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Regulation of NK Cells Activity

#K-315


Mechanisms of Regulation of NK Cell Activity in Toxoplasmosis

Tech Area / Field

  • BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
  • MED-DRG/Drug Discovery/Medicine

Status
3 Approved without Funding

Registration date
28.01.1999

Leading Institute
Institute of Molecular Biology and Biochemistry (Ajtkhozhin), Kazakstan, Almaty

Supporting institutes

  • Kazakh Research Antiplaque Institute, Kazakstan, Almaty

Project summary

The objective of the project is to study a role of some cytokines in regulation of antiparasitic activity of natural killer cells (NK) during development of acute toxoplasmosis.

The idea of the project is based on the literature data indicating the leading role of NK cells and IFN-g produced by them in antiparasitic immunity, the negative and positive regulation of which realizes by cytokines of a various cellular origin. The point of attention of the project is a mechanisms of weaken of NK cell immunity during progression of acute toxoplasmosis.

The activity of NK cells in acute toxoplasmosis is supposed to depend on a profile of stimulating and inhibiting cytokines. Dynamics of cytokine production at normal outcome of the immunological conflict (elimination of parasites) depends on consecutive replacement of activating (IL-12, IL-15, IL-2, IL-1, TNF-a) factors on suppressor (IL-10, IL-6, IL-3, TGF-b) one. Uneffectiveness of NK cell immunity in case of fatal outcome in toxoplasmosis is mostly connected to premature starting of suppressor mechanisms. Also transformation from the chronic and latent form of toxoplasmosis into acute is connected to them. It is supposed, that the main role in development of such suppressor mechanisms belongs, so-called, natural suppressor cells (NS).

This project is devoted to study a complete profile of known cytokines, the participation of which is proved or supposed in the mechanism of antiprotozoic NK immunity (IFN-g, TNF-a, IL-12, -15, -2, -1, -3, -10, -6, TGF-b), and also functional activity of NK and NS system in dynamics of development of infection from invassion up to death of animals.

The study of dynamics of complete spectrum of cytokines, stimulating and suppressing NK cell immunity in comparison to cytolitic activity of NK cells in toxoplasmosis was not carried out by anybody earlier. The participation of NS cells in toxoplasmosis was not suggested earlier by other researchers.

During the investigation it will be designed the correlations between a condition of studied cell activity and level of serum cytokine contents in dynamics of infectious process. It is expected to establish a phenomenological picture of effector and regulative humoral components of antiprotozoic NK cell immunity, as a basis for more complete understanding of complicated mechanisms of relations «parasite-host». It is supposed to estimate the importance of NS cells as potential suppressors of NK activity, and also the role of each suppressor cytokines in the development of immunological insufficiency as approaching to death of animals, infected with high virulent strain RH Toxoplasma gondii.

The results of the work will allow to prove necessity of realization of pathogenic therapy side by side with aetiological, including cytokine immunotherapy, at the complicated forms of toxoplasmosis, and also at conversion into chronical process.

The fulfilment of the project will make an essential contribution to development of fundamental and applied immunology and medical parasitology, and also to the decision of one of social problems, namely: will give to scientists of Kazakh Research Antiplaque Institute, working previous under the State orders of Ministry of Defence, opportunity to convert scientific priorities and apply their experience for realization of fundamental researches in the field of immunobiology and medicine in the peace purposes, to create a long-term prospect of fruitful activity within the framework of international scientific community.


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