it is estimated that 6~8% of the children , and 4% of the adult have immunoglobulin ( ig ) e - mediated hypersensitivity to food ag . the prevalence of food allergy has increased rapidly across the world in last few decades . research in the area of food allergy has advanced rapidly in recent years . however , the etiology and pathogenesis of food allergy are not fully understood . symptoms of food allergy vary from slightly abdominal discomfort to life - threatening anaphylactic shock reactions . food allergy reactions involve not only the intestinal tract , but other body systems as well , such as the skin , airway and cardiovascular system . the gastrointestinal tract has been described as the body 's largest immunologic organ . a single epithelial layer lines the gastrointestinal tract and receives multiple daily exposures to a variety of proteins from foods and microorganisms . although antigen in the intestine exposures are complicated and frequent , the result of these exposures is tolerance or development of allergy when proteins do not luminal digested completely . m cells in peyer 's patches can take up particulate antigens and deliver them to dendritic cells . soluble antigens are thought to cross the epithelium through transcellular or paracellular routes directly leading to t cell or macrophage encounters . the timing of initial exposure to a food allergen also likely influences the development of tolerance . oral antigen dose also seems important in determining which of two distinct effector mechanisms mediates the development of tolerance . in animal models , high doses of antigen lead to lymphocyte anergy or clonal deletion .. haptens are low molecular weight chemicals ( usually less than 500 daltons ) , which are low reactive organic molecules that can bind to proteins and peptides , rendering them allergenic . allergic reactions to chemical haptens occur , in the overwhelming majority of cases , as an inflammatory skin reaction to direct contact with the hapten . the key feature of food allergy is a th2-predominant allergen - specific immune response , with the production of ige antibodies specific for the food allergen . the t cells of t - helper ( th)2 phenotype are known to be involved in the development of allergic disease . th1 cells release type 1 cytokines such as interferon ( ifn)- , while the major cytokines secreted by th2 cells are interleukin ( il)-4 , il-5 , and il-13 . these cytokines play an important role in the production of antigen - specific ige and in mucus secretion , muscle contractility , and eosinophilia . thus , the activation of th2 cells is a critical step in the immune mechanisms of food allergy . yet it still remains unclear what are the initial steps of intestinal sensitization in human beings . the  hygiene hypothesis  postulates that limited exposure to bacterial and viral pathogens during early childhood results in an insufficient stimulation of t helper ( th)1 cells , which in turn can not counterbalance the expansion of th2 cells and results in a predisposition to allergy . while yielded conflicting results also raising the possibility that this model may be something of an over simplification . immunologic adjuvants are often included in vaccines to stimulate the immune system 's response to the target antigens . cholera toxins , freund 's adjuvant , etc are necessary in developing allergic animal models . there is a causal relationship between the increasing environmental pollution and the fast increasing of allergic diseases . the exogenic and endogenic noxious agents contributing to the total environmental load are primarily acting through immunotoxic , sensitizing and neurotoxic mechanisms in animal experiments and in humans . beside classic allergic - triggering factors , toxic environmental agents ( formaldehyde , industrial and traffic smog , wood preservatives , microbial toxins , additive - rich food , nicotine , alcohol , pesticides , solvents , amalgam - heavy metals ) are increasingly incriminated as causal factors for the complex symptomatology . studies showed that the intestinal mucosal barrier permeability is essential to prevent antigen uptake , while there are conflicting results concerning allergic diseases in inflammatory bowel diseases ( ibds ) , some studies suggest an increase of atopic diseases , whereas others have noted no difference from control populations . one explanation for the obviously increase in atopic disease in developed countries over the last 50 years has been the  hygiene hypothesis ; a reduced exposure to pathogenic microorganisms . hapten exposure via other surfaces such as the skin and airways might also be important in promoting atopic disease . the hapten - atopy hypothesis was put forward that oral and cutaneous exposure to chemicals generally and to haptens in particular , may have also contributed to the increased prevalence of atopic disease . consistent with this hypothesis it is apparent that over 40 years , with the huge increase in atopic diseases , there has also been an increase in dietary hapten exposure through processed food , formula milk and oral antibiotic and drug uses . local lymph node activation and increased total serum ige levels are suggested to be predictive parameters of airway hypersensitivity caused by low molecular weight ( lmw ) chemicals . studies showed that increased total serum ige after topical sensitization is associated with immediate - type specific airway reactivity after inhalation challenge