You are here

Apoptosis and its place in the regulation of immune homeostasis of animals’ body (review of literature and own studies)

In recent years, among the phenomenon of programmed determined process of aging and cell death – apoptosis is comprehensively studied by scientists of different specialties. This phenomenon of physiological regulation of body homeostasis constantly occurs in the body of all living beings, is regulated and controlled by a number of factors. Apoptosis is accompanied by a natural process of substitution and elimination of cells that have completed their life cycle, as well as cells that have undergone damage and mutations, which is extremely important in the early diagnosis of a variety of pathologies.

The modern clinical immunology annually updated with new methods, which require the researchers to broaden their knowledge in this area and specialized laboratories to be upgraded. The article deals with modern immunological aspects of apoptosis of immune competent detail reveals the effect of various factors and mechanisms that influence the induction and inhibition of apoptotic process. The authors have done research parallels of this issue with their own experimental studies, have carried out interpretation and synthesis of contemporary theoretical concepts and have defined the role of apoptosis in the formation of immune homeostasis animals. Today, science knows five basis groups of methods for assessing apoptosis, namely: morphological, immunohistochemical, biochemical, immunological and DNA micro-method.

The practical use of each of them is determined by the principal approach of the investigator while studying the process in the body or in the diagnosing specific diseases. Programmed cell death, as above, plays a special role in the functioning of the immune system. At all stages of the cell – proliferation and differentiation – it is the method of selection of immune cells, it regulates their response to antigenic signals, determines the nature of the immune response or the formation of immunological tolerance. Apoptosis is an active form of the response of immune cells as unfavorable, and the physiological and activating (antigens, mitogens ) impact factors.

Cell protection from apoptosis activation is provided by membrane molecules. Other important physiological regulators of apoptosis are cytokines ‒ a large group of proteins that have specific receptors on target cells. An important role in the regulation of apoptosis of immune cells belongs to other cytokines – interleukins, interferons. The phenomenon of apoptosis is the result of various factors that lead to cell death. It may be non-specific factors such as temperature, toxic agents, oxidants, free radicals, γ- and ultraviolet irradiation, bacterial toxins, etc.

In all these cases there is induction of apoptosis, but the increase of the influence of a particular agent triggers the disintegration of necrotic cells, which causes an increased interest of researchers, primarily on the hormonal regulation of apoptosis.

Our experimental studies have shown that the dynamics of mastitis of cows induction of apoptotic neutrophils took place in spite of the backdrop of metabolic activation reactivity of phagocytes. In the area of the pathological process a great amount of reactive Oxygen and other metabolites inflammation are found to accumulate causing not only a destructive effect on cells but also being specific activators of apoptosis.

Thus, apoptosis should be considered a natural mechanism for elimination of cell. The presence of physiological factors (inducers and inhibitors of apoptosis) in the body suggests that programmed cell death is dependent on the ratio of the factors that cause apoptosis and prevent it, as well as intracellular regulatory mechanisms. Noting that apoptosis is a general biological mechanism for the regulation and balance, which is responsible for maintaining the physiological balance of cell populations, as well as the destruction of distorted, mutated and defective cells new approaches to treating and preventing disease are being considered.

It is well known that disregulation of apoptosis leads to various diseases, so the study of the mechanisms of this phenomenon will allow affecting its separate stages in some way, both regulation and correction. Mechanisms of induction of apoptosis, leading to inhibition or contrary to the excessive activation of the process of cell death may be an important factor in the pathogenesis of various diseases. Therefore, the development and clinical use of different methods of recognition of apoptotic cells is important not only for the diagnosis and prognosis of the disease, but also for choosing the best method of treatment and monitoring its effectiveness. Thus, immunological reactivity implemented by a system of cellular and humoral responses provides dynamic regulation of homeostasis. All physiological processes in the body are controlled by the immune system. So in the present research it is necessary to use new assessment methods of apoptosis, which will be able to display the status of immune homeostasis normally and in the development of pathology.

