Skip to main content
SpringerLink
Log in

Pathophysiology of Anaphylaxis

  • Chapter
  • First Online:
Quick Guide to Anaphylaxis

  • 1967 Accesses

Abstract

Exposure to an allergen to which the patient has been previously sensitised is necessary for anaphylaxis. Sensitisation involves the formation of IgE to epitopes on the allergen at initial exposure. B cells are responsible for the secretion of IgE, which is then bound by receptors for IgE (known as FcεRI receptors) with high affinity. These receptors are found on the outer membrane of mast cells and basophils [1–5]. When an allergen is represented, IgE binds and this causes FcεRI receptors to come close to each other and cross-link. Following cross-linkage, a number of tyrosine kinases (e.g. Lyn, syk, fyn) become active intracellularly, allowing both up- and down-regulation of the signalling cascade [3, 4]. The degranulation function of mast cells is dependent upon the influx of calcium to the cell, a process which can be facilitated or inhibited through intracellular signalling mechanisms [3, 6, 7]. Both mast cells and basophils form chemical signalling molecules in advance which can then be released upon demand. These stored molecules include histamine, heparin, tryptase, chymase, and tumour necrosis factor alpha (TNFα). The cells can also secrete inflammatory mediator substances such as platelet-activating factor, nitric oxide, TNFα, the products of the arachidonic acid cycle involving cyclo-oxygenase (PGD2), and those involving lipoxygenase (in particular the leukotrienes LTC4, LTD4, and LTE4), but these are freshly synthesised rather than stored. Interleukins 4, 5, 13 plus GM-CSF may continue to be manufactured by the cell for some hours following exposure [6, 8].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Sampson HA, et al. Second symposium on the definition and management of anaphylaxis: summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117:391–7.

    Article  PubMed  Google Scholar 

  2. Simons FE. Anaphylaxis, killer allergy: long-term management in the community. J Allergy Clin Immunol. 2006;117:367–77.

    Article  PubMed  Google Scholar 

  3. Peavy RD, Metcalfe DD. Understanding the mechanisms of anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8(4):310–5. https://doi.org/10.1097/ACI.0b013e3283036a90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Metcalfe DD, Peavy RD, Gilfillan AM. Mechanisms of mast cell signaling in anaphylaxis. J Allergy Clin Immunol. 2009;124:639–46; quiz 647–648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Boden SR, Burks AW. Anaphylaxis: a history with emphasis on food allergy. Immunol Rev. 2011;242(1):247–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Bansal G, et al. Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13. Nat Immunol. 2008;9:73–80.

    Article  CAS  PubMed  Google Scholar 

  8. Brown SG. The pathophysiology of shock in anaphylaxis. Immunol Allergy Clin N Am. 2007;27:165–75. v.

    Article  Google Scholar 

  9. Simons FER. Anaphylaxis: recent advances in assessment and treatment. J Allergy Clin Immunol. 2009;124:625–36.

    Article  CAS  PubMed  Google Scholar 

  10. Lieberman PL. Anaphylaxis. In: Adkinson Jr NF, Bochner BS, Busse WW, Holgate ST, Lemanske Jr RF, Simons FER, editors. Middleton’s allergy: principles and practice. 7th ed. St. Louis: Mosby; 2009. p. 1027–49.

    Chapter  Google Scholar 

  11. Sampson HA, Burks AW. Adverse reactions to foods. In: Adkinson Jr NF, Bochner BS, Busse WW, Holgate ST, Lemanske Jr RF, Simons FER, editors. Middleton’s allergy: principles and practice. 7th ed. St. Louis: Mosby; 2009. p. 1139–67.

    Chapter  Google Scholar 

  12. Shek LPC, Lee BW. Food allergy in Asia. Curr Opin Allergy Clin Immunol. 2006;6:197–201.

    Article  CAS  PubMed  Google Scholar 

  13. Astier C, Moneret-Vautrin DA, Puillandre E, Bihain BE. First case report of anaphylaxis to quinoa, a novel food in France. Allergy. 2009;64:819–20.

    Article  CAS  PubMed  Google Scholar 

  14. Kleinheinz A, Lepp U, Hausen BM, Petersen A, Becker WM. Anaphylactic reaction to (mixed) fruit juice containing dragon fruit. J Allergy Clin Immunol. 2009;124:841–2.

