1887

Chapter 7 : Animal Models for Food Allergy

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

Animal Models for Food Allergy, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815721/9781555813758_Chap07-1.gif /docserver/preview/fulltext/10.1128/9781555815721/9781555813758_Chap07-2.gif

Abstract:

Animal models have been used to provide insight into the complex immunological and pathophysiological mechanisms of human type I allergic diseases. Therapeutic studies include allergen modifications, route of exposure, tolerance development with bacterial agents and/or herbal medicines, and cytokine skewing. Allergenic potential of novel proteins has received substantial interest in recent years, aimed at predicting allergenicity for genetically modified foods based upon known allergens, rare allergens, and nonallergens in different animal models. This chapter takes information from these sources and others to provide the reader with the author’s perspective on animal models and food allergy that could extrapolate to human type I allergic disease. An ideal food allergy animal model should include the following features. This chapter highlights the IgE-mediated gastrointestinal food hypersensitivity disorders (gastrointestinal anaphylaxis; oral allergy syndrome). The normal immune response in animals to dietary proteins is oral tolerance; however, abrogation of active immune suppression can result in adverse reactions, such as IgE-mediated food allergy. The chapter concludes that the most difficult task from one or more of these promising animal studies should be to extrapolate successfully to human disease.

Citation: Helm R. 2006. Animal Models for Food Allergy, p 171-185. In Maleki S, Burks A, Helm R (ed), Food Allergy. ASM Press, Washington, DC. doi: 10.1128/9781555815721.ch7

Key Concept Ranking

gamma delta T Cell
0.44033188
Transforming Growth Factor beta
0.41315255
0.44033188
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

References

/content/book/10.1128/9781555815721.ch07
1. Aalberse, R. C. 2000. Structural biology of allergens. J. Allergy Clin. Immunol. 106:228238.
2. Adel-Patient K.,, H. Bernard,, S. Ah-Leung,, C. Creminon, and, J.-M. Wal. 2005. Peanut- and cow’s milk-specific IgE, Th2 cells and local anaphylactic reaction are induced in BALB/c mice orally sensitized with cholera toxin. Allergy 60:658667.
3. Afuwape, A. O.,, M. W. Turner, and, S. Strobel. 2004. Oral administration of bovine whey proteins in mice elicits opposing immunoregulatory responses and is adjuvant dependent. Clin. Exp. Immunol. 136:4048.
4. Atkinson, H. A., and, K. Miller. 1994. Assessment of the brown Norway rat as a model for the investigation of food allergy. Toxicology 91:281288.
5. Bannon, G. A. 2004. What makes a food protein an allergen? Curr. Allergy Asthma Rep. 4:4346.
6. Bashir, M. E. H,, P. Andersen,, I. J. Fuss,, H. N. Shi, and, C. Nagler-Anderson. 2002. An effect of helminth infection protects against an allergic response to dietary antigen. J. Immunol. 169:32843292.
7. Basso, A. S.,, F. A. Costa-Pinto,, L. R. Britto,, L. C. de Sa-Rocha, and, J. Palermo-Neto. 2004. Neural pathways involved in food allergy signaling in the mouse brain: role of capsaicin-sensitive afferents. Brain Res. 1009:181188.
8. Betts, C. J.,, B. F. Flanagan,, H. T. Caddick,, R. J. Dearman, and, I. Kimber. 2004. Intradermal exposure of BALB/c strain mice to peanut protein elicits a type-2 cytokine response. Food Toxicol. 42:15891599.
9. Beyer, K.,, E. Morrow,, X. M. Li,, L. Bardina,, G. A. Bannon, and, A. W. Burks. 2001. Effects of cooking methods on peanut allergenicity. J. Allergy Clin. Immunol. 107:10771081.
10. Birmingham, N.,, S. Thanesvorakul, and, V. Gangur. 2002. Relative immunogenicity of commonly allergenic foods versus rarely allergenic and nonallergenic foods in mice. J. Food Prot. 65:19881991.
11. Bredehort, R., and, K. David. 2001. What establishes a protein as an allergen? J. Chromatogr. B. Biomed. Sci. Appl. 756:3340.
