Infection: Immunological Barriers


Microorganisms can infect a host through various portals of entry. The host attempts to counter microbial infection and dissemination using many physical, chemical and immunological strategical barriers. Among them, epithelial cell layer comprises the outer barrier defence of the body being in constant contact with microorganisms and full‐time communication with adjacent immune cells. In this matter, host immune system needs to develop the ability to distinguish members of the microbiota from pathogens in order to provide protection against harmful invaders without inciting unnecessary immune responses. In this article we will discuss the mechanisms by which innate and adaptive immune system can sense the external environment and through the crosstalk with epithelial cells can coordinate effective immune response in skin and mucosal surfaces.

Key Concepts

  • The skin and the mucosal surfaces comprise the major portals of entrance for microbes' colonisation and infection.
  • From birth, the skin and mucosal surfaces are naturally populated by microorganisms (bacteria, fungi, viruses) called microbiota, which helps to educate the host immune system to distinguish infectious agents from harmless particles.
  • The immune system encompasses nonspecific immune responses nominated innate immunity and highly‐specialised deference mechanisms called adaptive immunity.
  • Lamina propria consists the connective tissue immediately adjacent to epithelial cell layer rich of cells including fibroblasts, innate and adaptive immune cells.
  • Along with the epithelium and the basement membrane, lamina propria constitutes the mucosa which is present in the several tubes of the body such as respiratory, genitourinary and gastrointestinal tract.
  • The epithelial cell layer acts as a physical barrier and releases chemical substances that play a key role in innate immune responses.
  • Mucosal surfaces harbour a great number of T cells which due to the presence of T‐cell receptor (TCR) can recognise specific microorganisms and coordinate a specific response against the invader.
  • Cytokines and chemokines are chemical substances that signal between cells to communicate and activate cells and perform the immune responses.

Keywords: skin; mucosa; epithelium cells; innate immunity; adaptive immunity; T cells; antibodies; cytokines and chemokines

Figure 1. Mechanisms of defence and regulation of intestinal homeostasis. AG, antigen; PRRs, pattern‐recognition receptors; AMP, antimicrobial peptides; SCFAs, short‐chain fatty acids.
Figure 2. Short‐chain fatty acids (SCFAs) are products of the activity of commensal bacteria present in our gut as of dietary fibre intake. These metabolites generate several benefits for intestinal homeostasis and the body as a whole, mainly to avoid the colonisation of pathogenic microorganisms (they induce the expansion of commensal bacteria), induction of peripheral tolerance (increase of Treg differentiation and secretion of IgA by B lymphocytes) and improvement of the mechanism of physical barrier (mucus production and increased epithelial integrity).


Abel AM, Yang C, Thakar MS and Malarkannan S (2018) Natural killer cells: development, maturation, and clinical utilization. Frontiers in Immunology 9: 1869.

Abraham SN and Miao Y (2015) The nature of immune responses to urinary tract infections. Nature Reviews. Immunology 15 (10): 655–663.

Axelrad JE, Olen O, Askling J, et al. (2019) Gastrointestinal infection increases odds of inflammatory bowel disease in a nationwide case‐control study. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association 17 (7): 1311–1322e1317.

Bamias G, Arseneau KO and Cominelli F (2014) Cytokines and mucosal immunity. Current Opinion in Gastroenterology 30 (6): 547–552.

Belkaid Y and Harrison OJ (2017) Homeostatic immunity and the microbiota. Immunity 46 (4): 562–576.

Buckley A and Turner JR (2018) Cell biology of tight junction barrier regulation and mucosal disease. Cold Spring Harbor Perspectives in Biology 10 (1): p. a029314.

Bush A and Ferkol T (2006) Movement: the emerging genetics of primary ciliary dyskinesia. American Journal of Respiratory and Critical Care Medicine 174 (2): 109–110.

Cossart P and Sansonetti PJ (2004) Bacterial invasion: the paradigms of enteroinvasive pathogens. Science 304 (5668): 242–248.

Dickson RP, Erb‐Downward JR and Huffnagle GB (2013) The role of the bacterial microbiome in lung disease. Expert Review of Respiratory Medicine 7 (3): 245–257.

Ear T and McDonald PP (2008) Cytokine generation, promoter activation, and oxidant‐independent NF‐kappaB activation in a transfectable human neutrophilic cellular model. BMC Immunology 9: 14.

Elgueta R, Benson MJ, de Vries VC, et al. (2009) Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunological Reviews 229 (1): 152–172.

Gewirtz AT, Navas TA, Lyons S, Godowski PJ and Madara JL (2001) Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. Journal of Immunology 167 (4): 1882–1885.

Greenwald RJ, Freeman GJ and Sharpe AH (2005) The B7 family revisited. Annual Review of Immunology 23: 515–548.

Hernandez‐Ruiz M and Zlotnik A (2017) Mucosal chemokines. Journal of Interferon & Cytokine Research 37 (2): 62–70.

Holt PG, Strickland DH, Wikstrom ME and Jahnsen FL (2008) Regulation of immunological homeostasis in the respiratory tract. Nature Reviews. Immunology 8 (2): 142–152.

Huppa JB and Davis MM (2013) The interdisciplinary science of T‐cell recognition. Advances in Immunology 119: 1–50.

Jenkins MK and Moon JJ (2012) The role of naive T cell precursor frequency and recruitment in dictating immune response magnitude. Journal of Immunology 188 (9): 4135–4140.

Jia L and Wu C (2014a) Differentiation, regulation and function of Th9 cells. Advances in Experimental Medicine and Biology 841: 181–207.

