activation Release of mediators Effects

en tig An

Vasopermeability Preformed IgE-mediated mediators: Mucus secretion C3a, C5a Trauma Chemotactic factors Heat or cold Swelling and Chemotaxis release of Ca++ granules Smooth muscle Newly constriction synthesized Phospholipase A2 mediators: Increased pain response thromboxanes platelet-activating factor

Figure .. Type I . Immediate hypersensitivity is mediated by IgE. Th e primary cellular component in this hypersensitivity is the mast cell (as shown in this fi gure) or . Th e mechanism of reaction involves preferential production of IgE, in response to certain (). IgE has very high affi nity for its recep- tor on mast cells. A subsequent exposure to the same crosslinks the cell-bound IgE and triggers the release of various pharmacologically active substances. Figure courtesy of University of Indiana.

Antigen DC secretion

T cell

Macrophage Recruitment Cellular infiltrate PMN Swelling

Figure .. Type IV Hypersensitivity. Delayed type hypersensitivity results when an presenting cell (typically a tissue dendritic cell that has picked up an antigen, processed it, and displayed appropriate peptide fragments bound to Class II MHC) is contacted by an antigen-specifi c Th 1 cell patrolling the tissue. Th e resulting activation of the T-cell produces such as (for macrophages, other T-cells and, to a lesser extent, neutrophils), TNF-beta, and IFN-gamma. Th e consequences are a cellular infi ltrate in which mononuclear cells (T-cells and macrophages) tend to predominate. It is usually maximal in 48–72 hours. Figure courtesy of University of Cambridge, Department of Pathology. 1. Intestinal barrier function Sampling Microbial by DC Defense activation sensing by IEC after barrier breech M cell depended antigen uptake 2. Host- microbial interaction

Epithelium

3. MMA FLA TIO Innate Dendritic IN N and cells/MO Effector T cells adaptive Peyer’s patch immune 4. Imbalance of responses Inflammatory regulatory pathways pathways leading to IBD B cells Regulatory T cells

Endothelium Mesenteric lymph node

Figure .. Intestinal Barrier Function and Loss of Oral Tolerance. Microbial anti- gens are escorted across the intestinal epithelial cells (IEC) by dendritic cells that sense and sample via toll-like receptors (TLRs) or M cell dependent antigen uptake. Alternatively, antigens can “leak” across the epithelium if there are breaches in the integrity of the intestinal lining. Th e unregulated transport of microbial antigens can then trigger an immune response beyond the mucosal immune system’s capacity to attenuate. Once the regulatory pathways of oral tolerance are deranged, then infl am- matory pathways dominate, and chronic intestinal infl ammation can result in those who are genetically susceptible. Figure courtesy of www.science-autism.org . 0

∗∗∗ −50 Sham diet (n = 66)

−100

−150 True diet IBS symptom severity (n = 65)

−200 Low Medium High

Level of adherence

Figure - Reduction in the IBS Symptom severity index improves with higher levels of adherence. Mean change in symptom severity scores at 12 weeks according to degree of adherence. Diff erence between the groups with high adherence: 101 (95 % confi dence interval 54, 147). Reprinted with permission from Atkinson, et al. (2004) Gut, 53 (10), 1459–1464.

