https://orcid.org/0000-0003-3211-7716
ABSTRACT
The questionnaire survey and the study of 1334 people living in the north of the European part of the Russian Federation, of which 970 are women and 364 are men, was conducted. 707 residents of the Arkhangelsk region and 627 residents of the Nenets Autonomous Okrug. The results of the questionnaire were analyzed depending on the appetite state (decreased -102 respondents, increased - 276, normal appetite – 1096, as well as dietary compliance – 124 and adherence to vegetarianism – 139). The most pronounced combined defects of immune protection (deficiency of phagocytic protection, deficiency of the content of natural killers and T-helpers) occur in people who have been eating mainly cereals and bread for a long time. Increased appetite in people over 55 years of age is associated with the frequency of chronic diseases of the gastrointestinal tract (35.7%) and increased tolerance to food antigens (52.3%).
Introduction
The work used the base of clinical examination of people living in the Arkhangelsk region and the Nenets Autonomous Okrug within expeditionary conditions. Examination of people and laboratory studies were carried out by the employees of the Laboratory of Regulatory Mechanisms of Immunity and the Laboratory of Ecological Immunology, the Institute of Environmental Physiology, N. Laverov Federal Center for Integrated Arctic Research of the Ural Branch of the Russian Academy of Sciences.
The nature of the diet and the food product quality influence the state of local and systemic immune responses. Firstly, throughout the entire evolution of vertebrates, the lymphatic tissue is associated with the alimentary canal and the gastrointestinal tract; secondly, the contact with antigens in the digestive system is most intense, aggravated by the influence of a huge concentration of its own microflora and the products of its vital activity. However, this issue has not actually been studied actually despite the obvious evidence.
There is enough information about the consumption effect of foodstuff contaminated with pesticides and heavy metal salts on human health. Data are accumulated about the effect of food processing on the content and degradation rate of various pollutants. There are the results of epidemiological studies on the relationship of general morbidity, the diseases of individual organs and systems, as well as mortality from the nature of nutrition associated with low social income and malnutrition.
Legislative measures are being taken to improve the nutrition of certain population groups in a number of countries, including pregnant women, breastfeeding women, the people who have problems with food chewing and swallowing, and the patients with food allergies. In some countries, functional nutrition is recognized as an alternative to drug therapy. At the same time, specific ingredients of beneficial action are added to health food products, the medicinal value of which is proven and well known. The list of such dietary supplements includes lactic acid bacteria, vitamins, oligosaccharides, eicosapentaenoic acid, dietary fibers, flavonoids, antioxidants, polyunsaturated fatty acids, biologically significant micro- and macroelements, essential amino acids, peptides, proteins, cholines, and glycosides.
The participation of lymphatic formations in the functional activity of the gastrointestinal tract is predetermined phylogenetically, since lymphatic tissue is associated with the alimentary canal throughout the evolution of vertebrates. T.L. Setles and A. Dabelow showed that a fat diet and fasting leads to the accumulation of fat in the sinuses and Billroth's strands of the mesenteric nodes. Lymphocytes are released into the intestinal lumen during digestion (Bunting & Huston, Citation1921). It is believed that lymphocytes can stimulate the secretion of digestive enzymes.
The associated intestinal lymphoid tissue is the largest organ of the lymphatic system, it contains more than 1012 cells and produces the largest number of cytokines and secretory IgA and IgE (Gangopadhyay et al., Citation1998; Minami et al., Citation2001; Mayer, Citation2003; Jessup et al., Citation2004).
