T cell recognition of foreign peptide antigen and tolerance to self peptides is key to the proper function of the immune system. Usually, in the thymus T cells that recognize self MHC + self peptides are deleted and those with the potential to recognize self MHC + foreign peptides are selected to mature. However there are exceptions to these rules. Autoimmunity and allergy are two of the most common immune diseases that can be related to recognition of self. Many genes work together to lead to autoimmunity. Of those, particular MHC alleles are the most strongly associated, reflecting the key importance of MHC presentation of self peptides in autoimmunity. T cells specific for combinations of self MHC and self peptides may escape thymus deletion, and thus be able to drive autoimmunity, for several reasons: the relevant self peptide may be presented at low abundance in the thymus but at high level in particular peripheral tissues; the relevant self peptide may bind to MHC in an unusual register, not present in the thymus but apparent elsewhere; finally the relevant self peptide may be post translationally modified in a tissue specific fashion. In some types of allergy, the peptide + MHC combination may also be fully derived from self. However the combination in question may be modified by the presence of other ligands, such as small drug molecules or metal ions. Thus these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity.
Animals ; Autoantigens ; immunology ; Autoimmunity ; HLA Antigens ; immunology ; Humans ; Hypersensitivity ; immunology ; Receptors, Antigen, T-Cell ; metabolism ; T-Lymphocytes ; immunology ; metabolism

This study was aimed to evaluate the prevalence of soy protein hypersensitivity in cow's milk protein-sensitive children in Korea. A total of 1,363 patients with atopic dermatitis, urticaria, enterocolitis syndrome, bronchial asthma or allergic rhinitis were recruited. First, we estimated the prevalence of sensitization to soy in children sensitized to cow's milk. Specific IgE levels > 0.7 kU/L by CAP assay were considered positive. Next, the prevalence of soy allergy in cow's milk allergy (CMA) patients was investigated. Those children whose parents agreed to participate the open challenge test with soy had a convincing history of allergic reactions elicited by cow's milk and these symptoms were relieved by elimination. All of them had negative soy-specific IgE. Patients with positive soy-specific IgE accounted for 18.3% of 224 children sensitized to cow's milk protein. The prevalence of sensitization to soy decreased with age (36.8% in the first year of life, 16.4% in the second year, and 13.7% in the third year). Of 21 CMA patients, 42.9% (n=9) were determined to have soy allergy (mean age 10.3 months). Our results suggest that soy protein formula should be carefully used as a substitute for cow's milk in CMA patients, especially during infancy.
Adolescent ; Age Factors ; Allergens ; Asthma/immunology ; Child ; Child, Preschool ; Dermatitis, Atopic/immunology ; Enterocolitis/immunology ; Female ; Food Hypersensitivity/*epidemiology/immunology ; Human ; Hypersensitivity ; Immunoglobulin E/blood/metabolism ; Infant ; Korea ; Male ; Milk Hypersensitivity/*epidemiology/immunology ; Prevalence ; Rhinitis/immunology ; Soybean Proteins/*chemistry ; Urticaria/immunology

It is widely known that the cockroach is an inhalant allergen in atopic asthma and allergic rhinitis. Even though Bla g I and Bla g II are considered as the major allergens, several relatively high-molecular weight (MW) cockroach allergens have also been recently identified by IgE-immunoblot in western countries. However, the environmental control and diagnostic tests mainly focussed on Bla g I and Bla g II. Furthermore there is no data about major IgE-binding cockroach antigens in Korea. We performed this study to identify the major German cockroach allergens in Korean atopic children. By the results of allergy skin tests, 14 children with atopic asthma (9 were cockroach-sensitive and 5 were cockroach-nonsensitive atopics) were enrolled in this study. We conducted IgE immunoblot and autoradiographic analysis using Yonsei-extract of German cockroach antigen produced in our laboratory, individual sera from 9 cockroach- sensitive children, and the pooled sera of 5 house-dust-mites-only-sensitive children. We performed an allergic skin test to cockroach mix, and a radioallergosorbent test (RAST) using German cockroach crude extract on all subjects. German cockroach-specific IgE was detected in 6 out of 9 subjects by RAST. We identified at least 15 IgE-binding protein bands, and among them, the components of MWs of 76, 64, 50, 38, and <14 kilodaltons (kDa) were the major German cockroach allergens in study subjects. Therefore, Bla g I (25-30 kDa) and Bla g II (36 kDa) could not be the absolute indicators of German cockroach sensitization and parameters of environmental control.
Adolescence ; Allergens/analysis ; Animal ; Asthma/metabolism* ; Asthma/immunology ; Asthma/complications ; Child ; Child, Preschool ; Cockroaches/immunology ; Cockroaches/chemistry* ; Female ; Human ; Hypersensitivity/metabolism* ; Hypersensitivity/immunology ; Hypersensitivity/complications ; IgE/metabolism* ; Korea ; Male ; Tissue Extracts/metabolism*

