Overview of the Immunology of Food Allergy

  • Linglin Fu
  • Bobby J. Cherayil
  • Haining Shi
  • Yanbo Wang
  • Yang Zhu


Food allergies are caused by an abnormal immune response to ingested antigens. They manifest as urticaria, nausea, vomiting, abdominal pain, or anaphylaxis, usually within a short period after consumption of the relevant food, and can be either IgE-dependent or IgE-independent. They affect large numbers of people, particularly children in industrialized countries, and represent an important and increasing public health problem. The pathogenesis of food allergy involves a failure of the mechanisms that normally prevent or control immune reactivity to orally administered antigens. Treatment strategies include avoidance of the offending dietary component, control of symptoms with the appropriate pharmacologic agents, and immunologic approaches directed at restoring nonresponsiveness to the relevant allergen. This chapter will review current concepts in the immunology and treatment of food allergy.


  1. Bégin P et al (2014) Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using Omalizumab. Allergy Asthma Clin Immunol 10:1–10CrossRefGoogle Scholar
  2. Bingemann TA, Sood P, Jã¤Rvinen KM (2018) Food protein-induced enterocolitis syndrome. Immunol Allergy Clin N Am 38:141–152CrossRefGoogle Scholar
  3. Bird JA et al (2016) Conducting an oral food challenge to peanut in an infant. J Allergy Clin Immunol Pract 5:301–311.e1PubMedGoogle Scholar
  4. Boyce JA et al (2011) Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. Nutrition 27:253CrossRefGoogle Scholar
  5. Burks AW, Sampson HA, Plaut M, Lack G, Akdis CA (2018) Treatment for food allergy. J Allergy Clin Immunol 141:1–9CrossRefGoogle Scholar
  6. Church MK, Kolkhir P, Metz M, Maurer M (2018) The role and relevance of mast cells in urticaria. Immunol Rev 282:232–247CrossRefGoogle Scholar
  7. Commins SP (2017) Outpatient emergencies: anaphylaxis. Med Clin N Am 101:521–536CrossRefGoogle Scholar
  8. Czarnowicki T, Krueger JG, Guttman-Yassky E (2017) Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol 139:1723CrossRefGoogle Scholar
  9. Daniel M, Nino K, Agustin E, Momtchilo R, Lafaille JJ, Lafaille MA, Curotto D (2005) Oral tolerance in the absence of naturally occurring Tregs. J Clin Investig 115:1923–1933CrossRefGoogle Scholar
  10. Devasmitha V et al (2014) Filaggrin loss-of-function mutations are associated with food allergy in childhood and adolescence. J Allergy Clin Immunol 134:876–882.e874Google Scholar
  11. Domogalla MP, Rostan PV, Raker VK, Steinbrink K (2017) Tolerance through education: how tolerogenic dendritic cells shape immunity. Front Immunol 8:1764CrossRefGoogle Scholar
  12. Du Toit G et al (2015) Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 372:803–813. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Du TG et al (2016) Effect of avoidance on peanut allergy after early peanut consumption. N Engl J Med 374:1435CrossRefGoogle Scholar
  14. Du TG et al (2017) The allergen-specificity of early peanut consumption and the impact on the development of allergic disease in the LEAP Study Cohort. J Allergy Clin Immunol 141:1343–1353Google Scholar
  15. Elisa M, Lucia M, Giuseppe P, Maria R (2014) Oral tolerance can be established via gap junction transfer of fed antigens from CX3CR1? Macrophages to CD103? Dendritic cells. Immunity 40:248–261CrossRefGoogle Scholar
  16. Farbman KS, Michelson KA (2016) Anaphylaxis in children. Curr Opin Pediatr 28:294CrossRefGoogle Scholar
  17. Fleischer DM et al (2015) Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants. World Allergy Org J 8:1–4CrossRefGoogle Scholar
  18. Gensollen T, Iyer SS, Kasper DL, Blumberg RS (2016) How colonization by microbiota in early life shapes the immune system. Science 352:539–544CrossRefGoogle Scholar
  19. Han H, Roan F, Ziegler SF (2017) The atopic march: current insights into skin barrier dysfunction and epithelial cell-derived cytokines. Immunol Rev 278:116CrossRefGoogle Scholar
  20. Hong X et al (2015) Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. Nat Commun 6:6304. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Hong X et al (2016) Epigenome-wide association study links site-specific DNA methylation changes with cow’s milk allergy. J Allergy Clin Immunol 138:908–911.e909CrossRefGoogle Scholar
  22. Huang YJ, Marsland BJ, Bunyavanich S, O’Mahony L, Leung DYM, Muraro A, Fleisher TA (2017) The microbiome in allergic disease: current understanding and future opportunities—2017 PRACTALL document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology Retour Au Numéro. J Allergy Clin Immunol 139:1099CrossRefGoogle Scholar
  23. Jackson KD, Howie LD, Akinbami LJ (2013) Trends in allergic conditions among children: United States, 1997–2011. NCHS Data Brief 121:1–8Google Scholar
