Delayed hypersensitivity to house dust-storage mites Thyrophagus putrescentiae in experimental allergic dermatoses]

House dust mites and storage mites proved to be one of the main allergens causing hypersensitivity in atopic dermatitis in allergic patients. The authors reproduced experimental allergic dermatosis on the model of delayed type hypersensitivity in guinea pigs, caused by sensitization to the allergen from the mite's bodies Tyrophagus putrescentiae--species having wide distribution in the country. The results characteristic for T-cell type hypersensitivity have been obtained: delayed positive skin tests after 24 hours, typical histomorphological picture (strong allergic alteration, epidermis desquamation, vasculitis, dermis T-cell infiltration and spongiosis--Waksman's syndrome). It is concluded that side by side with humoral IgE-mediated reaction there is strong delayed T-cell hypersensitivity to the storage mites Tyrophagus putrescentiae.     

The high-affinity IgE receptor: lessons from structural analysis

The high affinity receptor for IgE, FcERI, is at the core of the allergic reaction. This receptor is expressed mainly on mast cells and basophils. Interaction of an allergen with its specific IgE bound to FcERI triggers cell activation, which induces the release of numerous mediators that are responsible for allergic manifestations. The recent increase in the prevalence of allergic diseases in developed countries has resulted in renewed efforts towards the development of new drugs. One of these is a humanised antibody directed against the IgE ligand. This antibody recognises specifically free but not FcERI-bound IgE thus preventing ligand binding and subsequent cell activation. This antibody has shown some efficacy in clinical trials involving patients with asthma and allergic rhinitis. The recent elucidation of the tridimensional structure of the complex between IgE and FcERI provides unexpected information regarding the mechanism of assembly of the complex, which now can be used to design small chemical compounds capable of specifically inhibiting this interaction.     

ALLERGIC BRONCHIAL ASTHMA AND RHINITIS—The Importance of Studies for Sensitivity to Foods

The authors consider sensitivity to foods and sensitivity to inhalants about equal in importance in bronchial asthma, allergic rhinitis and allergic bronchitis. Food allergens are the sole cause of bronchial and nasal allergic disease in 20 to 40 per cent of cases throughout life, including old age; inhalants are the sole cause in approximately an equal number; and sensitivity to foods and to inhalants are often associated.Their frequent recognition of sensitivity to foods as a cause of disease, the authors believe, depends on: (1) The recognition of the fallibility of skin testing and the usual negative skin reactions to allergenic foods in chronic and recurrent bronchial asthma and allergic rhinitis. (2) The adequate use of trial diets, especially cereal-free elimination diet. (3) The realization that ingested foods remain in the body usually for two to four weeks and that the diet must be continued until symptoms have been relieved for two to three times as long as preceding relief between attacks.     

Effect of decomplemantation on the course of several allergic skin reactions]

Experiments were conducted on mongrel albino mice; a study was made of the role played by the complement in the development of passive skin anaphylaxis after Ovarie and the so called reverse direct allergic (cytotoxic) reaction. Preliminary animal decomplementation 3 hours before the reactions were conducted failed to alter the intensity of Ovarie reaction, and decreased the intensity of the reverse direct allergic reaction significantly. Reproduction of Ovarie reaction and of the reverse direct allergic reaction on animals 24 hours after the decomplementation did not influence the manifestation of both reactions.     

Rapid inhibitory effect of corticosterone on histamine release from rat peritoneal mast cells.

Glucocorticoids are steroids endowed with powerful anti-inflammatory properties, which are routinely believed to require several hours to take effect through modulation of gene expression. Our recent report has shown that glucocorticoids could inhibit allergic reaction within 10 minutes, which the classical genomic mechanism could not explain. Histamine is thought to be one of major mediators in the allergic reaction, and IgE-mediated histamine release from mast cells plays a pivotal role in allergic diseases. Here, we have determined a rapid effect of corticosterone on histamine release from rat peritoneal mast cells, using fluorometric assay. The results showed that corticosterone could inhibit antigen-induced histamine release from rat peritoneal cells within 15 minutes (p<0.05), which could be mimicked by membrane-impermeable BSA conjugated corticosterone (p<0.05). Neither glucocorticoid nuclear receptor antagonist nor protein synthesis inhibitor could block the rapid action (p<0.05). The study provided evidence that nongenomic mechanism might be involved in rapid effect of glucocorticoids on mast cells in allergic disease.     

