Advertisement

Lymphadenoid Tissues in the Upper Airway

  • Jinkwan KimEmail author
  • David Gozal
Chapter
Part of the Respiratory Medicine book series (RM)

Abstract

The lymphadenoid tissues in the upper airway are relatively organized lymphoepithelial structures that play an important role in protecting the upper airway against foreign pathogens. The importance of the presence of lymphadenoid tissue in humans was recognized as long ago as 1884 by Waldeyer, who described its specific arrangement as a “ring” of lymphoid tissue, now termed as the Waldeyer’s ring. The palatine tonsils are major components of the lymphoid tissues contained in the Waldeyer’s ring and appear to function as the host’s first line of defense against exogenous microorganisms and other potential air pollutants and allergens. Since its initial description, obstructive sleep apnea (OSA) has emerged as a highly prevalent condition in the pediatric age range, and adenotonsillar hypertrophy has been recognized as the major pathophysiological contributor of OSA in children and also plays an important role in another frequent condition in children, namely, recurrent tonsillitis (RI). Therefore, in this chapter, we summarize the current cumulative evidence on the histological and pathological features of human lymphadenoid tissues, delineate their fundamental immunological functions, and provide insights into various interactions involved in the initiation of immune responses, such as to enable a better conceptual framework on the pathophysiology of pediatric OSA.

