[Morphofunctional changes of BALB/c and C57BL/6 mice's immune system under chronic bacterial gram-negative endotoxicosis].

Chronic endotoxicosis was modeled by subcutaneous injection of the sepharose in complex with LPS. In these conditions we have studied morphofunctional changes of the immune system of BALB/c and C57Bl/6 mice, which are characterized by the different types of the immune response (Th2 type is predominant in BALB/c, Th1--in C57Bl/6). In the 1st-7th day t in the serum of BALB/c mice the endotoxin level increased in 21.3 times, in C57Bl/6--in 20.6 times. The endotoxin antibodies significantly decreased in 1th-7th days, on the 14th day it increased in the serum of both mice's strains. Morphofunctional changes of the immune system after chronic endotoxicosis were different in BALB/c and C57BI/6 mice. On the 1th day after injection of LPS and sepharose, in the thymus of C57Bl/6 mice the cortex layer was exhausted because of cell death, in the thymus of BALB/c mice II-III stages of accidental involution were developed. On the 7-14th day after injection of LPS and sepharose in the spleen of C57Bl/6 mice T- and B-zones were hyperplastic, however in spleen of BALB/c mice only T-zone were enlarged. After LPS and sepharose injection changes of cytokine production synthesized by KonA activated splenic cells were found out. In both strains the level of proinflammatory cytokines--TNFalpha and IL-1beta decreased, as well the Th1-cytokine IL-2. The production o fTh2-cytokine - IL-4, significantly decreased only in C57BI/6 mice. We suggest that damaging effect of LPS injection is determined by predominant Th2 or Th2 types of the immune response.

Application potential of human fetal stem/progenitor cells in cell therapy.

We analyzed the possibility of using fetal stem and progenitor cells for the treatment of various pathologies. A comparative characteristic of stem cells from fetuses and adult donors is presented and advantages of the use of fetal biometerial for biotransplantation are described. The main tissue sources of fetal stem cells are characterized and experimental and clinical data on the use of fetal cells for cytotherapy are presented.

[Gene-engineering technologies and stem cells].

In the review it has been presented the conceptional analysis of modern state of stem cells use problem (SC) in gene therapy ex vivo. Principles of vectorial systems construction have been expounded, designed for SC transfection. It has been displayed results of experimental investigations and clinical data on transplantation of genetically modifiable SC at different monogenous and multifactorial diseases. Special attention is focused on the problem of biosecurity ensuring.

[The role of Toll-like receptors in regulation of immune responses in norm and pathology].

We have analyzed the recent data about Toll-like receptors (TLRs) that play the most important role in host immune defense. TLRs involved in induction and modulation of innate and acquired immunity as the integrators of their reactions. Genetic disorders of TLRs or their signaling pathways components were noticed with different pathologies. TLRs are the ideal molecular target for the therapy of many diseases including inflammatory, autoimmune, allergic and tumor diseases.

[Heat shock proteins and their role in the development of pathological processes].

Heat shock proteins (HSPs) are the most conserved proteins present in the archea, pro- and eukaryotes. HSPs have a dual function depending on their intra- or extracellular location. Intracellular HSPs play a cytoprotective role providing the cells with mechanisms to prevent damage caused by misfolded, damaged, aggregated, or insoluble proteins. Extracellularly located or membrane-bond HSPs participate in both innate and adaptive immune responses. The recent review focuses on the role of HSPs in the pathogenesis of infections, autoimmune, cardiovascular, oncological, neurodegenerative, and other diseases. HSPs may serve as potential molecular targets for therapeutic intervention in the treatment of various diseases, including cancer, Alzheimer's and Parkinson's diseases. Some HSPs may be used as immunoadjuvants or as HSP-based vaccines for the treatment of infections and cancers.

[Role of heat shock proteins in developing of innate immunity reactions].