The deep mucosa (lamina propria), which consists of connective tissue located between the muscle layer of the mucosa and the epithelium, is especially rich in immunocompetent cells. The lamina propria contains macrophages, mast cells, lymphocytes and plasma cells, as well as granulocytes, including eosinophils. Intraepithelial lymphocytes are located among the lamina propria epithelium. It is known that an adult body contains about 20 intraepithelial lymphocytes for every 100 adsorbing enterocytes. Most intraepithelial lymphocytes are identified as CD3 + mature T cells. Thus in 5 and 15% their populations have CD4 or CD8 on the membrane; the predominance of CD8 + is characteristic of the lamina propria lymphoid pool. Intraepithelial lymphocytes exhibit a cytotoxic effect, secrete lymphokines, regulate the mucous epithelium regeneration, and participate in tolerance provision to food antigens (Burmistrova, Citation1997).
The reactions of lymphoid tissue to the antigen appear much later than the reaction of preventive inflammation with the participation of neutrophils and monocytes in phylogenesis. During its development, there is some increase of acute phase protein secretion in association with various transport unita. And, although the functional meaning of such associations is not always and not completely clear, one thing is evident – all this is aimed at an abnormal deviation elimination concerning the concentration of one or another component of the extracellular environment (Clifton et al., Citation1985; Kumon et al., Citation1993; Banka et al., Citation1995; Yamada et al., Citation1996; Webb et al., Citation1997).
The positive effect of acute phase proteins consists not only in the transport system activity improvement, but also in the removed component neutralizing. This also applies to proteolysis inhibition, the increase of which occurs at the initial stages of the inflammatory reaction due to cathepsin volume increase in blood, secreted by neutrophils. Cathepsins are bound by acute phase proteins into inactive units and are removed from the bloodstream, including α2-macroglobulin and α1-acid glycoprotein, the concentration of which in plasma may even be reduced during this period (Larina & Becker, Citation2013).
The mediators of inflammation, including preventive one, increase the mucus content on epithelial cells; the thickness of the mucus layer increases several times during pathological processes. Mucus is not digested due to its resistance to the action of enzymes and protects the epithelium from the action of microflora enzymes, pancreatic juice and bile. The mucus carbohydrates are represented by mucin and glycoproteins, the protein component of mucus includes albumin, immunoglobulins, mainly secretory IgA and IgE, as well as α1 – antitrypsin, lysozyme, lactoferrin and epithelial growth factor. The composition of mucus indicates that it performs sorption, transport, antiseptic, enzymatic and regenerative function (Palсev & Volozhanina, Citation2007; Shtaborov, Citation2009).
The participation of cytokines in the initiation of preventive inflammation and the development of local inflammatory processes has been proved. The most common defects of the immune defense during inflammatory processes, at malignant neoplasms of the gastrointestinal tract and food allergies has determined. There is information about the blood content increase and the spectrum of autoantibodies expansion during the chronic course of gastroduodenitis, pancreatitis and colitis.
But the issues of nutrition nature influence on the general state of the immune background, local reactions of immune defense, the relationship of microflora and the immune background state, as well as the issues of tolerance to food antigens have not been resolved, and this area of knowledge only accumulates facts.
The purpose of research is to study the immune status characteristics of Northern individuals with different nutrition types.
Materials and methods
The questionnaire survey and the study of 1334 people living in the north of the European part of the Russian Federation, including 1100 born in the North, of which 970 are women and 364 are men, was conducted. (707 residents of the Arkhangelsk region and 627 residents of the Nenets Autonomous Okrug.) All studies were conducted with the consent of volunteers and in accordance with the requirements of the Helsinki Declaration of the World Medical Association on Ethical Principles of Medical Research. The research was approved by the positive conclusion of the Commission on Biomedical Ethics at the Institute of Environmental Physiology of the Ural Branch of the Russian Academy of Sciences on December 17, 2010. The examination and questioning of people was carried out during the absence of exacerbation of chronic diseases. The presence of chronic diseases was found out from the anamnesis, but they were mainly guided by the information in the medical records. Voluntary questionnaires and population surveys were carried out during the period 2010-2020. The dietary habits of the subjects were determined using an adapted questionnaire by food consumption frequency analysis, and evaluation of the actual nutrition and nutritional status of adults. Based on the analysis of the questionnaire results, the main groups for the subsequent work on the survey results included the persons of working age with a family and secondary vocational education (465 women and 235 men). Regardless of place of residence, family and social status, the results of the questionnaire were analyzed depending on the appetite state (decreased – 102 respondents, increased – 276, normal appetite – 1096, as well as dietary compliance – 124 and adherence to vegetarianism – 139). The group of vegetarians consisted of 139 people, including 54 rural residents and 85 urban residents.
