Untersuchungen der letzten Jahre deuten darauf hin, daß Virusinfektionen ein potentieller Modulator der menschlichen Allergieentstehung sind. Die folgende Studie untersucht, ob frühkindliche Infektionen mit CMV, EBV und VZV einen protektiven Effekt auf die Entstehung atopischer Erkrankungen im späteren Leben haben. Die Studie berücksichtigt sowohl die humorale, als auch die zelluläre Immunantwort auf Virusinfektion. Die humorale Immunantwort wurde serologisch im Verlauf bei 672 Kindern von Geburt bis zum 7. Lebensjahr untersucht (ELISA). Die Antikörper-Titer für CMV, EBV und VZV im Alter von 1 Jahr und 3 Jahren wurden mit den atopischen Manifestationen (atopische Dermatitis, Asthma bronchiale, Rhinokonjunktivitis, Gesamt-Serum-IgE und atopische Sensibilisierung) verglichen. Die TH1 Immunantwort (intrazelluläre IFN gamma Produktion) wurde bei 100 Kindern mit und ohne atopische Manifestationen im Alter von 1 Jahr bis 16 Jahren nach CMV Stimulation untersucht (Durchflußzytometrie). Signifikante Unterschiede in den Häufigkeiten atopischer Symptome zwischen Kindern mit positivem und negativem Antikörper-Titer gegen CMV, EBV und VZV konnten nicht gezeigt werden. Auf zellulärer Ebene zeigte sich, daß Kinder und Jugendliche ohne atopische Symptome auf Virus-Stimulation (CMV-Antigen bzw. Peptid) statistisch ebenso häufig mit einer IFN-gamma-Produktion (TH1-Immunantwort) reagieren wie Kinder und Jugendliche mit atopischen Krankheitszeichen. Die Ergebnisse der vorliegenden Studie können die Hypothese eines protektiven Effekts viraler Infektion, zumindest der Herpesgruppe, in den ersten Lebensjahren hinsichtlich einer späteren Allergieentstehung nicht bestätigen. Die Zusammenhänge der Entwicklung atopischer Erkrankungen sind bisher noch nicht vollständig geklärt. Es gilt weiterhin zu erforschen, in welchem Maße frühkindliche Infekte, neben Allergenexposition, Ernährung, Luftschadstoffen und familiärer Prädisposition die Allergogenese beeinflussen. / Studies of the last years indicated that virus infections are a potential modulator of the human allergogenesis. The following study analysed if infections with CMV, EBV and VZV in early childhood have a protective effect on the development of atopic disorders in later life. The study considered the humoral and cellular immuneresponse to virus infection. The humoral immuneresponse of 672 children were serologically followed up from birth to the age of seven years (ELISA). The antibody titres of CMV, EBV and VZV at the age of 1 year and 3 years were compared with the atopic manifestations (atopic dermatitis, asthma bronchiale, rhinoconjunctivitis, total serum IgE levels and atopic sensitiziation) at the age of seven years. The TH1 immuneresponse (intracellular IFN gamma production) of 100 atopic and nonatopic children at the age of 1 year to 16 years were analysed after CMV stimulation (flowcytometry). There was no significant difference in atopic manifestations between seven-year-old children with seropositivity and seronegativity (CMV, EBV, VZV) in early childhood. Nonatopic children showed the same T cell reactivity after CMV stimulation like atopic children. The study could not show a protective effect of herpesvirus infections in early childhood on the development of atopic disorders in later life. Further studies will help to understand the influence of virus infections on the human allergogenesis.

