Functional Defense Mechanisms of the Nasal Respiratory Epithelium
The sinonasal mucosa is exposed to large quantities of particulates, antigens, and potential pathogens. To address these possible threats, the human sinonasal epithelium has developed a range of protective functions that effectively clear foreign material
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Functional Defense Mechanisms of the Nasal Respiratory Epithelium Robert C. Kern and Jennifer R. Decker
Keywords
Sinonasal epithelium • Mucociliary clearance • Innate immunity • Adaptive immunity • Immune barrier • Toll-like receptors • Rhinosinusitis
Core Messages
• Sinonasal epithelium provides both a physical and immunologic barrier to infection. • Intracellular junctions, mucus composition, and mucociliary clearance compose the mechanical barrier to pathogen invasion. • Innate and adaptive immune responses form the immunologic barrier. • Innate immunity provides a first-line defense to pathogens that circumvent the physical mucosal barrier by recognizing conserved pathogen-associated
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• R.C. Kern, MD Department of Otolaryngology – Head and Neck Surgery, Northwestern Memorial Hospital, 676 N. St. Clair, Suite 1325, Chicago, IL 60611, USA e-mail: [email protected] J.R. Decker, MD (*) Department of Otolaryngology – Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, 676 N. St. Clair, Suite 1325, Chicago, IL 60611, USA e-mail: [email protected]
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markers and activating a nonspecific inflammatory response. Adaptive immunity confers memory to particular pathogens, providing faster response to repeated infections. Sufficient stimulation of the innate immune system results in activation of and directs the type of subsequent adaptive immune response. Fungus and staphylococcal superantigens appear to be disease modifiers in chronic rhinosinusitis rather than the direct cause. Dysregulation in the adaptive immune response is the key factor in the pathogenesis of chronic rhinosinusitis. Understanding of host-specific sinonasal immune defenses will influence future therapies for CRS.
Overview
The sinonasal epithelium is an important biological point of interface with the external environment, clearing foreign material without significant collateral tissue inflammation. Multiple components
T.M. Önerci (ed.), Nasal Physiology and Pathophysiology of Nasal Disorders, DOI 10.1007/978-3-642-37250-6_3, © Springer-Verlag Berlin Heidelberg 2013
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R.C. Kern and J.R. Decker
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carry out this task, and while they are typically considered separately, they are functionally integrated. The first component is mucus produced by nasal glands and the epithelial goblet cells which traps particulate matter to be swept into the nasopharynx via mucociliary flow. The mucus also contains tonic levels of host defense molecules with antimicrobial properties, limiting microbial survival and proliferation. The next anatomic barrier is the epithelial layer with cells bound together via junctional complexes. Breaching these mechanical barriers brings exogenous agents in contact with receptors that activate the innate response. Secretion of host defense molecules is augmented, and chemokines and cytokines are secreted. The latter initiates inflammation and fosters the accumulation and activation of innate effector cells. If the stimulus is sufficiently strong, dendritic cells are activated to i
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