Basic Aspects of Allergy and Hypersensitivity Reactions

  • Isabella Pali-Schöll
  • Erika Jensen-Jarolim
Part of the Allergy Frontiers book series (ALLERGY, volume 2)


Key players within immunologically mediated hypersensitivity reactions are allergen-specific IgE or IgG antibodies, immune complexes, or lymphocytes. According to these diverse pathophysiological mechanisms behind the clinical appearance, hypersensitivity reactions are classified into type I through IV. The focus of this chapter lies on the characterization of type I, i.e. IgE-mediated reactions.

In addition to small size and solubility of type I allergen molecules which both support penetration of mucosal and skin barriers, a tendency to form multimers, conformational stability to heat treatment, denaturation and persistence in gastrointestinal digestion are regarded as important features of allergens today. Furthermore, it is documented that the allergenicity of a compound can be enhanced through environmental factors like diesel exhaust, nitration or admixture with other substances contributing adjuvant activity.

Thus, considerable progress has been made in the understanding of the molecular and immunological conditions which are responsible for allergenicity and the consecutive induction of IgE-mediated hypersensitivity.


Atopic Dermatitis Celiac Disease Hypersensitivity Reaction Allergy Clin Immunol Grass Pollen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Gell PGH, and Coombs RRA (1963) The classification of allergic reactions underlying disease. Blackwell Science, Oxford.Google Scholar
  2. 2.
    Descotes J, and Choquet-Kastylevsky G (2001) Gell and Coombs's classification: is it still valid? Toxicology 158:43–49.PubMedCrossRefGoogle Scholar
  3. 3.
    Rajan TV (2003) The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation. Trends Immunol 24:376–379.PubMedCrossRefGoogle Scholar
  4. 4.
    Gupta R, Sheikh A, Strachan DP, and Anderson HR (2007) Time trends in allergic disorders in the UK. Thorax 62:91–96.PubMedCrossRefGoogle Scholar
  5. 5.
    Sampson HA (2004) Update on food allergy. J Allergy Clin Immunol 113:805–819; quiz 820.PubMedCrossRefGoogle Scholar
  6. 6.
    Yazdanbakhsh M, van den Biggelaar A, and Maizels RM (2001) Th2 responses without atopy: immunoregulation in chronic helminth infections and reduced allergic disease. Trends Immunol 22:372–377.PubMedCrossRefGoogle Scholar
  7. 7.
    Reali E, Greiner JW, Corti A, Gould HJ, Bottazzoli F, Paganelli G, Schlom J, and Siccardi AG (2001) IgEs targeted on tumor cells: therapeutic activity and potential in the design of tumor vaccines. Cancer Res 61:5517–5522.PubMedGoogle Scholar
  8. 8.
    Xiang Z, Block M, Lofman C, and Nilsson G (2001) IgE-mediated mast cell degranulation and recovery monitored by time-lapse photography. J Allergy Clin Immunol 108:116–121.PubMedCrossRefGoogle Scholar
  9. 9.
    Dvorak AM, Schleimer RP, and Lichtenstein LM (1987) Morphologic mast cell cycles. Cell Immunol 105:199–204.PubMedCrossRefGoogle Scholar
  10. 10.
    Ogawa Y, and Grant JA (2007) Mediators of anaphylaxis. Immunol Allergy Clin North Am 27:249–260.PubMedCrossRefGoogle Scholar
  11. 11.
    Gehlhar K, Rajashankar KR, Hofmann E, Betzel C, Weber W, Werner S, and Bufe A (2006) Lysine as a critical amino acid for IgE binding in Phl p 5b C terminus. Int Arch Allergy Immunol 140:285–294.PubMedCrossRefGoogle Scholar
  12. 12.
    Marti P, Truffer R, Stadler MB, Keller-Gautschi E, Crameri R, Mari A, Schmid-Grendelmeier P, Miescher SM, Stadler BM, and Vogel M (2007) Allergen motifs and the prediction of allergenicity. Immunol Lett 109:47–55.PubMedCrossRefGoogle Scholar
  13. 13.
    Stadler MB, and Stadler BM (2003) Allergenicity prediction by protein sequence. Faseb J 17:1141–1143.PubMedGoogle Scholar
  14. 14.
    Esch RE (2006) Allergens. Clin Rev Allergy Immunol 30:71–72.PubMedCrossRefGoogle Scholar
  15. 15.
