O etanol de cana-de-açúcar se consolida como combustível renovável, o que promove nova expansão da cultura da cana-de-açúcar no Brasil e, principalmente, no Estado de São Paulo. Como a queima prévia controlada da palha de cana-de-açúcar ainda é considerada uma prática agrícola necessária para a viabilização econômica da colheita, em mais de 70% dos municípios do Estado de São Paulo a população é obrigada a conviver com essa poluição. Para estudar a distribuição desse fator de risco e sua relação com a saúde, realizei um estudo epidemiológico ecológico nos 645 municípios de São Paulo. Usei um modelo Bayesiano de regressão multivariada relacionando os efeitos na saúde com a exposição à queima prévia da palha de cana-de-açúcar, sendo controlados os efeitos das variações socioeconômicas (saneamento, educação e renda) e climáticas (temperatura máxima, umidade mínima e precipitação), através da inserção das mesmas no modelo. O efeito sobre a saúde foi medido por meio da Razão de Mortalidade e Morbidade Padronizada (RMP) dos desfechos: óbitos por doenças respiratórias nas faixas etárias acima de 65 anos e internações por doença respiratória, nas faixas etárias menores de 5 anos e acima de 65 anos de cada um dos municípios. Usei como medida de exposição à queima prévia dados obtidos no INPE: percentual da área de cana colhida com queima (PMQ), níveis médios de Aerossol e Focos de queima, testadas separadamente. Para resolver a autocorrelação entre os dados, estes foram considerados conforme sua disposição espacial, através da construção de uma matriz de vizinhança dos 645 municípios do Estado. Utilizei o método de simulação de Monte Carlo via Cadeias de Markov (MCMC) para \'suavizar\' as estimativas da RMP. A análise demonstrou que existe associação entre a queima prévia da palha de cana-de-açúcar e a ocorrência de doenças respiratórias, porque o aumento nos focos de queima (Focos) esteve associado significativamente com o aumento das internações por doenças respiratórias, na faixa etária de menores de cinco anos. Os resultados mostraram que a queima prévia da palha da cana-de-açúcar oferece efetivamente risco à saúde da população e, adicionados aos mapas coropléticos gerados, oferecem subsídios para a vigilância epidemiológica e contribuem para o estabelecimento de políticas públicas para controle da poluição do ar, que contemplem além dos grandes centros urbanos, os pequenos municípios. A eliminação desse fator de risco deve fazer parte das medidas primordiais de prevenção à saúde a serem adotadas no Estado / Ethanol from sugarcane is consolidated as a renewable fuel which promotes further expansion of the culture of sugarcane in Brazil and especially in the State of São Paulo. As the controlled pre-harvest burning of sugarcane straw is still considered an agricultural practice necessary for the economic viability of this crop in more than 70% of municipalities in the State of São Paulo the population is forced to live with this pollution. To study the distribution of this risk factor and its relationship with the health of the population, I conducted an ecological study in the 645 municipalities of São Paulo. I used a Bayesian multivariate regression model relating the health effects and the exposure to previous straw burning of sugarcane, controlling the effects of socioeconomic factors (sanitation, education and income) and climate (maximum temperature, minimum humidity and precipitation) by the insertion of these variables in the model. The effect on health was measured by Standardized Mortality and Morbidity Ratio (SMR) of the outcomes: deaths from respiratory diseases in the age group above 65 years old and admissions for respiratory disease in children less than 5 years old and above 65 years old of each of the municipalities. I used as a measure of exposure to the pre-harvest burning data obtained at INPE: percent of sugarcane area harvest with burning (PMQ), levels of Aerosol and Spotlights of burning, tested separately. To solve the autocorrelation in the data these were considered as their spatial arrangement, by building a neighborhood matrix of the 645 municipalities in the state. I used the Markov Chain-Monte Carlo simulation method (MCMC) to \'soften\' the estimates of the SMR. The analysis showed that there is an association between previous straw burning of sugarcane and respiratory diseases, because the increase in outbreaks of burning (Spotlights) was significantly associated with increased hospital admissions for respiratory diseases in children aged under five years old. The results show that the previous straw burning of sugarcane effectively offers health risk to the population and added to the choropleth maps generated provide valuable information for epidemiological surveillance and contribute to the establishment of public policies for the control of air pollution, which should contemplate beyond the major urban centers, the small towns. The elimination of this risk factor should be part of a primordial prevention measure to be taken in the state