Immunotherapy using algal‐produced Ara h 1 core domain suppresses peanut allergy in mice

Peanut allergy is an IgE‐mediated adverse reaction to a subset of proteins found in peanuts. Immunotherapy aims to desensitize allergic patients through repeated and escalating exposures for several months to years using extracts or flours. The complex mix of proteins and variability between preparations complicates immunotherapy studies. Moreover, peanut immunotherapy is associated with frequent negative side effects and patients are often at risk of allergic reactions once immunotherapy is discontinued. Allergen‐specific approaches using recombinant proteins are an attractive alternative because they allow more precise dosing and the opportunity to engineer proteins with improved safety profiles. We tested whether Ara h 1 and Ara h 2, two major peanut allergens, could be produced using chloroplast of the unicellular eukaryotic alga, Chlamydomonas reinhardtii. C. reinhardtii is novel host for producing allergens that is genetically tractable, inexpensive and easy to grow, and is able to produce more complex proteins than bacterial hosts. Compared to the native proteins, algal‐produced Ara h 1 core domain and Ara h 2 have a reduced affinity for IgE from peanut‐allergic patients. We further found that immunotherapy using algal‐produced Ara h 1 core domain confers protection from peanut‐induced anaphylaxis in a murine model of peanut allergy.     

Plasma kallikrein during experimentally induced allergic rhinitis: role in kinin formation and contribution to TAME-esterase activity in nasal secretions

We have shown recently that kinins are generated during experimentally induced allergic rhinitis in man, and have demonstrated that substrates for kinin-forming enzymes are provided during the allergic response by a transudation of kininogens from plasma into nasal secretions. In light of this increased vascular permeability during the allergic reaction, we have extended our studies on the mechanisms of kinin formation to examine the potential involvement of plasma kallikrein. Allergic individuals (n = 7) and nonallergic controls (n = 7) were challenged intranasally with an allergen, and nasal lavages, obtained before and after challenge, were assayed for immunoreactive human plasma kallikrein/prekallikrein (iHPK). Post-challenge iHPK values were significantly elevated (p less than 0.01) in the allergic group (353 +/- 394 ng/ml; x +/- SD) as compared to the nonallergics (19 +/- 22 ng/ml), and correlated with increases in kinins, histamine, and N-alpha-tosyl-L-arginine methyl esterase (TAME-esterase) activity and with the onset of clinical symptoms. Gel filtration studies revealed that plasma prekallikrein is activated during the allergic response and contributes to kinin formation prior to interaction with plasma protease inhibitors. We also show that the majority of the TAME-esterase activity detected in nasal secretions during the allergic response is due to activities consistent with a plasma kallikrein/alpha 2-macroglobulin complex and with mast cell tryptase.     

The response of blood neutrophils (the PPN test) to pertussis allergen in children with pertussis and children immunized with ADPT vaccine]

The authors present materials on the study of the reaction of blood neutrophils (PPN test) to pertussis allergen in children suffering from pertussis and immunized with ADPT vaccine. Results obtained in examining 111 children showed that the PPN test was specific and could be used for assessment of allergic manifestations in children suffering from pertussis or immunized with ADPT vaccine. Taking into consideration the harmlessness and expressiveness of the PPN test it can be recommended for studying in dynamics in any age groups.     

