This is an advanced paper related to the results and prospects of research into marine hydrobionts that contain biologically active substances of unique chemical structure known to produce effect on various components of innate and acquired immunity. The Far East abounds in natural resources that suffice to stimulate regional production-scale extraction of biologically active substances. Due consideration is given to the study into immune modulating properties of polycationic and polyanionic polysaccharides (fucoidans, chitosan and their derivatives) and low-molecular compounds of marine origin (sulphated poly-oxysteroids, peptides, nucleic acids, and amino acid complexes) derived from marine invertebrates, algae and fish. The scientific basis to be developed in an effort to take next step forward in the evolution of biological technologies that are very likely to be applied in health care, medical and food industry, as well as the usage of high technologies for processing of biological resources in the export-oriented regional economy will allow to utilize the Far Eastern natural resources in an economically feasible and sustainable manner.

The paper gives due consideration to the effects of eukaryote's DNA, natural and synthetic oligodeoxynucleotides produced on humoral and cellular factors of innate and adaptive immunity, emphasizing the issues of DNA-Toll-like receptors interaction and innate immunity initiation. Imparting the information about immunostimulating, adjuvant and anti-infectious properties of the prokaryote's DNA, the authors highlight intensification of T-helper factor type-1 immune response that allows promising possibility to apply DNA and oligodeoxynucleotides for the treatment of allergic diseases, including bronchial asthma.

The authors present an overview of a promising trend in the immunotherapy of malignant neoplasms that consists in application of exogenous DNA enriched in unmethylated CpG motives and natural and synthetic CpG oligodeoxynucleotides. The authors provide results of a combined application of DNA-based drugs, chemotherapy and radiation treatment, and summarize their findings devoted to the study of efficiency of salmon milt-based DNA in preventing and administering complex therapy of oncological diseases.

The paper gives consideration to the adjuvant properties of cytokines studied by using experimental models. They induced immunogenic activities by means of rabies vaccine. Combined with a complex of recombinant cytokines, the vaccine exhibited the most noticeable effects. Augmenting immune response was observed in parallel to high-level virus neutralizing antibody formation. The immunoadjuvant effects were observed when using recombinant interleukin-lb and tumor necrosis factor-α for monodrug therapy and "Polyoxidonium". The research results were indicative of the possibility to apply cytokines and other immune-response modulating drugs as adjuvants capable of increasing immunogenic activities of the vaccines and highlight promising opportunities of researching into new approaches to immune response control.

The mammalian cell culture-derived vaccines contain some pro-inflammatory cytokines, the number and concentration of which depend on the vaccine type. Spontaneous and antigen-induced production of cytokines is subject on the cell line and nature of antigen. Diploid cell strains (M-22 and L-68) spontaneously secrete cytokines. Studying the cell culture-induced cytokine synthesis can serve as one of the criteria to choose substrate required to produce tissue culture vaccine. As the researches into adjuvanticity of cytokines and related immu-nomodulating drugs in some experiments show, there is a stimulatory effect produced by cytokines on the immunologic activity of the A and В hepatitis vaccines. Recombinant cytokines being tumor necrosis factor-α and interleukin-1 β as well as "Polyoxi-donium" and "Imunofan" are considered to have most evident immunomodulation properties.

The paper discusses immune-response modulating and membrane-acting effects of carotenoids derived from the Halocynthia aurantium ascidia tunic and gives consideration to 12 components, among which xanthophylls are dominant. These are: astaxanthin, alloxantin, diatoxanthine, halocynthi-axanthine, fucoxanthinol, and methylxanthine. Halocynthiax-anthine is peculiar to this form and used to identify halocynthi-axanthine-based drugs. Original patented method has allowed to derive oily extract from the ascidian tunic registered as dietary supplement. As shown, this medication induces bactericidal and phagocytic activities of neutrophils, antioxygenic properties of blood serum, inhibits peroxidation, and produces anti-inflammatory and hemostimulating effects. The ascidian tunic carotenoids have membrane-acting properties and capability to be bound together with phospholipids and stabilize membrane structure. The findings allow recommending the dietary supplement "Ascidian-Derived Oily Extract" for advanced clinical testing.

