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Understanding of the Molecular Mechanisms of Allergy

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Allergy

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2020))

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Abstract

The prevalence of allergic disease has dramatically increased over the past 30 years in Westernized countries. It is unlikely that the rapid increase in the prevalence of allergic disease is the result of genetic changes, which highlights the importance of environmental factors in the development of allergic disease. The “hygiene hypothesis” was put forward in 1989 and focused attention on the notion that exposure to microbes and their products in early life can modify the risk for development of allergic disease. Infections were thought to polarize the immunological response toward a Th2-mediated immune response causing allergic disease. However, it is likely that the Th1/Th2 imbalance is too simplistic to explain the increased prevalence of allergic disease. Current research is focusing on understanding the role of T-regulatory cells in inducing a state of tolerance and the resulting modified Th2 response observed in natural and induced tolerance.

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References

  1. Kay AB (2001) Allergy and allergic diseases. N Engl J Med 344:30–37

    Article  CAS  PubMed  Google Scholar 

  2. Johansson SGO, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T et al (2001) A revised nomenclature for allergy. Allergy 56:813–824

    Article  CAS  PubMed  Google Scholar 

  3. Holt PG, Thomas WR (2005) Sensitization to airborne environmental allergens: unresolved issues. Nat Immunol 6:957–960

    Article  CAS  PubMed  Google Scholar 

  4. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee (1998) Worldwide variation in prevalence of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 351:1225–1232

    Article  Google Scholar 

  5. Aberg N, Hesselmar B, Aberg B, Eriksson B (1995) Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991. Clin Exp Allergy 25:815–819

    Article  CAS  PubMed  Google Scholar 

  6. Celedon JC, Soto-Quiros ME, Hanson LA, Weiss ST (2002) The relationship among markers of allergy, asthma, allergic rhinitis, and eczema in Costa Rica. Pediatr Allergy Immunol 13:91–97

    Article  PubMed  Google Scholar 

  7. Ninan TK, Russell G (1992) Respiratory symptoms and atopy in Aberdeen school-children: evidence from two surveys 25 years apart. BMJ 304:873–875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. von Mutius E, Martinez FD, Fritzch C, Nicolai T, Roell G, Thiemann HH (1994) Prevalence of asthma and atopy in two areas of east and West Germany. Am J Respir Crit Care Med 149:358–364

    Article  Google Scholar 

  9. von Mutius E, Weiland SK, Fritasch C, Duhme H, Keil U (1998) Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany. Lancet 351:862–866

    Article  Google Scholar 

  10. Upham JW, Holt PG (2005) Environment and development of atopy. Curr Opin Allergy Clin Immunol 5:67–172

    Article  Google Scholar 

  11. Strachan DP (1989) Hay fever, hygiene and household size. BMJ 299:1259–1260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mosmann TR, Coffman RL (1989) Th1 and Th2 cells: differential patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145–173

    Article  CAS  PubMed  Google Scholar 

  13. Romagnani S (1994) Lymphokine production by human T cells in disease states. Annu Rev Immunol 12:27–257

    Article  Google Scholar 

  14. Cooke A, Zaccone P, Raine T, Phillips JM, Dunne DW (2004) Infection and autoimmunity: are we winning the war, only to lose the peace? Trends Parasitol 20:316–321

    Article  PubMed  Google Scholar 

  15. Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347:911–920

    Article  PubMed  Google Scholar 

  16. Strachan DP (1997) Allergy and family size, a riddle worth solving. Clin Exp Allergy 27:235–236

    Article  CAS  PubMed  Google Scholar 

  17. Karmaus W, Botezan C (2002) Does a higher number of siblings protect against the development of allergy and asthma? A review. J Epidemiol Community Health 56:209–217

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cullinan P (2006) Childhood allergies, birth order and family size. Thorax 61:3–5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sacks G, Sargent I, Redman C (1999) An innate view of human pregnancy. Immunol Today 20:114–118

    Article  CAS  PubMed  Google Scholar 

  20. Karmaus W, Arshad SH, Sadeghnejad A, Twiselton R (2004) Does maternal immunoglobulin E decrease with increasing order of live offspring? Investigation into maternal immune tolerance. Clin Exp Allergy 34:853–859