REFERENCES

American Academy of . ( 1996–2001 ). Th e allergy report: science based fi ndings on the diagnosis and treatment of allergic disorders . Milwaukee, WI : American Academy of Allergy and . André C , Heremans JF , Vaerman JP , Cambiaso CL. (1975 ). A mechanism for the induc- tion of immunological tolerance by antigen feeding: antigen-antibody complexes. J Exp Med , 142 , 1509 – 1519 . A t k i n s o n W , S h e l d o n T A , S h a a t h N , W h o r w e l l P J . ( 2 0 0 4 ) . F o o d e l i m i n a t i o n b a s e d o n IgG antibodies in irritable bowel syndrome: a randomized controlled trial . Gut , 53 ( 10 ), 1459 – 1464 . B r o s t o ff J. ( 1987 ). Mechanisms: An introduction . In J Brostoff , SJ Challacombe , (Eds.), and Intolerances. London : Baillere Tindall. (p. 433 – 455 ). B r o s t o ff J , Carini C , Wraith DG , et al . ( 1979 ). Immune complexes in . In: J Pepys , AM Edwards , (Eds.), Th e Mast Cell . London : Pittman Medical . (p. 380 ). B u c h a n a n A D , C h r i s t i e L , A l t h a g e K M , e t a l . ( 2 0 0 4 ) . T r e a t m e n t o f e g g a l l e r g y i n children in children through oral desensitization . J Allergy Clin Immunol 113 ( Suppl ), S150 . Challacombe SJ , Tomsai TB. (1987 ). Oral Tolerance. In Brostoff J CS , ed. Food Allergy and Intolerance. London : Bailliere Tindall. (pp. 255 – 268 ). C h r i s t i e L , H i n e R J , P a r k e r J G , B u r k s W. ( 2 0 0 2 ) . F o o d a l l e r g i e s i n c h i l d r e n a ff ect nutrient intake and growth . J Am Diet Assoc , 102 , 1 6 4 8 – 1 6 5 1 . D r i s k o J , B i s c h o ff B , H a l l M , M c C a l l u m R . ( 2 0 0 6 ) . T r e a t i n g i r r i t a b l e b o w e l s y n d r o m e with a food elimination diet followed by food challenge and probiotics. J Am Coll Nutr , 25 ( 6 ), 514 – 522 . Frankland AW. ( 1987 ). in relation to food allergy . In J Brostoff , S J Challacombe , (Eds.), Food allergy and Intolerances . London : Baillere Tindall . 456 – 466 . Herman PM , Drost LM. (2004 ). Evaluating the clinical relevance of food sensitivity test: a single subject experiment . Altern Med Rev , 9 ( 2 ), 198 – 207 . Khakoo GA , Roberts G , Lack G. (2000 ). Th e epidemiology of adverse food intolerance. Th e epidemiology of adverse food reactions. In: T. Dean T , (Ed.), Food Intolerance and the Food Industry. Cambridge, UK: Woodhead Publishing. (pp. 189 – 193 ). Lack G. (2008 ). Clinical practice. Food allergy. N Engl J Med , 359 , 1252 – 1260 . Leira R , Rodríguez R. ( 1996 ). Diet and Migraine . Rev Neurol , 24 , 534 – 538 . Maloney JM , Rudengren M. (2008 ). Th e use of serum-specifi c IgE measurements for the diagnosis of peanut, tree nut, and seed allergy. J Allergy Clin Immunol 122 ( 1 ), 145 – 151 . Meletis CD. (2003 ). Delayed-Onset Food . In MA Liebert (Ed.), Alternative & Complementary Th erapies . Larchmont , NY : Mary Ann Liebert, Inc . 61 – 65 . M u r a r o A , R o b e r t s G , C l a r k A , e t a l . ( 2 0 0 7 ) . Th e management of anaphylaxis in children: position paper of the European Academy of Allergology and Clinical Immunology. Allergy , 62 , 857 – 871 . Ou-Yang WX , You JY , Duan BP , Chen CB. (2008 ). Application of food allergens specifi c IgG antibody detection in chronic diarrhea in children [Article in Chinese] . Zhongguo Dang Dai Er Ke Za Zhi , 10 ( 1 ) , 2 1 – 2 4 . Postlethwaite AE. (2001 ). Can we induce tolerance in ? Curr Rheumatol Rep , 3 , 6 4 – 6 9 . R a d c l i ff e M. (1987 ). Diagnostic use of dietary regimes. In J Brostoff , S J C h a l l a c o m b e , (Eds.), Food allergy and Intolerances. London : Baillere Tindall. (pp. 806 – 822 ). R i n k e l H J . ( 1 9 3 6 ) . F o o d A l l e r g y . J Kansas Med Soc , 37 , 1 7 7 . Sampson H , Albergo R. (1984 ). Comparison of results of skin tests, RAST and double- blind, placebo-controlled food challenges in children with . J Allergy Clin Immunol , 74 ( 1 ), 26 – 33 . Simons F. ( 2004 ). First-aid treatment of anaphylaxis to food: focus on epinephrine . J Allergy Clin Immunol , 113 , 837 – 844 . Smith J. (2007 ). Genetically engineered foods may cause rising food allergies-Part! In June 8th ed 1 – 5 . Stapel S. ( 2008 ). Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report . Allergy 3 ( 7 ), 793 – 796 . Suen RM. ( 2004 ). Th e clinical relevance of IgG food allergy testing through ELISA- Enzyme-Linked Immunosorbent Assay . Townsend Letter , 1 – 10 . Vighi G , Marcucci F , Sensi L , et al . ( 2008 ). Allergy and the gastrointestinal system . Clin Exp Immunol , 153 , 3 – 6 . Westgard Quality Corporation. (2004 ). CLIA Requirements for Analytical Quality . Available at: www.westgard.com/clia.htm . W h o r w e l l P , L e a R . ( 2 0 0 4 ) . D i e t a r y t r e a t m e n t o f t h e i r r i t a b l e b o w e l s y n d r o m e . Curr Treat Options Gastroenterol , 7( 4 ), 307 – 316 . Ya n g C M , L i Y Q . ( 2 0 0 7 ) . Th e therapeutic eff ects of eliminating allergic foods according to food-specifi c IgG antibodies in irritable bowel syndrome. Zhonghua Nei Za Zhi , 46 ( 8 ), 641 – 643 . Z a r S , B e n s o n M J , K u m a r D . ( 2 0 0 5 ) . F o o d - s p e c i fi c serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome . Am J Gastroenterol , 100 ( 7 ), 1558 – 1559 . Z u o X L , L i Y Q , L i W J , e t a l . ( 2 0 0 7 ) . A l t e r a t i o n s o f f o o d a n t i g e n - s p e c i fi c serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Clin Exp Allergy , 37 ( 6 ) , 8 2 3 – 8 3 0 .