  24. Joeris T, Müllerluda K, Agace WW, Mowat AM (2017) Diversity and functions of intestinal mononuclear phagocytes. Mucosal Immunol 10:845CrossRefGoogle Scholar
  25. Kalekar LA, Mueller DL (2017) Relationship between CD4 regulatory T cells and anergy in vivo. J Immunol 198:2527–2533CrossRefGoogle Scholar
  26. Kitagawa Y, Sakaguchi S (2017) Molecular control of regulatory T cell development and function. Curr Opin Immunol 49:64CrossRefGoogle Scholar
  27. Lebwohl B, Sanders DS, Phr G (2017) Coeliac disease. Lancet 391:70–81CrossRefGoogle Scholar
  28. Leonard SA, Caubet JC, Kim JS, Groetch M, Nowak-Węgrzyn A (2015) Baked milk- and egg-containing diet in the management of milk and egg allergy. J Allergy Clin Immunol Pract 3:13–23CrossRefGoogle Scholar
  29. Li XM (2018) Complementary and alternative medicine for treatment of food allergy. Immunol Allergy Clin N Am 38:103–124CrossRefGoogle Scholar
  30. Lieping C, Flies DB (2013) Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 13:227–242CrossRefGoogle Scholar
  31. Loh W, Tang M (2018) Adjuvant therapies in food immunotherapy. Immunol Allergy Clin N Am 38:89–101CrossRefGoogle Scholar
  32. Macginnitie AJ et al (2017) Omalizumab facilitates rapid oral desensitization for peanut allergy. J Allergy Clin Immunol 139:873–881CrossRefGoogle Scholar
  33. Mcdole JR et al (2012) Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Isr Med Assoc J 483:345–349Google Scholar
  34. Ménard S, Cerf-Bensussan N, Heyman M (2010) Multiple facets of intestinal permeability and epithelial handling of dietary antigens. Mucosal Immunol 3:247CrossRefGoogle Scholar
  35. Nadeau KC, Schneider LC, Hoyte L, Borras I, Umetsu DT (2011) Rapid oral desensitization in combination with omalizumab therapy in patients with cow’s milk allergy. J Allergy Clin Immunol 127:1622–1624. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Niess JH, Reinecker HC (2005) CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science 307:254CrossRefGoogle Scholar
  37. Nowak-Węgrzyn A, Assa’Ad AH, Bahna SL, Bock SA, Sicherer SH, Teuber SS (2009) Work Group report: oral food challenge testing. J Allergy Clin Immunol 123:S365–S383CrossRefGoogle Scholar
  38. O’Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, Rothenberg ME (2018) Pathophysiology of eosinophilic esophagitis. Gastroenterology 2:41Google Scholar
  39. Ohno H (2016) Intestinal M cells. J Biochem 159:151CrossRefGoogle Scholar
  40. Osborne NJ et al (2011) Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol 127:668–676.e662CrossRefGoogle Scholar
  41. Reber LL, Hernandez JD, Galli SJ (2017) The pathophysiology of anaphylaxis. J Allergy Clin Immunol 140:335CrossRefGoogle Scholar
  42. Rescigno M et al (2001) Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2:361CrossRefGoogle Scholar
  43. Rock KL, Reits E, Neefjes J (2016) Present yourself! By MHC class I and MHC class II molecules. Trends Immunol 37:724–737CrossRefGoogle Scholar
  44. Savage J, Sicherer S, Wood R (2016) The natural history of food allergy. J Allergy Clin Immunol Pract 4:196–203CrossRefGoogle Scholar
  45. Schneider LC, Rima R, Jennifer L, Emily B, Mudita M, Umetsu DT (2013) A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients. J Allergy Clin Immunol 132:1368–1374CrossRefGoogle Scholar
  46. Sicherer SH, Sampson HA (2017) Food allergy: a review and update on epidemiology, pathogenesis, diagnosis, prevention and management. J Allergy Clin Immunol 141:41–58CrossRefGoogle Scholar
  47. Sicherer SH, Anne MOF, Godbold JH, Sampson HA (2010) US prevalence of self-reported peanut, tree nut, and sesame allergy: 11-year follow-up. J Allergy Clin Immunol 125:1322–1326CrossRefGoogle Scholar
  48. Supinda B et al (2014) Peanut allergy prevalence among school-age children in a US cohort not selected for any disease. J Allergy Clin Immunol 134:753–755CrossRefGoogle Scholar
  49. Tordesillas L, Berin MC (2018) Mechanisms of oral tolerance. Clin Rev Allergy Immunol 55(2):107–117CrossRefGoogle Scholar
  50. Torgerson TR et al (2007) Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 gene. Gastroenterology 132:1705–1717CrossRefGoogle Scholar
  51. Wambre E et al (2017) A phenotypically and functionally distinct human TH2 cell subpopulation is associated with allergic disorders. Sci Transl Med 9:eaam9171CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Linglin Fu
    • 1
  • Bobby J. Cherayil
    • 2
  • Haining Shi
    • 2
  • Yanbo Wang
    • 1
  • Yang Zhu
    • 3
  1. 1.School of Food Science and BiotechnologyZhejiang Gongshang UniversityHanghzouChina
  2. 2.Mucosal Immunology and Biology ResearchHarvard Medical SchoolCharlestownUSA
  3. 3.Bioprocess Engineering Group, Agrotechnology and Food SciencesWageningen University and ResearchWageningenThe Netherlands

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