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Respiratory Disorders of the Immune System and Their Pharmacological Treatment

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Abstract

The respiratory system comprising of the upper airway passages and bronchopulmonary tissues including the trachea and the lung are vital for the processes of gas exchange and cellular respiration. Inflammatory disorders of the lower respiratory tract such as asthma and chronic obstructive pulmonary disease (COPD) are a major cause of debilitating illness throughout the world and significantly contribute to mortality and increases in health care costs. In this chapter, we discuss the pathophysiology and the immunological basis of these diseases as well as the pharmacology of the drugs used in their treatment. The specific contributions of immune cells including TH2 cells, mast cells, and type 2 innate lymphoid cells are described in detail. Novel therapeutic agents in the treatment of asthma and COPD are also discussed. Lastly, the discovery of IgE antibodies is highlighted in the Bench to Bedside section.

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Suggested Reading

  • Akbari O, Stock P, DeKruyff RH, Umetsu DT. Role of regulatory T cells in allergy and asthma. Curr Opin Immunol. 2003;15:627–33.

    Article  CAS  PubMed  Google Scholar 

  • Arthur G, Bradding P. New developments in mast cell biology: clinical implications. Chest. 2016;150:680–93.

    Article  PubMed  Google Scholar 

  • Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015;517:293–301.

    Article  CAS  PubMed  Google Scholar 

  • Azzawi M, Bradley B, Jeffery PK, Frew AJ, Wardlaw AJ, Knowles G, et al. Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis. 1990;142:1407–13.

    Article  CAS  PubMed  Google Scholar 

  • Azzawi M, Johnston PW, Majumdar S, Kay AB, Jeffery PK. T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis. Am Rev Respir Dis. 1992;145:1477–82.

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ. Molecular mechanisms and cellular effects of glucocorticosteroids. Immunol Allergy Clin N Am. 2005;25:451–68.

    Article  Google Scholar 

  • Barnes PJ. Theophylline. Am J Respir Crit Care Med. 2013;188:901–6.

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2016;138:16–27.

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ. Cellular and molecular mechanisms of asthma and COPD. Clin Sci (Lond). 2017;131:1541–58.

    Article  CAS  Google Scholar 

  • Barnes PJ, Adcock IM. How do corticosteroids work in asthma? Ann Intern Med. 2003;139:359–70.

    Article  CAS  PubMed  Google Scholar 

  • Barnes KC, Neely JD, Duffy DL, Freidhoff LR, Breazeale DR, Schou C, et al. Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations. Genomics. 1996;37:41–50.

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ, Shapiro SD, Pauwels RA. Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003;22:672–88.

    Article  CAS  PubMed  Google Scholar 

  • Barnes PJ, Burney PG, Silverman EK, Celli BR, Vestbo J, Wedzicha JA, et al. Chronic obstructive pulmonary disease. Nat Rev Dis Primers. 2015;1:15076.

    Article  PubMed  Google Scholar 

  • Begin P, Nadeau KC. Epigenetic regulation of asthma and allergic disease. Allergy Asthma Clin Immunol. 2014;10:27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brusselle GG, Kips JC, Tavernier JH, van der Heyden JG, Cuvelier CA, Pauwels RA, et al. Attenuation of allergic airway inflammation in IL-4 deficient mice. Clin Exp Allergy. 1994;24:73–80.

    Article  CAS  PubMed  Google Scholar 

  • Burton OT, Oettgen HC. Beyond immediate hypersensitivity: evolving roles for IgE antibodies in immune homeostasis and allergic diseases. Immunol Rev. 2011;242:128–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Busse WW, Lemanske RF Jr. Asthma. N Engl J Med. 2001;344:350–62.

    Article  CAS  PubMed  Google Scholar 

  • Busse WW, Lemanske RF Jr. Management of asthma exacerbations. Thorax. 2004;59:545–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Busse WW, Coffman RL, Gelfand EW, Kay AB, Rosenwasser LJ. Mechanisms of persistent airway inflammation in asthma. A role for T cells and T-cell products. Am J Respir Crit Care Med. 1995;152:388–93.