in bn rats and thus may be a valuable parameter in testing for respiratory sensitization potential of lmw compounds . other studies compared rates of atopic dermatitis between patients with allergic contact dermatitis arising out of individual fragrance chemicals with known oral / cutaneous exposure against exclusively cutaneous exposure . their results showed that patients allergic to individual fragrances with dietary exposure have reduced rates of atopic dermatitis . this may indicate that patients with atopic dermatitis have heightened oral tolerance to dietary haptens , in contrast to the known close association of atopic dermatitis with food - protein allergy . interactions with foreign proteins / haptens in the gastrointestinal ( gi ) tract have a tolerogenic influence on interaction elsewhere such as in the skin . so they speculate that hapten exposure through the gi tract in the form of formula milk , antibiotics and food additives , through the skin in the form of skin care products and through respiratory tract in the form of airborne chemicals , will be potential to hamper any epithelial tolerance mechanisms to self - proteins and peptides , which may predispose to atopy / protein allergy while at the same time the haptens may induce self - tolerance . trinitrobenzene sulfonic acid ( tnbs ) is a chemical hapten that binds to tissue proteins and is capable of stimulating cell - mediated immunity . as a strong experimental sensitizer , tnbs was used in vitro in induction of allergic contact dermatitis , tnbs is a classical skin contactant which can induce delayed hypersensitivity reactions when applied to the skin because it haptenates body proteins with trinitrophenyl ( tnp ) groups and renders such self - protein immunogenic to the immune system . while , when tnbs is introduced into the colon of susceptible mice via intra - rectal instillation , it induces t cell - mediated immune response in the colonic mucosa , in this case leading to a massive mucosal inflammation characterized by the dense infiltration of t cells and macrophages throughout the entire wall of the large bowel , tnbs - colitis is regarded as thl t cell - mediated inflammation . another study showed that intratracheal ( it ) inoculation of 2,4,6-trinitrobenzene sulfonic acid ( tnbs ) led to maximal ear swelling 24 hr after challenge on the ear with 2,4,6-trinitrochlorobenzene ( tncb ) in carrier . the possibility was speculated that the alveolar macrophages in the lung possess a similar capability for antigen presentation of hapten in the induction of allergic contact dermatitis as does the langerhans cell . while it is still not clear whether tnbs as a representative hapten can combine the food proteins and play an important role in the inducing of food allergy , further research is needed to reveal the underlying mechanism . the intact protein antigens absorption into the intestinal tissue is regarded to be a prerequisite in the development of intestinal sensitization . most food allergens are water soluble glycoproteins with molecular weight from 10 - 75 kd and stable proteins that are resistant to the intestinal digestive effects , and may be absorbed in a relatively intact form to be able to trigger an immune response . examples are ovalbumin ( ova ) and milk casein protein . as a model food antigen chemical haptens , in contrast with food proteins , are low molecular weight ( usually < 500 d ) and have the ability to bind with proteins or peptides , rendering them antigenicity . with the increases of atopic diseases , dietary hapten exposure has distinctly increased in different ways , such as processed food , oral antibiotic , formula milk and drug use . contact dermatitis to chemical haptens may occur when direct contact with the haptens , while there are rarely studies about the reactions to haptens on other epithelial surfaces being reported . cutaneous hapten exposure may also be important in the development of atopic dermatitis , one possible mechanism by which haptens interfere with protein tolerance is through their known ability to covalently bind to peptides and proteins and thus alter their immunogenic profiles . thus , this modifications may cause atopic diseases , and most of the data are form experimental studies on contact allergy . if haptens do bind to skin proteins , then it may possibly be expected that these chemicals would also bind similarly to food proteins . it is still unknown about how hapten exposure on different epithelial surfaces such as the intestine , and the role of hapten in the pathogenesis of food allergy . further experimental studies about the effect of hapten on oral tolerance to food proteins are needed .
there has been a significant increase in the prevalence of allergic diseases especially over the past 2 to 3 decades . 
 however , the etiology and pathogenesis of food allergy are not fully understood . in recent years , with the huge increase in atopic disease , there has also been an increase in dietary hapten exposure . 
 allergic reactions to chemical haptens occur , in the overwhelming majority of cases , as an inflammatory reaction in the skin to direct contact with haptens . 
 while reactions to haptens on other epithelial surfaces have only rarely been investigated ; it is still not clear whether haptens can combine the food antigens and play a role in the induction of food allergen - related inflammation in the intestine . 
 further research is needed to reveal the underlying mechanism .