    Article  CAS  PubMed  Google Scholar 

  21. Westergaard T, Begtrup K, Rostgaard K, Krause TG, Benn CS, Melbye M (2003) Reproductive history and allergic rhinitis among 31145 Danish women. Clin Exp Allergy 33:301–305

    Article  CAS  PubMed  Google Scholar 

  22. Forastiere F, Sunyer J, Farchi S, Corbo G, Pistelli R, Baldacci S et al (2005) Number of offspring and maternal allergy. Allergy 60:510–514

    Article  CAS  PubMed  Google Scholar 

  23. Devereux G, Barker RN, Seaton A (2002) Antenatal determinants of neonatal immune responses to allergens. Clin Exp Allergy 32:43–50

    Article  CAS  PubMed  Google Scholar 

  24. Sunyer J, Anto JM, Harris J, Torrent M, Vall O, Cullinan P et al (2001) Maternal atopy and parity. Clin Exp Allergy 31:1352–1355

    Article  CAS  PubMed  Google Scholar 

  25. Karmaus W, Eneli I (2003) Maternal atopy and the number of offspring, is there an association? Pediatr Allergy Immunol 14:470–474

    Article  PubMed  Google Scholar 

  26. Harris JM, White C, Moffat S, Mills P, Newman Taylor AJ, Cullinan P (2004) New pregnancies and loss of allergy. Clin Exp Allergy 34:369–372

    Article  CAS  PubMed  Google Scholar 

  27. Aluvihare VR, Kallikourdis M, Betz AG (2004) Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 5:266–271

    Article  CAS  PubMed  Google Scholar 

  28. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT (2004) Normal human pregnancy is associated with an elevation in the immune suppressive CD25+CD4+ regulatory T-cell subset. Immunology 112:38–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Prescott SL, Taylor A, Roper J, Wahdan A, Noakes P et al (2005) Maternal reactivity to fetal alloantigens is related to newborn immune responses and subsequent allergic disease. Clin Exp Allergy 35:417–425

    Article  CAS  PubMed  Google Scholar 

  30. Thomas W, Hales B, Smith W (2005) Genetically engineered vaccines. Curr Allergy Asthma Rep 5:388–393

    Article  CAS  PubMed  Google Scholar 

  31. Platts-Mills T, Vaughan J, Squillace S, Woodfolk J, Sporik R (2001) Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen, a population-based cross-sectional study. Lancet 357:752–756

    Article  CAS  PubMed  Google Scholar 

  32. Cullinan P, MacNeill SJ, Harris J, Moffat S, White C, Mills P et al (2004) Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children, a cohort study. Thorax 59:855–861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Woodcock A, Lowe LA, Murray CS, Simpson BM, Pipis SD, Kissen P et al (2004) National Asthma Campaign Manchester Asthma and Allergy Study Group. Early life environmental control, effect on symptoms, sensitization, and lung function at age 3 years. Am J Respir Crit Care Med 170:433–439

    Article  PubMed  Google Scholar 

  34. Perzanowski MS, Ronmark E, Platts-Mills TA, Lundback B (2002) Effect of cat and dog ownership on sensitization and development of asthma among pre-teenage children. Am J Respir Crit Care Med 166:696–702

    Article  PubMed  Google Scholar 

  35. Ownby DR, Johnson CC, Peterson EL (2002) Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 288:963–972

    Article  PubMed  Google Scholar 

  36. Custovic A, Simpson BM, Simpson A, Hallam CL, Marolia H, Walsh D et al (2003) National Asthma Campaign Manchester Asthma and Allergy Study Group. Current mite, cat, and dog allergen exposure, pet ownership, and sensitization to inhalant allergens in adults. J Allergy Clin Immunol 111:402–407

    Article  CAS  PubMed  Google Scholar 

  37. Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J (2003) Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 197:403–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tulic MK, Holt PG, Sly PD (2002) Modification of acute and late-phase allergic responses to ovalbumin with lipopolysaccharide. Int Arch Allergy Immunol 129:119–128

