Mucosal Vaccination Challenges in Aging: Understanding Immunosenescence in the Aerodigestive Tract

  • Kohtaro FujihashiEmail author
  • Jerry R. McGhee
  • Hiroshi Kiyono
Living reference work entry


Many immunologists understand the importance of mucosal immunology, an area that is distinctly regulated from its systemic counterpart. Despite extensive current studies and their outcomes, it still remains for us to fill major gaps in our knowledge of the mucosal immune system in the aged, often described as mucosal immunosenescence. It is well established that pathogen-specific secretory immunoglobulin A (SIgA) antibody (Ab) is the major player for host defense from various pathogens at mucosal surfaces. Alterations in the mucosal immune system occur in advanced aging which ultimately results in a failure to elicit pathogen-specific SIgA Ab responses in order to protect the host from infectious diseases. Symptoms of mucosal immunosenescence were initially detected in the gastrointestinal (GI) immune system, especially in the gut-associated lymphoid tissues (GALT), i.e., the Peyer’s patches (PPs). Thus, a diminished size of PP tissues as well as reduced numbers of naïve CD4+ T cells, follicular dendritic cells (DCs), and antigen (Ag) uptake or microfold (M) cells were noted during the aging process. In contrast, immunological functions of nasopharyngeal-associated lymphoid tissues (NALT) remain intact during aging with notable signs of immunosenescence seen only in the elderly (2-year-old mice). To overcome the effects of immunologic aging in mucosal immunity, it is essential to develop novel immunologic strategies for health in the elderly including vaccines and immune therapies to combat pathogens. In this regard, it has been shown that stem cell transfer as well as several mucosal adjuvant and delivery systems for activation of and deposition of Ag to mucosal DCs or targeting M cells, respectively, are attractive and effective immunologic intervention approaches.


Mucosa Vaccines Aging Stem cells Adjuvants Gastrointestinal tract Upper respiratory tract 



Portions of the work described in this review chapter was supported by National Institutes of Aging (NIA) grant AG025873 (to KF) and research funding from BioMimetics Sympathy Inc. (Tokyo, Japan).


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Kohtaro Fujihashi
    • 1
    • 2
    Email author
  • Jerry R. McGhee
    • 1
  • Hiroshi Kiyono
    • 1
    • 3
    • 4
  1. 1.Department of Pediatric Dentistry, The Institute of Oral Health Research, The School of DentistryThe University of Alabama at BirminghamBirminghamUSA
  2. 2.International Research and Development Center for Mucosal Vaccines, The Institute of Medical ScienceThe University of TokyoTokyoJapan
  3. 3.Department of Mucosal Immunology, and International Research and Development Center for Mucosal Vaccines, The Institute of Medical ScienceThe University of TokyoTokyoJapan
  4. 4.Department of Immunology, Graduate School of MedicineChiba UniversityChibaJapan

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