Keywords

Obstructive Sleep Apnea Obstructive Sleep Apnea Syndrome Germinal Center Lymphoid Follicle Follicular Dendritic Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Brodsky L, Moore L, Stanievich JF, Ogra PL. The immunology of tonsils in children: the effect of bacterial load on the presence of B- and T-cell subsets. Laryngoscope. 1988;98(1):93–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Heier I, Malmstrom K, Pelkonen AS, et al. Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age. Thorax. 2008;63(8):703–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Gozal D, Capdevila OS, Kheirandish-Gozal L. Metabolic alterations and systemic inflammation in obstructive sleep apnea among nonobese and obese prepubertal children. Am J Respir Crit Care Med. 2008;177(10):1142–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Gozal D, Crabtree VM, SansCapdevila O, Witcher LA, Kheirandish-Gozal L. C-reactive protein, obstructive sleep apnea, and cognitive dysfunction in school-aged children. Am J Respir Crit Care Med. 2007;176(2):188–93.PubMedCrossRefGoogle Scholar
  5. 5.
    Leeson TS, Leeson CR, Paparo AA. Text/atlas of histology. Philadelphia: W.B. Saunders Company; 1988.Google Scholar
  6. 6.
    Hastings H. Frontal sinus suppuration. Cal State J Med. 1910;8(9):307–8.PubMedGoogle Scholar
  7. 7.
    Younis RT, Hesse SV, Anand VK. Evaluation of the utility and cost-effectiveness of obtaining histopathologic diagnosis on all routine tonsillectomy specimens. Laryngoscope. 2001;111(12):2166–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Arens R, Marcus CL. Pathophysiology of upper airway obstruction: a developmental perspective. Sleep. 2004;27(5):997–1019.PubMedGoogle Scholar
  9. 9.
    Jeans WD, Fernando DC, Maw AR, Leighton BC. A longitudinal study of the growth of the nasopharynx and its contents in normal children. Br J Radiol. 1981;54(638):117–21.PubMedCrossRefGoogle Scholar
  10. 10.
    Marcus CL, Lutz J, Hamer A, Smith PL, Schwartz A. Developmental changes in response to subatmospheric pressure loading of the upper airway. J Appl Physiol. 1999;87(2):626–33.PubMedGoogle Scholar
  11. 11.
    Kaditis AG, Ioannou MG, Chaidas K, et al. Cysteinyl leukotriene receptors are expressed by tonsillar T cells of children with obstructive sleep apnea. Chest. 2008;134(2):324–31.PubMedCrossRefGoogle Scholar
  12. 12.
    Ersu R, Arman AR, Save D, et al. Prevalence of snoring and symptoms of sleep-disordered breathing in primary school children in Istanbul. Chest. 2004;126(1):19–24.PubMedCrossRefGoogle Scholar
  13. 13.
    Siegel G, Linse R, Macheleidt S. Factors of tonsillar involution: age-dependent changes in B-cell activation and Langerhans’ cell density. Arch Otorhinolaryngol. 1982;236(3):261–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Jung KY, Lim HH, Choi G, Choi JO. Age-related changes of IgA immunocytes and serum and salivary IgA after tonsillectomy. Acta Otolaryngol Suppl. 1996;523:115–9.PubMedGoogle Scholar
  15. 15.
    Sato Y, Wake K, Watanabe I. Differentiation of crypt epithelium in human palatine tonsils: the microenvironment of crypt epithelium as a lymphoepithelial organ. Arch Histol Cytol. 1990;53(1):41–54.PubMedCrossRefGoogle Scholar
  16. 16.
    Perry ME. The specialised structure of crypt epithelium in the human palatine tonsil and its functional significance. J Anat. 1994;185(Pt 1):111–27.PubMedGoogle Scholar
  17. 17.
    Howie AJ. Scanning and transmission electron microscopy on the epithelium of human palatine tonsils. J Pathol. 1980;130(2):91–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Abbey K, Kawabata I. Computerized three-dimensional reconstruction of the crypt system of the palatine tonsil. Acta Otolaryngol Suppl. 1988;454:39–42.PubMedCrossRefGoogle Scholar
  19. 19.
    Nave H, Gebert A, Pabst R. Morphology and immunology of the human palatine tonsil. Anat Embryol (Berl). 2001;204(5):367–73.CrossRefGoogle Scholar
  20. 20.
    Reibel J, Sorensen CH. Association between keratin staining patterns and the structural and functional aspects of palatine tonsil epithelium. APMIS. 1991;99(10):905–15.PubMedCrossRefGoogle Scholar
  21. 21.
    van Kempen MJ, Rijkers GT, Van Cauwenberge PB. The immune response in adenoids and tonsils. Int Arch Allergy Immunol. 2000;122(1):8–19.PubMedCrossRefGoogle Scholar
  22. 22.
    Perry ME, Brown KA, von Gaudecker B. Ultrastructural identification and distribution of the adhesion molecules ICAM-1 and LFA-1 in the vascular and extravascular compartments of the human palatine tonsil. Cell Tissue Res. 1992;268(2):317–26.PubMedCrossRefGoogle Scholar
  23. 23.