Para avaliar os benefícios da comunicação rápida ao clínico do diagnóstico de vírus respiratórios, foi analisado a viabilidade econômica de 2 testes, com o tempo de entrega de resultado em 2 horas para teste rápido e 48 horas para Biologia Molecular. As amostras coletadas foram processadas utilizando técnicas convencionais e os testes disponíveis no mercado local. Foram escolhidos dois testes rápidos pelo método de imunocromatografia para quatro parâmetros analíticos: Influenza A, Influenza H1N1, Influenza B e Vírus Sincicial Respiratório (RSV) e em Biologia Molecular um teste de RT-PCR multiplex com 25 patógenos entre vírus e bactérias. O tipo de amostra utilizada foi swab e lavado de nasofaringe. A população escolhida para o estudo foi paciente adulto, em tratamento de câncer, que necessita de uma resposta rápida já que a maioria se encontra com comprometimento do sistema imune por doença ou por tratamento. O estudo foi transversal, realizado entre os anos de 2012 e 2013, para avaliar a viabilidade econômica da introdução de testes de diagnóstico da infecção respiratória aguda de etiologia viral a partir de amostras de nasofaringe em pacientes com câncer atendidos no Centro de Atendimento de Oncologia Intercorrência (CAIO ), do Instituto do Câncer do Estado de São Paulo (ICESP), hospital público que atende exclusivamente Sistema Único de Saúde (SUS) e Hospital A.C. Camargo, que atende tanto a pacientes do SUS como da rede privada. O estudo incluiu 152 pacientes em tratamento para qualquer tipo de câncer, predominantemente do sexo feminino (81 mulheres e 70 homens) com idades entre 18-86 anos. Para participar do estudo o paciente era consultado e o critério para escolha do paciente foi ser portador de câncer, com história de febre (ainda que referida) acompanhada de tosse ou dor de garganta, tosse e sintomas respiratórios agudos, atendidos por protocolo padronizado que inclui avaliação na admissão, seguimento e manejo antimicrobiano. Para a avaliação econômica os pacientes foram classificados de acordo com o estado geral de saúde, se apresentavam bom estado de estado de saúde poderiam receber alta e faziam uso da medicação em casa evitando 5 dias de internação se recebessem algum resultado para Influenza ou RSV, no entanto os pacientes que apresentavam outro vírus, resultado negativo ou o estado geral era ruim permaneciam internados por 7 dias em observação e cuidados com medicação adequada. Foram realizadas análises econômicas em dois âmbitos: o sistema de saúde publico e o privado considerando o fator diminuição de dias de internação. A analise de Custo-benefício foi eficiente no Sistema privado mas inadequada para o SUS assim como, qualquer outra medida monetária já que os valores de reembolso do SUS estão defasados do custo de qualquer internação. A análise de Custo-efetividade que olha para outros fatores além do monetário foi efetiva nos dois sistemas que enfrentam falta de leitos além da condição de saúde do paciente de evitar a ingestão desnecessária de antibióticos, evitar os gastos do acompanhante, perda de dias de trabalho e estudo. Não houve correspondência de resultados dos testes rápidos com o multiplex de Biologia Molecular / To evaluate the benefits of the rapid communication of the respiratory viruses\' diagnosis to the doctor, the economic feasibility of two tests was analyzed, with the result delivery time within 2-hours for the rapid test and 48 hours for Molecular Biology. The samples were processed using conventional techniques and the available tests in the local market. Two rapid tests were selected by the immunochromatography method for four analytical parameters: Influenza A, Influenza A H1N1, Influenza B, and Respiratory Syncytial Virus (RSV) and in Molecular Biology a multiplex RT-PCR assay with 25 pathogens between viruses and bacteria. The type of sample used was swab and nasopharyngeal wash. The population chosen for the study was of adult patients undergoing cancer treatment, which requires a rapid response since most have a compromised immune system due to the disease or treatment. The study, conducted between 2012 and 2013, was cross-sectional to evaluate the economic feasibility of introducing diagnostic tests for acute respiratory infection of viral etiology from nasopharyngeal samples of patients with cancer attended at the Oncology Intercurrence Care Center (CAIO), at the Cancer Institute of the São Paulo State (ICESP), at public hospital that attends exclusively the Unified Health System (SUS) and at AC Camargo hospital, which attends SUS patients as well as the private health system. The study included 152 patients undergoing treatment for any type of cancer, predominantly female (81 women and 70 men) between 18 and 86 years. To participate in the study, the patients were consulted and the criteria for choosing a patient was to be a cancer patient with a history of fever (even if referred) accompanied by cough or sore throat, coughing and acute respiratory symptoms, attended by standardized protocol that includes an evaluation at the admission, tracking and antimicrobial management. For the economic evaluation, patients were classified according to the general health condition. If they were in a good health condition, they could receive medical discharge and make use of the medication at home avoiding five days of