PULMONARY PATHOLOGIES AND MANAGEMENT STRATEGIES IN PRIMARY IMMUNODEFICIENCIES

pulmonary_pathologies_kapak

IMMUNOLOGICAL DEFENSE MECHANISMS OF THE RESPIRATORY SYSTEM

Elif Çetin Başaran1
Sait Yeşillik2

1University of Health Sciences, Gülhane Training and Research Hospital, Department of Immunology and Allergic Diseases, Ankara, Türkiye
2University of Health Sciences, Gülhane Training and Research Hospital, Department of Immunology and Allergic Diseases, Ankara, Türkiye

Çetin Başaran E, Yeşillik S. Immunological Defense Mechanisms of the Respiratory System. In: Arslan Ş editor. Pulmonary Pathologies and Management Strategies in Primary Immunodeficiencies. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.3-13.

ABSTRACT

The respiratory tract is constantly exposed to various elements in the inhaled air, such as pathogens, toxins, and allergens, which can cause inflammation or infection. The respiratory system has developed various physical, biochemical, and immunological defense mechanisms that provide and regulate appropriate responses to these harmful agents. These mechanisms include the respiratory tract epithelium, the innate immune system, and the adaptive immune system. These systems contain different physical, cellular and secretory factors.

The epithelial layer lining the respiratory tract, consisting of airway epithelial cells and separating the body from the environment, the mucociliary clearance activity consisting of mucus production and coordinated movement of cilia, the innate and adaptive immune system modulated by factors such as secreted antimicrobial peptides, chemokines, and cytokines constitute the immunological barrier mechanisms of the pulmonary system.

As the first line of defence, the innate immune system responds immediately to inhaled agents. The innate immune system identifies microorganisms nonspecifically and mounts a nonspecific response to antigens. Adaptive immunity provides pathogen-specific immune responses, immunological memory formation, and regulation of immune homeostasis. In addition to serving as a physical barrier, epithelial cells secrete various mediators such as surfactants, mucins, and antimicrobial peptides that contribute to host defense and help regulate the immune activity of nearby cells.

The respiratory system is a complex system equipped with different immunological defense mechanisms against many pathogens as a result of the features it possesses and develops.

Keywords: Respiratory system; Immune system; Adaptive immunity; Innate immunity; Humoral immunity; Cellular immunity