    Hoefakker S, van’t Erve EH, Deen C, et al. Immunohistochemical detection of co-localizing cytokine and antibody producing cells in the extrafollicular area of human palatine tonsils. Clin Exp Immunol. 1993;93(2):223–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Brandtzaeg P, Surjan Jr L, Berdal P. Immunoglobulin systems of human tonsils. I. Control subjects of various ages: quantification of Ig-producing cells, tonsillar morphometry and serum Ig concentrations. Clin Exp Immunol. 1978;31(3):367–81.PubMedGoogle Scholar
  25. 25.
    Banchereau J, Briere F, Liu YJ, Rousset F. Molecular control of B lymphocyte growth and differentiation. Stem Cells. 1994;12(3):278–88.PubMedCrossRefGoogle Scholar
  26. 26.
    Brachtel EF, Washiyama M, Johnson GD, Tenner-Racz K, Racz P, MacLennan IC. Differences in the germinal centres of palatine tonsils and lymph nodes. Scand J Immunol. 1996;43(3):239–47.PubMedGoogle Scholar
  27. 27.
    Liu YJ, Zhang J, Lane PJ, Chan EY, MacLennan IC. Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens. Eur J Immunol. 1991;21(12):2951–62.PubMedCrossRefGoogle Scholar
  28. 28.
    Dieu MC, Vanbervliet B, Vicari A, et al. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med. 1998;188(2):373–86.PubMedCrossRefGoogle Scholar
  29. 29.
    Tsunoda R, Heinen E, Sugai N. Follicular dendritic cells in vitro modulate the expression of Fas and Bcl-2 on germinal center B cells. Cell Tissue Res. 2000;299(3):395–402.PubMedCrossRefGoogle Scholar
  30. 30.
    Rademakers LH. Dark and light zones of germinal centres of the human tonsil: an ultrastructural study with emphasis on heterogeneity of follicular dendritic cells. Cell Tissue Res. 1992;269(2):359–68.PubMedCrossRefGoogle Scholar
  31. 31.
    Nieuwenhuis P, Opstelten D. Functional anatomy of germinal centers. Am J Anat. 1984;170(3):421–35.PubMedCrossRefGoogle Scholar
  32. 32.
    Curran RC, Jones EL. The lymphoid follicles of the human palatine tonsil. Clin Exp Immunol. 1978;31(2):251–9.PubMedGoogle Scholar
  33. 33.
    Garside P, Ingulli E, Merica RR, Johnson JG, Noelle RJ, Jenkins MK. Visualization of specific B and T lymphocyte interactions in the lymph node. Science. 1998;281(5373):96–9.PubMedCrossRefGoogle Scholar
  34. 34.
    MacLennan IC, Gulbranson-Judge A, Toellner KM, et al. The changing preference of T and B cells for partners as T-dependent antibody responses develop. Immunol Rev. 1997;156:53–66.PubMedCrossRefGoogle Scholar
  35. 35.
    Allen CD, Okada T, Cyster JG. Germinal-center ­organization and cellular dynamics. Immunity. 2007;27(2):190–202.PubMedCrossRefGoogle Scholar
  36. 36.
    Paus D, Phan TG, Chan TD, Gardam S, Basten A, Brink R. Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation. J Exp Med. 2006;203(4):1081–91.PubMedCrossRefGoogle Scholar
  37. 37.
    Benson MJ, Erickson LD, Gleeson MW, Noelle RJ. Affinity of antigen encounter and other early B-cell signals determine B-cell fate. Curr Opin Immunol. 2007;19(3):275–80.PubMedCrossRefGoogle Scholar
  38. 38.
    Shih TA, Meffre E, Roederer M, Nussenzweig MC. Role of BCR affinity in T cell dependent antibody responses in vivo. Nat Immunol. 2002;3(6):570–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Hiller AS, Tschernig T, Kleemann WJ, Pabst R. Bronchus-associated lymphoid tissue (BALT) and larynx-associated lymphoid tissue (LALT) are found at different frequencies in children, adolescents and adults. Scand J Immunol. 1998;47(2):159–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Debertin AS, Tschernig T, Tonjes H, Kleemann WJ, Troger HD, Pabst R. Nasal-associated lymphoid tissue (NALT): frequency and localization in young children. Clin Exp Immunol. 2003;134(3):503–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Bergler W, Adam S, Gross HJ, Hormann K, Schwartz-Albiez R. Age-dependent altered proportions in subpopulations of tonsillar lymphocytes. Clin Exp Immunol. 1999;116(1):9–18.PubMedCrossRefGoogle Scholar
  42. 42.
    Kuki K, Hotomi M, Yamanaka N. A study of apoptosis in the human palatine tonsil. Acta Otolaryngol Suppl. 1996;523:68–70.PubMedGoogle Scholar
  43. 43.
    Yamanaka N, Yokoyama M, Kawaguchi T, Tamaki K, Ishii H. Role of gamma delta-T cells in the palatine tonsil. Acta Otolaryngol Suppl. 1996;523:90–3.PubMedGoogle Scholar
  44. 44.
    Karchev T. Specialization of tonsils as analyzers of the human immune system. Acta Otolaryngol Suppl. 1988;454:23–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Andersson J, Abrams J, Bjork L, et al. Concomitant in vivo production of 19 different cytokines in human tonsils. Immunology. 1994;83(1):16–24.PubMedGoogle Scholar
  46. 46.
    Korsrud FR, Brandtzaeg P. Immune systems of human nasopharyngeal and palatine tonsils: histomorphometry of lymphoid components and quantification of immunoglobulin-producing cells in health and disease. Clin Exp Immunol. 1980;39(2):361–70.PubMedGoogle Scholar
  47. 47.
    Perry M, Whyte A. Immunology of the tonsils. Immunol Today. 1998;19(9):414–21.PubMedCrossRefGoogle Scholar
  48. 48.
