Features of Induction and Regulation of Immune Response in Conditions of the Intense Educational Process

Introduction: Combined with latent infection and elevated blood levels of low molecular weight chemical compounds, high academic workload can disrupt the balance of immune regulation in secondary school children.

Objective: To evaluate markers of immune regulation in secondary school children having excessive levels of academic pressure.

Materials and methods: The observation group consisted of 43 children attending a comprehensive school with in-depth study of subjects while the reference group comprised 93 children attending a typical comprehensive school. Blood concentrations of formaldehyde were measured using gas chromatography. CD3⁺, CD3⁺CD16⁺56⁺, CD19⁺, and CD8⁺ lymphocytes were determined using flow cytometry. Total IgE and IgG to the Epstein-Barr virus were tested using enzyme immunoassay, IgA, IgM, and IgG concentrations using the Manchini technique of radial immunodiffusion, and specific IgE antibodies to formaldehyde were detected using the allergosorbent test.

Results: Blood formaldehyde concentrations in the observation group were 11 and 3.1 times higher than the normal values and those measured in the reference group, respectively (p < 0.05). We found that the levels of CD3⁺ and CD19⁺ lymphocytes were increased in 20 %, and those of immunoglobulins A and G in 30 % of the adolescents from the observation group with a deficiency of up to 40 % in the number of NKT cells (p < 0.05). The production of IgG antibodies to the Epstein-Barr virus in this group was significantly increased by 50 % compared to the reference group. We established the relationship between heavy academic workload and the intensity of immune response to the viral burden (OR = 6.17; 95 % CI: 1.64-11.10) against the background of simultaneously developing reaginic tissue damage (total IgE, х² = 4.48; p < 0.05).

Conclusion: A distinctive feature of neurohormonal changes in puberty in the context of a highly intensive educational process is not only the excessive stress, but also insufficient protection, high susceptibility of the body to infection, which increases the risk of developing conditions associated with imbalanced induction and regulation of the immune response.

1. Turner L, Galante J, Vainre M, Stochl J, Dufour G, Jones PB. Immune dysregulation among students exposed to exam stress and its mitigation by mindfulness training: Findings from an exploratory randomised trial. Sci Rep. 2020;10(1):5812. doi: 10.1038/s41598-020-62274-7

2. Dolgikh OV, Dianova DG, Nikonoshina NA. Comparative evaluation of thyroid-stimulating hormone, cortisol and serotonin production as the neuroendocrine regulation markers of adaptation processes to the peculiarities of the educational process in male schoolchildren of different age groups. Pediatriya. Zhurnal im. G.N. Speranskogo. 2023;102(6):152-159. (In Russ.) doi: 10.24110/0031-403X-2023-102-6-152-159

3. Method Guidelines. School Medicine and Hygiene Series (in 5 parts). [Part 1: Prevention of Risks of Health Disorders in Schoolchildren.] Moscow: IVF RAO Publ.; 2023. (In Russ.)

4. Karkashadze GA, Namazova-Baranova LS, Zakharova IN, Makarova SG, Maslova OI. Syndrome of high academic loads in school-aged children and adolescents. Pediatricheskaya Farmakologiya. 2017;14(1):7-23. (In Russ.) doi: 10.15690/PF.V14I1.1697

5. Sakhvadze D, Jandieri G, Sakhvadze G, Saralidze B. Kelvin-Helmholtz effect during hydro-vacuum dispersion of metallurgical melts. In: Concepts for the Development of Society’s Scientific Potential: Proceedings of the 5th International Scientific and Practical Conference, Prague, Czech Republic, January 19–20, 2024. InterConf; 2024;(185):493-497. doi: 10.51582/interconf.19-20.01.2024.059

6. Setko NP, Bulycheva EV, Setko IA. The formation of stress and its manifestation in senior school pupils under various tensions in the educational process. Profilakticheskaya Meditsina. 2019;22(6-2):61-66. (In Russ.) doi: 10.17116/profmed20192206261

7. Dolgikh OV, Dianova DG. Features of hapten specific sensitization and immune status in different student age groups. Rossiyskiy Immunologicheskiy Zhurnal. 2020;23(2):209-216. (In Russ.) doi: 10.46235/1028-7221-266-FOH

8. Zhang N, Zuo Y, Jiang L, Peng Y, Huang X, Zuo L. Epstein-Barr virus and neurological diseases. Front Mol Biosci. 2022;8:816098. doi: 10.3389/fmolb.2021.816098

9. Zaitseva NV, Dolgikh OV, Dianova DG. Exposure to airborne nickel and phenol and features of the immune response mediated by E and G immunoglobulins. Health Risk Analysis. 2023;(2):160-168. doi: 10.21668/health.risk/2023.2.16.eng

10. Lvov ND, Dudukina EA. Key issues of current and diagnosis of Epstein-Barr virus infection. Infektsionnye Bolezni: Novosti. Mneniya. Obuchenie. 2013;(3(4)):24-32. (In Russ.)