12. Breiteneder, H., and, M. N. Clare Mills. 2005. Molecular properties of food allergens. J. Allergy Clin. Immunol. 115:1423.
13. Buchanan, B. B., and, O. L. Frick. 2002. The dog as a model for food allergy. Ann. N. Y. Acad. Sci. 964:173183.
14. Cara, D. C.,, A. A. Conde, and, N. M. Vaz. 1994. Immunological induction of flavor aversion in mice. Br. J. Med. Biol. Res. 27:13311341.
15. Cara, D. C.,, A. A. Conde, and, N. M. Vaz. 1997. Immunological induction of flavour aversion in mice. II. Passive/adoptive transfer and pharmacological inhibition. Scand. J. Immunol. 45:1620.
16. Chambers, S. J.,, M. S. J. Wickman,, M. Regoli,, E. Bertelli,, P. A. Gunning, and, C. Nicoletti. 2004. Rapid in vivo transport of proteins from digested allergen across pre-sensitized gut. Biochem. Biophys. Res. Commun. 325:12581263.
17. Charley, B. 1996. The immunology of domestic animals: its present and future. Vet. Immunol. Immunopathol. 54:36.
18. Charley, B., and, B. N. Wilkie. 1994. Why study the immunology of domestic animals. Immunologist 2:103105.
19. Chatel, J. M.,, L. Song,, B. Bhogal, and, F. M. Orson. 2003. Various factors (allergen nature, mouse strain, CpG/recombinant protein expressed) influence the immune response elicited by genetic immunization. Allergy 58:641647.
20. Dearman, R. J., and, I. Kimber. 2001. Determination of protein allergenicity: studies in mice. Toxicol. Lett. 120:181186.
21. Dearman, R. J.,, S. Stone,, H. T. Caddick,, D. A. Basketter, and, I. Kimber. 2003. Evaluation of protein allergenic potential in mice: dose-response analyses. Clin. Exp. Allergy 33:15861594.
22. Devey, M. E.,, K. J. Anderson,, R. R. Coombs,, M. S. Henschell, and, M. E. Coates. 1976. The modified anaphylaxis hypothesis for cot death. Anaphylactic sensitization in guinea-pigs fed cow’s milk. Clin. Exp. Immunol. 26:542548.
23. FAO/WHO. 2001. Evaluation of allergenicity of genetically modified foods: report of a joint FAO/WHO expert consultation on allergenicity of foods derived from biotechnology. FAO, Rome, Italy.
24. Ferreira, M. B.,, S. L. da Silva, and, A. G. Carlos. 2002. Atopy and helminths. Allerg. Immunol. 34:1012.
25. Frick, O. L.,, S. S. Teuber,, B. B. Buchanan,, S. Morigasaki, and, D. Umetsu. 2005. Allergen immunotherapy with heat-killed Listeria monocytogenes alleviates peanut and food induced anaphylaxis in dogs. Allergy 60:243250.
26. Fritsché, R. 2003. Animal models in food allergy: assessment of allergenicity and preventive activity of infant formulas. Toxicol. Lett. 140–141:303309.
27. Fritsché, R., and, M. Bonzon. 1990. Determination of cow milk formula allergenicity in the rat model by in vitro mast cell triggering and in vivo IgE induction. Int. Arch. Allergy Appl. Immunol. 93:289293.
28. Fujiwara, D.,, S. Inoue,, H. Wakabayashi, and, T. Fujii. 2004. The anti-allergic effects of lactic acid bacterial are strain dependent and mediated by effects on both Th1/Th2 cytokine expression and balance. Int. Arch. Allergy Immunol. 135:205215.
29. Guy-Grand,, D.,, N. Cerf-Bensussan,, B. Malassis-Seris,, C. Briottet, and, P. Vassalli. 1991. Two gut epithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J. Exp. Med. 173:471481.
30. Hein, W. R. 1995. Sheep as experimental animals for immunological research. Immunologist 3:1218.
31. Hein, W. R., and, P. J. Greibel. 2003. A road less traveled: large animal models in immunological research. Nat. Rev. Immunol. 3:7984.
32. Helm, R. M., and, A. W. Burks. 2004. Sensitization and allergic response and intervention therapy in animal models. J. AOAC Int. 87:14411447.