Morphological alteration of peritoneal mast cells and macrophages in the mouse peritoneal cavity during the early phases of an allergic inflammatory reaction

We investigated the presence of mast cell granules in macrophages following an in vivo model of an allergic reaction. Injection of ovalbumin (100 microg) into the peritoneal cavity of sensitised mice produced a rapid (within 2 h) influx of neutrophils followed by a slower (after >4 h) eosinophil migration. Ovalbumin treatment induced a high incidence (approximately 50%) of mast cell degranulation compared to control phosphated-buffered saline-treated mice. The majority (approximately 90%) of peritoneal macrophages contained mast cell granules as early as 2 h post-ovalbumin, with lower values at later time-points, as determined by staining with Toluidine blue and Berberine sulphate. This was confirmed by electron microscopy which enabled us to identify the complex mast cell granule sub-structural components in macrophage phagosomes. In conclusion, we used histochemical and ultrastructural analyses to show that mast cell granules become internalised with macrophages during the early stages of an experimental allergic reaction.     

The Problem of Allergy in Psychiatry

In recent years many authors have directed attention to allergic reactivity in mental disease. This problem has been studied with particular depth by O. V. Kerbikov (1) and his associates. (2) Clinical data, as well as, to some degree, laboratory research data demonstrate beyond all question that an allergic component often plays a substantial role in the genesis and shaping of various psychotic conditions. Also providing a basis for study of the problem of allergy in psychiatry are our data of pathophysiological studies in the field of allergy conducted in recent years (3-6), which demonstrate that the major role in the shaping of allergic reactions belongs to the central nervous system and that "nervous tissue may be the object in which the allergic reaction of antigen with antibody occurs" (A. D. Ado). Any pathological process modifies the immunological properties of the organism and causes adaptive defense reactions. Sometimes, under particular conditions, these defensive developments begin to play a pathogenic role. Under the influence of endogenic toxicosis, particularly in schizophrenia, autoantigens may be formed which acquire the nature of auto-or endo-allergens (A. D. Ado), which exercise a very pronounced effect upon the organism, including the central nervous system. In certain circumstances they facilitate the allergic genesis of psychopathological syndromes. The development of antibodies and auto-allergens in mental diseases may also be a consequence of the modification, under the influence of the pathological process and of various drugs, of the "normal flora" relationship characteristic of the given organism, and sometimes the result of this may be auto-infection.     

Expanded polytetrafluoroethylene threads for lip augmentation induce foreign body granulomatous reaction

Especially in cases of facial aesthetic surgery, the demands of the patients are high. The formation of a visible and painful nodule will cause not only discomfort but also dissatisfaction. When alloplastic materials are used for facial and lip augmentation, the possibility of migration, allergic reaction, and formation of a foreign body granuloma is always present. Although e-PTFE is the most bioinert alloplastic material available, the authors could show the formation of a foreign body granuloma. When using e-PTFE threads for facial augmentation, the surgeon should keep in mind and inform the patients that the threads can induce a foreign body granulomatous reaction.     

THE ROLE OF THE CONNECTIVE TISSUE GROUND SUBSTANCES (MUCOPOLYSACCHARIDES) IN ALLERGIC INJURY

The basic histologic reactions of the classic allergic diseases and of several systemic diseases in which allergic mechanisms appear to operate are described and illustrated. Particular attention is drawn to the ground substances—mucopolysaccharides—which constitute important elements of connective tissue and vascular structure. The intimate locus of the allergic reaction appears to be in and to involve a swelling of such substances. It is suggested that antibodies (and possibly antigens) may be attached to these mucinous ground substances of the connective tissues.     

Continuous Orally Administered Coffee Enhanced the Antigen-Specific Th1 Response and Reduced Allergic Development in a TCR-Transgenic Mice Model

Coffee is a globally consumed beverage. Although recent studies have suggested that coffee reduced the risk of lifestyle-related diseases, there are few studies regarding allergic response.

This study investigates the effects of orally administered coffee (91 ml/kg/d) on allergic responses using a T cell receptor (TCR)-transgenic DO11.10 mouse allergic model. Splenocytes from coffee-administered naïve mice increased antigen (Ag)-specific interleukin (IL)-12p40 secretion. When Ag sensitization and coffee administration were concurrently performed, the splenocytes from coffee-administered mice showed a decrease of IL-2 and an increase of IL-12p40 secretion. The Ag-specific cutaneous response and serum IgE level were reduced in coffee-administered mice, although, after establishing the allergy, coffee administration did not suppress the allergic reaction.