The authors present their study into immuneresponse modulating and anti-inflammatory activities of neo-mythilane that is a derivative from the mussels Crenomytilus gray-anus. Unlike the early mussel-derived polysaccharide mythilane, this product appears not to exhibit allergenic properties because it contains 1.5% of protein, at the most. The in vitro experiments show neomythilane potentiating the macrophage phagocytic activity by 25-30% and increasing activity of macrophage lysosomal enzymes more than two times, and inducing generation of active oxygen forms, as compared to mythilane. In this regard, both mythilane and neomythilane have no toxic properties in vivo, without exhibiting cytotoxic activity in vitro. As determined, neomythilane is capable of reducing lipid peroxidation and ni-troxide synthase activities. This allows to consider mythilane as a basis for producing medicines.

The paper presents experimental study into the effects of sulphated polysaccharides - fucoidans derived from the sea brown algae Laminaria cichorioides and Laminaria japonica on maturation of dendritic cells extracted from the mice bone marrow. As reported, the fucoidans tend to induce expression of terminal differentiation markers, intensify activation marker, adhesion molecules, surface antigen-presenting and bone marrow inducing molecules, as well as Toll-like receptors on the dendritic cell membranes that appears to be indicative of their maturation.

Both in clinic and laboratory, the authors have studied
immunomodulating effects of sulphated polysaccharides - carrageenans - derived from the red algae of Gigartinaceae and Tichocarpaceae families (Sea of Japan). In vitro studies allowed to define dependence between immunomodulating activity and polysaccharides structure. Lambda-carrageenan was deemed to have the most pronounced biological effect proved to increase calcium ion concentration in mice lymphocytes, generate active forms of oxygen in macrophages and induce apoptosis in Ehrlich>s carcinoma cells. Kappa and kappa/iota-carrageenans showed higher capability to induce generation of proinflammatory cytokines. There was concentration dependence between cytokine-induc-ing activity and polysaccharide concentration. Clinical testing allowed to note positive effects of carrageenan used in integrated treatment of patients suffering from acute enteric infections on the immune system and hemostatic parameters.

Applying bicolour flow cytometry technique by FACSCalibur (Becton Dickinson), the authors have determined effects produced by lipopolysaccharide derived from the sea proteobacteria Pseudoalteromonas nigrifaciens and its structural components on the early activation of human mononuclear blood cells. Lipopolysaccharide, O-specific polysaccharide (O-PS) and oligosaccharide cor (Cor) increased the CD69 and CD25 expression on the CD4+, CD8+, CD16+ lymphocytes and on the CD69 expression monocytes. Lipopolysaccharide increased CD95 expression on the CD4+, CD8+, CD16+ cells; OP-S and Cor increased the CD4⁺ expression. None of the glycopolymers under study induced statistically significant changes in the CD38 expression. Compared to the polysaccharide, O-PS and Cor caused more intense increase of activation marker expression on the monocytes and lymphocytes. To a greater extent, O-PS and Cor activated cells capable of producing cytotoxic effect.

The authors describe their own methods of identifying additional photometrical parameters of absorption spectra of plant-derived extracts. The set of these parameters can serve as quantitative indicator of extract and be used for production purposes to supervise manufacture of plantderived medicines.

The Fl (1CBA X C57BL/6) hybrid mice experiments allowed to study immuneresponse modulating effect produced by marine hydrobiont-derived haurantin. This substance appeared to have capability of giving immune response in intact animals and under immunosuppression caused by cyclophos-phan. As reported, when introducing into intact mice, haurantin tended to exhibit immune-response modulating and immuno-correcting activities to be seen via T-cell component of the immune system. In vitro immunosuppression simulation showed that haurantin has had no effects on the antibody formation immediately after injecting cytostatic agent (in 24 hours) but for certain induced the level of antibody-forming and rosetteforming cells in mice spleen during the period of active restoration of the antibody formation (in 9 days). The wellknown interferon-inducing activities can be deemed as one of the immunomodulation mechanisms caused by haurantin.

The paper provides an integrated study into the state of oxygen-dependent systems of phagocytes in blood. As shown, there was a dose-dependent stimulating effect produced by DNA on these cells that appeared to have capability of decreasing activity of ferments that participated in generation of superoxide anionic radical and, in contrast, increasing activity of myeloperoxidase being a catalyst of oxygen anion conversion into hydrogen peroxide. This allowed to consider the salmon milt DNA to have antioxidative effect with respect to hemato-phages. Besides, stimulatory effects of this substance on other phagocyte functions (intracellular contents of 5'-nucleotidases and cationic proteins) could be determinative for prospects of applying the salmon milt-derived DNA as immune-response stimulating drug because the cationic proteins have been known to be representatives of low-molecular intracellular regulators very likely to participate in signalling various physiological functions of an organism.

The authors have studied effect produced by echinochrome A on the kidneys morphology and functional parameters using model of 40-day white rats exposed prenatally to lead nitrate. The studies were aimed at defining parameters of free-radical oxidation in kidney homogenates and blood serum. The lead nitrate induced oxidative stress and destructive changes in kidneys. Echinochrome A prevented these disturbances.

The author studies behaviour of pentacene film surface exposed to atomic hydrogen by means of scanning tunneling microscopy. Due consideration is given to adsorption of atomic hydrogen on the pentacene surface and generation of point defects. Scanning tunneling microscopy allows researching into electronic structure of defects and showing their generation to be caused by chemical reactions between atomic hydrogen and surface. There are some charge traps in point defects. Special emphasis is focused on analyzing adsorption process and construction of qualitative model. The curve of adsorption is comprised of two linear areas with a fracture in point 25 Langmuir that is indicative of two various absorption mechanisms. The author makes qualitative model of surface open-up via pentacene molecule breakdown and proposes a method of fighting with this effect suitable for semiconductor surface restoration.

The authors have studied effects produced by plant immuneresponse modulating agents - leukinferon and tinrostim - on the phagocytic activity, oxygen-dependent mechanisms of bactericidal action and local production of opposite cytokines in case of experimental staphylococcal and pseudomonas pneumonias. As shown, intrinsic leukinferon effects were produced when stimulating oxygen-dependent mechanisms for the bactericidal activity of phagocytes; tinrostim induced immune response with respect to innate immunity. Leukinferon caused increasing γ-interferon; tinrostim more evidently intensified interleukin-10 production. The staphylococcal pneumonia model showed priming effect of the medications in vitro. The leukinferon and tinrostim produced similar effects on the parameters under study in vivo. In case of pseudomonas pneumonia, the most evident antiinflammatory effects were peculiar to the tinrostim.

The local immunity system in lungs is permanently exposed to injurious action of a number of chemical, physical and biological factors. Among other things, these are mineral
microparticles. This paper gives consideration to assessment of effects produced by the Vanginskiy and Kulikovskiy zeolite deposits on the local immunity in lungs. The authors used lowenergy laser radiation as a factor very likely to induce lipid peroxidation and reduce functional activity of alveolar macrophages and lymphocytes. The studies allow to conclude that unlike the Kulikovskiy deposit zeolites appeared to intensify free radical reactions and suppress the local immunity system, the Vanginskiy deposit zeolites exhibited immunoprotective and antioxidative properties.

The authors have revealed marked metabolic shifts in rabbits with experimental antigen-induced arthritis resulted in a metabolic imbalance between proteoglycans, intensification of lipid peroxidation and inadequacy of antioxidative protection system. The changes were observed in blood serum and articulations content. There were tense immunopathological reactions. Intraarticular introduction of the immune-response modulating agent ceruloplasmin in this experiment resulted in the correction of these changes and improvement of clinical picture and laboratory indices.

The paper gives consideration to the immunity-related structural elements of digestive system - Peyer>s patches. The authors were aimed to study accumulation of radioactive caesium in organisms of experimental animals (Wistar rats) when supplementing their diet with natural zeolite. Researching into dynamics of excreting caesium-137 and specific radioactivity of blood, bowels and Peyer's patches allowed to detect corrective effect produced by the natural zeolite on the patch lymphoid tissue structure being indicative of the immune function maintenance.

The paper discusses possibility of applying fucoidan derived from the brown algae Fucus evanescens to correct humoral and cellmediated immunity in cases of experimental en-do toxinemia caused by lipopolysaccharide. The authors revealed inhibition of higher level of proinflammatory cytokines, partial restoration of adhesive and bactericidal activities of neutrophilic leukocytes with parallel lipopolysaccharide-induced immunosuppression and reducing level of microcirculation disorders found in parenchymal organs very likely to increase animal's resistance to endotoxin.

The paper discusses antibacterial and antitoxic properties of chitosan and its derivatives (low molecular weight chitosan, acidified chitosan, chitooligosaccharides, and carboxypropyl chitosan) derived as a result of chemical or enzymatic degradation of the parent substance. As seen, the low molecular weight acidified and deacetylated chitosans that are capable of better dissolving in neutral and alkaline solutions and being better absorbed from the gastro-intestinal tract proved to exhibit more noticeable antibacterial and antitoxic effects, compared to the parent high-molecular chitosan.

Experimental tick-borne encephalitis models allowed in vivo and in vitro researches into combined medication Zostera asiatica-derived rosmarinic acid created on the basis of plant polyphenol compound of rosmarinic acid and bioflavonoids (luteolin, apigenin, etc.). As shown, when introduced orally (the most efficient mode of administration) this medication increased survival rate of mice infected with highly pathogenic strain of the tick-born encephalitis virus and prolonged their life. It did not cause a pig embryo kidney cell culture destruction and suppressed viral infection activity.

The paper provides experimental study into the protective effects of sulphated polysaccharide fucoidan derived from the sea brown algae Laminaria japonica after in vivo infecting mice with highly pathogenic strain of tick-borne encephalitis virus. As reported, the drug efficiency depends on dose and dosing regimen, and it allows obtaining adequate protection in infected animals. A wide range of biological effects produced by the sulphated polysaccharides extracted from the sea brown algae, low toxicity and environmentally friendly production technologies offer great opportunities of applying fucoidans in an effort to prevent and treat viral infections.

The authors have studied anticancer activities of fucoidans derived from nine brown algae species using the soft agar-agar model. As shown, the fucoidans are non-toxic to DLD-1 and HT-29 cells in concentrations of up to 200 μg/mL. The fucoidan extracted from Laminaria cichorioides and composed of 1.3-tie molecules alpha-L-fucose tends to inhibit growth of cancer cell colonies in bowels. The low sulphated fucogalactans derived from Sargassum swartzii, S. mcClurei and S. denticarpum do not really exhibit anticancer properties. The findings allowed considering application of the brown algae-derived fucoidans (Far Eastern seas) as very promising in effort to prevent and treat oncological diseases.

In vitro model of transplantable Lewis's pulmonary adenocarcinoma in C57BL/6 mice allowed to study anticancer and antimetastatic effect of the sulphated polysaccharide fucoidan derived from the Okhotsk Sea brown algae Fucus evanescens. As shown, the intensity of antimetastatic effects depended on the dose of the drug. Single or repeated introduction of the drug in the dose of 10 mg/kg induced spontaneous moderate antimetastatic effect and potentiated antimetastatic but not anticancer activity of cyclophosphan. The smaller and larger doses (5 and 25 mg/kg) did not result in any noticeable effects on the growth and dissemination of adenocarcinoma. Combined with cyclophosphan, the fucoidan applied in the dose of 25 mg/kg intensified toxic action of the cytostatic drug.

The paper provides detailed information about in vitro researching into the effects of molluskam being a complex of amino acids and dipeptides on the mucociliary system of airbearing part of lungs, and free radical processes under hypothermia. All the researches were performed on sixty malerates, the forty ones being cooled in the climatic chamber (including those twenty animals that had been receiving molluskam). Electron microscopic and biochemical studies allowed to see this dietary supplement having protective effect, preventing any changes in the mucous tunic of trachea and intensifying lipoperoxidation.

The models of alimentary hypercholesterolemia and alloxan diabetes in mice allowed to study effects of the immune response-modulating agent fucoidan derived from the brown algae Fucus evanescens on the state of antioxidative system, as well as identify capability of this polysaccharide to decrease levels of glucose and total cholesterol, normalize dissipation of this cholesterol between lipoprotein fractions, reduce atherogenicity factor, and stabilize lipid peroxidation level of the derivatives.

The examinations of 216 patients with community-acquired pneumonia allowed estimating receptor activity of immunocytes contained in peripheral blood, induced sputum and mucous tunic of large bronchi. Homogenous antibodies were used for cell differentiation. The acute phase of the disease leaded to a decreasing number of cells CD3⁺, CD4⁺, CD8⁺ and CD25⁺ contained in peripheral blood. There was a decreasing number of cells CDllb⁺, CD18+, CD4⁺, CD16+, CD25+, and HLA-DR⁺ found in induced sputum. The recovery period was characterized by decreasing number of cells CD3+ contained in blood. Low number of immunocytes was observed in populations CD3⁺, CD4⁺, CD8⁺, CD25+ and HLA-DR+ during the follow-up period. The quantity of cells CD4+, CD25+, CD16+, CD22+, CDllb⁺, CD18+ and HLA-DR+ found in the induced sputum after 20-day and 6-month periods did not reach control values. The followup period was characterized by increasing values of CDllb⁺-cells found in mucous tunic of large bronchi. No reliable differences were observed between the indices of various biological environments.