Referanslar

  1. Mettelman RC, Allen EK, Thomas PG. Mucosal immune responses to infection and vaccination in the respiratory tract. Immunity. 2022;55(5):749-780. [Crossref]  [PubMed]  [PMC]
  2. Hammad H, Lambrecht BN. Barrier Epithelial Cells and the Control of Type 2 Immunity. Immunity. 2015;43(1):29-40. [Crossref]  [PubMed]
  3. Crystal RG, Randell SH, Engelhardt JF, Voynow J, Sunday ME. Airway epithelial cells: current concepts and challenges. Proc Am Thorac Soc. 2008;5(7):772-7. [Crossref]  [PubMed]  [PMC]
  4. Hallstrand TS, Hackett TL, Altemeier WA, Matute-Bello G, Hansbro PM, Knight DA. Airway epithelial regulation of pulmonary immune homeostasis and inflammation. Clin Immunol. 2014;151(1):1-15. [Crossref]  [PubMed]
  5. Kageyama T, Ito T, Tanaka S. et al. Physiological and immunological barriers in the lung. Semin Immunopathol 2024;45:533-547. [Crossref]  [PubMed]  [PMC]
  6. Fokkens WJ, Scheeren RA. Upper airway defence mechanisms. Paediatr Respir Rev. 2000;1(4):336-41. [Crossref]  [PubMed]
  7. Tsai KS, Grayson MH. Pulmonary defense mechanisms against pneumonia and sepsis. Curr Opin Pulm Med. 2008;14(3):260-5. [Crossref]  [PubMed]
  8. Ma J, Rubin BK, Voynow JA. Mucins, Mucus, and Goblet Cells. Chest. 2018;154(1):169-176. [Crossref]  [PubMed]
  9. Widdicombe JH, Wine JJ. Airway Gland Structure and Function. Physiol Rev. 2015;95(4):1241-319. [Crossref]  [PubMed]
  10. Guillot L, Nathan N, Tabary O, Thouvenin G, Le Rouzic P, Corvol H, Amselem S, Clement A. Alveolar epithelial cells: master regulators of lung homeostasis. Int J Biochem Cell Biol. 2013;45(11):2568-73. [Crossref]  [PubMed]
  11. Hewitt RJ, Lloyd CM. Regulation of immune responses by the airway epithelial cell landscape. Nat Rev Immunol. 2021 Jun;21(6):347-362. [Crossref]  [PubMed]  [PMC]
  12. Parker D, Prince A. Innate immunity in the respiratory epithelium. Am J Respir Cell Mol Biol. 2011;45(2):189-201. [Crossref]  [PubMed]  [PMC]
  13. Naderi W, Schreiner D, King CG. T-cell-B-cell collaboration in the lung. Curr Opin Immunol. 2023;81:102284. [Crossref]  [PubMed]
  14. Heier I, Malmström K, Sajantila A, Lohi J, Mäkelä M, Jahnsen FL. Characterisation of bronchus-associated lymphoid tissue and antigen-presenting cells in central airway mucosa of children. Thorax. 2011;66(2):151-6. [Crossref]  [PubMed]
  15. Denney L, Ho LP. The role of respiratory epithelium in host defence against influenza virus infection. Biomed J. 2018;41(4):218-233. [Crossref]  [PubMed]  [PMC]
  16. Karaca NE, Aygun A, Velikova T. Immunological Defense Mechanisms of the Respiratory System. In: Yüksel H, Yilmaz O, Bayar Muluk N, Myer CM. (eds) Pediatric Airway Diseases. Comprehensive ENT. Springer, Cham.
  17. Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020;24:777-92. [Crossref]  [PubMed]
  18. Parnes JR, Molfino NA, Colice G, Martin U, Corren J, Menzies-Gow A. Targeting TSLP in Asthma. J Asthma Allergy. 2022;15:749-765. [Crossref]  [PubMed]  [PMC]
  19. Tecle T, Tripathi S, Hartshorn KL. Review: Defensins and cathelicidinsinlungimmunity.InnateImmun.2010;16(3):151-9. [Crossref]  [PubMed]
  20. Hiemstra PS, Amatngalim GD, van der Does AM, Taube C. Antimicrobial Peptides and Innate Lung Defenses: Role in Infectious and Noninfectious Lung Diseases and Therapeutic Applications. Chest. 2016;149(2):545-551. [Crossref]  [PubMed]
  21. Schutte BC, McCray PB Jr. [beta]-defensins in lung host defense. Annu Rev Physiol. 2002;64:709-48. [Crossref]  [PubMed]
  22. Cole AM, Waring AJ. The role of defensins in lung biology and therapy. Am J Respir Med. 2002;1(4):249-59. [Crossref]  [PubMed]
  23. Greene CM, Hiemstra PS. Innate Immunity of the Lung. J Innate Immun. 2020;12(1):1-3. [Crossref]  [PubMed]  [PMC]
  24. Gopallawa I, Dehinwal R, Bhatia V, Gujar V and Chirmule N. A four-part guide to lung immunology: Invasion, in ammation, immunity, and intervention. Front. Immunol. 2023;14:1119564. [Crossref]  [PubMed]  [PMC]
  25. Bustamante-Marin XM, Ostrowski LE. Cilia and Mucociliary Clearance. Cold Spring Harb Perspect Biol. 2017;9(4):a028241. [Crossref]  [PubMed]  [PMC]
  26. Wu D, Xiang Y. Role of mucociliary clearance system in respiratory diseases. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023;48(2):275-284. English, Chinese.
  27. Kopf M, Schneider C, Nobs SP. The development and function of lung-resident macrophages and dendritic cells. Nat Immunol. 2015;16(1):36-44. [Crossref]  [PubMed]
  28. Hussell T, Bell TJ. Alveolar macrophages: plasticity in a tissue-specific context. Nat Rev Immunol. 2014;14(2):81-93. [Crossref]  [PubMed]
