Harvey's Garden

Common mucosal immune system

3 min read

  • Core Concept: A specialized immune network that protects the vast mucosal surfaces (>300 m²) of the respiratory, gastrointestinal (GI), and urogenital tracts. It functions as an interconnected system, where stimulating one mucosal site can induce immunity at other distant mucosal surfaces. Its main goals are to protect against pathogens, prevent uptake of foreign antigens (like food), and maintain tolerance to commensal microbes.

  • Structure: Inductive and Effector Sites

    • Inductive Sites: Organized lymphoid tissues where immune responses are initiated.
      • MALT (Mucosa-Associated Lymphoid Tissue): Includes GALT (gut-), BALT (bronchus-), and NALT (nasal-associated lymphoid tissue).
      • Key Event: Antigen sampling occurs here. M cells (microfold cells), specialized epithelial cells overlying Peyer’s patches (a key part of GALT in the ileum), capture antigens from the lumen and transport them to underlying antigen-presenting cells (APCs) like dendritic cells.
    • Effector Sites: Areas where the immune response is carried out, such as the lamina propria of the GI tract, respiratory tract, and secretory glands (e.g., mammary, salivary).
      • Key Players: Contains antigen-specific effector cells, including T cells and IgA-producing plasma cells that migrated from inductive sites.

  • Key Players & Mechanism

    • M Cells: Sample antigens and pathogens from the lumen and deliver them to APCs in the MALT. This is a crucial first step for initiating mucosal immunity to both pathogens and commensal bacteria.
    • Dendritic Cells (DCs): After capturing antigen from M cells, DCs activate naive T cells.
    • T-Cells & B-Cell Class Switching: Activated T cells help B cells undergo isotype switching to produce IgA, the main antibody of the mucosal system. This process is driven by cytokines like TGF-β and IL-10.
    • Lymphocyte Homing: B and T cells activated in an inductive site (e.g., Peyer’s patch) enter circulation but are “imprinted” with specific homing receptors (e.g., integrin α4β7) that direct them to mucosal effector sites throughout the body.
    • Secretory IgA (sIgA): The hallmark of mucosal immunity.
      • Plasma cells in the lamina propria produce IgA as a dimer, connected by a J chain.
      • The dimeric IgA binds to the polymeric Ig receptor (pIgR) on the basolateral surface of epithelial cells.
      • It is then transcytosed across the cell and secreted into the lumen with a piece of the receptor called the secretory component, which protects it from proteases.
      • Function: sIgA performs “immune exclusion” by neutralizing toxins and binding pathogens, preventing their attachment to and invasion of epithelial surfaces.

  • Clinical Relevance & High-Yield Facts

    • Oral/Nasal Vaccines: The principle of the common mucosal immune system is the basis for oral and nasal vaccines (e.g., oral polio, rotavirus, intranasal influenza). Inducing an immune response in the GALT or NALT can provide protection at other mucosal sites, like the respiratory and urogenital tracts.
    • Oral Tolerance: The mucosal system is constantly exposed to food antigens and commensal bacteria. It must remain hyporesponsive to these harmless antigens, a state known as oral tolerance. Failure of this process can contribute to conditions like food allergies and inflammatory bowel disease (IBD).
    • Selective IgA Deficiency: The most common primary immunodeficiency. Patients often are asymptomatic but can present with recurrent sinopulmonary, GI (especially Giardia), and urinary tract infections, as well as an increased incidence of autoimmune diseases and atopy. IgM can partially compensate by being secreted across mucosal surfaces.

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