    Article  CAS  PubMed  Google Scholar 

  • Busse WW, Lemanske RF Jr, Gern JE. Role of viral respiratory infections in asthma and asthma exacerbations. Lancet. 2010;376:826–34.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cazzola M, Page CP, Rogliani P, Matera MG. beta2-agonist therapy in lung disease. Am J Respir Crit Care Med. 2013;187:690–6.

    Article  CAS  PubMed  Google Scholar 

  • Chatila TA. Interleukin-4 receptor signaling pathways in asthma pathogenesis. Trends Mol Med. 2004;10:493–9.

    Article  CAS  PubMed  Google Scholar 

  • Choby GW, Lee S. Pharmacotherapy for the treatment of asthma: current treatment options and future directions. Int Forum Allergy Rhinol. 2015;5(Suppl 1):S35–40.

    Article  PubMed  Google Scholar 

  • Cohn L, Elias JA, Chupp GL. Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol. 2004;22:789–815.

    Article  CAS  PubMed  Google Scholar 

  • Corrigan CJ, Hartnell A, Kay AB. T lymphocyte activation in acute severe asthma. Lancet. 1988;1:1129–32.

    Article  CAS  PubMed  Google Scholar 

  • Das J, Chen CH, Yang L, Cohn L, Ray P, Ray A. A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation. Nat Immunol. 2001;2:45–50.

    Article  CAS  PubMed  Google Scholar 

  • Deckers J, De Bosscher K, Lambrecht BN, Hammad H. Interplay between barrier epithelial cells and dendritic cells in allergic sensitization through the lung and the skin. Immunol Rev. 2017;278:131–44.

    Article  CAS  PubMed  Google Scholar 

  • Epstein MM. Do mouse models of allergic asthma mimic clinical disease? Int Arch Allergy Immunol. 2004;133:84–100.

    Article  PubMed  Google Scholar 

  • Finkelman FD. Identification of IgE as the allergy-associated Ig isotype. J Immunol. 2017;198:3–4.

    Article  CAS  PubMed  Google Scholar 

  • Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996;183:195–201.

    Article  CAS  PubMed  Google Scholar 

  • Fulkerson PC, Rothenberg ME, Hogan SP. Building a better mouse model: experimental models of chronic asthma. Clin Exp Allergy. 2005;35:1251–3.

    Article  CAS  PubMed  Google Scholar 

  • Galli SJ, Tsai M. Mast cells: versatile regulators of inflammation, tissue remodeling, host defense and homeostasis. J Dermatol Sci. 2008;49:7–19.

    Article  CAS  PubMed  Google Scholar 

  • Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18:693–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gavett SH, Chen X, Finkelman F, Wills-Karp M. Depletion of murine CD4+ T lymphocytes prevents antigen-induced airway hyperreactivity and pulmonary eosinophilia. Am J Respir Cell Mol Biol. 1994;10:587–93.

    Article  CAS  PubMed  Google Scholar 

  • Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, et al. The biology of IGE and the basis of allergic disease. Annu Rev Immunol. 2003;21:579–628.

    Article  CAS  PubMed  Google Scholar 

  • Gross NJ, Barnes PJ. New therapies for asthma and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;195:159–66.

    Article  CAS  PubMed  Google Scholar 

  • Grumelli S, Corry DB, Song LZ, Song L, Green L, Huh J, et al. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema. PLoS Med. 2004;1:e8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grunig G, Warnock M, Wakil AE, Venkayya R, Brombacher F, Rennick DM, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998;282:2261–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gurish MF, Austen KF. The diverse roles of mast cells. J Exp Med. 2001;194:F1–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halim TY, Steer CA, Matha L, Gold MJ, Martinez-Gonzalez I, McNagny KM, et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity. 2014;40:425–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamelmann E, Gelfand EW. IL-5-induced airway eosinophilia--the key to asthma? Immunol Rev. 2001;179:182–91.

