Lab. of Immunoregulation

Head - Irina S.Freidlin
corr.member of RAMS, prof., MD

Laboratory of immunoregulation is engaged in studying of cytokine's role in cellular interactions, inflammation, atherogenesis, in the specific immune response, oncogenesis and immunopathological disorders.

The basic experimental techniques include the use of primary cell cultures and cell lines. To solve the particular tasks we use experimental models of tumors and immunopathological processes. In parallel we carry out clinical immunological investigations together with clinicians (rheumatologists, pulmonologists, infectionists, cardiologists, paediatricians etc.). The research on immunomodulatory substances such as peptides of natural origin and synthetic peptides is also carried out.

New achievements in immunology are permanently introduced in clinic-immunological investigations. Substantiation is given to new principles of interpretation of the results of immunological investigations of the laboratory. Previously developed immunological methods are successfully adapted for solution of the tasks of the present-day clinic-immunological investigations. Studying the mechanisms of immunoregulation underlie the search for rational methods of immunocorrection.

The traditional scientific direction of the department is investigating problems of immunoregulation. The investigations have concretely defined the main points of the new scientific conception of the role of the early inflammatory response, proinflammatory and anti-inflammatory cytokines in immunoregulation as the early factors determining the form and character of the specific immune response. Members of the department concentrated their attention on investigating monocytes and macrophages, which are given an undeservedly little attention in the present-day immunology. The novelty and original character of the new approach consisted in a wide use of the primary and permanent cell cultures that allows the in vitro modelling of the conditions maximally close to those of organism, but having the privilege of a wide analytical access to single cells. The same approach was later used for studying the influence of cytokines and their combinations on the endothelial cells. Finally, a model system of joint cultivation of the endothelial cells and monocytes was worked out approximated to the conditions of interaction of these cells in blood channel.
The investigations performed are actual due to the fundamental and applied significance of the problem of immunoregulation and, in particular, of cytokine regulation of processes of proliferation, differentiation and functions of the cells. Different manifestations of biological activity of cytokines are being studied in detail. Under study are effects of different factors of the internal and external medium on intensity of production of cytokines with the purpose to find out the ways of its regulation. Special attention is being given to studying effects of different pharmacological agents on the production and activity of cytokines. The cytokine regulation network is being also studied in association with problems of infection immunology.

The model of growth of experimental tumors was used by a doctor of medical sciences E. P. Kisseleva to show that the early macrophage-cytokine response can support the growth of tumor at the expense of stimulation of angiogenesis. The modulating effect of the main angiogenic factor was shown on the functional activity of macrophages.

Professor A. V. Polevshchikov heads the resumed comparative-immunological investigations of regularities in the formation of congenital immunity.

The model of experimental allergic encephalomyelitis was used by senior research worker Yu. L. Zhitnukhin in common with the I. P.Pavlov department of physiology in fundamental investigations concerning pathogenesis and search for methods of treatment of demyenilizing processes.
The immunological aspects of atherosclerosis, mechanisms of the appearance and development of autoimmune reactions in particular, are actively investigated jointly with the department of biochemistry. The results obtained show bigger effecter  functions of the macrophages and their possible damaging action on the endothelium.

For past 10 years there has been 11 PhD dissertations defended by the employees of the department.

1. Bondarev I.E. Interaction of alpha-2-macroglobulin with TNFa. 1995.

2. Konjaev I.G. Comparison of biological effects of TNFa and synthetic oligopeptides, corresponding to the fragments of TNFa molecule. 1996.

3. Nikitina U.J. Ability of mononuclear phagocytes and endothelial cells to secret TNFa in response to atherogenic stimuli. 1997.

4. Malyshkin K.A. Immunological changes in alimentary insufficiency and immunocorrecting effects of alimentary additives. 1998.

5. Kuznetsova S.A. Influence of immune complexes on cytokine production by blood cells and on the expression of surface markers of endothelial cells activation. 2000.

6. Sokolov D.I. Influence of cytokines and their combinations on the expression of surface molecules and chemokine IL-8 secretion by ECV304 endothelial cells. 2001.

7. Sheikine Y.A. Regulation of macrophage activity in atherosclerotic lesions by IFNg. 2002.

8. Tendler E.V. "The role of immunological mechanisms in development of anticancer effect of antibodies to protein p53". 2005.

9. Starickova E.A. " Interaction of mononuclear phagocytes with endothelial cells: the role of cytokines". 2006.

10. Kissina T.E. "Studying of individual fitches of mononuclear cells of tuberculosis patients" (2006)

11. Amchislavskiy E.I. "Studying of the influence of cytokines on the funñtions of human endothelial cells of EA.Hy.926 line" (2007)

And one doctoral thesis:

Kisseleva E.P. Mechanisms of thymus involution and mononuclear phagocytes activation of in experimental tumours, 2002.

The laboratory supports creative contacts with other IEM departments (departments of biochemistry, neuropharmacology, molecular genetics, general pathology and pathophysiology, virology, molecular microbiology, Pavlov's physiological department), and with other research institutes in St.Petersburg and Moscow (Otto scientific research institute of obstetrics and gynaecology, St.Petersburg State Pavlov Medical University, scientific research institute of cytology, scientific research institute of children's infections, scientific research institute phthysiopulmonology, Military medical academy, Shemyakin scientific research institute of bioorganic chemistry).

The laboratory is ready to carry out contract investigations on the following topics:
1. study of immunomodulatory effects of various pharmacological agents, natural and synthetic preparations,
2. study of proangiogenic and antiangiogenic effects of various natural and synthetic preparations on the model of human endothelial cell line
3. study of cytostatic and cell proliferation stimulating effects of various natural and synthetic preparations,
4. realization of purposeful, pathogenetically based clinical immunological investigations including "full serological analysis",
5. design of non-standard systems for immunoenzyme analysis with the purpose of revealing specific antigens or antibodies,
6. use of methodological variant of "Cellular immunoenzyme analysis" for the estimation of expression of surface cell molecules.
7. use of the new equipment  Epics Altra flow cytometr

In out laboratory we teach students and provide professional training in the areas of:
à) immunological methods of investigation,
á) methods of experimental immunology,
â) methods of tissue culture research (running cell lines).