These results suggest that coffee could induce a Th1-type response of the immune system and prevent an allergy developing. Further studies on the optimum dose, cultivar differences, and roasted degree need to be undertaken.     

Oleanolic Acid Controls Allergic and Inflammatory Responses in Experimental Allergic Conjunctivitis

Pollen is the most common aeroallergen to cause seasonal conjunctivitis. The result of allergen exposure is a strong Th2-mediated response along with conjunctival mast cell degranulation and eosinophilic infiltration. Oleanolic acid (OA) is natural a triterpene that displays strong anti-inflammatory and immunomodulatory properties being an active anti-allergic molecule on hypersensitivity reaction models. However, its effect on inflammatory ocular disorders including conjunctivits, has not yet been addressed. Hence, using a Ragweed pollen (RWP)-specific allergic conjunctivitis (EAC) mouse model we study here whether OA could modify responses associated to allergic processes. We found that OA treatment restricted mast cell degranulation and infiltration of eosinophils in conjunctival tissue and decreased allergen-specific Igs levels in EAC mice. Th2-type cytokines, secreted phospholipase A₂ type-IIA (sPLA₂-IIA), and chemokines levels were also significantly diminished in the conjunctiva and serum of OA-treated EAC mice. Moreover, OA treatment also suppressed RWP-specific T-cell proliferation. In vitro studies, on relevant cells of the allergic process, revealed that OA reduced the proliferative and migratory response, as well as the synthesis of proinflammatory mediators on EoL-1 eosinophils and RBL-2H3 mast cells exposed to allergic and/or crucial inflammatory stimuli such as RWP, sPLA₂-IIA or eotaxin. Taken together, these findings demonstrate the beneficial activity of OA in ocular allergic processes and may provide a new intervention strategy and potential therapy for allergic diseases.     

THE GUILLAIN-BARRé DISEASE COMPLEX—An Analysis of the Disease with Therapeutic Suggestions and Report of 26 Cases

The Guillain-Barré disease complex may result from a number of causes and have a wide variety of effects. The basic mechanism seems to be an immunizing or allergic reaction to many pathogens or their products, causing edema of the nerve roots in the spine, specifically about the meningeal covering. Resulting pressure on the axon causes nerve damage proportional to the severity and duration of pressure.Results in the 26 cases here reported and in other reports indicate that corticosteroids are the treatment of choice, the purpose being to reduce edema as promptly as possible. As might be expected, this therapy is of little value in the post-inflammatory stage of the disease, although prophylactic administration should continue for several months.Nerve and muscle rehabilitation are the chief aims of later treatment.     

Allergic bronchial asthma and rhinitis; the importance of studies for sensitivity to foods

The authors consider sensitivity to foods and sensitivity to inhalants about equal in importance in bronchial asthma, allergic rhinitis and allergic bronchitis. Food allergens are the sole cause of bronchial and nasal allergic disease in 20 to 40 per cent of cases throughout life, including old age; inhalants are the sole cause in approximately an equal number; and sensitivity to foods and to inhalants are often associated. THEIR FREQUENT RECOGNITION OF SENSITIVITY TO FOODS AS A CAUSE OF DISEASE, THE AUTHORS BELIEVE, DEPENDS ON: (1) The recognition of the fallibility of skin testing and the usual negative skin reactions to allergenic foods in chronic and recurrent bronchial asthma and allergic rhinitis. (2) The adequate use of trial diets, especially cereal-free elimination diet. (3) The realization that ingested foods remain in the body usually for two to four weeks and that the diet must be continued until symptoms have been relieved for two to three times as long as preceding relief between attacks.     