L’allergie alimentaire est un problème majeur de santé publique. Sa prévalence est estimée à 5 % chez l’adulte et à 8 % chez l’enfant dans les pays industrialisés. L’objectif de cette thèse est d’apporter une contribution à la diététique diagnostique et thérapeutique de l’allergie alimentaire. Nos travaux ont porté sur l’allergie alimentaire au pois jaune et au sésame. Le pois jaune est un allergène émergent à risque de réaction grave. Son seuil réactogène est bas, soit 0,13 g de protéines alors que la teneur des aliments peut atteindre 20 g/100g. L’étude de 35 personnes allergiques au sésame a permis de définir que le seuil réactogène pouvant déclencher une réaction chez 5% de la population allergique se situe entre 1,2 et 4,0 mg de protéines de sésame. Nous avons validé la progression optimale des doses de sésame pour le test de provocation orale en lien avec le consensus européen Europrevall. L’absence d’harmonisation internationale concernant les allergènes à déclaration obligatoire, nous a conduit dans une seconde partie, à étudier l’impact de l’allergie alimentaire sur la décision, l’organisation et le déroulement d’un séjour à l’étranger. Cette étude réalisée en collaboration avec l’Observatoire Régional de Santé et des Affaires Sociales de Lorraine et les associations française et belge pour la prévention des allergies montre, sur un panel de 102 répondants, que l’allergie alimentaire contraint 14 % des répondants à ne pas voyager à l’étranger et que 30% des personnes ayant voyagé ont présenté une réaction allergique. Les accidents sont survenus principalement dans les restaurants. Ces résultats soulignent la nécessité de développer un système d’information et de formation des personnes allergiques et des professionnels de l’alimentation pour mettre en oeuvre des stratégies de prévention du risque. / Food allergy is a major public health problem. Its prevalence is estimated at 5% in adults and 8% in children in industrialized countries. The objective of this thesis is to bring a contribution to the diagnostic and therapeutic dietetics in food allergy. Our work focused on yellow pea and sesame food allergies. Yellow pea is an emerging allergen with risk of a severe reaction. Its reactogenic threshold is of 0.13 g of protein while the content of food can reach 20 g / 100g. The study of 35 people allergic to sesame has enabled the identification of the reactogenic threshold that can trigger a reaction in 5% of the allergic population. It is estimated between 1.2 and 4.0 mg of sesame protein. We validated optimal progression dosing scheme for sesame for oral challenge test taking in account the European consensus Europrevall. Lack of international harmonization on mandatory allergens, led us in a second part of this thesis, to study the impact of food allergy on the decision, trip organization and a stay abroad of an allergic person. This study, conducted in collaboration with the regional health observatory and Social Affairs of Lorraine and the French and Belgian associations for allergy prevention shows, on a panel of 102 respondents, that food allergy forced 14% of respondents do not travel abroad and that 30% of people who have traveled had an allergic reaction. The accidents occurred mainly in restaurants. These results highlight the need to develop an information system and training of allergies and food professionals to implement risk prevention strategies.

Background: Food allergy affects an estimated 8% of children and 3% of adults in the United States. Food‐allergic individuals increasingly use the web for medical information. We sought to determine the educational quality of food allergy YouTube videos. Methods: We performed a YouTube search using keywords “food allergy” and “food allergies”. The 300 most viewed videos were included and analyzed for characteristics, source, and content. Source was further classified as healthcare provider, alternative medicine provider, patient, company, media, and professional society. A scoring system (FA‐DQS) was created to evaluate quality (−10 to +34 points). Negative points were assigned for misleading information. Eight reviewers scored each video independently. Results: Three hundred videos were analyzed, with a median of 6351.50 views, 19 likes, and 1 dislike. More video presenters were female (54.3%). The most common type of video source was alternative medicine provider (26.3%). Alternative treatments included the following: water fast, juicing, Ayurveda, apple cider, yoga, visualization, and sea moss. Controversial diagnostics included kinesiology, IgG testing, and pulse test. Almost half of the videos depicted a non‐IgE‐mediated reaction (49.0%).Videos by professional societies had the highest FA‐DQS (7.27). Scores for videos by professional societies were significantly different from other sources (P < .001). There was a high degree of agreement among reviewers (ICC = 0.820; P < .001). Conclusion: YouTube videos on food allergy frequently recommend controversial diagnostics and commonly depict non‐IgE‐mediated reactions. There is a need for high‐quality, evidence‐based, educational videos on food allergy.

