histological lesions of the kidneys, liver, heart, and lungs were studied in CBA/Sto, C3HA/Mv and F1 (C3HA/Mv x CBA/Sto) mice for 15 days after i.v. injections with S. aureus pathogenic strains CFU B-243 in doses of 10(9), 10(8) and 2.5 x 10(8) microbial cells. CBA/Sto mice were found relatively resistant and C3HA/Mv mice, susceptible to infection caused by different doses of S. aureus, this being associated with different morphological picture in the viscera. F1 hybrids were at least as susceptible to the infections as any of the parent strains, suggesting recessive inheritance of resistance to staphylococcal infection.

Animals↗

[A new method of the evaluation of lymphocytes and monocytes during immune response in patients with tuberculosis and sarcoidosis].

Examination which included 21 patients with tuberculosis, 6 with sarcoidosis and 9 healthy volunteers was aimed at determining the amount and intensity of surface fluorescence of CD+3, CD+4, CD+8 lymphocytes and CD14+, KIM+I monocytes. The findings demonstrate that determination of the fluorescence intensity of lymphocytes and monocytes provides a more exact characterization of the morphofunctional state of cells involved in the immune response. It is shown in particular that tuberculosis and sarcoidosis patients exhibit a varying density of the expressed antigenic markers of lymphocytes, which increases only in sarcoidosis, except a suppressor subpopulation (cytotoxic lymphocytes). Patients with tuberculosis had decreased density of CD9+, CD14+ and KIMI markers on the particular subpopulations.

Adult↗

[The blood count of regulatory T-lymphocyte subpopulations in patients with pulmonary tuberculosis].

Important aspects are discussed of clinical evaluation of regulatory subpopulations of T-lymphocytes (T-helpers and T-suppressors) in the blood of patients with pulmonary tuberculosis. Imbalance of these subpopulations in the patients with normal values of E-REG BTR with PHA allows to establish immunity disorders in supplementary group of patients. Subpopulation imbalance is an unfavourable prognostic sign and one of indications to immunomodulating therapy.

Female↗

[Regulation of antitubercular immunity in mice by genes of the H-2 complex].

Development of DTH reaction and survival time after M. tuberculosis H37Rv infection have been studied in H-2 congenic and recombinant mice pretreated with high doses of BCG vaccine. In addition, in vitro proliferation of lymphocytes from infected CBA, B6 and 4R mice to PPD was studied in the presence of anti-I-A and anti-I-E mAbs. High doses of BCG vaccination (1 mg/mouse) have led to a significant inhibition of DTH and diminution of survival time in B10.M (H-2f) mice only, and to opposite effects in all other strains tested (H-2a, b, d, k, h4). In I-A+, I-E- 4R mice anti-I-Ak mAbs abrogated lymphocyte proliferation to PPD completely, while in I-A+, I-E- CBA mice only the mixture of anti-I-Ak and anti-I-Ek mAbs was effective.

Animals↗