Forty clinical observations performed by authors allowed studying the role of T-cell dysfunctions in the development of lower limb atherosclerosis and finding out that peripheral lymphocyte subpopulation indices were within the value range indicating satisfactory immune system functions. Increasing number of circulating lymphocytes and intensified expression of interleukin-2 receptor, class II major histocompatibility antigens and apoptosis marker on the lymphocyte surface indicated that the T-cell activation was not restricted to the atherosclerotic plaque area. The parameters which characterized relation of lymphocyte subpopulations and intensity of activation processes confirmed participation of activated T- lymphocytes in the pathogenesis of atherosclerosis. As reported, biological dietary supplement "Fucolam" created on the basis of the Fucus evanescens brown algae fucoidan exhibited corrective effect on the intensity of inflammatory process in patients with lower limb atherosclerosis.

Clinical experiment conducted by authors in respect of 12 children aged 7 to 12 with chronic inflammatory lung diseases in the remission period occurred as a result of the respiratory system malformations allowed to study effect produced by the echinochrome A on the free radical oxidation processes. This drug increased antioxidative antiradical protection of an organism and efficiently decreased intensity of the free radical oxidation processes, including during the lipid peroxidation.

The paper provides estimation of efficiency of administering koumiss treatment in specialized sanatorium. Analyzing the examination of 215 patients operated for cholelithiasis allows to conclude that the koumiss is conductive to restoration of immune status, decrease of concentrations of circulating immune complexes and immunoglobulins associated with a regress of postoperative clinical symptoms.

The authors have examined two groups of patients with chronic obstructive pulmonary disease (24 patients without hypoxemia and 17 patients with hypoxemia) and revealed interdependence between hypoxemia level and system inflammation and haemosta-sis. The levels of systemic inflammation markers, hypercoagulation and fibrinolytic system suppression in patients with hypoxemia was considerably higher than those of the patients with normal parameters of the arterial blood oxygen saturation that was indicative of a considerable role of hypoxemia in pathogenesis of inflammatory reaction in case of chronic obstructive pulmonary disease.

The paper provides estimation of efficiency of dietary supplement "Chitosan Primorskiy" as a maintenance medication for baseline therapy of gastric and duodenal ulcer. The gastroenterological examination of 60 patients allowed to consider the dietary supplement exhibiting restorative effect: scarring of ulcerous defects and reduction of major clinical symptoms.

Examination of 67 patients with in-hospital pneumonia included determination of cytokine content and cell composition of liquids found as a result of bronchoalveolar lavage. The marked neutrophilia as a component of local inflammatory response was associated with pseudomonas pneumonia. The neutrophilia and large quantities of bronchial epithelium was characteristic of the pneumonia caused by Escherichia coli; neutrophil and macrophage cell composition of the bronchoalveolar liquid was indicative of staphylococcal pneumonia. The levels of soluble type I receptors of the tumor necrosis factor-α amounting to more than 700 pg/mL and interleukin-8 of over 1200 pg/ mL were the markers of pneumonia associated with Pseudomonas aeruginosa; the interleukin-8 content of less than 300 pg/mL was indicative of the Staphylococcus aureus-induced pneumonia.

The authors have studied adequacy and role of analgesia in developing endothelial and immune dysfunctions during the early peri-operative period with respect to 20 patients aged 40 to 60 with serious lower limb injuries. As shown, there were cellular and humoral dysfunctions of innate and adaptive immunity in the form of depression. These were observed by the moment of surgical treatment at the background of endothelial dysfunction. Lacking significant differences in the parameters indicating the state of immune system and endothelium in the dynamics of the early peri-operative period were indicative of an adequate character of anaesthesia. The analgesic of peripheral action (ke-toprofen) was combined with opioids (promedol) and allowed to maintain postoperative homeostasis and balance between pro-and anti-inflammatory potentials of immunocompetent cells, thus preventing extended stress response to the surgery.

The paper provides results of regular medical checkup of 106 patients with HIV infection associated with tuberculosis and gives consideration to epidemiological, clinical and laboratory data as well as immunological examinations conducted at various stages of the disease. The studies allowed revealing T-cell immunodeficiency at all the HIV infection stages and close negative correlation between the HIV load level and absolute T-lymphocyte content (including T-helpers) at IVB and V stages. There was considerable increase in proinflammatory cytokine level. The hypocytokinemia correlated with the severity of the persistent infection. As far as the disease aggravated, there was differently directed character of dynamics of immunoglobulin level.