Parasitische Würmer wie Filarien können das Immunsystem ihres Wirtes modulieren. Diese Immunmodulation schützt nicht nur den Parasiten, sondern kann auch den Wirt vor allergischen Reaktionen schützen. In der vorliegenden Arbeit konnte belegt werden, dass Filariencystatin, ein sezernierter Proteinaseinhibitor des Fadenwurms Acanthocheilonema viteae Th2-assoziierte Entzündungen und die daraus resultierende Atemwegserkrankung im murinen Asthmamodell supprimiert. Diese Effekte von Cystatin beruhen wahrscheinlich auf der Induktion von IL-10 sezernierenden Makrophagen. Dafür spricht, dass sowohl die Depletion von Makrophagen, als auch die Blockierung von IL-10 den schützenden Effekt von Cystatin aufhoben. In einem murinen Dermatitismodell konnte durch Cystatinapplikation die Entzündung der Haut ebenfalls unterbunden werden. Die Verbesserung der atopischen Dermatitis führte zu einem Anstieg von TGF-Beta in den Ekzemregionen. Zusammenfassend belegen die Daten, dass ein einzelnes rekombinantes Helminthenprotein den anti-allergischen Effekt einer Gesamtwurminfektion nachahmen kann. Des weiteren wurde untersucht, ob die Immunmodulation von Helminthen an die Biologie des Wurmes gebunden ist. Der Einfluss einer gastrointestinalen Wurminfektion mit Heligmosomoides polygyrus wurde in Modellen mucosa-assoziierter allergischer Atemwegsentzündung und nicht-mukosa-assoziierter, kutanen Dermatitis untersucht. Im Asthmamodell konnte eine Reduzierung der Inflammation beobachtet werden, im Dermatitis Modell keinerlei Verbesserung des klinischen Bildes. Die Wurminfektion führte zu erhöhten Werten von Foxp3+ regulatorischen T-Zellen (Treg) in peribronchialen Lymphknoten, im Gegensatz dazu konnten keine Treg Zellen in ekzematöser Haut nachgewiesen werden. Diese Ergebnisse sind ein wichtiger Aspekt beim Einsatz von Helminthen zur Behandlung allergischer Erkrankungen, da die Lokalisation des Wurmes ein entscheidender Faktor in Richtung Verbesserung oder Verschlimmerung allergischer Erkrankungen zu sein scheint. / Parasitic worms, like filariae, have the intriguing capacity to modulate immune responses directed against them. This immunomodulation protects the parasite and was found to mediate a negative correlation between parasite infections and the prevalence of allergic disease. In the present study filarial cystatin (Av17), a secreted protease inhibitor of the filarial nematode Acanthocheilonema viteae, was found to suppress Th2-related inflammation and allergic airway responsiveness in mice. These effects of Av17 on allergic airway inflammation were probably due to induction of IL-10 secreting macrophages. Depletion of macrophages as well as blocking of IL-10 by application of anti-IL-10 receptor antibodies, prevented the curative effects and restored allergic airway inflammation. Treatment with cystatin in a model of allergic skin disease, suppressed inflammation, too. The protective effect on atopic dermatitis was accompanied by an increase of TGF-Beta in the eczema region. Hence, the data demonstrate that treatment with a single recombinant helminth protein can exert the anti-allergic effects of helminth infections. Furthermore this study investigated if immunomodulation by helminths is dependent on the biology of the worm. Infection with the gastrointestinal nematode Heligmosomoides polygyrus, was analyzed in models of mucosa-associated airway disease and non-mucosal, cutaneous atopic dermatitis. Infected mice showed reduced signs of allergic airway inflammation but no differences in phenotypical signs of dermatitis. Worm infection was associated with elevated numbers of Foxp3+ regulatory T cells (Treg) in peribronchial lymph nodes in the asthma model, whereas Treg cells were basically absent in eczematous skin. These findings might be an important aspect for future considerations of helminths for treatment of allergic diseases, as localisation of the parasites might be a crucial factor leading to amelioration or aggravation of allergic disease.