33. Helm, R. M.,, R. W. Ermel, and, O. L. Frick. 2003. Non murine animal models of food allergy. Environ. Health Perspect. 111:239244.
34. Helm, R. M.,, G. T. Furuta,, J. S. Stanley,, J. Ye,, G. Cockrell,, C. Connaughton,, P. Simpson,, G. A. Bannon, and, A. W. Burks. 2002. A neonatal swine model for peanut allergy. J. Allergy Clin. Immunol. 109:136142.
35. Holland, M. J.,, Y. M. Harcus,, P. L. Riches, and, R. M. Maizel. 2000. Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses. Eur. J. Immunol. 30:19771987.
36. Hsieh, K. Y.,, C. I. Hsu,, J. Y. Lin,, C. C. Tsai, and, R. H. Lin. 2003. Oral administration of an edible-mushroom-derived protein inhibits the development of food-allergic reactions in mice. Clin. Exp. Allergy 33:15951602.
37. Ishida, Y.,, I. Bandou,, H. Kanzato, and, N. Yamamoto. 2003. Decrease in ovalbumin IgE of mice serum after oral uptake of lactic acid bacteria. Biosci. Biotechnol. Biochem. 67:951957.
38. Jenkins, J. A.,, S. Griffiths-Jones,, P. R. Shewry,, H. Pretender, and, E. N. Clare Mills. 2005. Structural relatedness of plant food allergens with specific reference to cross-reactive allergens: an in silico analysis. J. Allergy Clin. Immunol. 115:163170.
39. Jensen-Jarolim,, E.,, U. Wiedermann,, E. Ganglberger,, A. Zurcher,, B. M. Stadler,, G. Boltz-Nitulescu,, O. Scheiner O, and, H. Breiteneder. 1999. Allergen mimotopes in food enhance type I allergic reactions in mice. FASEB J. 13:15861592.
40. Kalliomaki, M., and, E. Isolauri. 2002. Pandemic of atopic diseases—a lack of microbial exposure in early infancy. Curr. Drug Targets Infect. Disord. 2:193199.
41. Kennis, R. A. 2002. Use of atopic dogs to investigate adverse reactions to food. J. Am. Vet. Med. Assoc. 221:638640.
42. Kim, H.,, K. Kwack,, D-Y. Kim, and, G. E. Ji. 2005. Oral probiotic bacterial administration suppressed allergic responses in an oval-induced allergy mouse model. FEMS Immunol. Med. Microbiol. 45:259267.
43. Kimber, I.,, R. J. Dearman,, A. H. Penninks,, L. M. J. Knippels,, R. B. Buchanan,, B. Hammerberg,, H. A. Jackson, and, R. M. Helm. 2003. Assessment of protein allergenicity on the basis of immune reactivity: animal models. Environ. Health Perspect. 111:11251130.
44. Knippels, L. M. J., and, A. H. Penninks. 2003. Assessment of the allergic potential of food protein extracts and proteins on oral application using the brown Norway rat model. Environ. Health Perspect. 111:233238.
45. Knippels, L. M. J.,, W. Femke, and, A. H. Penninks. 2004. Food allergy: what do we learn from animal models? Curr. Opin. Allergy Clin. Immunol. 4:205209.
46. Knippels, L. M.,, J., A. H. Penninks,, J. J. Smit, and, G. F. Houben. 1999. Immune-mediated effects upon oral challenge of ovalbumin-sensitized brown Norway rats: further characterization of a rat food allergy model. Toxicol. Appl. Pharmacol. 156:161169.
47. Kosecka, U.,, M. C. Berin, and, M. H. Perdue. 1999. Pertussis adjuvant prolongs intestinal hypersensitivity. Int. Arch. Allergy Immunol. 119:205211.
48. Knippels, L. M. J.,, A. H. Penninks,, S. Spanhaak, and, G. F. Houben. 1998. Oral sensitization to food proteins: a brown Norway rat model. Clin. Exp. Allergy 28:368375.
49. Lack, G.,, D. Fox,, K. Northstone, and, J. Golding. 2003. Factors associated with the development of peanut allergy in childhood. N. Engl. J. Med. 348:977985.