Key words: apoptosis, immune system, immunocompetent cells, mechanisms of regulation, homeostasis.

1. Neutrophil apoptosis: impact of granulocyte macrophage colony stimulating factor on cell survival and viability in chronic kidney disease and hemodialysis patients / N. Zahran, A. Sayed, I. William [et al.] // Arch. Med. Sci. − 2013. − Dec. 30. − Vol. 9 (6). − P. 984−993.

2. MLK3-MKK3/6-P38MAPK cascades following N-methyl-D-aspartate receptor activation contributes to amyloid-β peptide-induced apoptosis in SH-SY5Y cells / F. Zhou, Y. Xu, X. Y. Hou // J. Neurosci. Res. − 2014. − Jan. 31. − Vol. 10. − P. 1002−1017.

3. Mangiavini L. TUNEL Assay on Skeletal Tissue Sections to Detect Cell Death / L. Mangiavini, E. Schipani // Methods. Mol. Biol. − 2014. − Vol. 5. − P. 1130−1378.

4. A rapid detection method for apoptosis and necrosis measurement using the Cellometer imaging cytometry / L.L. Chan, N. Lai, E. Wang [et al.] // Apoptosis. − 2011. − Dec.16 (12). − P. 1295−1398.

5. Accurate measurement of peripheral blood mononuclear cell concentration using image cytometry to eliminate RBC-induced counting error / L. L. Chan, D. J. Laverty, T. Smith [et al.] // J. Immunol. Methods. − 2013. − Feb. 28. − Vol. 388(1−2). − P. 25−32.

6. Walt D. R. Optical methods for single molecule detection and analysis / D. R. Walt // Analytical Chem. − 2013. − Feb. 5. − Vol. 85 (3). − P. 1258−1263.

7. Rekomendacii' shhodo cytologichnoi' diagnostyky ta vizualizacii' apoptozu imunokompetentnyh klityn sekretu molochnoi' zalozy koriv : naukovo-metodychni rekomendacii' / [Jablons'kyj V. A., Ljubec'kyj V. J., Zhelavs'kyj M. M., Bodnar O.O.]. − Kyi'v, 2012. − 23 s.

8. Jablons'kyj V.A. Apoptoz imunokompetentnyh klityn krovi koriv u period laktacii' / V. A. Jablons'kyj, M. M. Zhelavs'kyj // Nauk. visnyk Nacion. agrar. un-tu. − K., 2008. − Vyp. 126. − S. 233−236.

9. Development of new photon-counting detectors for single-molecule fluorescence microscopy / [X. Michalet, R. A. Colyer, G. Scalia et al.] // Philos. Trans. R. Soc. Lond. B. Biol. Sci. − 2012. − Dec. 24. − Vol. 368 (1611). − P. 2012−2047.

10. Breaking the concentration limit of optical single-molecule detection / [P. Holzmeister, G.P. Acuna, D. Grohmann et al.] // Chem. Soc. Rev. − 2014. − Feb. 21, Vol. 43 (4). − P. 1014−1028.

11. Yoshie T. Optical microcavity: sensing down to single molecules and atoms / T. Yoshie, L. Tang, S.Y. Su // Sensors (Basel). − 2011. − Vol. 11 (2). − P. 1972−1791.

12. Staphylococcal protein A, Panton-Valentine leukocidin and coagulase aggravate the bone loss and bone destruction in osteomyelitis / T. Jin, Y.L. Zhu, J. Li, J. Shi [et al.] // Cell. Physiol. Biochem. − 2013. − Vol. 32 (2). − P. 322−333.

13. Oberoi-Khanuja T.K. Ubiquitination of Rac1 by Inhibitors of Apoptosis (IAPs) / T.K. Oberoi-Khanuja, K. Rajalingam // Methods Mol. Biol. − 2014. − Vol. 1120. − P. 43−54.

14. Fil'chenkov O.O. Apoptoz i rak: vid teorii' do praktyky / O.O. Fil'chenkov, R.S. Stojka. − Ternopil': Tern. derzh. med. un-t, 2006. − 524 s.