    Article  CAS  PubMed  Google Scholar 

  • Hamelmann E, Oshiba A, Schwarze J, Bradley K, Loader J, Larsen GL, et al. Allergen-specific IgE and IL-5 are essential for the development of airway hyperresponsiveness. Am J Respir Cell Mol Biol. 1997;16:674–82.

    Article  CAS  PubMed  Google Scholar 

  • Hamid Q, Azzawi M, Ying S, Moqbel R, Wardlaw AJ, Corrigan CJ, et al. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest. 1991;87:1541–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hammad H, Lambrecht BN. Barrier epithelial cells and the control of type 2 immunity. Immunity. 2015;43:29–40.

    Article  CAS  PubMed  Google Scholar 

  • He JQ, Hallstrand TS, Knight D, Chan-Yeung M, Sandford A, Tripp B, et al. A thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness. J Allergy Clin Immunol. 2009;124:222–9.

    Article  CAS  PubMed  Google Scholar 

  • Hekking PP, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135:896–902.

    Article  PubMed  Google Scholar 

  • Hershey GK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA. The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med. 1997;337:1720–5.

    Article  CAS  PubMed  Google Scholar 

  • Hirota N, Martin JG. Mechanisms of airway remodeling. Chest. 2013;144:1026–32.

    Article  PubMed  Google Scholar 

  • Holt PG, Strickland DH, Wikstrom ME, Jahnsen FL. Regulation of immunological homeostasis in the respiratory tract. Nat Rev Immunol. 2008;8:142–52.

    Article  CAS  PubMed  Google Scholar 

  • Johansson SG. The history of IgE: from discovery to 2010. Curr Allergy Asthma Rep. 2011;11:173–7.

    Article  CAS  PubMed  Google Scholar 

  • Kabesch M, Tzotcheva I, Carr D, Hofler C, Weiland SK, Fritzsch C, et al. A complete screening of the IL4 gene: novel polymorphisms and their association with asthma and IgE in childhood. J Allergy Clin Immunol. 2003;112:893–8.

    Article  CAS  PubMed  Google Scholar 

  • Kabesch M, Schedel M, Carr D, Woitsch B, Fritzsch C, Weiland SK, et al. IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma. J Allergy Clin Immunol. 2006;117:269–74.

    Article  CAS  PubMed  Google Scholar 

  • Kalesnikoff J, Galli SJ. New developments in mast cell biology. Nat Immunol. 2008;9:1215–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawakami T, Blank U. From IgE to omalizumab. J Immunol. 2016;197:4187–92.

    Article  CAS  PubMed  Google Scholar 

  • Kay DSRAB. Mechanisms of allergic asthma: a Th2 disease. In: Yssel JBH, editor. Immunotherapy in asthma. First ed. New York: Marcel Dekker, Inc; 1999. p. 19–41.

    Google Scholar 

  • Kay MLAB. CD4 T lymphocytes in allergic asthma. In: Lambrecht BN, Hoogsteden H, Diamant Z, editors. The immunological basis of asthma. 1st ed. New York: Marcel Dekker, Inc; 2003. p. 53–81.

    Google Scholar 

  • Kim HY, DeKruyff RH, Umetsu DT. The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat Immunol. 2010;11:577–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knutsen AP, Bush RK, Demain JG, Denning DW, Dixit A, Fairs A, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol. 2012;129:280–91; quiz 92–3.

    Article  PubMed  Google Scholar 

  • Kubo M. Innate and adaptive type 2 immunity in lung allergic inflammation. Immunol Rev. 2017;278:162–72.