50. Ladics, G. S.,, M. P. Holsapple,, J. D. Astwood,, I. Kimber,, L. M. J. Knippels,, R. M. Helm, and, W. Dong. 2003. Workshop overview: approaches to the assessment of the allergenic potential of food from genetically modified crops. Toxicol. Sci. 73:816.
51. Lee, S. Y.,, C. K. Huang,, T. F. Zhang,, B. H. Schofield,, A. W. Burks,, G. A. Bannon,, H. A. Sampson, and, X. M. Li. 2001. Oral administration of IL-12 suppresses anaphylactic reactions in a murine model of peanut hypersensitivity. Clin. Immunol. 101:220228.
52. Li, X. M., and, H. A. Sampson. 2002. Novel approaches for the treatment of food allergy. Curr. Opin. Allergy Clin. Immunol. 2:273278.
53. Li, X. M.,, C. K. Huang,, B. H. Schofield,, A. W. Burks,, G. A. Bannon,, K. H. Kim,, S. K. Huang, and, H. A. Sampson. 1999. Strain-dependent induction of allergic sensitization caused by DNA immunization in mice. J. Immunol. 162:30453052.
54. Li, X. M.,, D. Serebrisky,, S. Y. Lee,, C. K. Huang., L. Bardina,, B. H. Schofield,, J. S. Stanley,, A. W. Burks,, G. A. Bannon, and, H. A. Sampson. 2000. A murine model of peanut anaphylaxis: T- and B-cell responses to major peanut allergens mimic human responses. J. Allergy Clin. Immunol. 106:150158.
55. Li, X. M.,, T. F. Zhang,, C. K. Huang,, K. Srivastava,, A. A. Teper,, L. Zhang,, B. H. Schofield, and, H. A. Sampson. 2001. Food allergy herbal formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model. J. Allergy Clin. Immunol. 108:639646.
56. Li, X. M.,, K. Srivastava,, A. Grishin,, C. K. Huang., B. Schofield,, A. W. Burks, and, H. A. Sampson. 2003a. Persistent protective effect of heat-killed Escherichia coli producing ‘engineered,’ recombinant peanut proteins in a murine model of peanut allergy. J. Allergy Clin. Immunol. 112:159167.
57. Li, X. M.,, K. Srivastava,, J. W. Huleatt,, K. Bottomly,, A. W. Burks, and, H. A. Sampson. 2003b. Engineered recombinant peanut protein and heat-killed Listeria monocytogenes coadministration protects against peanut-induced anaphylaxis in a murine model. J. Immunol. 170:32893295.
58. Lynch, N. R.,, I. Hagel,, M. Perez,, R. Prisco,, R. Lopez, and, N. Alvarez. 1993. Effect of anti-helminthic treatment on the allergic reactivity of children in tropical slum. J. Allergy Clin. Immunol. 92:404411.
59. Madsen, C., and, K. Pilegaard. 2003. No priming of the immune response in newborn brown Norway rats dosed with ovalbumin in the mouth. Int. Arch. Allergy Immunol. 130:6672.
60. Majamma, H., and, E. Isolauri. 1997. Probiotics: a novel approach in the management of food allergy. J. Allergy Clin. Immunol. 99:179185.
61. Maleki, S. J.,, S. Y. Chung,, E. T. Champagne, and, J. P. Raufman. 2000. The effects of roasting on the allergenic properties of peanut proteins. J. Allergy Clin. Immunol. 106:763768.
62. Matysiak-Budnik,, T.,, G. van Niel,, F. Megraud,, K. Mayo,, C. Bevilacqua,, V. Gaboriau-Routhiau,, M. C. Moreau, and, M. Heyman. 2003. Gastric Helicobacter infection inhibits development of oral tolerance to food antigens in mice. Infect. Immunol. 71:52195224.
63. Morafo, V.,, K. Srivastava,, C. K. Huang,, G. Kleiner,, S. Y. Lee,, H. A. Sampson, and, X. M. Li. 2003. Genetic susceptibility to food allergy is linked to differential Th2-Th1 responses in C3H/HeJ and BALB/c mice. J. Allergy Clin. Immunol. 111:11221128.