The complex of immunological research included the study of a hemogram of venous blood taken on an empty stomach in the morning, (number of platelets, erythrocytes, leukocytes, total hemoglobin in the blood, leukogram with 5-component differentiation of leukocytes) on an automatic hematological analyzer, phagocytic activity of neutrophilic leukocytes of peripheral blood in blood smears stained by the Romanovsky-Gimse method. Phagocytic activity of blood neutrophils was determined by the absorption of latex particles with the diameter of 0.9 μm.
A lymphocyte suspension was obtained in a density gradient of ficoll-urografin (the density made 1.077 g/ml). The content of lymphocyte phenotypes was studied by flow cytometry using Beckman Coulter Epics XL apparatus with “Immunotech a Beckman Coulter Company” reagents and in an indirect immunoperoxidase reaction using monoclonal antibodies (“Sorbent”, Moscow). The results of the study were processed statistically with the determination of the mean values and presented as the arithmetic mean ± the mean error (M ± m), the significance of the differences was assessed using the Student's t-test.
Results and discussion
The results of the questionnaire survey of 1334 people gave us the opportunity to identify rather homogeneous groups of people for further analysis of the diet peculiarities. Besides, the screening questionnaire made it possible to assess the registration frequency of the persons among the rural and urban population of vegetarians, who observe and who do not observe diets, and the people with different appetites ().
Table 1. Results of the primary survey of practically healthy people, % (absolute).
Among the rural population, 4.7% of rural residents and 15.3% of those living in rural settlements observe the diet (in the sense of trying to consume dietary food); among the population of the Nenets Autonomous Okrug 5.3% of the adult population observe the diet, in the Arkhangelsk region 13.5% of residents try to do this. Among urban dwellers, the opinion about appetite increase is registered more often (21 and 6.8%, respectively); according to the level of opinion about the appetite decrease, a sharp increase of its frequency is recorded among the residents of cities in the Arkhangelsk region (19.6%). The majority of respondents (61.8 - 70.2%) note a normal appetite without significant differences depending on the place of residence; the exception is the opinion of 43.9% of urban residents of the Arkhangelsk region, who note the appetite decrease or increase. Increased appetite was observed in 39.4% of cases within the age group of 51–60 year olds, the presence of chronic diseases of the gastrointestinal tract was more often recorded (35.7%) in the same age group.
Table 2. The results of the questionnaire on the composition of the average daily diet of the rural population.
As can be seen from the presented data, the diet of the rural population of the Nenets Autonomous Okrug is slightly less (p < 0.05-0.01) dairy products, vegetables and fruits ().
There were no significant differences in the diets of the urban population of the Nenets Autonomous Okrug and the Arkhangelsk Region; the villagers consume less dairy products and more products indicated in the questionnaire as the “fruits and berries” ().
Table 3. Results of the questionnaire on the composition of the average daily diet of the urban population.
The analysis of individual questionnaires gave us the basis to identify the groups of people who mainly consume certain groups of products: meat, dairy, fish and grain. The term “preferential” use of products was applied in the cases when a product is included in the diet 4 or more times a week.
A rather monotonous diet with the predominant use of the same product was noted among 582 people out of the total number of respondents (1334) ().
Figure 1. Groups of people who systematically consume mostly monotonous food. (n = 582).