    Article  PubMed  Google Scholar 

  15. Commins SP, Satinover SM, Hosen J, Mozena J, Borish L, Lewis BD, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2009;123:426–33.

    Article  CAS  PubMed  Google Scholar 

  16. Sanchez-Borges M, Iraola V, Fernandez-Caldas E, Capriles-Hulett A, Caballero-Fonseca F. Dust mite ingestion-associated, exercise-induced anaphylaxis. J Allergy Clin Immunol. 2007;120:714–6.

    Article  PubMed  Google Scholar 

  17. Petithory JC. New data on anisakiasis. Bull Acad Natl Med. 2007;191:53–65.

    PubMed  Google Scholar 

  18. Simons FER. Anaphylaxis. J Allergy Clin Immunol. 2010;125(2):S161–81.

    Article  PubMed  Google Scholar 

  19. Celik W, Pichler WJ, Adkinson NF Jr. Drug allergy. In: Adkinson Jr NF, Bochner BS, Busse WW, Holgate ST, Lemanske Jr RF, Simons FER, editors. Middleton’s allergy: principles and practice. 7th ed. St. Louis: Mosby; 2009. p. 1205–26.

    Chapter  Google Scholar 

  20. Novembre E, Mori F, Pucci N, Bernardini R, Romano A. Cefaclor anaphylaxis in children. Allergy. 2009;64:1233–5.

    Article  CAS  PubMed  Google Scholar 

  21. Berges-Gimeno M, Martin-Lazaro J. Allergic reactions to nonsteroidal anti-inflammatory drugs: is newer better? Curr Allergy Asthma Rep. 2007;7:35–40.

    Article  CAS  PubMed  Google Scholar 

  22. Perez-Calderon R, Gonzalo-Garijo MA. Anaphylaxis due to loperamide. Allergy. 2004;59:369–70.

    Article  CAS  PubMed  Google Scholar 

  23. Kishimoto TK, Viswanathan K, Ganguly T, Elankumaran S, Smith S, Pelzer K, et al. Contaminated heparin associated with adverse clinical events and activation of the contact system. N Engl J Med. 2008;358:2457–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nishitani N, Adachi A, Fukumoto T, Ueno M, Fujiwara N, Ogura K, et al. Folic acid-induced anaphylaxis showing cross-reactivity with methotrexate: a case report and review of the literature. Int J Dermatol. 2009;48:522–4.

    Article  CAS  PubMed  Google Scholar 

  25. Ji KM, Li M, Chen JJ, Zhan ZK, Liu ZG. Anaphylactic shock and lethal anaphylaxis caused by Houttuynia Cordata injection, a herbal treatment in China. Allergy. 2009;64:816–7.

    Article  PubMed  Google Scholar 

  26. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008;358:1109–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cheifetz A, Smedley M, Martin S, Reiter M, Leone G, Mayer L, et al. The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenterol. 2003;98:1315–24.

    Article  CAS  PubMed  Google Scholar 

  28. Limb SL, Starke PR, Lee CE, Chowdhury BA. Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma. J Allergy Clin Immunol. 2007;120:1378–81.

    Article  CAS  PubMed  Google Scholar 

  29. Rezvani M, Bernstein DI. Anaphylactic reactions during immunotherapy. Immunol Allergy Clin N Am. 2007;27:295–307.

    Article  Google Scholar 

  30. Rodriguez-Perez N, Ambriz-Moreno M, Canonica GW, Penagos M. Frequency of acute systemic reactions in patients with allergic rhinitis and asthma treated with sublingual immunotherapy. Ann Allergy Asthma Immunol. 2008;101:304–10.

    Article  CAS  PubMed  Google Scholar 

  31. Kelso JM, Li JT, Nicklas RA, Bernstein DI, Blessing-Moore J, Cox L, et al. Adverse reactions to vaccines. Ann Allergy Asthma Immunol. 2009;103(suppl):S1–S14.

    Article  CAS  PubMed  Google Scholar 

  32. Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A, et al. Postlicensure safety surveillance for quadrivalent human papillomavirus recombinant vaccine. JAMA. 2009;302:750–7.

    Article  CAS  PubMed  Google Scholar 

  33. Erlewyn-Lajeunesse M, Brathwaite N, Lucas JSA, Warner JO. Recommendations for the administration of influenza vaccine in children allergic to egg. BMJ. 2009;339:b3680.