    Quiding-Jarbrink M, Granstrom G, Nordstrom I, Holmgren J, Czerkinsky C. Induction of compartmentalized B-cell responses in human tonsils. Infect Immun. 1995;63(3):853–7.PubMedGoogle Scholar
  49. 49.
    Schriever F, Korinth D, Salahi A, Lefterova P, Schmidt-Wolf IG, Behr SI. Human T lymphocytes bind to germinal centers of human tonsils via integrin alpha4/VCAM-1 and LFA-1/ICAM-1 and -2. Eur J Immunol. 1997;27(1):35–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Westermann J, Pabst R. Lymphocyte subsets in the blood: a diagnostic window on the lymphoid system? Immunol Today. 1990;11(11):406–10.PubMedCrossRefGoogle Scholar
  51. 51.
    Baekkevold ES, Yamanaka T, Palframan RT, et al. The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. J Exp Med. 2001;193(9):1105–12.PubMedCrossRefGoogle Scholar
  52. 52.
    Zidan M, Jecker P, Pabst R. Differences in lymphocyte subsets in the wall of high endothelial venules and the lymphatics of human palatine tonsils. Scand J Immunol. 2000;51(4):372–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med. 2000;192(11):1553–62.PubMedCrossRefGoogle Scholar
  54. 54.
    Weatherly RA, Mai EF, Ruzicka DL, Chervin RD. Identification and evaluation of obstructive sleep apnea prior to adenotonsillectomy in children: a survey of practice patterns. Sleep Med. 2003;4(4):297–307.PubMedCrossRefGoogle Scholar
  55. 55.
    Friedman M, Wilson M, Lin HC, Chang HW. Updated systematic review of tonsillectomy and adenoidectomy for treatment of pediatric obstructive sleep apnea/hypopnea syndrome. Otolaryngol Head Neck Surg. 2009;140(6):800–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Katz ES, D’Ambrosio CM. Pathophysiology of pediatric obstructive sleep apnea. Proc Am Thorac Soc. 2008;5(2):253–62.PubMedCrossRefGoogle Scholar
  57. 57.
    Webb CJ, Osman E, Ghosh SK, Hone S. Tonsillar size is an important indicator of recurrent acute ­tonsillitis. Clin Otolaryngol Allied Sci. 2004;29(4):369–71.PubMedCrossRefGoogle Scholar
  58. 58.
    Darrow DH, Siemens C. Indications for tonsillectomy and adenoidectomy. Laryngoscope. 2002;112(8 Pt 2 Suppl 100):6–10.PubMedCrossRefGoogle Scholar
  59. 59.
    Schechter MS. Technical report: diagnosis and management of childhood obstructive sleep apnea syndrome. Pediatrics. 2002;109(4):e69.PubMedCrossRefGoogle Scholar
  60. 60.
    Tal A, Bar A, Leiberman A, Tarasiuk A. Sleep characteristics following adenotonsillectomy in children with obstructive sleep apnea syndrome. Chest. 2003;124(3):948–53.PubMedCrossRefGoogle Scholar
  61. 61.
    Marcus CL, Ward SL, Mallory GB, et al. Use of nasal continuous positive airway pressure as treatment of childhood obstructive sleep apnea. J Pediatr. 1995;127(1):88–94.PubMedCrossRefGoogle Scholar
  62. 62.
    Lipton AJ, Gozal D. Treatment of obstructive sleep apnea in children: do we really know how? Sleep Med Rev. 2003;7(1):61–80.PubMedCrossRefGoogle Scholar
  63. 63.
    Bhattacharjee R, Kheirandish-Gozal L, Spruyt K, et al. Adenotonsillectomy outcomes in treatment of OSA in children: A Multicenter Retrospective Study. Am J Respir Crit Care Med. 2010;182(5):676–83. Epub ahead of print.PubMedCrossRefGoogle Scholar
  64. 64.
    Boyd JH, Petrof BJ, Hamid Q, Fraser R, Kimoff RJ. Upper airway muscle inflammation and denervation changes in obstructive sleep apnea. Am J Respir Crit Care Med. 2004;170(5):541–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Li AM, Hung E, Tsang T, et al. Induced sputum inflammatory measures correlate with disease severity in children with obstructive sleep apnoea. Thorax. 2007;62(1):75–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Goldbart AD, Veling MC, Goldman JL, Li RC, Brittian KR, Gozal D. Glucocorticoid receptor subunit expression in adenotonsillar tissue of children with obstructive sleep apnea. Pediatr Res. 2005;57(2):232–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Goldbart AD, Goldman JL, Li RC, Brittian KR, Tauman R, Gozal D. Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of children with obstructive sleep apnea syndrome or recurrent infection. Chest. 2004;126(1):13–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Kim J, Bhattacharjee R, Dayyat E, et al. Increased ­cellular proliferation and inflammatory cytokines in tonsils derived from children with obstructive sleep apnea. Pediatr Res. 2009;66(4):423–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Khalyfa A, Gharib SA, Kim J, et al. Transcriptomic analysis identifies phosphatases as novel targets for adenotonsillar hypertrophy of pediatric obstructive sleep apnea. Am J Respir Crit Care Med. 2010;181(10):1114–20.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of PediatricsThe University of ChicagoChicagoUSA
  2. 2.Department of PediatricsPritzker School of Medicine, Comer Children’s Hospital, The University of ChicagoChicagoUSA

Personalised recommendations