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Kids and the Immune System

Our immune system is made up of a number of cells, tissues and organs that throughout our life, protect us from invading pathogens, keeps us healthy and prevent repeated infection.(1) There are more than 1600 genes involved in innate and adaptive immune responses, these genes are of great importance for sustaining life in a hostile environment. At birth, the immune system is relatively immature and evolves throughout life when faced with different exposures. Therefore, our immune system is continually adapting from birth, through childhood, via young and mature adulthood (including pregnancy) and into old age.(2) 


In utero, the foetal environment demands that the immune system remains tolerant to maternal alloantigen’s. After birth, the sudden enormous exposure to environmental antigens calls for a rapid change to make distinct immune responses appropriate for early life.(2) 


During childhood the innate and adaptive immune system starts to mature, however, they are still at risk from many pathogenic viruses including bacteria, fungi and parasites. In developing countries, children still have a good chance of survival. Before there was adequate nutrition, hygiene and vaccinations, the mortality rate in infants and young children was high.(2) In the 1900, the UK infant mortality rate was 140 per 1000 children, this fell to 7 per 1000 by 2000.(3) This reduction in infant mortality rate was accounted by better prevention and control of infections via nutrition, hygiene and vaccinations.(2) 


The immune system gradually matures during infancy. Early immune protection as an infant is supplied by the mother. IgG antibodies are transferred to the infant from the mother transplacentally and in the milk the infant is breastfed. Once that fades away, young children become more vulnerable to infections however, by then they are better armed with the maturing innate and adaptive immune systems to overcome these infections.(2)     


Risks of infections are markedly reduced due to the vaccinations which stimulate protective immune responses. Nevertheless, children may still acquire vital, bacteria and parasitic infections that have to be fought off and controlled by immune responses, as well as promoting recovery. Therefore, over time the immune system will develop, and young adults suffer fewer infections. This accumulation of immunological memory is an evolving feature of the adaptive immune response.(2) This memory persists into old age(4) but then fades.(2)  


Gut bacteria and the immune system

Many of the bacteria that colonise the gut and other mucosa sites are essential for a healthy life, including digestion of food, acquisition of vital nutrients and the development of the immune system.(5) Approximately 20% of all lymphocytes (one of the main types of immune cells) reside in the gut.(6) Gut bacteria influence the development of several immune cells including Th17 cells(7), Treg cells(8) and memory T cells.(9-11) During childhood, T memory cells increase. Whilst some of these cells could have been stimulated by infection with specific pathogens and vaccines, a number may be primed by the microbiome - not only in the gut but in the respiratory tract and skin. Within the microbiome sequences, there are numerous perfect and near matches to known virus peptide epitopes (such as those from HIV-1)(9,10), these could easily be responsible for generating the memory T cells specific for pathogen epitopes the person has never encountered. These primed memory T cells are able to respond to subsequent infections through cross reactions.(2)


The link between the gut microbiome and the immune system has been demonstrated in germ-free (GF) mice models. GF mice have immunodeficiencies, these deficiencies can be corrected in several days by adding a single mouse, with a normal gut microbiota, to the cage of GF mouse.(12,13) This animal model supports the notion that the gut microbiome is responsible in part, of the maturation of the immune system.(2)   


What have the studies shown

Lactobacillus GG has been demonstrated to benefit the immune defence by contributing to the integrity of the intestinal epithelial barrier and stimulating the innate and adaptive immune response.(19)


Children across the world contract gastroenteritis and respiratory infections each year as their immune systems are continually being exposed to new pathogens. Several studies have shown that Lactobacillus GG can help prevent and reduce the duration and severity of gastrointestinal and respiratory infections in children. Lactobacillus GG can reduce the number of sick days children have throughout the year by supporting the children’s immune system throughout the year.(14-16)  


SOURCES

  1. Children's C. Kids and the Immune System - CHOC Children's [Internet]. CHOC Children's. 2019 [cited 29 August 2019]. Available from: https://www.choc.org/health-topics/kids-immune-system/ 
  2. Simon A, Hollander G, McMichael A. Evolution of the immune system in humans from infancy to old age. Proceedings of the Royal Society B: Biological Sciences. 2015;282(1821):20143085. 
  3. Hicks J, Allen G. 1999. A century of change: trends in UK statistics since 1900. Research paper 99/111. London, UK: House of Commons Library 
  4. Walker JM, Slifka MK. 2010. Longevity of T-cell memory following acute viral infection. Adv. Exp. Med. Biol. 684, 96–107. (10.1007/978-1-4419-6451-9_8) 
  5. Round JL, Mazmanian SK. 2009. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323. (10.1038/nri2515)Ganusov VV, De Boer RJ. 2007. 
  6. Ganusov VV, De Boer RJ. 2007. Do most lymphocytes in humans really reside in the gut? Trends Immunol. 28, 514–518. (10.1016/j.it.2007.08.009) 
  7.  Yang Y, et al. 2014. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature 510, 152–156. (10.1038/nature13279)
  8. Ivanov II, et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498. (10.1016/j.cell.2009.09.033) 
  9. Ivanov II, et al. 2009. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498. (10.1016/j.cell.2009.09.033) 
  10. Round JL, O'Connell RM, Mazmanian SK. 2010. Coordination of tolerogenic immune responses by the commensal microbiota. J. Autoimmun. 34, J220–J225. (10.1016/j.jaut.2009.11.007) 
  11. Su LF, Kidd BA, Han A, Kotzin JJ, Davis MM. 2013. Virus-specific CD4+ memory-phenotype T cells are abundant in unexposed adults. Immunity 38, 373–383. (10.1016/j.immuni.2012.10.021) 
  12. Macpherson AJ, Harris NL. 2004. Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 4, 478–485. (10.1038/nri1373) 
  13. Macpherson AJ, Hunziker L, McCoy K, Lamarre A. 2001. IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect. 3, 1021–1035. (10.1016/S1286-4579(01)01460-5) 
  14. Hojsak I, Snovak N, Abdovic S, Szajewska H, Misak Z, Kolacek S. Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: A randomized, double-blind, placebo-controlled trial. Clinical Nutrition. 2010;29(3):312-316. 
  15. Hatakka K, Savilahti E, Ponka A, et al. Effect of long term consumption of probiotic milk on infections in children attending day care centres: Double blind, randomised trial. Br Med J. 2001;322(7298):1327-1329. 
  16. Kumpu M, Kekkonen RA, Kautiainen H, et al. Milk containing probiotic lactobacillus rhamnosus GG and respiratory illness in children: A randomized, double-blind, placebo controlled trial. Eur J Clin Nutr. 2012;66(9):1020-1023.    


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