The state of the immune status of the examined people, depending on the place of residence, differs in the frequency of registration of neutropenia, the deficiency of phagocytic activity of neutrophils, the severity level of monocytosis and eosinophilia, which are slightly higher among the residents of the Nenets Autonomous Okrug (p < 0.05–0.01). Among the inhabitants of the Arctic zone, the total content of lymphocytes is higher (p < 0.01-0.001), lymphocytosis is more often recorded (p < 0.001). However, the content of mature T cells among circulating lymphocytes is slightly lower (p < 0.01), and all cases of lymphocytosis are explained by immature cell concentration increase morphologically related to small lymphocytes (up to 8 μm in diameter) with almost indistinguishable cytoplasm (Gavrilov et al., Citation1976; ICRP, Citation1975) ().
Table 4. Hematological and immunological parameters in urban and rural residents of the Nenets Autonomous Okrug and the Arkhangelsk region (M ± m).
No significant differences were found in the immune background of rural and urban residents of the Nenets Autonomous Okrug and the Arkhangelsk Region; among the inhabitants of the Nenets Autonomous Okrug the content of eosinophils and lymphocytes is higher, and accordingly eosinophilia and lymphocytosis are detected more often (p < 0.01-0.001). The deficit of natural killer Statistical is noticeably more often recorded (p < 0.001) among urban residents, and the average content of natural killers is lower urban residents (p < 0.01).
Among the persons with decreased appetite, the content of circulating neutrophils was lower, the deficiency of active phagocytes, a low content of monocytes and monocytosis, as well as eosinophilia were recorded more often. Besides, the persons with decreased appetite complaints have lower content of natural killers and their deficiency is 4 times more likely. The concentration of mature T-lymphocytes in the blood and the record frequency of their deficiency are significantly lower among these people, which is manifested by a low content of activated T-cells circulating in the blood with a receptor for IL-2 (CD25+) and transferrin (CD71+); a higher level of T-helper record for this category of people, the average content of these cells is lower. And activated T-lymphocytes of the CD25 + phenotypes with the IL-2 receptor and with the transferrin receptor (CD71+) are also reduced. Only one feature was established among the persons with increased appetite – the lowest proportion of phagocytic defense deficiency, which was 2.5 times lower than among the people with normal appetite and, in fact, 4 times lower than among people with decreased appetite. As for vegetarians, the same features of immunocompetent cell content in the blood were observed as among the people with decreased appetite: the level of circulating mature cell deficiency, their activated phenotypes and T-helpers were higher. So, the state of decreased appetite is associated with the reduction of mature T-lymphocytes and their activated phenotypes in the peripheral blood with the record frequency of these signs up to 55-53% (28% in the group of people with normal appetite) ().
Table 5. Hematological and immunological parameters in the inhabitants of the North, depending on the level of appetite (M ± m).
Some differences in the immune status parameters were obtained during the analysis of immunograms, depending on the predominant use of food products ().
Table 6. Hematological and immunological parameters of venous blood depending on the predominant use of food (M ± m).
Among the people whose diet is dominated by meat or fish, the frequency of neutropenia record, the deficiency of active phagocytes, natural killer cells and mature T cells are lower. Accordingly, these people have slightly higher blood levels of cytotoxic CD8+ T-cells and T-helpers CD4+ (p < 0.001). Among the people who prefer dairy products, these distinctive features are less pronounced as compared to those with a predominant grain diet: neutropenia, deficits during phagocytic protection and the content of mature T cells are recorded less often. The signs of reserve capacity reduction in immune homeostasis regulation with a deficit of circulating T-lymphocytes are observed among the people who mainly eat vegetables (35.78%). But the most pronounced defects of the immune defense occur among the individuals who eat cereals and bread during a relatively long period. With a lack of products of animal and fish origin, the most often detected deficiency of phagocytic defense is the deficiency of natural killer cells and T-helpers, i.e. actually uncompensated T-helper immunodeficiency.