    Article  CAS  PubMed  Google Scholar 

  34. Zanoni G, Puccetti A, Dolcino M, Simone R, Peretti A, Ferro A, et al. Dextran-specific IgG response in hypersensitivity reactions to measles-mumps-rubella vaccine. J Allergy Clin Immunol. 2008;122:1233–5.

    Article  CAS  PubMed  Google Scholar 

  35. Golden DBK. Insect allergy. In: Adkinson Jr NF, Bochner BS, Busse WW, Holgate ST, Lemanske Jr RF, Simons FER, editors. Middleton’s allergy: principles and practice. 7th ed. St. Louis: Mosby; 2009. p. 1005–17.

    Chapter  Google Scholar 

  36. Bilo MB, Bonifazi F. The natural history and epidemiology of insect venom allergy: clinical implications. Clin Exp Allergy. 2009;39:1467–76.

    Article  CAS  PubMed  Google Scholar 

  37. Freeman TM. Clinical practice. Hypersensitivity to hymenoptera stings. N Engl J Med. 2004;351:1978–84.

    Article  CAS  PubMed  Google Scholar 

  38. Tankersley MS. The stinging impact of the imported fire ant. Curr Opin Allergy Clin Immunol. 2008;8:354–9.

    Article  PubMed  Google Scholar 

  39. Shek LPC, Ngiam NSP, Lee BW. Ant allergy in Asia and Australia. Curr Opin Allergy Clin Immunol. 2004;4:325–8.

    Article  PubMed  Google Scholar 

  40. Peng Z, Beckett AN, Engler RJ, Hoffman DR, Ott NL, Simons FER. Immune responses to mosquito saliva in 14 individuals with acute systemic allergic reactions to mosquito bites. J Allergy Clin Immunol. 2004;114:1189–94.

    Article  CAS  PubMed  Google Scholar 

  41. Yunginger JW. Natural rubber latex allergy. In: Adkinson Jr NF, Bochner BS, Busse WW, Holgate ST, Lemanske Jr RF, Simons FER, editors. Middleton’s allergy: principles and practice. 7th ed. St. Louis: Mosby; 2009. p. 1019–26.

    Chapter  Google Scholar 

  42. Basagana M, Bartolome B, Pastor C, Torres F, Alonso R, Vivanco F, et al. Allergy to human seminal fluid: cross-reactivity with dog dander. J Allergy Clin Immunol. 2008;121:233–9.

    Article  CAS  PubMed  Google Scholar 

  43. Gawlik R, Pitsch T. Allergy to horse. Ann Allergy Asthma Immunol. 2006;96:631.

    Article  CAS  PubMed  Google Scholar 

  44. Ogawa Y, Grant JA. Mediators of anaphylaxis. Immunol Allergy Clin N Am. 2007;27:249–60.

    Article  Google Scholar 

  45. Simons FE, Frew AJ, Ansotegui IJ, et al. Risk assessment in anaphylaxis: current and future approaches. J Allergy Clin Immunol. 2007;120:S2–24.

    Article  CAS  PubMed  Google Scholar 

  46. Finkelman FD, Rothenberg ME, Brandt EB, et al. Molecular mechanisms of anaphylaxis: lessons from studies with murine models. J Allergy Clin Immunol. 2005;115:449–57.

    Article  CAS  PubMed  Google Scholar 

  47. Strait RT, Morris SC, Yang M, et al. Pathways of anaphylaxis in the mouse. J Allergy Clin Immunol. 2002;109:658–68.

    Article  CAS  PubMed  Google Scholar 

  48. Baeza ML, Zubeldia JM. Immunology of anaphylaxis: lessons from murine models. Curr Allergy Asthma Rep. 2007;7:49–55.

    Article  CAS  PubMed  Google Scholar 

  49. Nauta A, Knippels L, Garssen J, Redegeld F. Animal models of anaphylaxis. Curr Opin Allergy Clin Immunol. 2007;7:355–9.

    Article  PubMed  Google Scholar 

  50. Finkelman FD. Anaphylaxis: lessons from mouse models. J Allergy Clin Immunol. 2007;120(3):506–15; quiz 516–7.

    Article  CAS  PubMed  Google Scholar 

  51. Nieuwenhuizen N, Herbert DR, Lopata AL, Brombacher F. CD4+ T cell-specific deletion of IL-4 receptor alpha prevents ovalbumin-induced anaphylaxis by an IFN-gamma-dependent mechanism. J Immunol. 2007;179:2758–65.