    Article  CAS  PubMed  Google Scholar 

  • Lambrecht BN, Hammad H. Taking our breath away: dendritic cells in the pathogenesis of asthma. Nat Rev Immunol. 2003;3:994–1003.

    Article  CAS  PubMed  Google Scholar 

  • Lambrecht BN, Hammad H. Biology of lung dendritic cells at the origin of asthma. Immunity. 2009;31:412–24.

    Article  CAS  PubMed  Google Scholar 

  • Lambrecht BN, Hammad H. Lung dendritic cells in respiratory viral infection and asthma: from protection to immunopathology. Annu Rev Immunol. 2012;30:243–70.

    Article  CAS  PubMed  Google Scholar 

  • Lee NA, Gelfand EW, Lee JJ. Pulmonary T cells and eosinophils: coconspirators or independent triggers of allergic respiratory pathology? J Allergy Clin Immunol. 2001;107:945–57.

    Article  CAS  PubMed  Google Scholar 

  • Lemanske RF Jr, Busse WW. Asthma: clinical expression and molecular mechanisms. J Allergy Clin Immunol. 2010;125:S95–102.

    Article  PubMed  PubMed Central  Google Scholar 

  • Liang HE, Reinhardt RL, Bando JK, Sullivan BM, Ho IC, Locksley RM. Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity. Nat Immunol. 2011;13:58–66.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lloyd CM, Hessel EM. Functions of T cells in asthma: more than just T(H)2 cells. Nat Rev Immunol. 2010;10:838–48.

    Article  CAS  PubMed  Google Scholar 

  • Lloyd CM, Gonzalo JA, Coyle AJ, Gutierrez-Ramos JC. Mouse models of allergic airway disease. Adv Immunol. 2001;77:263–95.

    Article  CAS  PubMed  Google Scholar 

  • Lotvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127:355–60.

    Article  PubMed  Google Scholar 

  • Lukacs NW, Strieter RM, Chensue SW, Kunkel SL. Interleukin-4-dependent pulmonary eosinophil infiltration in a murine model of asthma. Am J Respir Cell Mol Biol. 1994;10:526–32.

    Article  CAS  PubMed  Google Scholar 

  • MacKenzie JR, Mattes J, Dent LA, Foster PS. Eosinophils promote allergic disease of the lung by regulating CD4(+) Th2 lymphocyte function. J Immunol. 2001;167:3146–55.

    Article  CAS  PubMed  Google Scholar 

  • Martinez FD. Early-life origins of chronic obstructive pulmonary disease. N Engl J Med. 2016;375:871–8.

    Article  PubMed  Google Scholar 

  • Mathias CB. Natural killer cells in the development of asthma. Curr Allergy Asthma Rep. 2015;15:500.

    Article  PubMed  CAS  Google Scholar 

  • Mathias CB, Freyschmidt EJ, Caplan B, Jones T, Poddighe D, Xing W, et al. IgE influences the number and function of mature mast cells, but not progenitor recruitment in allergic pulmonary inflammation. J Immunol. 2009;182:2416–24.

    Article  CAS  PubMed  Google Scholar 

  • Mattes J, Yang M, Siqueira A, Clark K, MacKenzie J, McKenzie AN, et al. IL-13 induces airways hyperreactivity independently of the IL-4R alpha chain in the allergic lung. J Immunol. 2001;167:1683–92.

    Article  CAS  PubMed  Google Scholar 

  • Medoff BD, Thomas SY, Luster AD. T cell trafficking in allergic asthma: the ins and outs. Annu Rev Immunol. 2008;26:205–32.

    Article  CAS  PubMed  Google Scholar 

  • Moller GM, Overbeek SE, Van Helden-Meeuwsen CG, Van Haarst JM, Prens EP, Mulder PG, et al. Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clin Exp Allergy. 1996;26:517–24.

    Article  CAS  PubMed  Google Scholar 

  • Ober C. Susceptibility genes in asthma and allergy. Curr Allergy Asthma Rep. 2001;1:174–9.