  29. Cook PC, MacDonald AS. Dendritic cells in lung immunopathology. Semin Immunopathol. 2016;38(4):449-60. [Crossref]  [PubMed]  [PMC]
  30. Iwasaki A. Mucosal dendritic cells. Annu Rev Immunol. 2007;25:381-418. [Crossref]  [PubMed]
  31. Athari SS, Athari SM, Beyzay F, Movassaghi M, Mortaz E, Taghavi M. Critical role of Toll-like receptors in pathophys iology of allergic asthma. Eur J Pharmacol. 2017;808:21-27. [Crossref]  [PubMed]
  32. Juarez E, Nuñez C, Sada E, Ellner JJ, Schwander SK, Torres M. Differential expression of Toll-like receptors on human alveolar macrophages and autologous peripheral monocytes. Respir Res. 2010;11(1):2. [Crossref]  [PubMed]  [PMC]
  33. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373-84. [Crossref]  [PubMed]
  34. Erjefält JS. Mast cells in human airways: the culprit? Eur Respir Rev. 2014;23(133):299-307. [Crossref]  [PubMed]  [PMC]
  35. Greenlee-Wacker MC. Clearance of apoptotic neutrophils and resolution of inflammation. Immunol Rev. 2016;273(1):357-70. [Crossref]  [PubMed]  [PMC]
  36. Cording S, Medvedovic J, Aychek T, Eberl G. Innate lymphoid cells in defense, immunopathology and immunotherapy. Nat Immunol. 2016;17(7):755-7. [Crossref]  [PubMed]
  37. Sonnenberg GF, Artis D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat Med. 2015;21(7):698-708. [Crossref]  [PubMed]  [PMC]
  38. Klose CS, Artis D. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat Immunol. 2016 ;17(7):765-74. [Crossref]  [PubMed]
  39. Doherty TA, Khorram N, Lund S, Mehta AK, Croft M, Broide DH. Lung type 2 innate lymphoid cells express cysteinyl leukotriene receptor 1, which regulates TH2 cytokine production. J Allergy Clin Immunol. 2013;132(1):205-13. [Crossref]  [PubMed]  [PMC]
  40. Varsano S, Kaminsky M, Kaiser M, Rashkovsky L. Generation of complement C3 and expression of cell membrane complement inhibitory proteins by human bronchial epithelium cell line. Thorax. 2000;55(5):364-9. [Crossref]  [PubMed]  [PMC]
  41. Hasenberg M, Stegemann-Koniszewski S, Gunzer M. Cellular immune reactions in the lung. Immunol Rev. 2013;251(1):189-214. [Crossref]  [PubMed]
  42. Lloyd CM, Hessel EM. Functions of T cells in asthma: more than just T(H)2 cells. Nat Rev Immunol. 2010;10(12):838-48. [Crossref]  [PubMed]  [PMC]
  43. Stambas J, Lu C, Tripp RA. Innate and adaptive immune responses in respiratory virus infection: implications for the clinic. Expert Rev Respir Med. 2020;14(11):1141-1147. [Crossref]  [PubMed]
  44. Schmidt ME, Varga SM. The CD8 T Cell Response to Respiratory Virus Infections. Front Immunol. 2018;9:678. [Crossref]  [PubMed]  [PMC]
  45. Iwasaki A, Foxman EF, Molony RD. Early local immune defences in the respiratory tract. Nat Rev Immunol. 2017;17(1):7-20. [Crossref]  [PubMed]  [PMC]
  46. Hazar E, Karaselek MA, Keles S. Innate and Adaptive Immunity of the Respiratory System. In: Yüksel, H., Yilmaz, O., Bayar Muluk, N., Myer, C.M. (eds) Pediatric Airway Diseases. Comprehensive ENT. Springer, Cham. 2024 [Crossref]
  47. Schattgen SA, Thomas PG. TRH cells, helpers making an impact in their local community. Sci Immunol. 2021;6(55):eabf2886. [Crossref]  [PubMed]
  48. Galeas-Pena M, McLaughlin N, Pociask D. The role of the innate immune system on pulmonary infections. Biol Chem. 2019;400(4):443-56. [Crossref]  [PubMed]  [PMC]
  49. D'Alessio FR, Tsushima K, Aggarwal NR, et al. CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury. J Clin Invest. 2009;119(10):2898-913. [Crossref]  [PubMed]  [PMC]
  50. Purwar R, Campbell J, Murphy G, et al. Resident memory T cells (T(RM)) are abundant in human lung: diversity, function, and antigen specifcity. PLoS One. 2011;6(1):e16245. [Crossref]  [PubMed]  [PMC]
  51. Swarnalekha N, Schreiner D, Litzler LC, Iftikhar S, Kirchmeier D, Künzli M, Son YM, Sun J, Moreira EA, King CG. T resident helper cells promote humoral responses in the lung. Sci Immunol. 2021;6(55):eabb6808. [Crossref]  [PubMed]  [PMC]
  52. Barker KA, Etesami NS, Shenoy AT, et al. Lung-resident memory B cells protect against bacterial pneumonia. J Clin Invest. 2021;131(11):e141810. [Crossref]  [PubMed]  [PMC]
  53. Zarogoulidis P, Darwiche K, Yarmus L, Spyratos D, Secen N, Hohenforst-Schmidt W, Katsikogiannis N, Huang H, Gschwendtner A, Zarogoulidis K. Defense mechanisms of the respiratory system and aerosol production systems. Med Chem. 2014;10(2):123-36. [Crossref]  [PubMed]
  54. Sato S, Kiyono H. The mucosal immune system of the respiratory tract. Curr Opin Virol. 2012;2(3):225-32. [Crossref]  [PubMed]