64. Nguyen, M. D.,, N. Cinman,, J. Yen, and, A. A. Horner. 2001. DNA-based vaccination for the treatment of food allergy. Allergy 56:127130.
65. Oehlschlager, S.,, P. Reece,, A. Brown,, E. Hughson,, H. Hird,, J. Chisholm,, J. Atkinson,, C. Meredith,, R. Pumphrey,, P. Wilson, and, J. Sunderland. 2001. Food allergy—towards predictive testing for novel foods. Food Addit. Contam. 18:10991107.
66. Ogawa, T.,, S. Miura,, Y. Tsuzuki,, T. Ogino,, K. Teramoto,, T. Inamura,, C. Watanabe,, R. Hokari,, H. Nagata, and, H. Ishii. 2004. Chronic allergy to dietary ovalbumin induces lymphocyte migration to rat small intestinal mucosa that is inhibited by MAdCAM-1. Am. J. Physiol. Gastrointest. Liver Physiol. 6:702710.
67. Pauli, G.,, F. de Blay,, J. C. Bessot, and, A. Dietemann. 1992. The association between respiratory allergies and food hypersensitivities. ACI News 4:4347.
68. Petsch, D., and, F. B. Ansparch. 2000. Endotoxin removal from protein solutions. J. Biotechnol. 76:97119.
69. Piacentini, G.,, L., A. Bertolini,, E. Spezia,, T. Piscione, and, A. L. Boner. 1994. Ability of a new infant formula prepared from partially hydrolyzed bovine whey to induce anaphylactic sensitization: evaluation in a guinea pig model. Allergy 49:361364.
70. Pilegaard, K., and, C. Madsen. 2004. An oral brown Norway rat model for food allergy: comparison of age, sex, dosing volume, and allergen preparation. Toxicology 196:247257.
71. Pohjavuari, E.,, M. Viljanen,, R. Korpela,, M. Kuitunen,, M. Tittanen,, O. Vaarala, and, E. Savilahti. 2004. Lactobacillus GG effect in increasing IFN-gamma production in infants with cow’s milk allergy. J. Allergy Clin. Immunol. 114:131136.
72. Poulsen, O. M., and, J. Hau. 1987. Murine passive cutaneous anaphylaxis test (PCA) for ‘all or none’ determination of allergenicity of bovine whey proteins and peptides. Clin. Allergy 17:7583.
73. Pritchard, D. I.,, C. Hewitt, and, R. Moqbel. 1997. The relationship between immunological responsiveness controlled by T-helper 2 lymphocytes and infections with parasitic helminths. Parasitology 115:S33S44.
74. Rich, G. T.,, R. M. Bailey,, M. L. Parker,, M. S. J. Wickman, and, A. J. Fillery-Travis. 2003a. Solubilization of carotenoids from carrot juice and spinach in lipid phases. I. Modeling the gastric lumen. Lipids 38:933945.
75. Rich, G. T.,, R. M. Faulks,, M. S. J. Wickman, and, A. J. Fillery-Travis. 2003b. Solubilization of carotenoids form carrot juice and spinach in lipid phases. II. Modeling the duodenal environment. Lipids 38:947956.
76. Roy, K.,, H. Q. Mao,, S. K. Huang, and, K. W. Leong. 1999. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat. Med. 5:387391.
77. Saldanha, J. C. S.,, D. L. Garfiulo,, S. S. Silva,, F. H. Carmo-Pinto,, M. C. Andrade,, J. I. Alvarez-Leite,, M. M. Teixeira, and, D. C. Cara. 2004. A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice. Braz. J. Med. Biol. Res. 37:809816.
78. Sampson, H. A. 2005. Food allergy: when mucosal immunity goes wrong. J. Allergy Clin. Immunol. 115:139141.
79. Srivistava, K. D.,, J. D. Kattan,, Z. M. Zou,, J. H. Li,, L. Zhang, and, S. Wallenstein. 2005. The Chinese herbal medicine formula FAHF-2 completely blocks anaphylactic reactions in a murine model of peanut allergy. J. Allergy Clin. Immunol. 115:171178.