    Article  CAS  PubMed  Google Scholar 

  • Ober C, Leavitt SA, Tsalenko A, Howard TD, Hoki DM, Daniel R, et al. Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations. Am J Hum Genet. 2000;66:517–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oettgen HC, Geha RS. IgE regulation and roles in asthma pathogenesis. J Allergy Clin Immunol. 2001;107:429–40.

    Article  CAS  PubMed  Google Scholar 

  • Pejler G, Ronnberg E, Waern I, Wernersson S. Mast cell proteases: multifaceted regulators of inflammatory disease. Blood. 2010;115:4981–90.

    Article  CAS  PubMed  Google Scholar 

  • Platts-Mills TAE. The continuing effect of the discovery of IgE by Kimishige Ishizaka. J Allergy Clin Immunol. 2018;142:788–9.

    Article  PubMed  Google Scholar 

  • Platts-Mills TA, Rakes G, Heymann PW. The relevance of allergen exposure to the development of asthma in childhood. J Allergy Clin Immunol. 2000;105:S503–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Platts-Mills TA, Heymann PW, Commins SP, Woodfolk JA. The discovery of IgE 50 years later. Ann Allergy Asthma Immunol. 2016;116:179–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Polukort SH, et al. IL-10 enhances IgE-mediated mast cell responses and is essential for the development of experimental food allergy in IL-10-deficient mice. J Immunol. 2016;196:4865–76.

    Article  CAS  PubMed  Google Scholar 

  • Postma DS, Rabe KF. The asthma-COPD overlap syndrome. N Engl J Med. 2015;373:1241–9.

    Article  CAS  PubMed  Google Scholar 

  • Postma DS, Bleecker ER, Amelung PJ, Holroyd KJ, Xu J, Panhuysen CI, et al. Genetic susceptibility to asthma--bronchial hyperresponsiveness coinherited with a major gene for atopy. N Engl J Med. 1995;333:894–900.

    Article  CAS  PubMed  Google Scholar 

  • Pulendran B, Artis D. New paradigms in type 2 immunity. Science. 2012;337:431–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reynolds LA, Finlay BB. Early life factors that affect allergy development. Nat Rev Immunol. 2017;17:518–28.

    Article  CAS  PubMed  Google Scholar 

  • Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992;326:298–304.

    Article  CAS  PubMed  Google Scholar 

  • Saluzzo S, Gorki AD, Rana BMJ, Martins R, Scanlon S, Starkl P, et al. First-breath-induced type 2 pathways shape the lung immune environment. Cell Rep. 2017;18:1893–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scanlon ST, McKenzie AN. The messenger between worlds: the regulation of innate and adaptive type-2 immunity by innate lymphoid cells. Clin Exp Allergy. 2015;45:9–20.

    Article  CAS  PubMed  Google Scholar 

  • Shirakawa I, Deichmann KA, Izuhara I, Mao I, Adra CN, Hopkin JM. Atopy and asthma: genetic variants of IL-4 and IL-13 signalling. Immunol Today. 2000;21:60–4.

    Article  CAS  PubMed  Google Scholar 

  • Stanworth DR. The discovery of IgE. Allergy. 1993;48:67–71.

    Article  CAS  PubMed  Google Scholar 

  • Torgerson DG, Ampleford EJ, Chiu GY, Gauderman WJ, Gignoux CR, Graves PE, et al. Meta-analysis of genome-wide association studies of asthma in ethnically diverse north American populations. Nat Genet. 2011;43:887–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trejo Bittar HE, Yousem SA, Wenzel SE. Pathobiology of severe asthma. Annu Rev Pathol. 2015;10:511–45.

    Article  CAS  PubMed  Google Scholar 

  • Umetsu DT, McIntire JJ, Akbari O, Macaubas C, DeKruyff RH. Asthma: an epidemic of dysregulated immunity. Nat Immunol. 2002;3:715–20.