11. Hedström AK, Huang J, Brenner N, et al. Smoking and Epstein-Barr virus infection in multiple sclerosis development. Sci Rep. 2020;10(1):10960. doi: 10.1038/s41598-020-67883-w

12. Lupia T, Milia MG, Atzori C, et al. Presence of Epstein-Barr virus DNA in cerebrospinal fluid is associated with greater HIV RNA and inflammation. AIDS. 2020;34(3):373-380. doi: 10.1097/QAD.0000000000002442

13. Lee GH, Kim J, Kim HW, Cho JW. Clinical significance of Epstein-Barr virus in the cerebrospinal fluid of immunocompetent patients. Clin Neurol Neurosurg. 2021;202:106507. doi: 10.1016/j.clineuro.2021.106507

14. Silva JM, Alves CEC, Pontes GS. Epstein-Barr virus: The mastermind of immune chaos. Front Immunol. 2024;15:1297994. doi: 10.3389/fimmu.2024.1297994

15. Lv JJ, Kong XM, Zhao Y, et al. Global, regional and national epidemiology of allergic disorders in children from 1990 to 2019: Findings from the Global Burden of Disease study 2019. BMJ Open. 2024;14(4):e080612. doi: 10.1136/bmjopen-2023-080612

16. Shtina IE, Valina SL, Ustinova OYu, Eisfeld DA, Zenina MT. Peculiarities of autonomous and thyroidal state in school children under different intensity of educational process. Gigiena i Sanitariya. 2019;98(2):183-188. (In Russ.) doi: 10.18821/0016-9900-2019-98-2-183-188

17. Titov LP, Kirilchik EYu, Kanashkova TA. [Features of the structure, development and functioning of the immune system of a child.] Meditsinskie Novosti. 2009;(5):7-16. (In Russ.)

18. Ainslie RJ, Simitsidellis I, Kirkwood PM, Gibson DA. RISING STARS: Androgens and immune cell function. J Endocrinol. 2024;261(3):e230398. doi: 10.1530/JOE-23-0398

19. Harding AT, Heaton NS. The impact of estrogens and their receptors on immunity and inflammation during infection. Cancers (Basel). 2022;14(4):909. doi: 10.3390/cancers14040909

20. Sorokin OV. Non-linear relationship between the activity of autonomic nervous system departments and the quantitative and functional characteristics of peripheral blood mononuclear cells from healthy adolescents. Byulleten’ Sibirskogo Otdeleniya Rossiyskoy Akademii Meditsinskikh Nauk. 2007;27(6):49-54. (In Russ.)

21. Akinfieva OV, Bubnova LN, Bessmeltsev SS. NKT cells: Characteristic features and functional significance in the immune response regulation. Onkogematologiya. 2010;5(4):39-47. (In Russ.)

22. Letafati A, Ardekani OS, Naderisemiromi M, et al. Uncovering dynamic mechanisms of natural killer cells in viral infections: Insights and implications. Virol J. 2024;21(1):18. doi: 10.1186/s12985-024-02287-0

23. Zhang Y, Huang C, Zhang H, et al. Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis. Front Pediatr. 2023;11:1060053. doi: 10.3389/fped.2023.1060053

24. Mestecky J, Julian BA, Raska M. IgA nephropathy: Pleiotropic impact of Epstein-Barr virus infection on immunopathogenesis and racial incidence of the disease. Front Immunol. 2023;14:1085922. doi: 10.3389/fimmu.2023.1085922

25. Liu KL, Hsu WL, Bu W, et al. Association between antibodies that bind Epstein-Barr virus (EBV) gp350 and gH/ gL and shedding of EBV in saliva from nasopharyngeal carcinoma multiplex family members in Taiwan. Open Forum Infect Dis. 2024;11(9):ofae464. doi: 10.1093/ofid/ofae464

26. Bhaduri-McIntosh S, Landry ML, Nikiforow S, Rotenberg M, El-Guindy A, Miller G. Serum IgA antibodies to Epstein-Barr virus (EBV) early lytic antigens are present in primary EBV infection. J Infect Dis. 2007;195(4):483-492. doi: 10.1086/510916