As alergias alimentares em cães representam cerca de 1% das dermatoses dos cães, é uma doença pouco conhecida com relação a sua etiopatogenia, diagnóstico e tratamento. O objetivo geral é analisar a bibliografia de 1990 até 2003 e levantar o estado atual da arte sobre “Alergia Alimentar em cães". Foi realizada revisão bibliográfica consultando o sistema de base de dados CAB Abstracts (Commonwealth Agriculture Bureau) e AGRIS. Utilizamos os unitermos: “Dog", “sensitivity", “ hipersensitivity", “ food "e “allergy". Ao todo, foram coletados 160 trabalhos do CAB e 58 do AGRIS, somando 218 trabalhos. Destes 218 trabalhos, foram eliminados 74 escritos em outras línguas, que não a língua inglesa ou portuguesa, e 38 trabalhos que foram encontrados tanto no CAB quanto no AGRIS. Dos 106 trabalhos restantes, 21 foram escolhidos para serem inseridos neste trabalho de revisão. Quanto ao desenho de estudo foram coletados: 10 ensaios clínicos, nove revisões e dois levantamentos. Dos 21 trabalhos, 13 foram publicados nos Estados Unidos, cinco no Reino Unido, dois na Nova Zelândia e um na Austrália. Os anos com o maior número de publicações foram: 1992, 1994 e 2002. Os trabalhos foram divididos em seis temas, para melhor abordá-los: definição de conceitos, utilização do cão atópico como modelo de estudo, diagnóstico e tratamento, dietas testes, reações pseudo-alérgicas e mecanismos imunológicos. Quanto à terminologia, elas são utilizadas muitas vezes de forma errada, confundindo as verdadeiras alergias alimentares (IgE mediadas) e as reações adversas aos alimentos, comprometendo o diagnóstico, tratamento e prevenção da doença. Os mecanismos imunológicos não estão ainda totalmente definidos. Não foram encontradas discussões a respeito da “Transição Epidemiológica" ou sobre a “Hipótese da Higiene" e não foi possível verificar com a análise dos trabalhos selecionados a possível relação entre a mudança brusca de alimentação que sofreram os cães na última década e o provável aumento do número de casos de alergia alimentar. / The alimentary allergies in dogs represent about 1% of the dogs’ dermatosis, it is an illness little known with regard to its etiopathic, diagnosis and treatment.The general objective is to analyze the bibliography since 1990 up to 2003 and to raise the current position of the art on "Alimentary Allergy in dogs". Bibliographical revision was carried out consulting system data-base CAB Abstracts (Commonwealth Agriculture Bureau) and AGRIS. We use for key words: "Dog", "sensitivity", "hypersensitivity", "food" and "allergy". Altogether, 160 works of CAB and 58 of the AGRIS had been collected, adding 218 works. Of these 218 works, 74 writings in other languages, that not in English or Portuguese, and 38 works that had been found in CAB in AGRIS had been left out. Of the 106 remaining studies, 21 had been chosen to be added in this work of revision based on: title of the work, author, sample size, drawing of clear-cut study, impact factor of the publication magazine and subject directly related to the objective of the present study. As for the study drawing had been collected: 10 clinical assays, nine revisions and two surveys. Of the 21 works, 13 had been published in the United States, five in the United Kingdom, two in New Zealand and one in Australia. The years that had more number of publications had been: 1992, 1994 and 2002. The studies had been divided in six subjects to better approach them: definition of concepts, use of atopic dogs as study model, diagnosis and treatment, diets tests, pseudo-allergic reactions and immunological mechanisms. Several times the terminologies is used in wrong way, confusing the true alimentary allergies (IgE mediated) and the adverse reactions to foods, compromising the diagnostic, treatment and prevention of the illness. The immunological mechanisms still are not total defined. Discussion concerning on the "Epidemiological Transition" or on the "Hygiene’s Hypothesis" had not been found and it was not possible to verify with the analyze of the selected works the possible relation between the brusque change of feeding that the dogs had suffered in finish decade and the probable increase of the number of cases of alimentary allergy in dogs.