    Article  CAS  PubMed  Google Scholar 

  39. Portengen L, Preller L, Tielen M, Doekes G, Heederik D (2005) Endotoxin exposure and atopic sensitization in adult pig farmers. J Allergy Clin Immunol 115:797–802

    Article  CAS  PubMed  Google Scholar 

  40. Lau S, Illi S, Platts-Mills TA, Riposo D, Nickel R, Gruber C, Niggemann B et al (2005) Multicentre Allergy Study Group. Longitudinal study on the relationship between cat allergen and endotoxin exposure, sensitization, cat-specific IgG and development of asthma in childhood--report of the German Multicentre Allergy Study (MAS 90). Allergy 60:766–773

    Article  CAS  PubMed  Google Scholar 

  41. Platts-Mills JA, Custis NJ, Woodfolk JA, Platts-Mills TA (2005) Airborne endotoxin in homes with domestic animals, implications for cat-specific tolerance. J Allergy Clin Immunol 116:384–389

    Article  CAS  PubMed  Google Scholar 

  42. Lieutier-Colas F, Meyer P, Pons F, Edelin G, Larsson P, Malmberg P et al (2002) Prevalence of symptoms, sensitization to rats, and airborne exposure to major rat allergen (Rat n 1) and to endotoxin in rat-exposed workers, a cross-sectional study. Clin Exp Allergy 32:1424–1429

    Article  CAS  PubMed  Google Scholar 

  43. Dahlgren MW, Molofsky AB (2018) All along the watchtower: group 2 innate lymphoid cells in allergic responses. Curr Opin Immunol 54:13–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Crawford G, Hayes MD, Seoane RC et al (2018) Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response. Nat Immunol 19:859–870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jeal H, Draper A, Harris J, Newman Taylor A, Cullinan P, Jones M (2004) Determination of the T cell epitopes of the lipocalin allergen, rat n 1. Clin Exp Allergy 34:1919–1925

    Article  CAS  PubMed  Google Scholar 

  46. Ebner C, Schenk S, Najafian N, Siemann U, Steiner R, Fischer GW et al (1995) Nonallergic individuals recognize the same T cell epitopes of Bet v 1, the major birch pollen allergen, as atopic patients. J Immunol 154:1932–1940

    CAS  PubMed  Google Scholar 

  47. O’Hehir RE, Verhoef A, Panagiotopoulou E, Keswani S, Hayball JD, Thomas WR et al (1993) Analysis of human T cell responses to the group II allergen of Dermatophagoides species, localization of major antigenic sites. J Allergy Clin Immunol 92:105–113

    Article  PubMed  Google Scholar 

  48. Verhoef A, Higgins JA, Thorpe CJ, Marsh SG, Hayball JD, Lamb JR et al (1993) Clonal analysis of the atopic immune response to the group 2 allergen of Dermatophagoides spp, identification of HLA-DR and -DQ restricted T cell epitopes. Int Immunol 5:1589–1597

    Article  CAS  PubMed  Google Scholar 

  49. Van Neerven RJ, Van de Pol MM, Van Milligen FJ, Jansen HM, Aalberse RC, Kapsenberg ML (1994) Characterisation of cat ander-specific T lymphocytes from atopic patients. J Immunol 152:4203–4210

    PubMed  Google Scholar 

  50. Carballido JM, Carballido-Perrig N, Kagi MK, Meloen RH, Wuthrich B, Heusser CH et al (1993) T cell epitope specificity in human allergic and nonallergic subjects to bee venom phospholipase A2. J Immunol 150:3582–3591

    CAS  PubMed  Google Scholar 

  51. Hesselmar B, Aberg B, Eriksson B, Bjorksten B, Aberg N (2003) High-dose exposure to cat is associated with clinical tolerance--a modified Th2 immune response? Clin Exp Allergy 33:1681–1685

    Article  CAS  PubMed  Google Scholar 

  52. Jeal H, Draper A, Harris J, Newman Taylor AJ, Cullinan P, Jones M (2006) Modified TH2 responses at high dose exposures to allergen. Using an occupational model. Am J Respir Crit Care Med 174(1):21–25