    Wedemeyer J, and Galli SJ (2000) Mast cells and basophils in acquired immunity. Br Med Bull 56:936–955.PubMedCrossRefGoogle Scholar
  16. 16.
    Jelinek DF (2000) Regulation of B lymphocyte differentiation. Ann Allergy Asthma Immunol 84:375–385; quiz 385–377.PubMedGoogle Scholar
  17. 17.
    Pomes A, Vailes LD, Helm RM, and Chapman MD (2002) IgE reactivity of tandem repeats derived from cockroach allergen, Bla g 1. Eur J Biochem 269:3086–3092.PubMedCrossRefGoogle Scholar
  18. 18.
    Beezhold DH, Hickey VL, Sutherland MF, and O'Hehir RE (2004) The latex allergen hev B 5 is an antigen with repetitive murine B-cell epitopes. Int Arch Allergy Immunol 134:334–340.PubMedCrossRefGoogle Scholar
  19. 19.
    Ayuso R, Lehrer SB, and Reese G (2002) Identification of continuous, allergenic regions of the major shrimp allergen Pen a 1 (tropomyosin). Int Arch Allergy Immunol 127:27–37.PubMedCrossRefGoogle Scholar
  20. 20.
    Schöll I, Kalkura N, Shedziankova Y, Bergmann A, Verdino P, Knittelfelder R, Kopp T, Hantusch B, Betzel C, Dierks K, Scheiner O, Boltz-Nitulescu G, Keller W, and Jensen-Jarolim E (2005) Dimerization of the major birch pollen allergen Bet v 1 is important for its in vivo IgE-cross-linking potential in mice. J Immunol 175:6645–6650.PubMedGoogle Scholar
  21. 21.
    van Oort E, Dieker MC, de Heer PG, Peltre G, Aalberse RC, and van Ree R (2005) The major grass pollen group 5 allergen from Dactylis glomerata and its C-terminal split product both behave as dimers: implications for allergen standardization. Int Arch Allergy Immunol 136:113–122.CrossRefGoogle Scholar
  22. 22.
    Mahler V, Vrtala S, Kuss O, Diepgen TL, Suck R, Cromwell O, Fiebig H, Hartl A, Thalhamer J, Schuler G, Kraft D, and Valenta R (2004) Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1. Clin Exp Allergy 34:115–122.PubMedCrossRefGoogle Scholar
  23. 23.
    Gafvelin G, Thunberg S, Kronqvist M, Gronlund H, Gronneberg R, Troye-Blomberg M, Akdis M, Fiebig H, Purohit A, Horak F, Reisinger J, Niederberger V, Akdis CA, Cromwell O, Pauli G, Valenta R, and van Hage M (2005) Cytokine and antibody responses in birch-pollen-allergic patients treated with genetically modified derivatives of the major birch pollen allergen Bet v 1. Int Arch Allergy Immunol 138:59–66.PubMedCrossRefGoogle Scholar
  24. 24.
    Clare DA, Gharst G, and Sanders TH (2007) Transglutaminase polymerization of peanut proteins. J Agric Food Chem 55:432–438.PubMedCrossRefGoogle Scholar
  25. 25.
    Reese G, Ballmer-Weber BK, Wangorsch A, Randow S, and Vieths S (2007) Allergenicity and antigenicity of wild-type and mutant, monomeric, and dimeric carrot major allergen Dau c 1: destruction of conformation, not oligomerization, is the roadmap to save allergen vaccines. J Allergy Clin Immunol 119:944–951.PubMedCrossRefGoogle Scholar
  26. 26.
    van Boxtel EL, van Beers MM, Koppelman SJ, van den Broek LA, and Gruppen H (2006) Allergen Ara h 1 occurs in peanuts as a large oligomer rather than as a trimer. J Agric Food Chem 54:7180–7186.PubMedCrossRefGoogle Scholar
  27. 27.
    Ganglberger E, Grunberger K, Sponer B, Radauer C, Breiteneder H, Boltz-Nitulescu G, Scheiner O, and Jensen-Jarolim E (2000) Allergen mimotopes for 3-dimensional epitope search and induction of antibodies inhibiting human IgE. Faseb J 14:2177–2184.PubMedCrossRefGoogle Scholar
  28. 28.
    Svenson M, Jacobi HH, Bodtger U, Poulsen LK, Rieneck K, and Bendtzen K (2003) Vaccination for birch pollen allergy. Induction of affinity-matured or blocking IgG antibodies does not account for the reduced binding of IgE to Bet v 1. Mol Immunol 39:603–612.PubMedGoogle Scholar
  29. 29.