hospitalization when receiving a result for influenza or RSV. However, the patients with other viruses, negative results or with bad general condition remained hospitalized for seven days under observation and care with proper medication. Economic analyzes were carried out in two areas: the public health system and private health system considering the factor decreased length of hospital stay. The cost-benefit analysis was efficient in the private system but inadequate for the NHS as well as any other monetary measure since the SUS reimbursement values are too low when compared to the cost of any other hospital. The cost-effectiveness analysis that looks at other factors besides money was effective in both systems that were facing lack of beds in addition to the health condition of the patient to avoid unnecessary intake of antibiotics, avoid the costs of the accompanying person, loss of working and study days. There were no results correspondences of the rapid tests with the Molecular Biology multiplex

Made available in DSpace on 2016-01-26T12:51:40Z (GMT). No. of bitstreams: 1 joabatistasalomao_dissert.pdf: 485965 bytes, checksum: a1e9ad096dff68d92c37d5033056c5f6 (MD5) Previous issue date: 2001-06-12 / Objective Evaluate, social competence and behavior disorders in children with moderate to severe asthma according to parental perception. Casuistics: Sixty-two patients were studied, 36 male and 26 female, ages ranging from 7 to 16 years (MA: 10.94; SD: 2.28), with clinical diagnosis of moderate to severe asthma, without comorbidity, seen at the Pediatric Pneumology Service and the Allergy and Immunology Service at a University Hospital, from March to September, 2000. A control group was simultaneously studied and included 62 patients, 37 male and 25 female, ages ranging from 7 to 16 years (MA: 10.26; SD: 2.37), seen at the Orthopedics and Ophthalmology Outpatient Wards at the same hospital, without symptoms of asthma, respiratory allergy and no chronic diseases. Material and method An Identification Form, a Clinical Data Form and the CBCL (Child Behavior Checklist), a tool to evaluate social competence and behavior disorders, were used. Results Results were evaluated by the proportional tests, Student s t test and ANADEP and ANADEPMU and a significance level of 0.05 was chosen. Patients were classified according to the clinical manifestations of asthma: 42 had moderate asthma and 20 had severe asthma, most of them (93.55%) had been diagnosed since 3 years of age. There was no significant difference in age and gender between the group with asthma and the control group. There was a marked association between overall social competence and asthma (with p=0.000) and between social competence associated to activities (with p=0.001) and school (with p=0.01). There was no difference between children with asthma and the control group for social markers (with p=0.23). There was no correlation between gender and age when evaluating social competence, or overall social competence specific parameters: activities, school and social activities. The evaluation of social competence and type of asthma did not show a correlation. There was a strong association between the presence of behavior disorders and asthma (p=0.005), specially internalizing disorders (p=0.001). There was no association between the externalizing disorders and the disease. Behavior disorders were not associated to gender, age and type of asthma. Conclusions Children with asthma showed alterations in overall social competence and social competence related to activities and school, when compared to the control group. They also showed overall and internalizing disorders, which may be harmful to their development, their quality of life, compliance with the treatment and adequate management of the disease. The integration of biological, psychological and social factors is essential to establish adequate programs for the treatment of children with asthma and their families. / Objetivo - avaliar competência social e transtornos comportamentais em crianças com asma moderada e grave, a partir de percepção dos pais. Causística: foram estudados 62 pacientes, 36 do sexo masculino e 26 do sexo feminino, com idade entre 7 e 16 anos (im:10,94; dp:2,28), com diagnóstico clínico de asma moderada e grave, sem comorbidade, atendidos nos serviços de pneumologia infantil e alergia e imunologia de um hospital escola, no perído de março e setembro de 2000. Um grupo de controle foi estudado no mesmo período, composto de 62 pacientes, 37 do sexo masculino e 25 do sexo feminino, com idade entre 7 e 16 anos (im: 10,26; dp: 2,37), atendidos nos ambulatório de ortopedia e oftalmologia do mesmo hospital, sem qualquer sintomatologia de asma, de alergia respiratória e sem qualquer doença crônica. Material e método - foram utilizados na obtenção dos dados uma ficha de identificação, uma ficha de dados clínicos e um instrumento que avalia competência social e transtornos comportamentais - child behavior checklist (cbcl). Resultados - os resultados foram analisados com testes proporção x (ao quadrado), teste t de student, anadep e anadepmu, adotando-se nível de significância de 0,05. Os pacientes