    Article  CAS  PubMed  Google Scholar 

  53. Cullinan P, Cook A, Gordon S, Nieuwenhuijsen MJ, Tee RD, Venables KM et al (1999) Allergen exposure, atopy and smoking as determinants of allergy to rats in a cohort of laboratory employees. Eur Respir J 13:1139–1143

    Article  CAS  PubMed  Google Scholar 

  54. Holt PG (1994) A potential vaccine strategy for asthma and allied atopic diseases during early childhood. Lancet 344:456–458

    Article  CAS  PubMed  Google Scholar 

  55. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K et al (2003) IL-10 and TGF-Beta cooperate in the regulatory cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33:1205–1214

    Article  CAS  PubMed  Google Scholar 

  56. Jutel M, Akdis M, Blaser K, Akdis CA (2005) Are regulatory T cells the target of venom immunotherapy? Curr Opin Allergy Clin Immunol 116:608–613

    Article  CAS  Google Scholar 

  57. Dombrowicz D (2005) Exploiting the innate immune system to control allergic asthma. Eur J Immunol 35:2786–2788

    Article  CAS  PubMed  Google Scholar 

  58. Akbari O, Faul JL, Hoyte EG, Berry GJ, Wahlstrom J, Kronenberg M et al (2006) CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma. N Engl J Med 354:1117–1129

    Article  CAS  PubMed  Google Scholar 

  59. Akbari O, DeKruyff RH, Umetsu DT (2001) Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2:725–731

    Article  CAS  PubMed  Google Scholar 

  60. Hawrylowicz CM (2005) Regulatory T cells and IL-10 in allergic inflammation. J Exp Med 202:1459–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Akdis CA, Blaser K (1999) IL-10 induced anergy in peripheral T cell and reactivation by microenvironmental cytokines, two key steps in specific immunotherapy. FASEB J 13:603–609

    Article  CAS  PubMed  Google Scholar 

  62. Ling EM, Robinson DS (2004) Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease. Lancet 363:608–615

    Article  CAS  PubMed  Google Scholar 

  63. Bellinghausen I, Konig B, Bottcher I, Knop J, Saloga J (2005) Regulatory activity of human CD4+CD25+ T cells depends on allergen concentration, type of allergen and atopy status of the donor. Immunology 116:103–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Verhoef A, Alexander C, Kay AB, Larche M (2005) T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity. PLoS Med 2(3):e78

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Francis JN, Till SJ, Durham SR (2003) Induction of IL-10+CD4+CD25+ T cells by grass pollen immunotherapy. J Allergy Clin Immunol 111:1255–1261

    Article  CAS  PubMed  Google Scholar 

  66. Tarzi M, Klunker S, Texier C, Verhoef A, Stapel SO, Akdis CA et al (2006) Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy 36:465–474

    Article  CAS  PubMed  Google Scholar 

  67. Akdis CA, Blesken T, Akdis M, Wuthrich B, Blaser K (1998) Role of interleukin 10 in specific immunotherapy. J Clin Invest 102:98–106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Akdis M, Blaser K, Akdis CA (2005) T regulatory cells in allergy, novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J Allergy Clin Immunol 116:961–968

    Article  CAS  PubMed  Google Scholar 

  69. Woodfolk JA (2005) High-dose allergen exposure leads to tolerance. Clin Rev Allergy Immunol 28:43–58

    Article  CAS  PubMed  Google Scholar 

  70. Jones MG, Nielsen J, Welch J, Harris J, Welinder H, Bensryd I et al (2004) Association of HLA-DQ5 and HLA-DR1 with sensitization to organic acid anhydrides. Clin Exp Allergy 34:812–816

    Article  CAS  PubMed  Google Scholar 

  71. Map CE, Balboni A, Baricordi R, Fabbri LM (1997) Human leukocyte antigen associations in occupational asthma induced by isocyanates. Am J Respir Crit Care Med 156:S139–S143