Conclusion
Information about the effect of nutrition on immunological reactivity is at the stage of accumulation of facts. It is known that with general malnutrition, migration activity and the content of mature T cells and ligand molecules, regulatory cytokines are lower, but the concentration of pro-inflammatory cytokines and the level of lymphocyte apoptosis are higher (Badr et al., Citation2011; Miron & Cristea, Citation2012; Losada-Barragán et al., Citation2017). Depletion of the cell membrane by lipoproteins causes inhibition of lymphocyte proliferation (Chazov & Smirnov, Citation1989; Karpov et al., Citation1990). The idea that malnutrition is observed only periodically and in very limited segments of the population is far from the truth. Alimentary insufficiency is no exception and is a serious problem accompanying poverty and other types of social disharmony in all countries. But diets enriched with fat increase sensitivity to infections, reduce the activity of innate immunity reactions, complement production and phagocytic activity, as well as suppressing the synthesis of immunoglobulins (Dotsenko et al., Citation2001).
The problem of modern civilization is a fairly large number of overweight people, found in almost a third of the population, and associated with dyslipidemia, hypertension and coronary heart disease. Overweight people are characterized by significantly higher mortality from diseases attributed to the group of the most common causes of sudden death. Despite the fact that obese people have to do much more work to carry their excess weight, they spend much less energy to perform normal physiological functions because the mechanisms of energy tension in obesity function much more efficiently. In adipose tissue, the conversion of glucose to α-glycerophosphate is combined with the inhibition of its oxidation by mitochondrial dehydrogenase. as a result, the proportion of glucose used for the formation of glycerol increases, and the esterification of fatty acids begins to prevail over the release of free fatty acids from cells.
With obesity, the insulin content in the blood increases, which not only increases the uptake of glucose by cells, but also stimulates lipogenesis by inducing the synthesis of acetyl-CoA-carboxylase and fatty acid synthetase. An increase in insulin content, in addition, suppresses the synthesis of hormone-sensitive lipase.
In the North, in conditions of heat shortage, in order to ensure a prolonged 10-15% increased energy demand, it is necessary to increase the content of animal fats in food. At the same time, there is now a tendency to reduce the consumption of fish, meat, milk and dairy products. Among people whose diet is dominated by meat or fish foods, the blood content of cytotoxic T cells and T helper cells is higher and the frequency of occurrence of environmentally dependent neutropenia, deficiency of active phagocytes, natural killers and mature T cells is lower.
The state of reduced appetite and the vegetarian type of diet are associated with an increase in the frequency of registration of deficiency of active phagocytes, a reduction in the content of mature T-lymphocytes and activated T-cells with a receptor for IL-2 and transferrin with a frequency of registration of these signs up to 55-53% (at 28% in the group of people with normal appetite). Transferrin is known to activate T lymphocytes, stimulate IL-2 secretion, DNA synthesis and proliferation (Los et al., Citation1995). The transferrin receptor is expressed on a wide variety of cells, the expression of its gene increases during proliferation and is regulated by the content of intracellular iron (Shipp & Look, Citation1993; Harris et al., Citation1994). There is evidence of a positive relationship between the level of transferrin content and the prognostic nutritional index of Onoder (Gimou et al., Citation2008).
Due to the prevailing socio-economic conditions, not all people living in the North can have a balanced diet (Khmelevsky & Podberezkina, Citation1990; Akopyan et al., Citation1999; Martinchik et al., Citation1998; Chiglintsev & Privalova, Citation2017). According to the results of a survey of adults who made up the main group for subsequent analysis, it was found that with very significant differences and large ranges of fluctuations in the specific gravity of the product used and its absolute content, there is a noticeable deficiency in the diet of fats.
The most pronounced combined defects of immune protection (deficiency of phagocytic protection, deficiency of the content of natural killers and T-helpers) occur in people who have been eating mainly cereals and bread for a long time. The opinion about the need to increase fats in the diet of Northerners is relevant (Panin, Citation1980; Krivoshapkin et al., Citation2015; Mikusheva, Citation2017; Istomin et al., Citation2018) to ensure energy-consuming immune reactions.