A crotoxina (CTX) é a principal toxina do veneno de serpentes Crotalus durissus terrificus, caracterizada como <font face=\"Symbol\">b-neurotoxina com ação principalmente pré-sináptica, inibindo a liberação de acetilcolina nas junções neuro-musculares. No entanto, vários dados de literatura têm mostrado que, adicionalmente à atividade neurotóxica, a CTX apresenta efeitos imunomodulatórios antiinflamatório, analgésico e anti-tumoral. Apesar destes dados, não foi ainda determinada a ação desta toxina sobre modelos experimentais de alergia, como por exemplo, a inflamação alérgica pulmonar. Este trabalho teve por objetivo investigar o possível efeito inibitório da CTX sobre a gênese e o desenvolvimento de resposta inflamatória pulmonar induzida em ratos pela sensibilização com Ovalbumina (OVA), bem como a sua possível interferência na alergia já estabelecida. Em conjunto, os resultados sugerem que a CTX interfere com a inflamação pulmonar acarretada pela sensibilização e desafio por OVA, modulando mecanismos indutores e efetores da resposta alérgica. / Crotoxin (CTX) is the main toxin of the venom of South American rattlesnake Crotalus durissus terrificus, corresponding to 65% of the protein content of the crude venom. CTX is a <font face=\"Symbol\">b-neurotoxin that displays mainly pre-synaptic action, inhibiting the release of acetylcholine in the neuromuscular junctions. However, some experimental and clinical data have shown that, in addition to the neurotoxic activity, CTX displays immunomodulatory, antiinflammatory, analgesic and anti-tumoral properties. Despite these observations, the possible inhibitory action of this toxin in experimental models of allergy, such as lung allergic inflammation, was not determined yet. Therefore, this study aims to investigate the inhibitory effect of CTX on the genesis and development of lung inflammation induced in rats by sensitization with Ovalbumin (OVA). Together, these results suggest that CTX inhibits lung inflammation induced by sensitization and challenge with OVA, interfering with the initiators and effectors mechanisms of allergic inflammation.

Wang, Shuxin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 191-212). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese; appendixes includes Chinese.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-04-19T12:01:26Z No. of bitstreams: 1 Érika Campos Gomes.pdf: 620457 bytes, checksum: 3e9a7035999fd61c70de3db7af57ca5d (MD5) / Made available in DSpace on 2017-04-19T12:01:26Z (GMT). No. of bitstreams: 1 Érika Campos Gomes.pdf: 620457 bytes, checksum: 3e9a7035999fd61c70de3db7af57ca5d (MD5) Previous issue date: 2017-04-06 / Food allergies have increased considerably and it affects approximately 8% of children. To this day, there are no available cures and the only way of coping with the allergies is to avoid contact with the allergen and emergency treatment of symptoms in case of accidental exposure. The constant dread of anaphylaxis incidents and the vigilance needed to avoid the exposure to the allergen puts significant pressure on the family as a whole, affecting daily activities and consequently quality of life. The objective of this qualitative research is to investigate the main effects of allergy management, its effects on fraternal relationships and intervention techniques to conflict situations arising from the allergy in sibling relations. In this research, we studied mothers found in an online allergy support group hosted on Facebook who had a son/daughter diagnosed with a food allergy age 12 and below and with siblings ages 15 and below who may or may not have a food allergy. The participants answered a questionnaire to better define the family, to gather further information on the allergies and took part