    Article  CAS  PubMed  Google Scholar 

  • van Rijt L, von Richthofen H, van Ree R. Type 2 innate lymphoid cells: at the cross-roads in allergic asthma. Semin Immunopathol. 2016;38:483–96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Virchow JC Jr, Walker C, Hafner D, Kortsik C, Werner P, Matthys H, et al. T cells and cytokines in bronchoalveolar lavage fluid after segmental allergen provocation in atopic asthma. Am J Respir Crit Care Med. 1995;151:960–8.

    PubMed  Google Scholar 

  • Walker C, Kaegi MK, Braun P, Blaser K. Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol. 1991;88:935–42.

    Article  CAS  PubMed  Google Scholar 

  • Wenzel SE. Emergence of biomolecular pathways to define novel asthma phenotypes. Type-2 immunity and beyond. Am J Respir Cell Mol Biol. 2016;55:1–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wenzel SE, Balzar S, Ampleford E, Hawkins GA, Busse WW, Calhoun WJ, et al. IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression. Am J Respir Crit Care Med. 2007;175:570–6.

    Article  CAS  PubMed  Google Scholar 

  • Wills-Karp M. Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol. 1999;17:255–81.

    Article  CAS  PubMed  Google Scholar 

  • Wills-Karp M. Interleukin-13 in asthma pathogenesis. Immunol Rev. 2004;202:175–90.

    Article  CAS  PubMed  Google Scholar 

  • Wills-Karp M, Ewart SL. Time to draw breath: asthma-susceptibility genes are identified. Nat Rev Genet. 2004;5:376–87.

    Article  CAS  PubMed  Google Scholar 

  • Wills-Karp Marsha HGKK. Immunological mechanisms of allergic disorders. In: Paul WE, editor. Fundamental immunology. Philadelphia: Lippincott-Raven Publishers; 2003. p. 1439–79.

    Google Scholar 

  • Wills-Karp M, Luyimbazi J, Xu X, Schofield B, Neben TY, Karp CL, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258–61.

    Article  CAS  PubMed  Google Scholar 

  • Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol. 2001;1:69–75.

    Article  CAS  PubMed  Google Scholar 

  • Wright JL, Churg A. Cigarette smoke causes physiologic and morphologic changes of emphysema in the Guinea pig. Am Rev Respir Dis. 1990;142:1422–8.

    Article  CAS  PubMed  Google Scholar 

  • Yiamouyiannis CA, Schramm CM, Puddington L, Stengel P, Baradaran-Hosseini E, Wolyniec WW, et al. Shifts in lung lymphocyte profiles correlate with the sequential development of acute allergic and chronic tolerant stages in a murine asthma model. Am J Pathol. 1999;154:1911–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang DH, Yang L, Cohn L, Parkyn L, Homer R, Ray P, et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity. 1999;11:473–82.

    Article  CAS  PubMed  Google Scholar 

  • Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations (∗). Annu Rev Immunol. 2010;28:445–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, USA

    Clinton B. Mathias

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Editors and Affiliations

  1. Department of Pharmaceutical and Administrative Sciences College of Pharmacy and Health Sciences, Western New England University, Springfield, MA, USA

    Clinton B. Mathias

  2. Pharmaceutical Science and Research School of Pharmacy, Marshall University, Huntington, WV, USA

    Jeremy P. McAleer

  3. Department of Pharmaceutical Sciences School of Pharmacy and Physician Assistant Studies, University of Saint Joseph, Hartford, CT, USA

    Doreen E. Szollosi

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Mathias, C.B. (2020). Respiratory Disorders of the Immune System and Their Pharmacological Treatment. In: Mathias, C., McAleer, J., Szollosi, D. (eds) Pharmacology of Immunotherapeutic Drugs. Springer, Cham. https://doi.org/10.1007/978-3-030-19922-7_4

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