15. Comparative analysis of apoptotic changes in peripheral immune organs and lungs following experimental infection of piglets with highly pathogenic and classical porcine reproductive and respiratory syndrome virus / W. Gang, H. Yuli, T. Yabin [et al.] / Virol J. − 2014. − Vol. 12. − P. 111−117.

16. Feig C. How apoptosis got the immune system in shape / C. Feig, M. Peter // Eur. J. Immunol. − 2007. − Vol. 37. − P. 61−70.

17. Immune Response and Apoptosis – Introduction / J. Charles, H. Azizul, A. Nancy [et al.] // J. Clin. Cell. Immunol [Electronic resourse]. − Mode of access: http: //www.omicsonline.org / 2155-9899/2155-9899-S3-e001.php.aid=3585.

18. CDK6 kinase activity is required for thymocyte development / M.G. Hu, A. Deshpande, N. Schlichting [et al.] // Blood. − 2011.  − Vol. 117. − P. 6120−6131.

19. Akt1 and Akt2 are required for αβ thymocyte survival and differentiation / M.M. Juntilla, J.A. Wofford, M.J. Birnbaum [et al.] // Proc Natl. Acad. Sci. USA. − 2007. − Vol. 104. − P. 12105−12110.

20. Hernandez J.B. Life and death in the thymus – cell death signaling during T cell development / J.B.Hernandez, R.H. Newton, C.M. Walsh // Curr. Opin. Cell. Biol. − 2010. − Vol. 22. − P. 865−871.

21. The Wnt antagonist Dkk1 regulates intestinal epithelial homeostasis and wound repair / [S. Koch, S. Nava, C. Addis et al.] // Gastroenterology. − 2011. − Vol. 141. − P. 259−268.

22. An emerging player in adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes / G. Curtale, F. Citarella, C. Carissimi [et al.] // Blood. − 2010. − Vol. 115. − P. 265−273.

23. Commensal Escherichia coli Reduces epithelial apoptosis through induction of IFN-αAmediated guanylate binding protein-1 in human and murine models of developing intestine / J. Mirpuri, J.C. Brazil, A.J. Berardinelli [et al.] // J. Immunol. − 2010. − Vol. 184. − P. 7186−7195.

24. Guanylate-binding protein-1 is expressed at tight junctions of intestinal epithelial cells in response to interferon-γ and regulates barrier function through effects on apoptosis / M. Schnoor, A. Betanzos, D. A Weber [et al.] // Mucosal. Immunol. − 2009. − Vol. 2. − P. 33−42.

25. Jablonskij V.A. Lokal'nyj immunitet i apoptoz immunokompetentnyh kletok pri subklinicheskom mastite korov / V.A. Jablonskij, N.N. Zhelavskij // Sovremennye problemy veterinarnogo obespechenija reproduktivnogo zdorov'ja zhivotnyh: Materialy Mezhdun. nauch.-praktich. konf., posvjashhennoj 100-letiju so dnja rozhdenija professora V. A. Akatova (Voronezh, 27-29 maja 2009 g.). − Voronezh: Istoki, 2009. − S. 393−397.

26. Malemud C. J. Pearlman E Targeting JAK/STAT signaling pathway in inflammatory diseases / C.J. Malemud, E. Pearlman // Curr Signal Transduct Ther. − 2009. − Vol. 4. − P. 201−221.

27. Vallabhapurapu S. Regulation and function of NF-κB transcription factors in the immune system / S. Vallabhapurapu, M. Karin // Annu. Rev. Immunol. − 2009. − Vol. 27. − P. 693−733.

28. Jablons'kyj V.A. Doslidzhennja apoptozu klityn imunnoi' systemy u period laktacii' / V.A. Jablons'kyj, M.M. Zhelavs'kyj // Visnyk Bilocerkiv. derzh. agrar. un-tu: Zbirnyk naukovyh prac'. − Bila Cerkva, 2008. − Vyp. 57. − S. 166−169.