The major house-dust-mite allergen, Der p I, stimulates the phospholipase D (PLD) in peripheral blood mononuclear cells (PBMC) from allergic patients with maximal responses after 30 min exposure. At 30 min, Der p I stimulated PLD activity by 1.4-fold in mild, 1.6-fold in moderate and 2-fold in severe allergic patients over control values (p < 0.05). When the cells were pretreated for 24 h with phorbol myristate acetate to down-regulate protein kinase C (PKC), PLD stimulation by Der p I was largely abolished. These results indicate that in PBMC from allergic patients, Der p I can stimulate PLD activity, and that PKC activation is involved in this stimulation.
Adult ; Allergens/metabolism* ; Allergens/immunology ; Animal ; Down-Regulation (Physiology) ; Glycoproteins/metabolism* ; Glycoproteins/immunology ; Human ; Hypersensitivity/metabolism ; Hypersensitivity/immunology ; Hypersensitivity/blood ; IgE/blood ; In Vitro ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/immunology ; Mites/metabolism ; Mites/immunology ; Phospholipase D/metabolism* ; Phospholipase D/immunology ; Protein Kinase C/metabolism* ; Skin Tests ; Tetradecanoylphorbol Acetate/pharmacology

To evaluate the in vivo effect of autologous serum including antibodies to house dust mite in atopic individuals, we observed the immediate (15 mins) and late (6 hours) skin reactions (ISR, LSR) on intradermal (ID) test of serially diluted Dermatophagoides farinae antigens (DFa, Allergopharma, Germany) mixed with autologous sera (DFa-S) and diluent alone (DFa-D). We tested 34 DFa-skin reactive atopic individuals including 12 asthmatics (BA), 8 asthmatics on immunotherapy with DFa (IT), and 14 healthy atopic controls (AC). We observed complete inhibition of ISR in the lowest allergen dose of DFa-S in 7 (58.3%) of 12 BA, 3 (37.5%) of 8 IT, and 2 (14.3%) of 14 AC. In BA, the inhibition of ISR was more frequent than AC (p< 0.05). We observed larger late reactions in half of LSR positive cases on ID test by DFa-S than by DFa-D (> or = 1.5 X size; accentuation of LSR). Accentuation of LSR were shown more frequently by DFa mixed with larger amount of serum (25% in 1:1 mix; 80% in 1:3 mix, p< 0.05). But there were no differences of DFa-specific IgE and IgG subclass antibodies regardless of the inhibition of ISR or the accentuation of LSR. In conclusion, some autologous sera from DFa-sensitive individuals showed the inhibition of ISR and the accentuation of LSR on DFa-ID test.
Animal ; *Blood Physiology ; Dermatitis, Atopic/blood/*immunology ; Human ; Hypersensitivity, Delayed/*immunology ; Hypersensitivity, Immediate/*immunology ; Immunoglobulin E/metabolism ; Immunoglobulin G/metabolism ; Intradermal Tests ; Mites/*immunology ; Skin/*immunology ; Support, Non-U.S. Gov't

Although rabbits are common domestic pets, severe respiratory allergic reactions to rabbits in households are unusual. Ory c 1, a 17-kDa glycoprotein found in saliva and fur, has previously been identified as a major rabbit allergen. In this report, we describe the cases of three patients with rabbit allergy who presented with asthma and/or rhinitis while living in households with detectable levels of serum-specific IgE and major IgE binding components. Three patients with rabbit allergy and 18 unexposed nonatopic healthy controls were enrolled. Enzyme-linked immunosorbent assays (ELISA) for serum-specific IgE and IgG4 to rabbit epithelium and inhibition ELISA were performed followed by sodium dodecye sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and IgE immunoblotting. All three patients with rabbit allergy had high serum-specific IgE antibody levels compared with controls. The results of the inhibition ELISA showed significant inhibition with the addition of rabbit epithelium, whereas no significant inhibition was noted with the addition of cat and dog epithelia. Two IgE-binding components with molecular weights of 16 kDa and 67.5 kDa were identified by IgE immunoblotting. In conclusion, rabbit exposure may induce IgE-mediated bronchial asthma and/or rhinitis in domestic settings.
Adolescent ; Adult ; Allergens/*blood ; Animals ; Asthma/*immunology/metabolism ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; Humans ; Hypersensitivity/*immunology/metabolism ; Hypersensitivity, Immediate/immunology ; Immunoblotting ; Immunoglobulin E/*blood/*chemistry ; Immunoglobulin G/chemistry ; Male ; Rabbits ; Rhinitis/*immunology/metabolism

To achieve immune homeostasis in such a harsh environment as the intestinal mucosa, both active and quiescent immunity operate simultaneously. Disruption of gut immune homeostasis leads to the development of intestinal immune diseases such as colitis and food allergies. Among various intestinal innate immune cells, mast cells (MCs) play critical roles in protective immunity against pathogenic microorganisms, especially at mucosal sites. This suggests the potential for a novel MC-targeting type of vaccine adjuvant. Dysregulated activation of MCs also results in inflammatory responses in mucosal compartments. The regulation of this yin and yang function of MCs remains to be elucidated. In this review, we focus on the roles of mucosal MCs in the regulation of intestinal allergic reaction, inflammation and their potential as a new target for the development of mucosal adjuvants.
Adjuvants, Immunologic/*therapeutic use ; Animals ; Humans ; Hypersensitivity/*immunology/prevention & control ; Inflammation/immunology/metabolism/prevention & control ; Intestinal Mucosa/cytology/*immunology ; Mast Cells/*immunology