foram classificadossegundo manifestações clínicas da asma: 42 com asma moderada e 20 com asma grave, sendo que 93,55% receberam o diagnóstico da doença antes dos 3 anos de idade. Não houve diferença significante em termos de idade e sexo entre os grupos com asma e controle. Houve associação entre competência social e global e asma (p=0,000) e entre competência social associada a atividades (p=0,001) e escola (p=0,01). Não houve diferença entre crianças com asma e o grupo controle em relação ao aspecto social (p=0,23). Não houve relação entre sexo e idade na análise da competência social, nem quanto à competência social global nem quanto aos aspectos específicos: atividades, escola e social. A análise entre competência social e tipo de asma também não mostrou associação. Houve associação entre presença de transtornos comportamentais e asma (p=0,005), principalmente os transtornos internalizantes (p=0,001). Não houve associação dos externalizantes com a doença. Os transtornos comportamentais não se mostraram associados ao sexo, idade da amostra e tipo de asma. Conclusões - as crianças com asma apresentaram alterações na competência social e global e competência social relacionada a atividades e escola, quando comparadas ao grupo controle. Apresentaram ainda transtornos globais e internalizantes, que podem prejudicar o seu desenvolvimento, sua qualidade de vida, a adesão ao tratamento e o manejo adequado da doença. A integração dos aspectos biológicos, psicológicos e sociais é imprescindível para o delineamento de programas adequados de atendimento à criança portadora de asma e a seus familiares.

Para avaliar os benefícios da comunicação rápida ao clínico do diagnóstico de vírus respiratórios, foi analisado a viabilidade econômica de 2 testes, com o tempo de entrega de resultado em 2 horas para teste rápido e 48 horas para Biologia Molecular. As amostras coletadas foram processadas utilizando técnicas convencionais e os testes disponíveis no mercado local. Foram escolhidos dois testes rápidos pelo método de imunocromatografia para quatro parâmetros analíticos: Influenza A, Influenza H1N1, Influenza B e Vírus Sincicial Respiratório (RSV) e em Biologia Molecular um teste de RT-PCR multiplex com 25 patógenos entre vírus e bactérias. O tipo de amostra utilizada foi swab e lavado de nasofaringe. A população escolhida para o estudo foi paciente adulto, em tratamento de câncer, que necessita de uma resposta rápida já que a maioria se encontra com comprometimento do sistema imune por doença ou por tratamento. O estudo foi transversal, realizado entre os anos de 2012 e 2013, para avaliar a viabilidade econômica da introdução de testes de diagnóstico da infecção respiratória aguda de etiologia viral a partir de amostras de nasofaringe em pacientes com câncer atendidos no Centro de Atendimento de Oncologia Intercorrência (CAIO ), do Instituto do Câncer do Estado de São Paulo (ICESP), hospital público que atende exclusivamente Sistema Único de Saúde (SUS) e Hospital A.C. Camargo, que atende tanto a pacientes do SUS como da rede privada. O estudo incluiu 152 pacientes em tratamento para qualquer tipo de câncer, predominantemente do sexo feminino (81 mulheres e 70 homens) com idades entre 18-86 anos. Para participar do estudo o paciente era consultado e o critério para escolha do paciente foi ser portador de câncer, com história de febre (ainda que referida) acompanhada de tosse ou dor de garganta, tosse e sintomas respiratórios agudos, atendidos por protocolo padronizado que inclui avaliação na admissão, seguimento e manejo antimicrobiano. Para a avaliação econômica os pacientes foram classificados de acordo com o estado geral de saúde, se apresentavam bom estado de estado de saúde poderiam receber alta e faziam uso da medicação em casa evitando 5 dias de internação se recebessem algum resultado para Influenza ou RSV, no entanto os pacientes que apresentavam outro vírus, resultado negativo ou o estado geral era ruim permaneciam internados por 7 dias em observação e cuidados com medicação adequada. Foram realizadas análises econômicas em dois âmbitos: o sistema de saúde publico e o privado considerando o fator diminuição de dias de internação. A analise de Custo-benefício foi eficiente no Sistema privado mas inadequada para o SUS assim como, qualquer outra medida monetária já que os valores de reembolso do SUS estão defasados do custo de qualquer internação. A análise de Custo-efetividade que olha para outros fatores além do monetário foi efetiva nos dois sistemas que enfrentam falta de leitos além da condição de saúde do paciente de evitar a ingestão desnecessária de antibióticos, evitar os gastos do acompanhante, perda de dias de trabalho e estudo. Não houve correspondência de resultados dos testes rápidos com o multiplex de Biologia Molecular / To evaluate the benefits of the rapid communication of the respiratory viruses\' diagnosis to the doctor, the economic feasibility of two tests was analyzed, with the result delivery time within 2-hours for the rapid test and 48 hours for Molecular Biology. The samples were processed using conventional techniques and the available tests in the local market. Two rapid tests were