in an online discussion board. We identified as the most prominent effects of food allergy changes in daily routine, internal conflicts, conflicts within the nuclear family, conflicts within the extended family and the overall experiences regarding living in with risk. We observed support, complicity and feelings of jealousy and anger in sibling relations as consequences of the food allergy. Conflict mediation strategies used by mothers to deal with conflict in sibling relations involve privation and negotiation. Understanding the complexities and individuality of the particular effects of food allergies in family life, especially in sibling relations is important in order to develop coping techniques which take into account the everlasting care regarding the allergy and the needs of all family members, especially each sibling / A alergia alimentar tem aumentado consideravelmente e afeta aproximadamente 8% das crianças. Até o momento, não existe cura e as únicas formas de enfrentamento são evitar contato com o alérgeno e o tratamento emergencial de sintomas em caso de exposição acidental. O receio constante de episódios de anafilaxia e a vigilância necessária para evitar a exposição ao alergênico coloca uma pressão significativa sobre a família, impactando nas atividades diárias e qualidade de vida. Esta pesquisa qualitativa teve como objetivo investigar os principais efeitos familiares do gerenciamento da alergia alimentar, sua interferência na relação fraterna e as formas de intervenção em situações de conflito que podem surgir entre os irmãos em função da alergia. Participaram desta pesquisa mães originárias de um grupo de apoio do Facebook focado em alergia alimentar, que tinham um filho de até 12 anos com diagnóstico de alergia alimentar e com irmãos com até 15 anos, sendo estes, alérgicos ou não. As participantes responderam a um questionário de identificação das famílias e de detalhamento das alergias e participaram de um fórum de discussão on-line. Foi possível verificar como principais efeitos familiares do gerenciamento da alergia: as especificidades da rotina diária, as consequências das restrições alimentares que envolvem conflitos internos, com a família nuclear e extensa, e a experiência de conviver com risco. O apoio e a cumplicidade, assim como sentimentos de ciúmes e raiva, foram observados no relacionamento fraterno como decorrências da alergia. As estratégias de manejo de conflitos entre os irmãos relativos à alergia envolvem a privação e a negociação. Compreender a complexidade e individualidade do efeito da alergia alimentar na vida familiar, especialmente no relacionamento fraterno, mostra-se importante para elaborar formas de enfrentamento que levem em consideração os cuidados indispensáveis à alergia e as demandas de cada membro da família, em particular, de cada filho

Les mastocytes (MCs) sont issus des cellules hématopoïétiques multipotentes non engagées, CD34+, et jouent un rôle important dans l’initiation de la réponse immunitaire innée et adaptative, ainsi que dans les réactions allergiques IgE-dépendantes. Les mastocytoses sont des néoplasies myéloïdes caractérisées par une accumulation anormale et l'activation fréquente de mastocytes dans divers organes. Les organes généralement atteints sont la moelle osseuse, la peau, le foie et le tractus gastro-intestinal. Elles sont caractérisées dans l’immense majorité des cas par la présence de mutations acquises de la structure du récepteur KIT (plus particulièrement KIT D816V) qui induisent l’activation constitutive de ce récepteur à activité tyrosine kinase intrinsèque. Le traitement actuel de ces pathologies est décevant car la mutation KIT D816V résiste à la plupart des inhibiteurs de tyrosine kinases (ITKs).Dès le début de ma thèse, nous