Immune Responses at Mucosal Surfaces


The mucosal surfaces of the gastrointestinal or respiratory tracts form vast interfaces of the host organism with the environment and constitute major entry ports for pathogens. Strategies to defend mucosal surfaces have developed early in evolution and in mammals engage the innate as well as the adaptive arms of the immune system. This article depicts aspects of anatomy, development and function of the mucosa‐associated lymphoid tissues (MALT) with a focus on the intestinal immune system. The intestinal epithelium is continuously exposed to large amounts of foreign antigens. Thus, one of the key challenges of the intestinal immune system is to tolerate harmless food derived antigen and to keep peace with the commensal microbiota populating the gut tube, while efficiently combating pathogens and their toxins.

Key Concepts:

  • Innate and adaptive immunity synergise to protect mucosal surfaces.

  • Adaptive immune responses at mucosal sites are initiated in Mucosa associated lymphoid tissues (MALT), such as the gut‐associated lymphoid tissue (GALT), the bronchus‐associated lymphoid tissue (BALT) and the nasal‐associated lymphoid tissue (NALT).

  • The intestinal immune system is continuously challenged by innocuous antigen derived from food and the commensal microbiota.

  • Interaction of the host with the commensal microbiota is required for the full maturation of the intestinal immune system whereas in turn the intestinal immune system restricts the growth and controls the composition of our commensal microbiota.

  • Secretory IgA (SIgA) is the predominant Immunoglobulin at mucosal surfaces.

  • Dysbiosis of the commensal microflora promotes diseases such as inflammatory bowel disease (IBD), diabetes and obesity and enhances the susceptibility to infection with enteropathogenic bacteria.

  • Failure to induce oral tolerance towards food derived antigens manifests in allergy or coeliac disease.

Keywords: mucosa; intestinal barrier; gut‐associated lymphoid tissue; immunoglobulin A; oral tolerance; microbiota; inflammatory bowel disease; Peyer's Patches; isolated lymphoid follicles

Figure 1.

Architecture of the gut epithelium. The mucosal epithelium lining the gut tube is heavily unfolded, thereby creating villi protruding into the gut lumen as well as a basal crypt zone. The majority of cells are absorptive enterocytes, however, mucus secreting Goblet cells and Paneth cells producing anti‐microbial compounds are also present in high numbers. Intraepithelial lymphocytes (IEL) are located at the basement membrane. Intestinal epithelial cells rapidly proliferate and derive from stem cells located at the crypt zone. Although newly generated enterocytes and Goblet cells migrate towards the villus tip, Paneth cells migrate downwards and settle close to the crypt zone.

Figure 2.

(SIgA). Plasma cells in the Lamina propria mucosae produce huge amounts of IgA. Two IgA monomers and a joining J chain assemble into the secretory SIgA dimer. The J chain binds to the poly Ig receptor (pIgR) expressed on the basolateral side of the epithelial cells, facilitating the transport of the SIgA molecule across the epithelium into the gut lumen. SIgA protects the epithelium by neutralising bacteria and their toxins.

Figure 3.

The Lamina propria mucosae contains a plethora of innate and adaptive immune cells. Intraepithelial lymphocytes (IEL) sit above the basement membrane. Gut resident macrophages are also in intimate contact to the epithelium and capable of extending dendrites into the gut lumen to sample luminal antigens. In contrast, classical dendritic cells and Lamina propria T cells locate to the core of the villus.

Figure 4.

Peyer's patches – architecture and vascularisation. Peyer′s patches (PP) are the most prominent structures of the gut‐associated lymphoid tissue (GALT) and the main inductive sites of adaptive intestinal immune responses. PP consist of several B cell follicles containing a germinal centre, fringed by an interfollicular T cell zone. Antigens delivered from the gut lumen via M cells in the overlying epithelium are readily taken up by dendritic cells (DC) located in the subepithelial dome. Upon antigen contact activated T cells migrate into the B cell follicle and help in the induction of antigen specific B cells. B cells undergo class switch recombination and start differentiating into IgA producing plasma cells. Via efferent lymphatics (blue lines) activated B and T cells migrate via the gut draining mesenteric lymph nodes (mLN) into the thoracic duct and finally home back into the intestinal Lamina propria via the blood (red lines).



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Further Reading

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Herbrand, Heike, and Pabst, Oliver(Jul 2012) Immune Responses at Mucosal Surfaces. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000901.pub2]