Jia L and Wu C (2014b) The biology and functions of Th22 cells. Advances in Experimental Medicine and Biology 841: 209–230.

Johansson ME, Larsson JM and Hansson GC (2011) The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host‐microbial interactions. Proceedings of the National Academy of Sciences of the United States of America 108 (Suppl 1): 4659–4665.

Josefowicz SZ, Lu LF and Rudensky AY (2012) Regulatory T cells: mechanisms of differentiation and function. Annual Review of Immunology 30: 531–564.

Kagnoff MF and Eckmann L (1997) Epithelial cells as sensors for microbial infection. The Journal of Clinical Investigation 100 (1): 6–10.

Laarman A, Milder F, van Strijp J and Rooijakkers S (2010) Complement inhibition by gram‐positive pathogens: molecular mechanisms and therapeutic implications. Journal of Molecular Medicine (Berlin, Germany) 88 (2): 115–120.

Li J, Chen S, Xiao X, et al. (2017) IL‐9 and Th9 cells in health and diseases‐From tolerance to immunopathology. Cytokine & Growth Factor Reviews 37: 47–55.

Liang J, Balachandra S, Ngo S and O'Brien LE (2017) Feedback regulation of steady‐state epithelial turnover and organ size. Nature 548 (7669): 588–591.

Macpherson AJ, McCoy KD, Johansen FE and Brandtzaeg P (2008) The immune geography of IgA induction and function. Mucosal Immunology 1 (1): 11–22.

Maynard CL and Weaver CT (2009) Intestinal effector T cells in health and disease. Immunity 31 (3): 389–400.

Mazmanian SK, Round JL and Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453 (7195): 620–625.

McColl KE (2005) When saliva meets acid: chemical warfare at the oesophagogastric junction. Gut 54 (1): 1–3.

Miyara M and Sakaguchi S (2007) Natural regulatory T cells: mechanisms of suppression. Trends in Molecular Medicine 13 (3): 108–116.

Mora JR and von Andrian UH (2008) Differentiation and homing of IgA‐secreting cells. Mucosal Immunology 1 (2): 96–109.

Mowat AM (2003) Anatomical basis of tolerance and immunity to intestinal antigens. Nature Reviews. Immunology 3 (4): 331–341.

Rescigno M, Urbano M, Valzasina B, et al. (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nature Immunology 2 (4): 361–367.

Roager HM and Licht TR (2018) Microbial tryptophan catabolites in health and disease. Nature Communications 9 (1): 3294.

Rochman Y, Spolski R and Leonard WJ (2009) New insights into the regulation of T cells by gamma(c) family cytokines. Nature Reviews. Immunology 9 (7): 480–490.

Sanmarco LM, Eberhardt N, Ponce NE, et al. (2017) New insights into the immunobiology of mononuclear phagocytic cells and their relevance to the pathogenesis of cardiovascular diseases. Frontiers in Immunology 8: 1921.

Sansonetti PJ, Kopecko DJ and Formal SB (1982) Involvement of a plasmid in the invasive ability of Shigella flexneri. Infection and Immunity 35 (3): 852–860.

Sansonetti PJ (2004) War and peace at mucosal surfaces. Nature Reviews. Immunology 4 (12): 953–964.

Suzuki H, Iijima K, Moriya A, et al. (2003) Conditions for acid catalysed luminal nitrosation are maximal at the gastric cardia. Gut 52 (8): 1095–1101.

Thorburn AN, Macia L and Mackay CR (2014) Diet, metabolites, and "western‐lifestyle" inflammatory diseases. Immunity 40 (6): 833–842.

Tsakovska I, Pajeva I, Al Sharif M, et al. (2017) Quantitative structure‐skin permeability relationships. Toxicology 387: 27–42.

Tsukerman P, Stern‐Ginossar N, Yamin R, et al. (2014) Expansion of CD16 positive and negative human NK cells in response to tumor stimulation. European Journal of Immunology 44 (5): 1517–1525.

Vignali DA, Collison LW and Workman CJ (2008) How regulatory T cells work. Nature Reviews. Immunology 8 (7): 523–532.

Whitsett JA and Alenghat T (2015) Respiratory epithelial cells orchestrate pulmonary innate immunity. Nature Immunology 16 (1): 27–35.

Wong R, Geyer S, Weninger W, Guimberteau JC and Wong JK (2016) The dynamic anatomy and patterning of skin. Experimental Dermatology 25 (2): 92–98.

Zhou JZ, Way SS and Chen K (2018) Immunology of uterine and vaginal mucosae: (Trends in Immunology 39, 302–314, 2018). Trends in Immunology 39 (4): 355.

Further Reading

Janeway CA, Travers P, Walport M and Shlomchik MJ (2004) Immunobiology: The Immune System in Health and Disease, 6th edn. Garland Publishing: London and New York.

Male D, Brostoff J, Roth DB and Roitt I (2006) Immunology, 7th edn. Mosby: London.

Mims C, Dockrell HM, Goering RV, et al. (2004) Medical Microbiology, 3rd edn. Mosby: London.

Whitton JL and Oldstone MBA (2001) The immune response to viruses. In: Fields BN, Knipe DM and Howley PM (eds) Fields' Virology, 4th edn, pp 285–320. Raven Press: New York.

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Cipelli, Marcella, Ignacio, Aline, and Saraiva Camara, Niels Olsen(Sep 2019) Infection: Immunological Barriers. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000940.pub3]