avons pu établir, à partir de cellules souches hématopoïétiques de sang de cordon humain normal cultivées à long terme en présence de stem cell factor (SCF), une nouvelle lignée mastocytaire humaine stable, dénommée ROSA KIT WT, restant strictement dépendante pour sa survie et sa prolifération du SCF, exprimant le récepteur de haute affinité aux IgE (FcεRI), et présentant un récepteur KIT de structure normale. Cette lignée, facile à cultiver en grandes quantités, permet d’envisager l’étude approfondie des évènements intracellulaires menant à l’activation mastocytaire IgE-dépendante et la mise au point de tests de criblage à haut débit dans le domaine de la thérapeutique anti-allergique et/ou anti-inflammatoire.Par ailleurs, afin de pouvoir étudier le rôle transformant des mutants de KIT retrouvés au cours des mastocytoses, nous avons transfecté les cellules ROSA KIT WT par des vecteurs lentiviraux apportant une construction codant pour le KIT muté en D816V ou le KIT muté Delta 417-419 insY. Nous avons ainsi obtenu deux nouvelles lignées mastocytaires humaines SCF-indépendantes, ROSA KIT D816V et ROSA KIT Delta 417-419 insY, pour lesquelles nous avons montré qu’il existe une activation constitutive de KIT, mais aussi de STAT5 et d’AKT. Ces deux lignées de pourront être utilisées soit pour étudier l’impact des mutations de KIT sur la signalisation intracellulaire, soit pour le criblage molécules à activité antiproliférative potentielle dirigées soit contre KIT muté, soit contre l'une ou l’autre des molécules intracellulaires impliquées dans la transduction du signal KIT muté / Mast cells are cells with ubiquitous tissue distribution, derived from CD34 + multipotent hematopoietic cells. These cells play a fundamental role in the initiation of innate and adaptive immune response and in IgE-dependent allergic reactions or in various inflammatory reactions.Mastocytosis is defined as a myeloproliferative neoplastic disorder, caused by an abnormal accumulation of mast cells in one or more organ systems. Mastocytosis presents in cutaneous and systemic forms. In patients with systemic mastocytosis, the most frequent point mutation is KIT D816V, whereas in pediatric patients, where the disease is usually restricted to the skin, different KIT defects have been detected, mostly in the extracellular portion of KIT.In a primary culture of mast cells made from precursors of one cord blood, we have successfully isolated a new human mast cell line called ROSA KIT WT with a phenotype and reactivity comparable to those of normal mast cells. This cell line is dependent on SCF for growth and expresses the KIT receptor wild. It is easy to grow in large quantities, to freeze and to activate by IgE-anti IgE couple or a couple of allergen and corresponding specific IgE. This cell line can be used to study pathophysiologic mechanisms of allergy and to develop and use high-throughput screening tests of molecules in search of anti-allergic properties.In addition, we transfected these cells by lentiviral vectors providing constructs encoding the mutated KIT D816V or the mutated KIT Delta 417-419 insY, two KIT abnormalities encountered in the course of mastocytosis. This allowed us to establish two new cell lines independent of SCF for proliferation, ROSA KIT D816V and ROSA KIT Delta417-419 insY, which are particularly easy to grow in large quantities, and whose phenotype is similar to that of abnormal mast cells during mastocytosis. These two cell lines can be used for pathophysiologic studies on mastocytosis and for high throughput screening of molecules in search of antiproliferative effects specifically directed against the mutated KIT or against one or other of the intracellular molecules involved in signal transduction induced by mutant KIT.