    Spangfort MD, Mirza O, Ipsen H, Van Neerven RJ, Gajhede M, and Larsen JN (2003) Dominating IgE-binding epitope of Bet v 1, the major allergen of birch pollen, characterized by X-ray crystallography and site-directed mutagenesis. J Immunol 171:3084–3090.PubMedGoogle Scholar
  30. 30.
    Rafnar T, Brummet ME, Bassolino-Klimas D, Metzler WJ, and Marsh DG (1998) Analysis of the three-dimensional antigenic structure of giant ragweed allergen, Amb t 5. Mol Immunol 35:459–467.PubMedCrossRefGoogle Scholar
  31. 31.
    Masuch GI, Franz JT, Schoene K, Musken H, and Bergmann KC (1997) Ozone increases group 5 allergen content of Lolium perenne. Allergy 52:874–875.PubMedCrossRefGoogle Scholar
  32. 32.
    Traidl-Hoffmann C, Kasche A, Jakob T, Huger M, Plotz S, Feussner I, Ring J, and Behrendt H (2002) Lipid mediators from pollen act as chemoattractants and activators of polymorphonuclear granulocytes. J Allergy Clin Immunol 109:831–838.PubMedCrossRefGoogle Scholar
  33. 33.
    Gutermuth J, Bewersdorff M, Traidl-Hoffmann C, Ring J, Mueller MJ, Behrendt H, and Jakob T (2007) Immunomodulatory effects of aqueous birch pollen extracts and phytoprostanes on primary immune responses in vivo. J Allergy Clin Immunol 120(2), 293–299.PubMedCrossRefGoogle Scholar
  34. 34.
    Traidl-Hoffmann C, Mariani V, Hochrein H, Karg K, Wagner H, Ring J, Mueller MJ, Jakob T, and Behrendt H (2005) Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization. J Exp Med 201:627–636.PubMedCrossRefGoogle Scholar
  35. 35.
    Plotz SG, Traidl-Hoffmann C, Feussner I, Kasche A, Feser A, Ring J, Jakob T, and Behrendt H (2004) Chemotaxis and activation of human peripheral blood eosinophils induced by pollen-associated lipid mediators. J Allergy Clin Immunol 113:1152–1160.PubMedCrossRefGoogle Scholar
  36. 36.
    Gruijthuijsen YK, Grieshuber I, Stocklinger A, Tischler U, Fehrenbach T, Weller MG, Vogel L, Vieths S, Poschl U, and Duschl A (2006) Nitration enhances the allergenic potential of proteins. Int Arch Allergy Immunol 141:265–275.PubMedCrossRefGoogle Scholar
  37. 37.
    D'Amato G, Liccardi G, D'Amato M, and Cazzola M (2002) Outdoor air pollution, climatic changes and allergic bronchial asthma. Eur Respir J 20:763–776.PubMedCrossRefGoogle Scholar
  38. 38.
    Ji Y, and Bennett BM (2003) Activation of microsomal glutathione s-transferase by peroxynitrite. Mol Pharmacol 63:136–146.PubMedCrossRefGoogle Scholar
  39. 39.
    Uversky VN, Yamin G, Munishkina LA, Karymov MA, Millett IS, Doniach S, Lyubchenko YL, and Fink AL (2005) Effects of nitration on the structure and aggregation of alpha-synuclein. Brain Res Mol Brain Res 134:84–102.PubMedCrossRefGoogle Scholar
  40. 40.
    Astwood JD, Leach JN, and Fuchs RL (1996) Stability of food allergens to digestion in vitro. Nat Biotechnol 14:1269–1273.PubMedCrossRefGoogle Scholar
  41. 41.
    Schöll I, Untersmayr E, Bakos N, Roth-Walter F, Gleiss A, Boltz-Nitulescu G, Scheiner O, and Jensen-Jarolim E (2005) Antiulcer drugs promote oral sensitization and hypersensitivity to hazelnut allergens in BALB/c mice and humans. Am J Clin Nutr 81:154–160.PubMedGoogle Scholar
  42. 42.
    Moneo I, Gomez M, Sanchez-Monge R, Alday E, de las Heras M, Esteban I, Bootello A, and Salcedo G (1999) Lack of crossreaction with Bet v 1 in patients sensitized to Dau c 1, a carrot allergen. Ann Allergy Asthma Immunol 83:71–75.PubMedCrossRefGoogle Scholar
  43. 43.