We have reported that a 24 kDa protein (22U homologous; As22U) of Anisakis simplex larvae could elicit several Th2-related chemokine gene expressions in the intestinal epithelial cell line which means that As22U may play a role as an allergen. In order to determine the contribution of As22U to allergic reactions, we treated mice with 6 times intra-nasal application of recombinant As22U (rAs22U). In the group challenged with rAs22U and ovalbumin (OVA), the number of eosinophils in the bronchial alveolar lavage fluid (BALF) was significantly increased, as compared to the group receiving only OVA. In addition, mice treated with rAs22U and OVA showed significantly increased airway hyperresponsiveness. Thus, severe inflammation around the airway and immune cell recruitment was observed in mice treated with rAs22U plus OVA. The levels of IL-4, IL-5, and IL-13 cytokines in the BALF increased significantly after treatment with rAs22U and OVA. Similarly, the levels of anti-OVA specific IgE and IgG1 increased in mice treated with rAs22U and OVA, compared to those treated only with OVA. The Gro-alpha (CXCL1) gene expression in mouse lung epithelial cells increased instantly after treatment with rAs22U, and allergy-specific chemokines eotaxin (CCL11) and thymus-and-activation-regulated-chemokine (CCL17) gene expressions significantly increased at 6 hr after treatment. In conclusion, rAs22U may induce airway allergic inflammation, as the result of enhanced Th2 and Th17 responses.
Administration, Intranasal ; Animals ; Anisakiasis/*immunology/parasitology ; Anisakis/*immunology/metabolism ; Bronchoalveolar Lavage Fluid ; Chemokines/metabolism ; Cytokines/analysis/*metabolism ; Eosinophils/metabolism ; Female ; Gene Expression Regulation/*immunology ; Helminth Proteins/*immunology ; Hypersensitivity/*immunology/parasitology ; Immunoglobulin E/immunology ; Immunoglobulin G/immunology ; Larva/immunology/metabolism ; Lung/metabolism ; Mice ; Mice, Inbred C57BL ; Recombinant Proteins/immunology ; Th17 Cells/metabolism ; Th2 Cells/metabolism

Mast cells have been regarded for a long time as effector cells in IgE mediated type I reactions and in host defence against parasites. However, they are resident in all environmental exposed tissues and express a wide variety of receptors, suggesting that these cells can also function as sentinels in innate immune responses. Indeed, studies have demonstrated an important role of mast cells during the induction of life-saving antibacterial responses. Furthermore, recent findings have shown that mast cells promote and modulate the development of adaptive immune responses, making them an important hinge of innate and acquired immunity. In addition, mast cells and several mast cell-produced mediators have been shown to be important during the development of allergic airway diseases. In the present review, we will summarize findings on the role of mast cells during the development of adaptive immune responses and highlight their function, especially during the development of allergic asthma.
Animals ; Anti-Infective Agents/pharmacology ; Asthma/*immunology/metabolism ; Cytokines/metabolism ; Histamine/metabolism ; Humans ; Hypersensitivity/*immunology/metabolism ; Immune System ; Immunoglobulin E/immunology ; Leukotrienes/metabolism ; Mast Cells/*cytology ; Mice ; Models, Biological ; Prostaglandins/metabolism ; Tumor Necrosis Factor-alpha/metabolism

The prevalence of allergic diseases in children has increased for several decades. We evaluated the correlation between pollen count of weeds and their sensitization rate in Seoul, 1997-2009. Airborne particles carrying allergens were collected daily from 3 stations around Seoul. Skin prick tests to pollen were performed on children with allergic diseases. Ragweed pollen gradually increased between 1999 and 2005, decreased after 2005 and plateaued until 2009 (peak counts, 67 in 2003, 145 in 2005 and 83 grains/m3/day in 2007). Japanese hop pollen increased between 2002 and 2009 (peak counts, 212 in 2006 and 492 grains/m3/day in 2009). Sensitization rates to weed pollen, especially ragweed and Japanese hop in children with allergic diseases, increased annually (ragweed, 2.2% in 2000 and 2.8% in 2002; Japanese hop, 1.4% in 2000 and 1.9% in 2002). The age for sensitization to pollen gradually became younger since 2000 (4 to 6 yr of age, 3.5% in 1997 and 6.2% in 2009; 7 to 9 yr of age, 4.2% in 1997 and 6.4% in 2009). In conclusion, sensitization rates for weed pollens increase in Korean children given increasing pollen counts of ragweed and Japanese hop.
Adolescent ; Allergens/*immunology ; Ambrosia/immunology/*metabolism ; Asthma/epidemiology/immunology ; Child ; Child, Preschool ; Female ; Humans ; Hypersensitivity/*epidemiology/immunology ; Male ; Pollen/*immunology ; Prevalence ; Republic of Korea/epidemiology ; Rhinitis, Allergic, Seasonal/epidemiology/immunology ; Skin Tests