    Article  Google Scholar 

  72. Newman Taylor AJ, Cullinan P, Lympany PA, Harris JM, Dowdeswell RJ, du Bois RM (1999) Interaction of HLA phenotype and exposure intensity in sensitization to complex platinum salts. Am J Respir Crit Care Med 160:435–438

    Article  CAS  PubMed  Google Scholar 

  73. Young RP, Barker RD, Pile KD, Cookson WO, Newman Taylor AJ (1995) The association of HLA-DR3 with specific IgE to inhaled acid anhydrides. Am J Respir Crit Care Med 151:219–221

    Article  CAS  PubMed  Google Scholar 

  74. Jeal H, Draper A, Jones M, Harris J, Welsh K, Newman Taylor A, Cullinan P (2003) HLA associations with occupational sensitisation to rat lipocalin allergens, a model for other animal allergies? J Allergy Clin Immunol 111:759–759

    Article  CAS  Google Scholar 

  75. Francis J, Larche M (2005) Peptide-based vaccination, where do we stand? Curr Opin Allergy Clin Immunol 5:537–543

    Article  CAS  PubMed  Google Scholar 

  76. van de Veen W, Stanic B, Wirz OF et al (2016) Role of regulatory B cells in immune tolerance to allergens and beyond. J Allergy Clin Immunol 138:654–665

    Article  PubMed  CAS  Google Scholar 

  77. Gehlhar K, Schlaak M, Becker W, Bufe A (1999) Monitoring allergen immunotherapy of pollen-allergic patients, the ratio of allergen-specific IgG4 to IgG1 correlates with clinical outcome. Clin Exp Allergy 29:497–506

    Article  CAS  PubMed  Google Scholar 

  78. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz MA, Blaser K (2003) IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33:1205–1214

    Article  CAS  PubMed  Google Scholar 

  79. Nouri-Aria KT, Wachholz PA, Francis JN, Jabobson MR, Walker SM, Wilcock LK et al (2004) Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 172:3252–3259

    Article  CAS  PubMed  Google Scholar 

  80. Djurup R, Osterballe O (1984) IgG subclass antibody response in grass pollen-allergic patients undergoing specific immunotherapy. Prognostic value of serum IgG subclass antibody levels early in immunotherapy. Allergy 39:433–441

    Article  CAS  PubMed  Google Scholar 

  81. Golden DB, Meyers DA, Kagey-Sobotka A, Valentine MD, Lichtenstein LM (1982) Clinical relevance of the venom-specific immunoglobulin G antibody level during immunotherapy. J Allergy Clin Immunol 69:489–493

    Article  CAS  PubMed  Google Scholar 

  82. Daeron M, Malbec O, Latour S, Arock M, Fridman WH (1995) Regulation of high affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors. J Clin Invest 95:577–585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Daeron M (1997) Negative regulation of mast cell activation by receptors for IgG. Int Arch Allergy Immunol 113:138–141

    Article  CAS  PubMed  Google Scholar 

  84. Zhu D, Kepley CL, Zhang M, Zhang K, Saxon A (2002) A novel human immunoglobulin Fc gamma Fc epsilon bifunctional fusion protein inhibits Fc epsilon R1-mediated degranulation. Nat Med 8:518–521

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ball T, Sperr WR, Valent P, Lidholm J, Spitzauer S, Ebner C et al (1999) Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy. Eur J Immunol 29:2026–2036

    Article  CAS  PubMed  Google Scholar 

  86. Wachholz PA, Durham SR (2003) Induction of ‘blocking’ IgG antibodies during immunotherapy. Clin Exp Allergy 33:1171–1174

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Occupational and Environmental Medicine, Imperial College London, London, UK

    Meinir G. Jones

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  1. Core Facilities, St. George’s University of London, London, UK

    Penny Lympany

  2. Department of Occupational and Environmental Medicine, Imperial College London, London, UK

    Meinir G. Jones

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Jones, M.G. (2019). Understanding of the Molecular Mechanisms of Allergy. In: Lympany, P., Jones, M. (eds) Allergy. Methods in Molecular Biology, vol 2020. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9591-2_1

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  • DOI: https://doi.org/10.1007/978-1-4939-9591-2_1

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