selected by the immunochromatography method for four analytical parameters: Influenza A, Influenza A H1N1, Influenza B, and Respiratory Syncytial Virus (RSV) and in Molecular Biology a multiplex RT-PCR assay with 25 pathogens between viruses and bacteria. The type of sample used was swab and nasopharyngeal wash. The population chosen for the study was of adult patients undergoing cancer treatment, which requires a rapid response since most have a compromised immune system due to the disease or treatment. The study, conducted between 2012 and 2013, was cross-sectional to evaluate the economic feasibility of introducing diagnostic tests for acute respiratory infection of viral etiology from nasopharyngeal samples of patients with cancer attended at the Oncology Intercurrence Care Center (CAIO), at the Cancer Institute of the São Paulo State (ICESP), at public hospital that attends exclusively the Unified Health System (SUS) and at AC Camargo hospital, which attends SUS patients as well as the private health system. The study included 152 patients undergoing treatment for any type of cancer, predominantly female (81 women and 70 men) between 18 and 86 years. To participate in the study, the patients were consulted and the criteria for choosing a patient was to be a cancer patient with a history of fever (even if referred) accompanied by cough or sore throat, coughing and acute respiratory symptoms, attended by standardized protocol that includes an evaluation at the admission, tracking and antimicrobial management. For the economic evaluation, patients were classified according to the general health condition. If they were in a good health condition, they could receive medical discharge and make use of the medication at home avoiding five days of hospitalization when receiving a result for influenza or RSV. However, the patients with other viruses, negative results or with bad general condition remained hospitalized for seven days under observation and care with proper medication. Economic analyzes were carried out in two areas: the public health system and private health system considering the factor decreased length of hospital stay. The cost-benefit analysis was efficient in the private system but inadequate for the NHS as well as any other monetary measure since the SUS reimbursement values are too low when compared to the cost of any other hospital. The cost-effectiveness analysis that looks at other factors besides money was effective in both systems that were facing lack of beds in addition to the health condition of the patient to avoid unnecessary intake of antibiotics, avoid the costs of the accompanying person, loss of working and study days. There were no results correspondences of the rapid tests with the Molecular Biology multiplex

In Enterobacteriaceae, the transcriptional regulator AmpR, a member of the LysR family, regulates the expression of a chromosomal β-lactamase AmpC. The regulatory repertoire of AmpR is broader in Pseudomonas aeruginosa, an opportunistic pathogen responsible for numerous acute and chronic infections including cystic fibrosis. Previous studies showed that in addition to regulating ampC, P. aeruginosa AmpR regulates the sigma factor AlgT/U and production of some quorum sensing (QS)-regulated virulence factors. In order to better understand the ampR regulon, the transcriptional profiles generated using DNA microarrays and RNA-Seq of the prototypic P. aeruginosa PAO1 strain with its isogenic ampR deletion mutant, PAO∆ampR were analyzed. Transcriptome analysis demonstrates that the AmpR regulon is much more extensive than previously thought influencing the differential expression of over 500 genes. In addition to regulating resistance to β-lactam antibiotics via AmpC, AmpR also regulates non-β-lactam antibiotic resistance by modulating the MexEF-OprN efflux pump. Virulence mechanisms including biofilm formation, QS-regulated acute virulence, and diverse physiological processes such as oxidative stress response, heat-shock response and iron uptake are AmpR-regulated. Real-time PCR and phenotypic assays confirmed the transcriptome data. Further, Caenorhabditis elegans model demonstrates that a functional AmpR is required for full pathogenicity of P. aeruginosa. AmpR, a member of the core genome, also regulates genes in the regions of genome plasticity that are acquired by horizontal gene transfer. The extensive AmpR regulon included other transcriptional regulators and sigma factors, accounting for the extensive AmpR regulon. Gene expression studies demonstrate AmpR-dependent expression of the QS master regulator LasR that controls expression of many virulence factors. Using a chromosomally tagged AmpR, ChIP-Seq studies show direct AmpR binding to the lasR promoter. The data demonstrates that AmpR functions as a global regulator in P. aeruginosa and is a positive regulator of acute virulence while negatively regulating chronic infection phenotypes. In summary, my dissertation sheds light on the complex regulatory circuit in P. aeruginosa to provide a better understanding of the bacterial response to antibiotics and how the organism coordinately regulates a myriad of virulence factors.