Increased appetite in people over 55 years of age is associated with the frequency of chronic diseases of the gastrointestinal tract (35.7%) and increased tolerance to food antigens (52.3%). An increase in the frequency of gastrointestinal diseases with age is known (Dobrodeeva & Sergeeva, Citation2014; Bichkaeva et al., Citation2021; Krivonogova, Citation2011). The increase in appetite under these circumstances can be explained by the need for additional protection of irritated mucous membranes, a decrease in the activity of secretion of digestive enzymes (Palсev & Volozhanina, Citation2007; Makarov, Citation2008; Dobrodeeva et al., Citation2018).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
References
- Akopyan, A. S., Kharchenko, V. I., & Mishiev, V. G. (1999). State of health and mortality of children and adults of reproductive age in modern russia 162. Republican Center of Human Reproduction.
- Badr, G., Sayed, D., Alhazza, I. M., Elsayh, K. I., Ahmed, E. A., & Alwasel, S. H. (2011). T lymphocytes from malnourished infants are sport-lived and dysfunctional cells. Immunology, 216(3), 309–315. https://doi.org/10.1016/j.imbio.2010.07.007
- Banka, C. L., Yuan, Т, de Beer, M. C., Kindy, M., Curtiss, L. K., & de Beer, F. C. (1995). Serum amyloid A (SAA): influence on HDL-mediated cellular cholesterol efflux. Journal of Lipid Research, 36(5), 1058–1065. https://doi.org/10.1016/S0022-2275(20)39863-1
- Bichkaeva, F. A., Kovalenko, T. B., Bichkaev, A. A., Shengof, B. A., & Tretyakova, T. V. (2021). Age-related changes in glucose, proinsulin and insulin levels in the blood of residents of the Russian Arctic. Human Ecology, 4(4), 30–39. https://doi.org/10.33396/1728-0869-2021-4-30-39.
- Bunting, C. H., & Huston, J. (1921). Fate of the lymphocyte. Journal of Experimental Medicine, 33(5), 593–600. https://doi.org/10.1084/jem.33.5.593
- Burmistrova, A. L. (1997). Immune homeostasis and microsymbiocenosis. Metamorphoses and ways of development of inflammatory bowel diseases 215. Chelyabinsk House of Printing.
- Chazov, E. I., & Smirnov, V. N. (1989). Human atherosclerosis: collection of scientific papers / USSR Academy of Sciences, Section Chemical-technol. and Biol. sciences, Academy of Medical Sciences of the USSR, All-Union. cardiol. scientific Center; ed.: . – Moscow: Nauka, - 311 p.
- Chiglintsev, V. M., & Privalova, A. G. (2017). Physiology of micronutrient status among representatives of the indigenous nationality of Ugra. Progress of Modern Science, 5(1), 7–14.
- Clifton, P. M., Mackinnon, A. M., & Barter, P. J. (1985). Effect of serum amyloid A protein (SAA) on composition size and density of high density lipoprotein in subjects with myocardial infarction. Journal of Lipid Research, 26(12), 1389–1398. https://doi.org/10.1016/S0022-2275(20)34244-9
- Dobrodeeva, L. K., & Sergeeva, E. V.. (2014). The state of the immune system in the aging process. (pp. 136). Ural Branch of the Russian Academy of Sciences. ISBN 9785769123757.
- Dobrodeeva, L. K., Shtaborov, V. A., Menshikova, E. A., & Dobrodeev, K. G.. (2018). Activity of immune reactions depending on the nature of nutrition and the state of the gastrointestinal tract (pp. 172). Ural Branch of the Russian Academy of Sciences. ISBN 978-5-7691-2505-8.
- Dotsenko, E. A., Yupatov, G. I., & Chirkin, A. A. (2001). Cholesterol and low-density lipoproteins as endogenous immunomodulators. Immunopathology, Allergology, Infectology, 1(3), 6–15.