    Untersmayr E, Schöll I, Swoboda I, Beil WJ, Förster-Waldl E, Walter F, Riemer A, Kraml G, Kinaciyan T, Spitzauer S, Boltz-Nitulescu G, Scheiner O, and Jensen-Jarolim E (2003) Antacid medication inhibits digestion of dietary proteins and causes food allergy: a fish allergy model in BALB/c mice. J Allergy Clin Immunol 112:616–623.PubMedCrossRefGoogle Scholar
  44. 44.
    Untersmayr E, Bakos N, Schöll I, Kundi M, Roth-Walter F, Szalai K, Riemer AB, Ankersmit HJ, Scheiner O, Boltz-Nitulescu G, and Jensen-Jarolim E (2005) Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients. Faseb J 19:656–658.PubMedGoogle Scholar
  45. 45.
    Schöll I, Ackermann U, Ozdemir C, Blumer N, Dicke T, Sel S, Wegmann M, Szalai K, Knittelfelder R, Untersmayr E, Scheiner O, Garn H, Jensen-Jarolim E, and Renz H (2007) Antiulcer treatment during pregnancy induces food allergy in mouse mothers and a Th2-bias in their offspring. Faseb J 21:1264–1270.PubMedCrossRefGoogle Scholar
  46. 46.
    Clynes R, and Ravetch JV (1995) Cytotoxic antibodies trigger inflammation through Fc receptors. Immunity 3:21–26.PubMedCrossRefGoogle Scholar
  47. 47.
    Sylvestre D, Clynes R, Ma M, Warren H, Carroll MC, and Ravetch JV (1996) Immunoglobulin G-mediated inflammatory responses develop normally in complement-deficient mice. J Exp Med 184:2385–2392.PubMedCrossRefGoogle Scholar
  48. 48.
    Ravetch JV, and Clynes RA (1998) Divergent roles for Fc receptors and complement in vivo. Annu Rev Immunol 16:421–432.PubMedCrossRefGoogle Scholar
  49. 49.
    Wakayama H, Hasegawa Y, Kawabe T, Hara T, Matsuo S, Mizuno M, Takai T, Kikutani H, and Shimokata K (2000) Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRgamma-deficient mice. Eur J Immunol 30:1182–1190.PubMedCrossRefGoogle Scholar
  50. 50.
    Skokowa J, Ali SR, Felda O, Kumar V, Konrad S, Shushakova N, Schmidt RE, Piekorz RP, Nurnberg B, Spicher K, Birnbaumer L, Zwirner J, Claassens JW, Verbeek JS, van Rooijen N, Kohl J, and Gessner JE (2005) Macrophages induce the inflammatory response in the pulmonary Arthus reaction through G alpha i2 activation that controls C5aR and Fc receptor cooperation. J Immunol 174:3041–3050.PubMedGoogle Scholar
  51. 51.
    Otten EJ, and McKimm D (1983) Venomous snakebite in a patient allergic to horse serum. Ann Emerg Med 12:624–627.PubMedCrossRefGoogle Scholar
  52. 52.
    Matic G, Schutt W, Winkler RE, Tiess M, and Ramlow W (2000) Extracorporeal removal of circulating immune complexes: from non-selective to patient-specific. Blood Purif 18:156–160.PubMedCrossRefGoogle Scholar
  53. 53.
    Sanchez-Morillas L, Reano Martos M, Iglesias Cadarso A, Perez Pimiento A, Rodriguez Mosquera M, and Dominguez Lazaro AR (2005) Vasculitis during immunotherapy treatment in a patient with allergy to Cupressus arizonica. Allergol Immunopathol (Madr) 33:333–334.CrossRefGoogle Scholar
  54. 54.
    Cabrera GE, Citera G, Gutierrez M, Scopelitis E, and Espinoza LR (1993) Digital vasculitis following allergic desensitization treatment. J Rheumatol 20:1970–1972.PubMedGoogle Scholar
  55. 55.
    Clark BM, Kotti GH, Shah AD, and Conger NG (2006) Severe serum sickness reaction to oral and intramuscular penicillin. Pharmacotherapy 26:705–708.PubMedCrossRefGoogle Scholar
  56. 56.
    Slavin RG (2007) What the allergist should know about hypersensitivity pneumonitis. Allergy Asthma Proc 28:25–27.PubMedCrossRefGoogle Scholar
  57. 57.