80. Strid, J.,, J. Hourihane,, I. Kimber,, R. Callard, and, S. Strobel. 2004a. Disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response. Eur. J. Immunol. 34:21002109.
81. Strid, J.,, M. Thomson,, J. Hourihane,, I. Kimber, and, S. Strobel. 2004b. A novel model of sensitization and oral tolerance to peanut protein. Immunology 113:293303.
82. Taylor, S. E., and, S. L. Hefle. 2002. Genetically engineered foods: implications for food allergy. Curr. Opin. Allergy Clin. Immunol. 2:249252.
83. Teuber, S. S.,, G. Del Val,, S. Morigasaki,, H. R. Jung,, P. H. Eisele,, O. L. Frick, and, B. B. Buchanan. 2002. The atopic dog as a model of peanut and tree nut allergy. J. Allergy Clin. Immunol. 110:921927.
84. Untersmayer, E.,, I. Scholl,, I. Swoboda,, W. J. Beil,, E. Forster-Wadl,, F. Walter,, A. Riemer,, G. Kraml,, T. Kinaciyan,, S, Spitzauer,, G. Boltz-Nitulescu,, O. Scheiner, and, E. Jensen-Jarolim. 2003. Antacid medication inhibits digestion of dietary proteins and causes food allergy: a fish allergy model in BALB/c mice. J. Allergy Clin. Immunol. 112:616623.
85. Valenta, R., and, D. Kraft. 1996. Type 1 allergic reactions to plant-derived food: a consequence of primary sensitization to pollen allergens. J. Allergy Clin. Immunol. 97:893895.
86. van Ree,, R.,, M. Cabanes-Macheteau,, J. Akkerdaas,, J-P. Milazzo,, C. Loutelier-Bourhis,, C. Rayon,, M., Villalba,, S. J. Koppelman,, R. C. Aalberse,, R. Rodriquez,, L. Faye, and, P. Lerouge. 2000. β(1,2)-xylose and α(1,3)-fucose residues have a strong contribution in IgE binding to plant glycoproteins. J. Biol. Chem. 275:1145111458.
87. van Witk,, F.,, D. Hartgring,, S. J. Koppelman,, R. Pierters, and, L. M. J. Knippels. 2004. Mixed antibody and T cell responses to peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3, and Ara h 6 in an oral sensitization. Clin. Exp. Allergy 34:14221428.
88. van Witk,, F.,, S. Hocks,, S. Nierkens,, S. J. Koppelman,, P. van Kooten,, L. Boon,, L. M. J. Knippels, and, R. Pieters. 2005. CTLA-4 signaling regulates the intensity of hypersensitivity responses to food antigens, but is not decisive in the induction of sensitization. J. Immunol. 174:174179.
89. Vila, L.,, K. Beyer,, K. M. Jarvinen,, P. Chatchatee,, L. Bardina, and, H. A. Sampson. 2001. Role of conformational and linear epitopes in the achievement of tolerance in cow’s milk allergy. Clin. Exp. Allergy 31:15991606.
90. Viney, J.,, T. T. McDonald, and, J. Spencer. 1990. Gamma/delta T cells in the gut epithelium. Gut 31:841844.
91. Watzl, B.,, C. Neudecker,, G. M. Hansch,, G. Rechkemmer, and, B. L. Pool-Zobell. 2001. Dietary wheat germ agglutinin modulates ovalbumin-induced immune responses in brown Norway rats. Br. J. Nutr. 85:483490.
92. Wilson, M. S., and, R. M. Maizels. 2004. Regulation of allergy and autoimmunity in helminth infection. Clin. Rev. Allergy Immunol. 26:3550.
93. Yazdankbakhsh, M., and, P. M. Matricardi. 2004. Parasites and the hygiene hypothesis: regulating the immune response. Clin. Rev. Allergy Immunol. 26:1524.
94. Yeung, V. P.,, R. S. Gieni,, D. Umetsu, and, R. H. DeKruyff. 1998. Heat killed Listeria monocytogenes as an adjuvant converts established Th2-dominant immune responses into Th1-dominated responses. J. Immunol. 161:41464152.
95. Zacharia, B., and, P. Sherman. 2003. Atopy, helminths, and cancer. Med. Hypotheses 60:15.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error