Background: Cystic fibrosis (CF) remains the most common fatal monogenic disease in the US, affecting 1 in 3,300 live births. CF is the result of mutations in CFTR, a chloride channel and regulator of other ion channels. The mechanisms by which CFTR mutations cause chronic lung disease in CF are not fully defined, but may include the combined effects of altered ion and water transport across the airway epithelium and aberrant inflammatory and immune responses to pathogens within the airways. We have shown that Cftr-/- mice mount an exaggerated IgE response towards Aspergillus fumigatus (Af) when compared to Cftr+/+ mice. Along with the increased IgE levels, the Cftr-/- mice had higher levels of IL-13 and IL-4, mimicking both the Th-2 biased immune responses and predilection to mounting Af-specifc IgE seen in CF patients. Herein we hypothesize that these immune aberrations are primarily due to the lack of Cftr expression in lymphocytes rather than with Cftr deficiency in the epithelium. Results: Our results indicate that adoptive transfer experiments with Cf splenocytes confer higher IgE response to Af in host mice as compared to hosts receiving wild-type splenocytes. The predilection of Cftr-deficient lymphocytes to mount Th2 responses was confirmed by in vitro antigen recall experiments, where higher levels of IL-13 and IL-4 where seen only in the presence of Cftr-deficient lymphocytes. Conclusive data on this phenomenon were obtained with conditional Cftr knockout mice, where mice lacking Cftr in T-cell lineages developed the higher IgE titers as compared to their wild-type littermate controls. Further analysis of Cftr-deficient lymphocytes revealed an enhanced intracellular Ca 2+ flux in response to T cell receptor activation as compared to normal lymphocytes. This was accompanied by a significant increase in nuclear localization of the calcium-sensitive transcription factor NFAT, which could contribute to the enhanced secretion of IL-13 and other cytokines. Conclusions: In summary, our data identified that CFTR dysfunction in T cells can lead directly to aberrant immune responses. This is the first instance that a CF related phenotype has been entirely modeled in vivo by selectively knocking out CFTR in the immune system. Specifically, Cftr deficient lymphocytes directed skewed responses to Aspergillus fumigatus , leading to a higher than normal IgE response. These findings implicate the lymphocyte population as a potentially important target for therapeutics directed to the treatment of CF lung disease.

<p>Food allergies are immune system-driven diseases that lead to reproducible adverse reactions which can be fatal. These severe systemic reactions are primary mediated by immunoglobulin E (IgE) that is derived from B cells which have been activated by T helper type 2 (Th2) cells. While much work has advanced the clinical and pharmacological management of patients with allergic diseases, much remains to be elucidated about how individuals initially acquire allergy. This Thesis details a mechanism linking initial gastrointestinal exposure to peanut (PN) allergen, to the generation of Th2 cells: PN allergen activates epithelial cell secretion of interleukin (IL)-33 and eosinophil degranulation of eosinophil peroxidase, which causes CD103+ dendritic cell (DC) activation and migration to mesenteric lymph nodes where DC OX40L engages naïve T cells to secrete IL-4 in an autocrine/paracrine manner to promote and consolidate Th2 cell differentiation. These events are followed by B cell activation and PN-specific IgE production, which sensitizes mast cells to be hypersensitive to PN re-exposure by causing immediate allergic reactions including anaphylaxis. This is later followed by eosinophilic inflammation that is partially mediated by innate lymphoid cells. As food allergy also serves as a unique model to better understand mechanisms of adaptive immunity, especially Th2 immunobiology, both basic science and clinical implications are discussed in this Thesis. Major themes include Th2 and disease heterogeneity, identification of ‘the original source of IL-4’, an unprecedented <em>in vivo </em>requirement for eosinophils in priming adaptive immune responses, and the need to weigh basic science findings against the human disease <em>in natura </em>litmus test. Looking forward, many questions remain to be answered in the field of food allergy research, but the findings of this Thesis may be one step towards the prevention, management or cure of a disease with growing public concern, potentially fatal consequences, and an unmet need in understanding its pathogenesis.</p> / Doctor of Philosophy (Medical Science)