    Rittner C, Sennekamp J, Mollenhauer E, Rosinger N, Niese D, Luttkenhorst M, Baur MP, and Stroehmann I (1983) Pigeon breeder's lung: association with HLA-DR 3. Tissue Antigens 21:374–379.PubMedCrossRefGoogle Scholar
  58. 58.
    Patel AM, Ryu JH, and Reed CE (2001) Hypersensitivity pneumonitis: current concepts and future questions. J Allergy Clin Immunol 108:661–670.PubMedCrossRefGoogle Scholar
  59. 59.
    Krasteva M (1993) Contact dermatitis. Int J Dermatol 32:547–560.PubMedCrossRefGoogle Scholar
  60. 60.
    Gibbs JH, Grange JM, Beck JS, Jawad E, Potts RC, Bothamley GH, and Kardjito T (1991) Early delayed hypersensitivity responses in tuberculin skin tests after heavy occupational exposure to tuberculosis. J Clin Pathol 44:919–923.PubMedCrossRefGoogle Scholar
  61. 61.
    Clayton TH, Wilkinson SM, Rawcliffe C, Pollock B, and Clark SM (2006) Allergic contact dermatitis in children: should pattern of dermatitis determine referral? A retrospective study of 500 children tested between 1995 and 2004 in one U.K. centre. Br J Dermatol 154:114–117.CrossRefGoogle Scholar
  62. 62.
    Imayama S, Hashizume T, Miyahara H, Tanahashi T, Takeishi M, Kubota Y, Koga T, Hori Y, and Fukuda H (1992) Combination of patch test and IgE for dust mite antigens differentiates 130 patients with atopic dermatitis into four groups. J Am Acad Dermatol 27:531–538.PubMedCrossRefGoogle Scholar
  63. 63.
    Fabrizi G, Romano A, Vultaggio P, Bellegrandi S, Paganelli R, and Venuti A (1999) Heterogeneity of atopic dermatitis defined by the immune response to inhalant and food allergens. Eur J Dermatol 9:380–384.PubMedGoogle Scholar
  64. 64.
    Pastar Z, Lipozencic J, and Ljubojevic S (2005) Etiopathogenesis of atopic dermatitis — an overview. Acta Dermatovenerol Croat 13:54–62.PubMedGoogle Scholar
  65. 65.
    Novak N, Bieber T, and Leung DY (2003) Immune mechanisms leading to atopic dermatitis. J Allergy Clin Immunol 112:S128–139.PubMedCrossRefGoogle Scholar
  66. 66.
    Toma T, Mizuno K, Okamoto H, Kanegane C, Ohta K, Ikawa Y, Miura M, Kuroda M, Niida Y, Koizumi S, and Yachie A (2005) Expansion of activated eosinophils in infants with severe atopic dermatitis. Pediatr Int 47:32–38.PubMedCrossRefGoogle Scholar
  67. 67.
    Dickson BC, Streutker CJ, and Chetty R (2006) Coeliac disease: an update for pathologists. J Clin Pathol 59:1008–1016.PubMedCrossRefGoogle Scholar
  68. 68.
    Hausch F, Shan L, Santiago NA, Gray GM, and Khosla C (2002) Intestinal digestive resistance of immunodominant gliadin peptides. Am J Physiol Gastrointest Liver Physiol 283:G996–G1003.PubMedGoogle Scholar
  69. 69.
    Dieterich W, Esslinger B, and Schuppan D (2003) Pathomechanisms in celiac disease. Int Arch Allergy Immunol 132:98–108.PubMedCrossRefGoogle Scholar
  70. 70.
    Krupickova S, Tuckova L, Flegelova Z, Michalak M, Walters JR, Whelan A, Harries J, Vencovsky J, and Tlaskalova-Hogenova H (1999) Identification of common epitopes on gliadin, enterocytes, and calreticulin recognised by antigliadin antibodies of patients with coeliac disease. Gut 44:168–173.PubMedGoogle Scholar
  71. 71.
    Burgin-Wolff A, Dahlbom I, Hadziselimovic F, and Petersson CJ (2002) Antibodies against human tissue transglutaminase and endomysium in diagnosing and monitoring coeliac disease. Scand J Gastroenterol 37:685–691.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Isabella Pali-Schöll
    • 1
  • Erika Jensen-Jarolim
    • 1
  1. 1.Department of PathophysiologyMedical University of ViennaViennaAustria

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