Immune Defense at Mucosal Surfaces

Marian R. Neutra; Jean-Pierre Kraehenbuhl

doi:10.1128/9781555816872.ch7

Chapter 7 : Immune Defense at Mucosal Surfaces

Authors: Marian R. Neutra¹, Jean-Pierre Kraehenbuhl²

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Affiliations: 1: Department of Pediatrics, Harvard Medical School, GI Cell Biology Laboratory, Children’s Hospital, Boston, MA 02115; 2: Health Sciences eTraining (HSeT) Foundation, CH 1066 Epalinges, Switzerland

Content Type: Monograph

Publication Year: 2011

Category: Immunology; Clinical Microbiology

Book DOI: 10.1128/9781555816872

Chapter DOI: 10.1128/9781555816872.ch7

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Abstract:

The mucosal surfaces of the body together represent a vast surface area separated from the outside world only by delicate epithelial barriers. Isolated lymphoid follicles (ILFs) are common at mucocutaneous transitions such as the anal-rectal junction and near the ducts of secretory glands that empty onto mucosal surfaces. Most mucosal cells involved in immune defense are distributed diffusely throughout the subepithelial connective tissue and are directly or indirectly responsible for immune effector functions. Induction of mucosal immune responses is complicated by the fact that antigens and microorganisms on mucosal surfaces are separated from cells of the mucosal immune system by epithelial barriers. Infection of local target cells and dissemination of virus to regional lymph nodes and other tissues occur rapidly after deposition of virus on mucosal surfaces. Five to seven days are required for initial induction in organized mucosal lymphoid tissues, directed migration, and terminal differentiation of cells in widespread mucosal sites. B cells from Peyer's patches and other organized mucosa-associated lymphoid tissues (MALT) complete their differentiation only after arrival in the lamina propria. Responses to mucosal vaccines are greatly amplified by local boosts, due to the abundant populations of memory T and B cells in mucosal tissues that allow for local amplification of effector responses on reexposure to an antigen. Local exposure to an antigen and/or adjuvant evokes cytokines and chemokines from epithelia, DCs, and other cells and up-regulates expression of addressins on local endothelia, increasing the numbers and enhancing the functions of mucosal effector cells.

Citation: Neutra M, Kraehenbuhl J. 2011. Immune Defense at Mucosal Surfaces, p 97-107. In Kaufmann S, Rouse B, Sacks D (ed), The Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555816872.ch7

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Immune Defense at Mucosal Surfaces

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FIGURE 1

Antigen sampling across epithelial barriers. Antigen sampling strategies at mucosal surfaces involve collaborations between epithelial and dendritic cells (DCs). The diverse mechanisms involved are adapted to the nature of the local epithelial barrier. At most mucosal surfaces where the epithelium is stratified, pseudostratified, or simple columnar, DCs are stationed immediately under the epithelium, migrate into the epithelial layer, and may extend dendrites into the lumen to capture antigens. These DCs generally travel to the nearest draining lymph node to present antigen to T cells. At sites of organized mucosal lymphoid tissues, specialized M cells in the lymphoid follicle-associated epithelium deliver antigens by transcytosis across the epithelial barrier, directly to intraepithelial and subepithelial DCs. These DCs then migrate to adjacent mucosal T-cell areas to present antigen. (Reproduced from Neutra & Kozlowski, 2006 ).

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FIGURE 1

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FIGURE 2

Mechanisms of immune protection at mucosal surfaces. Mucosal immune protection depends on the contributions of multiple cell types. Antigen-specific effector B and T cells that bear mucosal homing receptors recognize addressins on mucosal high endothelial venules and enter the mucosa. In response to epithelial and dendritic cell signals, the B cells terminally differentiate to become mucosal plasma cells. Most plasma cells produce dimeric IgA that is exported into secretions as S-IgA to intercept antigens and pathogens and prevent mucosal invasion. IgA, as well as IgG from local plasma cells or blood, can also neutralize pathogens within the mucosa. Local cytotoxic T cells and antibodies collaborate to kill infected cells. Pathogens are also captured by dendritic cells (DC) and macrophages (Mf), and carried to draining lymph nodes. (Reproduced from Neutra & Kozlowski, 2006 ).

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FIGURE 2

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