Utilizando modelo de coinflamação tuberculose e alergia (TB/OVA), nosso grupo mostrou que camundongos BALB/c coinflamados apresentaram diminuição significativa no número de bacilos, associada com diminuição no infiltrado granulomatoso no pulmão, aumento na produção de leucotrieno B4 e no número de células CD8+, quando comparados ao grupo infectado com Mycobacterium tuberculosis (TB). No presente estudo, nosso objetivo foi avaliar os mecanismos envolvidos na restrição ao crescimento dos bacilos nos animais do grupo TB/OVA. Quatro estratégias foram usadas: I) Para avaliar o papel dos linfócitos CD8+ no modelo TB/OVA, foram utilizados camundongos deficientes para a molécula CD8 (CD8KO). Foi observado que não houve diferenças significativas no crescimento do bacilo no pulmão dos animais CD8KO-TB/OVA e WT-TB/OVA. No entanto, nos pulmões dos animais WT-TB/OVA houve maior crescimento de bacilos em relação aos animais WT-TB, diferente do previamente observado com os animais TB/OVA da linhagem BALB/c. Para avaliar o papel dos leucotrienos foram usadas as seguintes estratégias: II). Camundongos da linhagem 129Sv tratados com MK886, inibidor da enzima 5-lipoxigenase (5LO), envolvida na síntese de mediadores lipídicos; III) animais 129Sv, deficientes para a expressão da 5LO (5LOKO). Foi observado que o tratamento com MK886 não afetou o número de bacilos no pulmão do grupo coinflamado TB/OVA quando comparado ao grupo TB/OVA. Além disso, diferente do que foi previamente observado em animais BALB/c, os animais 129Sv coinflamados foram mais susceptíveis que os animais 129Sv infectados. Do contrário, animais 5LOKO-TB/OVA foram mais resistentes que os camundongos WT-TB/OVA. Para avaliar se alterações no infiltrado granulomatoso estavam relacionadas com o infiltrado de macrófagos no pulmão, usamos a quarta estratégia: IV) quantificação das populações de macrófagos M1 e M2. Foi observado que os animais TB/OVA apresentaram aumento da população de macrófagos M2 no pulmão, enquanto a população de macrófagos M1 manteve-se inalterada comparado-se ao grupo apenas infectado. A diminuição no crescimento de bacilos nos animais TB/OVA foi dependente dos macrófagos M2, pois animais deficientes para a expressão do receptor de IL-33 submetidos ao protocolo de coinflamação tiveram diminuição da população de macrófagos M2, e foram susceptíveis à infecção. Esses resultados mostram que a diminuição no crescimento de bacilos nos animais coinflamados TB/OVA é dependente do aumento da população de macrófagos M2. / Using model of coinfection allergy and tuberculosis (TB / OVA), our group showed that coinfected BALB/c showed a significant decrease in the number of bacilli, associated with a decrease in granulomatous infiltrate the lung, increased production of leukotriene B4 and the number of cells CD8+, compared to the group infected with Mycobacterium tuberculosis (TB). To evaluate the mechanisms involved in reducing the growth of bacilli in group TB/OVA, were used four strategies: I) To assess the role of CD8+ lymphocytes in model TB/OVA, we used mice deficient for the molecule CD8 (CD8KO).We was observed that the number of bacilli in the lungs of animals in the group CD8KO-TB/OVA and WT-TB/OVA was similar. However, the lungs of animals WT-TB/OVA growth of bacillus was higher compared to WT animals, TB, unlike what was previously observed with background genetic BALB/c. To evaluate the role of leukotrienes, we use the following strategies: II) strain 129Sv mice treated with MK886, an inhibitor of the enzyme 5-lipoxygenase (5LO), involved in the synthesis of lipid mediators, III) 129Sv animals deficient for the expression of 5LO (5LOKO). We observed that treatment with MK886 did not affect the number of bacilli in the lung of the coinfected group TB/OVA. Moreover, unlike what was previously observed in animals BALB/c mice, coinfected 129Sv were more susceptible than the animals infected 129Sv. On the contrary, 5LOKO-TB/OVA animals were more resistant than mice WT-TB/OVA. To assess whether changes in granulomatous infiltrates were related to macrophages, we use the fourth strategy: IV) quantification of macrophage populations M1 and M2. We observed that M2 population in animals TB/OVA showed increased lung. The decrease in bacilli growth of animals TB/OVA was dependent on macrophage M2, since animals deficient for the expression of IL-33 protocol submitted to coinfected protocol had decreased macrophage population M2, and were susceptible to infection. These results show that the reduction in growth of bacilli in coinfected animals TB/OVA is dependent increase in macrophage population M2.