Minireview: Autoimmune responses to myelin proteolipid protein

The authors present a brief historical sketch of the development of our understanding of immune responses to myelin proteolipid protein (PLP) and the acceptance of PLP as a potent antigen in the induction of experimental allergic encephalomyelitis (EAE). The distinct characteristics of the PLP molecule that may contribute to complex immune responses to this protein are reviewed and these responses are compared with those to MBP, both in the pathology of EAE and at the level of the T cell. Recent evidence demonstrating differences between T cell responses to PLP and MBP is reviewed. Finally, the potential contribution of immune responses to PLP in human diseases, particularly mutiple sclerosis (MS), that have been identified to date are then summarized.For the authors to write a review on PLP and its role in EAE without Marjorie is like their sailing a ship without a captain, compass or rudder. This review is largely based on work and ideas generated in Marjorie's laboratory, but it was prepared without her input. Consequently, it lacks her meticulous reflection on the structure of each of its sentences and on the use of each word. Papers written with Marjorie are usually honed to near perfection late into the evening at her kitchen table in Newton, where food, ideas, and warmth abound, and where her very patient and accommodating husband Sidney and a demanding but lovable canine are close at hand. Writing this essay gave the authors a chance to recognize our scientific forebears, to consider where we are at this point and to contemplate our future directions in studying immune responses to PLP. We are, indeed, very grateful and indebted to Marjorie for her generous personal and scientific support, wise guidance, inspiration, strength, energy and, most importantly, friendship. Marjorie, we thank you, you are our role model, and we affectionately anticipate many more years of continued collaboration with you.Abbreviations used in this paper CNS central nervous system - EAE experimental allergic encephalomyelitis - MBP myelin basic protein - MHC major histocompatibility complex - MOG myelin oligodendrocyte cyte glycoprotein - MS multiple sclerosis - PLP myelin proteolipid protein - PNS peripheral nervous system - TcR T cell receptor Special issue dedicated to Dr. Marjorie B. Lees.     

IL-4 induces allergic-like inflammatory disease and alters T cell development in transgenic mice

We have assessed the biologic role of IL-4 by fusing its gene to an immunoglobulin promoter/enhancer and introducing it into transgenic mice. By attenuating the transgene promoter through the insertion of E. coli lac operator sequences, we have created a series of animals that constitutively express varying amounts of IL-4. Overexpression of IL-4 results in a marked increase in serum IgE levels and the appearance of an inflammatory ocular lesion (blepharitis) with characteristic histopathologic features seen in allergic reactions. In addition, expression of the IL-4 transgene in the thymus perturbs T cell maturation, reducing the population of immature CD4+CD8+ thymocytes and peripheral T cells while increasing the population of mature CD8+ thymocytes. These results demonstrate that deregulation of a single cytokine gene in vivo can induce a complex inflammatory reaction resembling that observed in human allergic disease.     

Total and specific serum IgE decreases with age in patients with allergic rhinitis,asthma and insect allergy but not in patients with atopic dermatitis

Concerning allergic diseases, the incidence of allergic symptoms, as well as their severity, seems to decrease with age. The decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total and specific IgE. Atopic disorders are complex diseases that involve interactions among several physiological systems, e.g. skin, lung, mucosae, and the immune system. It was the aim of this study to compare the effects of age on total and specific IgE in patients with atopic dermatitis (AD), allergic rhinitis or asthma, and insect allergy, respectively.     

Diagnostic significance of immunoglobulins in infectious allergic bronchial asthma

In 100 patients with infectious allergic bronchial asthma the levels of IgM. IgG and IgA were determined by Mancini's method and the levels of IgE, tissue and microbial antibodies by the Prausnitz - Küstner test before and after combined treatment carried out under conditions of the microclimate of the salt mines in the village of Solotvino. The data on the content of immunoglobulins in the blood serum allowed the authors to establish 3 types of immediate hypersensitivity. THe decreased content of IgM in the blood serum indirectly revealed the role of immune complexes in the pathogenesis of infectious allergic bronchial asthma. The high content of IgE suggested that atopy could take some part in the infectious process.