- Gangopadhyay, A., Lazure, D. A., & Thomas, P. (1998). Adhesion of colorectal carcinoma cells to the endothelium is mediated by cytokines from CEA stimulated kupffer cells. Clinical & Experimental Metastasis, 16(8), 703–712. https://doi.org/10.1023/A:1006576627429
- Gavrilov, O. K., Chertkov, I. L., & Kozinetz, G. I.. (1976). N. A. Fedorov (Ed.), Normal hematopoiesis and its regulation (pp. 543). Medicine.
- Gimou, M. M., Charrondiere, U. R., Leblanc, J. C., & Pouillot, R. (2008). Dietary exposure to pesticide residues in yaoundé: The Cameroonian total diet study. Food Additives & Contaminants: Part A, 25(4), 458–471. https://doi.org/10.1080/02652030701567475
- Harris, N. L., Jaffe, E. S., Stein, H., Banks, P. M., Chan, J. K., Cleary, M. L., Delsol, G., De Wolf Peeters, C., Falini, B., & Gatter, K. C. (1994). A revised European-American classification of lymphoid neoplasms: A proposal from the International lymphoma study group [see comments]. Blood, 84(5), 1361–1392 . https://doi.org/10.1182/blood.V84.5.1361.1361
- ICRP. (1975). Report of the task group on Reference Man. ICRP publication 23. Pergamon Press. https://doi.org/10.1016/S0074-2740(75)80015-8
- Istomin, A. V., Fedina, I., Shkurikhina, S. V., & Kutakova, N. S. (2018). Nutrition and the north: Hygienic problems of the Arctic zone of Russia (the review of the literature). Hygiene and Sanitation, 97(6), 557–563. https://doi.org/10.18821/0016-9900-2018-97-6-557-563
- Jessup, J. M., Anguinge, L., Lin, S., Samara, R., Aufman, K., Battle, P., Frantz, M., Edmiston, K. H., & Thomas, P. (2004). Carcinoembryonic antigen induction of IL-10 and IL-6 inhibits hepatic ischemic/reperfusion injury to colorectal carcinoma cells. International Journal of Cancer, 111(3), 332–337. https://doi.org/10.1002/ijc.20264
- Karpov, R. S., Kanskaya, N. V., & Osipov, S. G. (1990). The role of the immune system in the development of hyperlipoproteidemia. In R. S. Karpov (Ed.), Research Institute of cardiology of the Tomsk scientific Center of the USSR Academy of Medical sciences (pp. 164). Tomsk University Publishing House. ISBN 5-7511-0102-2.
- Khmelevsky, Y. V., & Podberezkina, N. B. (1990). Vitamins and human age p. 168. Naukova dumka.
- Krivonogova, O. V. (2011). The influence of cancer-embryonic antigen on the state of immune reactions in practically healthy people: specialty 03.03.01: dissertation for the degree of Candidate of Biological Sciences / Krivonogova Olga Vyacheslavovna. - Arkhangelsk, 109 p.
- Krivoshapkin, V. G., Sivtseva, A. I., & Sivtseva, E. N. (2015). Actual nutrition of indigenous small-numbered peoples of the North (on the example of the evenks of the oleneksky district of the Republic of Sakha (Yakutia)). Yakut Medical Journal, 3(51), 58–61.
- Kumon, Y., Suehiro, Т., Ikeda, Y., Yoshida, K., Hashimoto, K., & Ohno, F. (1993). Influence of serum amyloid A protein on high density lipoprotein in chronic inflammatory disease. Clinical Biochemistry, 26(6), 505–511. https://doi.org/10.1016/0009-9120(93)80016-N
- Larina, O. N., & Becker, A. M. (2013). Decrease in the level of positive acute phase proteins in blood plasma during the initiation of acute phase response mechanisms when modeling the effects of microgravity. XXII Congress of the I.P.Pavlov Physiological Society. Moscow-Volgograd. - p. 291.
