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      Antiviral B cell and T cell immunity in the lungs

      review-article
      ,
      Nature Immunology
      Nature Publishing Group US
      Mucosal immunology, Adaptive immunity, Antimicrobial responses

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          Abstract

          The lungs are the main site of entry for most viral pathogens. In this Focus Review, Chiu and Openshaw discuss adaptive immune responses to lung-tropic viruses and implications for vaccine development.

          Abstract

          Respiratory viruses are frequent causes of repeated common colds, bronchitis and pneumonia, which often occur unpredictably as epidemics and pandemics. Despite those decimating effects on health and decades of intensive research, treatments remain largely supportive. The only commonly available vaccines are against influenza virus, and even these need improvement. The lung shares some features with other mucosal sites, but preservation of its especially delicate anatomical structures necessitates a fine balance of pro- and anti-inflammatory responses; well-timed, appropriately placed and tightly regulated T cell and B cell responses are essential for protection from infection and limitation of symptoms, whereas poorly regulated inflammation contributes to tissue damage and disease. Recent advances in understanding adaptive immunity should facilitate vaccine development and reduce the global effect of respiratory viruses.

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          Most cited references91

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          Understanding immunosenescence to improve responses to vaccines.

          In the older adult, the benefits of vaccination to prevent infectious disease are limited, mainly because of the adaptive immune system's inability to generate protective immunity. The age-dependent decrease in immunological competence, often referred to as 'immunosenescence', results from the progressive deterioration of innate and adaptive immune responses. Most insights into mechanisms of immunological aging have been derived from studies of mouse models. In this Review, we explore how well such models are applicable to understanding the aging process throughout the 80-100 years of human life and discuss recent advances in identifying and characterizing the mechanisms that underlie age-associated defective adaptive immunity in humans.
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            Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection.

            We identify in this article a new class of lung tissue-resident memory CD4 T cells that exhibit tissue tropism and retention independent of Ag or inflammation. Tissue-resident memory CD4 T cells in the lung did not circulate or emigrate from the lung in parabiosis experiments, were protected from in vivo Ab labeling, and expressed elevated levels of CD69 and CD11a compared with those of circulating memory populations. Importantly, influenza-specific lung-resident memory CD4 T cells served as in situ protectors to respiratory viral challenge, mediating enhanced viral clearance and survival to lethal influenza infection. By contrast, memory CD4 T cells isolated from spleen recirculated among multiple tissues without retention and failed to mediate protection to influenza infection, despite their ability to expand and migrate to the lung. Our results reveal tissue compartmentalization as a major determining factor for immune-mediated protection in a key mucosal site, important for targeting local protective responses in vaccines and immunotherapies.
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              The airway epithelium: soldier in the fight against respiratory viruses.

              The airway epithelium acts as a frontline defense against respiratory viruses, not only as a physical barrier and through the mucociliary apparatus but also through its immunological functions. It initiates multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. The interaction between respiratory viruses and airway epithelial cells results in production of antiviral substances, including type I and III interferons, lactoferrin, β-defensins, and nitric oxide, and also in production of cytokines and chemokines, which recruit inflammatory cells and influence adaptive immunity. These defense mechanisms usually result in rapid virus clearance. However, respiratory viruses elaborate strategies to evade antiviral mechanisms and immune responses. They may disrupt epithelial integrity through cytotoxic effects, increasing paracellular permeability and damaging epithelial repair mechanisms. In addition, they can interfere with immune responses by blocking interferon pathways and by subverting protective inflammatory responses toward detrimental ones. Finally, by inducing overt mucus secretion and mucostasis and by paving the way for bacterial infections, they favor lung damage and further impair host antiviral mechanisms.
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                Author and article information

                Contributors
                c.chiu@imperial.ac.uk
                p.openshaw@imperial.ac.uk
                Journal
                Nat Immunol
                Nat. Immunol
                Nature Immunology
                Nature Publishing Group US (New York )
                1529-2908
                1529-2916
                18 December 2014
                2015
                : 16
                : 1
                : 18-26
                Affiliations
                GRID grid.7445.2, ISNI 0000 0001 2113 8111, Centre for Respiratory Infection, National Heart and Lung Institute, Imperial College London, ; London, UK
                Article
                BFni3056
                10.1038/ni.3056
                7097128
                25521681
                4dc2a70d-e170-42d5-9352-cc3dd69ff93b
                © Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. 2015

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 8 September 2014
                : 14 November 2014
                Categories
                Article
                Custom metadata
                © The Author(s), under exclusive licence to Springer Nature America, Inc. 2015

                Immunology
                mucosal immunology,adaptive immunity,antimicrobial responses
                Immunology
                mucosal immunology, adaptive immunity, antimicrobial responses

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