Increasing interest to heat shock proteins (HSP) from biologists and medics is connected to widespread distribution of HSP in live nature and reflects their key role in support of life functions which is based on the unique polyfunctionality of these biomolecules. Together with main function, which is defense of biologic systems from stress effects, some HSP in the process of evolution acquired the ability to incorporate in the reactions of the immune system. The in vestmen of this protein in practical reactions of innate immunity system are described. Analysis of mechanisms underlying the adjuvant effect of pro- and eukaryotic HSP in innate immunity system is presented. HSP receptor structures on target cells as well as triggered intracellular signaling pathways are described.

[Mesenchymal progenitor cells. Biological characteristic and prospects for their use].

Imunophenotic characteristic of the mesenchymal stem and progenitor cells, their tissue origin and functional peculiarities as well as immunological aspects of its transplantation are presented in the article. Also the address migration and the site-specific differentiation of mesenchymal stem cells its age-related and pathological process induced changes are discussed. Prospects of clinical use of mesenchymal stem cells for the treatment of degenerative arthritis, spinal cord injuries, myocardial infarction and other disorders are shown.

[Functions of heat shock proteins in the system of adaptive immunity. Construction of vaccines].

One of the most important aspects of heat shock proteins (HSP) functioning, namely their role in reactions of innate and adaptive immunity, was reviewed in the article. Mechanisms of involvement of HSP in processing and presentation of antigens to T-lymphocytes were described. Principles of construction of prophylactic and therapeutic vaccines on the basis of HSP were set out. Assessment of range of indications for their use and possible risks related with inductive action of vaccines on the development of immunopathologic processes was a specially discussed topic.

Dynamics of morphofunctional changes in immune organs of BALB/c mice with experimental hepatitis.

The time course of morphofunctional changes in the liver, thymus, and spleen was observed in BALB/c mice with Con A-induced experimental hepatitis. The progress of alterative changes in the liver was paralleled by intensification of accidental involution of the thymus. On day 1 of hepatitis development high proliferative and cytostatic activity of splenocytes was paralleled by hemorrhagic necroses and depletion of the peri-arteriolar lymphoid sheaths in the spleen (T-zones), presumably due to migration of activated lymphocytes to the liver and barrier tissues. Later normalization of lymphocyte proliferative activity was paralleled by recovery and hyperplasia of the splenic T-cell zones.

Comparative characterization of cytokine production by concanavalin A-activated splenocytes from BALB/c and C57BL/6 mice after cold exposure.

The level of cytokines produced by ConA activated splenocytes was studied in male BALB/c and C57Bl/6 mice after single and repeated cold exposure (-20 degrees C, 3 min). Single cold exposure significantly decreased IL-2, -3, -4, -5, -10, -12, IFN-gamma production in BALB/c mice and decreased IL-2 content and increased TNF-alpha level in C57Bl/6 mice. Repeated cold exposure normalized the content of IL-2, -4, -10, -12, and IFN-gamma in BALB/c mice, which reflects the development of adaptive immune reactions. In C57Bl/6 mice IL-2, -3, -5, -10, -12, and IFN-gamma production remained significantly decreased, which attested to dysadaptive processes.

[Current views on the biology of the stem cell]. / Sovremennye predstavleniia o biologii stvolovoi kletki.

Stem cells (SC) represent a unique cell population capable of self renewing and differentiation. Embryonal SC, represented in the internal cell mass blastocyst, give rise to cells of all three germ leaves. SC are also represented in many tissues of the adult organism. Their physiological function consists in renewing or restoration of the differentiated cells pool during the life span of the organism. The majority of regional SC of the adults differentiate into the limited number of cell types though some regional SC have a wider differential potential. Perfection of SC investigation methods at the molecular genetic level will help to reveal subtle mechanisms of these cells functioning.

[The effect of epitope density on the immunogenic properties of hapten-protein conjugates]. / Vliianie plotnosti épitopa na immunogennye svoistva kon''iugatov gapten--belok.

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.