- Los, M., Schenk, H., Hexel, K., Baeuerle, P. A., Droge, W., & Schulze-Osthoff, K. (1995). IL-2 gene expression and NF-kB activation through CD28 requires reactive oxygen production by 5-lipoxygenase. The EMBO Journal, 14(15), 3731–3740. https://doi.org/10.1002/j.1460-2075.1995.tb00043.x
- Losada-Barragán, M., Umaña-Pérez, A, Cuervo-Escobar, S., Berbert, L. R., Porrozzi, R., Morgado, F. N., Mendes-da-Cruz, D. A., Savino, W., Sánchez-Gómez, M., & Cuervo, P. (2017). Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with leishmania infantum. Scientific Reports, 7(45991), 1–15. https://doi.org/10.1038/srep45991
- Makarov, A. I. (2008). Immune reactions in acute inflammatory diseases of the abdominal cavity organs in surgical patients: specialty 14.00.2714.00.36: abstract of the dissertation for the degree of Doctor of Medical Sciences / Makarov Alexander Ivanovich. - Arkhangelsk, 41 p.
- Martinchik, A. N., Baturin, A. K., & Zohuri, N. (1998). Actual consumption of energy and basic nutrients by children and adolescents in Russia in the mid-90s. Disease Prevention and Health Promotion, (3), 15–21.
- Mayer, L. (2003). Mucosal immunity. Pediatrics, 111(Supplement_3), 1595–1600. https://doi.org/10.1542/peds.111.S3.1595
- Mikusheva, T. Y. (2017). Food consumption and human health in the North (based on the materials of the Komi Republic). Bulletin of the Komi Republican Academy of Public Service and Management. Theory and practice of management. No. 18 (23). pp. 143-148.
- Minami, S., Furui, J., & Kanematsu, T. (2001). Role of carcinoembryonic antigen in the progression of colon cancer cells that express carbohydrate antigen. Cancer Research, 61(6), 2732–2735.
- Miron, N., & Cristea, V. (2012). Enterocytes: Active cells in tolerance to food and microbial antigens in the gut. Clinical and Experimental Immunology, 167(3), 405–412. https://doi.org/10.1111/j.1365-2249.2011.04523.x
- Palсev, A. I., & Volozhanina, A. G. (2007). Features of adaptive-compensatory processes in elderly patients with gastroesophageal reflux disease. [text]. Siberian Council. Medical and Pharmaceutical Journal, 7(62), 223–224.
- Panin, L. E. (1980). Features of energy metabolism. In V. P. Kaznacheev (Ed.), Mechanisms of human adaptation in conditions of high latitudes (pp. 87–97). Leningrad.
- Shipp, M. A., & Look, A. T. (1993). Hematopoietic differentiation antigens that are membrane associated enzymes: Cutting is the key!. Blood, 82(4), 1052–1070. https://doi.org/10.1182/blood.V82.4.1052.1052
- Shtaborov, V. A. (2009). The ratio of general and local reactions of immune protection in the inhabitants of the North: specialty 03.00.13: dissertation for the degree of Candidate of Biological Sciences / Vyacheslav Anatolyevich Shtaborov. - Arkhangelsk, p. 130.
- Webb, N. R., de Beer, M. C., van der Westhuyzen, D. R., Kindy, M. S., Banka, C. L., Tsukamoto, K., Rader, D. L., & de Beer, F. C. (1997). Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice. Journal of Lipid Research, 38(8), 1583–1590. https://doi.org/10.1016/S0022-2275(20)37176-5
- Yamada, Т., Miida, Т., Itoh, Y., Kawai, T., & Benson, M. D. (1996). Characterization of serum amyloid A4 as a plasma apolipoprotein. Clinica Chimica Acta, 251(1), 105–112. https://doi.org/10.1016/0009-8981(96)06296-1