    Article  CAS  PubMed  Google Scholar 

  52. Johansson SG, Bieber T, Dahl R, Friedmann PS, Lanier BQ, Lockey RF, et al. Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J Allergy Clin Immunol. 2004;113(5):832–6.

    Article  CAS  PubMed  Google Scholar 

  53. Mustafa SS. Anaphylaxis. In: Kaliner MA, editor. Medscape. http://emedicine.medscape.com/article/135065-overview#showall. Accessed 10 July 2016.

  54. Wang J, Sampson HA. Food anaphylaxis. Clin Exp Allergy. 2007;37(5):651–60.

    Article  CAS  PubMed  Google Scholar 

  55. Osborne NJ, Koplin JJ, Martin PE, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol. 2011;127(3):668–76.e1–2.

    Article  CAS  PubMed  Google Scholar 

  56. Hourihane JO’B, Kilburn SA, Nordlee JA, Hefle SL, Taylor SL, Warner JO. An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein: a randomized, double-blind, placebo-controlled food challenge study. J Allergy Clin Immunol. 1997;100(5):596–600.

    Article  Google Scholar 

  57. Decker WW, Campbell RL, Manivannan V, et al. The etiology and incidence of anaphylaxis in Rochester, Minnesota: a report from the Rochester Epidemiology Project. J Allergy Clin Immunol. 2008;122(6):1161–5. [Medline]. [Full Text].

    Article  PubMed  PubMed Central  Google Scholar 

  58. Greenhawt MJ, Li JT, Bernstein DI, et al. Administering influenza vaccine to egg allergic recipients: a focused practice parameter update. Ann Allergy Asthma Immunol. 2011;106(1):11–6.

    Article  PubMed  Google Scholar 

  59. Centers for Disease Control and Prevention. Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011;60(33):1128–32. [Guideline].

    Google Scholar 

  60. Mertes PM, Malinovsky JM, Jouffroy L, et al. Reducing the risk of anaphylaxis during anesthesia: 2011 updated guidelines for clinical practice. J Investig Allergol Clin Immunol. 2011;21(6):442–53.

    CAS  PubMed  Google Scholar 

  61. Golden DB. Insect sting anaphylaxis. Immunol Allergy Clin N Am. 2007;27(2):261–72.

    Article  Google Scholar 

  62. Gilfillan AM, Tkaczyk C. Integrated signalling pathways for mast-cell activation. Nat Rev Immunol. 2006;6:218–30.

    Article  CAS  PubMed  Google Scholar 

  63. Tkaczyk C, Okayama Y, Metcalfe DD, Gilfillan AM. Fcgamma receptors on mast cells: activatory and inhibitory regulation of mediator release. Int Arch Allergy Immunol. 2004;133:305–15.

    Article  CAS  PubMed  Google Scholar 

  64. Hong H, Kitaura J, Xiao W, et al. The Src family kinase Hck regulates mast cell activation by suppressing an inhibitory Src family kinase Lyn. Blood. 2007;110:2511–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Xiao W, Nishimoto H, Hong H, et al. Positive and negative regulation of mast cell activation by Lyn via the FcepsilonRI. J Immunol. 2005;175:6885–92.

    Article  CAS  PubMed  Google Scholar 

  66. Parravicini V, Gadina M, Kovarova M, et al. Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nat Immunol. 2002;3:741–8.

    Article  CAS  PubMed  Google Scholar 

  67. Bansal G, Xie Z, Rao S, et al. Suppression of immunoglobulin E-mediated allergic responses by regulator of G protein signaling 13. Nat Immunol. 2008;9:73–80.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. ENT Department, Faculty of Medicine, Eskişehir Osmangazi University, Eskisehir, Turkey

    Cemal Cingi

  2. ENT Department, Faculty of Medicine, Kırıkkale University, Kırıkkale, Turkey

    Nuray Bayar Muluk

Authors
  1. Cemal Cingi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nuray Bayar Muluk
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cingi, C., Bayar Muluk, N. (2020). Pathophysiology of Anaphylaxis. In: Quick Guide to Anaphylaxis. Springer, Cham. https://doi.org/10.1007/978-3-030-33639-4_3

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-33639-4_3

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-33638-7

  • Online ISBN: 978-3-030-33639-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation