<p>T lymphocytes regulate the initiation, duration, and magnitude of adaptive immune responses and function as effector cells in cell mediated immunity. To become immunologically competent they must generate functional antigen receptors. This process takes place in the thymus and requires somatic recombination of T cell receptor (TCR) genes. It is mediated by the endonucleases recombination activating gene-1 (RAG1) and RAG2. Although the thymus regresses at puberty, T cells are present throughout life implying that other tissues must provide the proper milieu for T cell development. This thesis describes extrathymic T cell maturation in man. RAG1, RAG2, and the preTα-chain (pTα), which is exclusively utilized in developing T cells, were used as markers for TCR gene rearrangement. Two new exons (1A and 1B) encoding sequences in the 5’ untranslated region (5’UTR) of mRNA were discovered in the human RAG1 gene. The previously described 5’UTR exon (renamed 1C) was located between the new exons and exon 2, the latter containing the entire coding sequence. We found that small intestinal lymphocytes of the T cell lineage expressed the new exons in three different splice forms. RAG1 mRNA containing the 1C exon was not expressed in small intestinal lymphocytes. In contrast, splice forms containing the 1A exon were not expressed in thymocytes. RAG1 and pTα mRNA expressing lymphocytes were seen both within the epithelium and in lamina propria. Thymocyte-like CD2⁺CD7⁺CD3^-, CD4⁺CD8⁺, CD1a⁺, and IL7-R+ lymphocytes were identified in the small intestinal mucosa. CD2⁺CD7⁺CD3^- cells had the highest expression levels of mRNA for RAG1 and pTα, suggesting that the small intestinal mucosa is indeed a site for T cell maturation. Small intestinal T lymphocytes were also shown to kill via the Fas/FasL pathway in a TCR/CD3 independent manner and via the perforin/granzyme pathway in a TCR/CD3 dependent manner. The Fas/FasL-mediated cytotoxicity may reflect an ongoing selection process of extrathymically maturated T cells. </p><p>The nasopharyngeal tonsil is the major inductive site for immune reactions against inhaled antigens. Previous demonstration of RAG1 expression in tonsillar B cells was interpreted as antigen driven receptor revision. The present study confirms the expression of RAG1 in B cells. We also found that RAG1, RAG2, and pTa mRNAs were expressed in lymphocytes of the T cell lineage. A small population of cells with the immature phenotype CD2+CD7+CD3- was demonstrated. This population had the highest expression levels of mRNA for RAG1, RAG2, pTα and terminal deoxynucleotidyl transferase. All four splice-forms of RAG1 mRNA were expressed. RAG1 and pTα mRNA expressing cells were mainly located in the proximity of the surface epithelium and in the outer rim of the follicles. These results suggest that the nasopharyngeal tonsil is a site where extrathymic T cell development and antigen driven TCR revision are occurring in parallel. </p><p>Celiac disease (CD) is a small intestinal enteropathy characterized by permanent intolerance to gluten. Gluten reactive intestinal T cells are central in the pathogenesis and CD can be regarded as a failure to maintain tolerance to this food antigen. Expression of the RAG1 1A/2 splice form was significantly decreased in small intestinal T cell subsets of CD patients suggesting that impaired TCR gene rearrangement could contribute to failure of maintain tolerance in CD. </p><p>Together, these findings show that both small intestinal and nasopharyngeal tonsillar lymphocytes of T cell lineage have the molecular machinery for antigen receptor rearrangement and that thymocyte-like lymphocytes are present in both tissues. Thus these organs are likely sites of T lymphocyte ontogeny as well as for secondary T cell receptor rearrangement in man. </p>

T lymphocytes regulate the initiation, duration, and magnitude of adaptive immune responses and function as effector cells in cell mediated immunity. To become immunologically competent they must generate functional antigen receptors. This process takes place in the thymus and requires somatic recombination of T cell receptor (TCR) genes. It is mediated by the endonucleases recombination activating gene-1 (RAG1) and RAG2. Although the thymus regresses at puberty, T cells are present throughout life implying that other tissues must provide the proper milieu for T cell development. This thesis describes extrathymic T cell maturation in man. RAG1, RAG2, and the preTα-chain (pTα), which is exclusively utilized in developing T cells, were used as markers for TCR gene rearrangement. Two new exons (1A and 1B) encoding sequences in the 5’ untranslated region (5’UTR) of mRNA were discovered in the human RAG1 gene. The previously described 5’UTR exon (renamed 1C) was located between the new exons and exon 2, the latter containing the entire coding sequence. We found that small intestinal lymphocytes of the T cell lineage expressed the new exons in three different splice forms. RAG1 mRNA containing the 1C exon was not expressed in small intestinal lymphocytes. In contrast, splice forms containing the 1A exon were not expressed in thymocytes. RAG1 and pTα mRNA expressing lymphocytes were seen both within the epithelium and in lamina propria. Thymocyte-like CD2+CD7+CD3-, CD4+CD8+, CD1a+, and IL7-R+ lymphocytes were identified in the small intestinal mucosa. CD2+CD7+CD3- cells had the highest expression levels of mRNA for RAG1 and pTα, suggesting that the small intestinal mucosa is indeed a site for T cell maturation. Small intestinal T lymphocytes were also shown to kill via the Fas/FasL pathway in a TCR/CD3 independent manner and via the perforin/granzyme pathway in a TCR/CD3 dependent manner. The Fas/FasL-mediated cytotoxicity may reflect an ongoing selection process of extrathymically maturated T cells. The nasopharyngeal tonsil is the major inductive site for immune reactions against inhaled antigens. Previous demonstration of RAG1 expression in tonsillar B cells was interpreted as antigen driven receptor revision. The present study confirms the expression of RAG1 in B cells. We also found that RAG1, RAG2, and pTa mRNAs were expressed in lymphocytes of the T cell lineage. A small population of cells with the immature phenotype CD2+CD7+CD3- was demonstrated. This population had the highest expression levels of mRNA for RAG1, RAG2, pTα and terminal deoxynucleotidyl transferase. All four splice-forms of RAG1 mRNA were expressed. RAG1 and pTα mRNA expressing cells were mainly located in the proximity of the surface epithelium and in the outer rim of the follicles. These results suggest that the nasopharyngeal tonsil is a site where extrathymic T cell development and antigen driven TCR revision are occurring in parallel. Celiac disease (CD) is a small intestinal enteropathy characterized by permanent intolerance to gluten. Gluten reactive intestinal T cells are central in the pathogenesis and CD can be regarded as a failure to maintain tolerance to this food antigen. Expression of the RAG1 1A/2 splice form was significantly decreased in small intestinal T cell subsets of CD patients suggesting that impaired TCR gene rearrangement could contribute to failure of maintain tolerance in CD. Together, these findings show that both small intestinal and nasopharyngeal tonsillar lymphocytes of T cell lineage have the molecular machinery for antigen receptor rearrangement and that thymocyte-like lymphocytes are present in both tissues. Thus these organs are likely sites of T lymphocyte ontogeny as well as for secondary T cell receptor rearrangement in man.

Introdução: A incidência do carcinoma epidermóide de orofaringe (CEO) aumentou em todo o mundo nos últimos 30 anos. Estudos identificaram o papiloma vírus humano (HPV) como um fator de risco para essa neoplasia. Objetivos: O objetivo do presente estudo foi verificar a frequência do HPV em pacientes com CEO e em pacientes sem neoplasia maligna e avaliar a existência de uma diferença estatisticamente significativa na frequência do HPV entre os dois grupos. O objetivo secundário foi estudar a correlação entre a infecção pelo HPV e a localização do tumor na orofaringe, o estadiamento clínico e o grau de diferenciação tumoral. Métodos: Foi realizado um estudo de caso-controle com 59 pacientes com CEO e 54 pacientes sem neoplasia, no qual foram analisados os blocos de parafina contendo material tumoral e tecido não neoplásico. Foram analisadas respectivamente a frequência do HPV e sua atividade viral utilizando a técnica de hibridização in situ cromogênica (CISH) para HPV de baixo risco (BR) e alto risco (AR) e a expressão imunoistoquímica da proteína P16. Resultados: A frequência do HPV foi maior no grupo caso em comparação ao grupo controle quando utilizamos a expressão imunoistoquímica da proteína P16 como método de detecção isolado (OR=10,3; P<0,001) e quando utilizamos a CISH e a expressão imunoistoquímica da proteína P16 em conjunto (OR=21,4; P<0,001). A CISH isoladamente não mostrou uma diferença estatisticamente significativa na frequência do HPV entre os grupos estudados (P=0,572). A localização tumoral na orofaringe e o estadiamento clínico não mostraram correlação com a infecção pelo HPV em nenhum dos métodos utilizados, assim como o grau de diferenciação tumoral (P>0,20). Conclusão: Utilizando-se a técnica de imunoistoquímica para P16 isolada ou combinada com a técnica de CISH, observou-se uma maior positividade para o HPV no grupo de pacientes com CEO. A localização do tumor na orofaringe, o estadiamento clínico e o grau de diferenciação tumoral não tiveram correlação com a positividade para o HPV. / Introduction: The incidence of oropharyngeal squamous cell carcinoma (OSCC) has increased worldwide over the last 30 years. Studies have identified human papillomavirus (HPV) infection as a risk factor for OSCC. Objectives: To compare the frequency of HPV infection in patients with OSCC and patients with benign oral or oropharyngeal disease and ascertain whether a statistically significant difference in HPV frequency exists between these two groups. As a secondary objective, to assess potential correlations between HPV positivity, anatomic site of OSCC, tumor staging, and degree of tumor differentiation. Methods: Case-control study. The sample comprised 59 patients with OSCC and 54 non-OSCC controls who underwent surgery for benign oral or oropharyngeal conditions. Paraffin-embedded specimens from cases and controls were tested for HPV positivity by chromogenic in situ hybridization (CISH) for low-risk (LR) and high-risk (HR) HPV, and HPV activity was assessed by P16 immunohistochemistry (IHC). Results: The frequency of HPV positivity was higher in the case group than in the control group when assessed by P16 IHC alone (OR=10.3, P<0.001) or by CISH and P16 IHC in combination (OR=21.4, P<0.001). CISH alone did not detect any significant between-group difference in HPV frequency (P=0.572). Tumor site, staging, and differentiation did not correlate with HPV positivity with any of the methods employed (P>0.20). Conclusion: Using a P16 IHC assay alone or combined with CISH, the authors showed a higher rate of HPV positivity among patients with OSCC, as compared with patients with benign disease. Tumor site within the oropharynx, tumor stage, and degree of differentiation did not correlate with HPV positivity.

Introdução: A incidência do carcinoma epidermóide de orofaringe (CEO) aumentou em todo o mundo nos últimos 30 anos. Estudos identificaram o papiloma vírus humano (HPV) como um fator de risco para essa neoplasia. Objetivos: O objetivo do presente estudo foi verificar a frequência do HPV em pacientes com CEO e em pacientes sem neoplasia maligna e avaliar a existência de uma diferença estatisticamente significativa na frequência do HPV entre os dois grupos. O objetivo secundário foi estudar a correlação entre a infecção pelo HPV e a localização do tumor na orofaringe, o estadiamento clínico e o grau de diferenciação tumoral. Métodos: Foi realizado um estudo de caso-controle com 59 pacientes com CEO e 54 pacientes sem neoplasia, no qual foram analisados os blocos de parafina contendo material tumoral e tecido não neoplásico. Foram analisadas respectivamente a frequência do HPV e sua atividade viral utilizando a técnica de hibridização in situ cromogênica (CISH) para HPV de baixo risco (BR) e alto risco (AR) e a expressão imunoistoquímica da proteína P16. Resultados: A frequência do HPV foi maior no grupo caso em comparação ao grupo controle quando utilizamos a expressão imunoistoquímica da proteína P16 como método de detecção isolado (OR=10,3; P<0,001) e quando utilizamos a CISH e a expressão imunoistoquímica da proteína P16 em conjunto (OR=21,4; P<0,001). A CISH isoladamente não mostrou uma diferença estatisticamente significativa na frequência do HPV entre os grupos estudados (P=0,572). A localização tumoral na orofaringe e o estadiamento clínico não mostraram correlação com a infecção pelo HPV em nenhum dos métodos utilizados, assim como o grau de diferenciação tumoral (P>0,20). Conclusão: Utilizando-se a técnica de imunoistoquímica para P16 isolada ou combinada com a técnica de CISH, observou-se uma maior positividade para o HPV no grupo de pacientes com CEO. A localização do tumor na orofaringe, o estadiamento clínico e o grau de diferenciação tumoral não tiveram correlação com a positividade para o HPV. / Introduction: The incidence of oropharyngeal squamous cell carcinoma (OSCC) has increased worldwide over the last 30 years. Studies have identified human papillomavirus (HPV) infection as a risk factor for OSCC. Objectives: To compare the frequency of HPV infection in patients with OSCC and patients with benign oral or oropharyngeal disease and ascertain whether a statistically significant difference in HPV frequency exists between these two groups. As a secondary objective, to assess potential correlations between HPV positivity, anatomic site of OSCC, tumor staging, and degree of tumor differentiation. Methods: Case-control study. The sample comprised 59 patients with OSCC and 54 non-OSCC controls who underwent surgery for benign oral or oropharyngeal conditions. Paraffin-embedded specimens from cases and controls were tested for HPV positivity by chromogenic in situ hybridization (CISH) for low-risk (LR) and high-risk (HR) HPV, and HPV activity was assessed by P16 immunohistochemistry (IHC). Results: The frequency of HPV positivity was higher in the case group than in the control group when assessed by P16 IHC alone (OR=10.3, P<0.001) or by CISH and P16 IHC in combination (OR=21.4, P<0.001). CISH alone did not detect any significant between-group difference in HPV frequency (P=0.572). Tumor site, staging, and differentiation did not correlate with HPV positivity with any of the methods employed (P>0.20). Conclusion: Using a P16 IHC assay alone or combined with CISH, the authors showed a higher rate of HPV positivity among patients with OSCC, as compared with patients with benign disease. Tumor site within the oropharynx, tumor stage, and degree of differentiation did not correlate with HPV positivity.

Introdução: A incidência do carcinoma epidermóide de orofaringe (CEO) aumentou em todo o mundo nos últimos 30 anos. Estudos identificaram o papiloma vírus humano (HPV) como um fator de risco para essa neoplasia. Objetivos: O objetivo do presente estudo foi verificar a frequência do HPV em pacientes com CEO e em pacientes sem neoplasia maligna e avaliar a existência de uma diferença estatisticamente significativa na frequência do HPV entre os dois grupos. O objetivo secundário foi estudar a correlação entre a infecção pelo HPV e a localização do tumor na orofaringe, o estadiamento clínico e o grau de diferenciação tumoral. Métodos: Foi realizado um estudo de caso-controle com 59 pacientes com CEO e 54 pacientes sem neoplasia, no qual foram analisados os blocos de parafina contendo material tumoral e tecido não neoplásico. Foram analisadas respectivamente a frequência do HPV e sua atividade viral utilizando a técnica de hibridização in situ cromogênica (CISH) para HPV de baixo risco (BR) e alto risco (AR) e a expressão imunoistoquímica da proteína P16. Resultados: A frequência do HPV foi maior no grupo caso em comparação ao grupo controle quando utilizamos a expressão imunoistoquímica da proteína P16 como método de detecção isolado (OR=10,3; P<0,001) e quando utilizamos a CISH e a expressão imunoistoquímica da proteína P16 em conjunto (OR=21,4; P<0,001). A CISH isoladamente não mostrou uma diferença estatisticamente significativa na frequência do HPV entre os grupos estudados (P=0,572). A localização tumoral na orofaringe e o estadiamento clínico não mostraram correlação com a infecção pelo HPV em nenhum dos métodos utilizados, assim como o grau de diferenciação tumoral (P>0,20). Conclusão: Utilizando-se a técnica de imunoistoquímica para P16 isolada ou combinada com a técnica de CISH, observou-se uma maior positividade para o HPV no grupo de pacientes com CEO. A localização do tumor na orofaringe, o estadiamento clínico e o grau de diferenciação tumoral não tiveram correlação com a positividade para o HPV. / Introduction: The incidence of oropharyngeal squamous cell carcinoma (OSCC) has increased worldwide over the last 30 years. Studies have identified human papillomavirus (HPV) infection as a risk factor for OSCC. Objectives: To compare the frequency of HPV infection in patients with OSCC and patients with benign oral or oropharyngeal disease and ascertain whether a statistically significant difference in HPV frequency exists between these two groups. As a secondary objective, to assess potential correlations between HPV positivity, anatomic site of OSCC, tumor staging, and degree of tumor differentiation. Methods: Case-control study. The sample comprised 59 patients with OSCC and 54 non-OSCC controls who underwent surgery for benign oral or oropharyngeal conditions. Paraffin-embedded specimens from cases and controls were tested for HPV positivity by chromogenic in situ hybridization (CISH) for low-risk (LR) and high-risk (HR) HPV, and HPV activity was assessed by P16 immunohistochemistry (IHC). Results: The frequency of HPV positivity was higher in the case group than in the control group when assessed by P16 IHC alone (OR=10.3, P<0.001) or by CISH and P16 IHC in combination (OR=21.4, P<0.001). CISH alone did not detect any significant between-group difference in HPV frequency (P=0.572). Tumor site, staging, and differentiation did not correlate with HPV positivity with any of the methods employed (P>0.20). Conclusion: Using a P16 IHC assay alone or combined with CISH, the authors showed a higher rate of HPV positivity among patients with OSCC, as compared with patients with benign disease. Tumor site within the oropharynx, tumor stage, and degree of differentiation did not correlate with HPV positivity.

Abstract The aim of this work was to examine distinct dentofacial and pharyngeal features in children with sleep-disordered breathing (SDB). A further aim was to test the validity of the conventional methods used in orthodontics for recognition of obstructed airways. Seventy children (36 girls, 34 boys, age range 4.2–11.9 years), who were diagnosed as having SDB during the years 2000–2002, constituted the source of subjects for four separate studies. The study protocol included otorhinolaryngological and orthodontic examinations. Dental impressions and lateral cephalograms were taken. In addition, upper airway was imaged in 36 children in different head postures by magnetic resonance imaging (MRI). Age- and gender-matched healthy children were used as controls. The results showed that children with SDB had increased overjet, smaller overbite, narrower upper and shorter lower dental arches and higher incidence of anterior open bite and distal molar relationship when compared with control children. The severity of the obstruction correlated with larger deviations from normal in the dental characteristics. There were more children with crowding and with anterior open bite with increased severity of the disorder. Children with SDB displayed an increased sagittal jaw relationship, a more vertical growth pattern of the mandible, a longer and thicker soft palate, a lower hyoid bone position, larger craniocervical angles and narrower pharyngeal airway measured at multiple levels, when compared with the controls. Deviation in pharyngeal variables showed highest correlation with the severity of SDB. MRI indicated a smaller than normal oropharyngeal airway in children with SDB. The effect of head posture on pharyngeal airway dimensions differed in children with SDB when compared with the controls. These findings verify that the developmental course of occlusal characteristics and craniofacial structures may be modulated by breathing pattern, and, on the other hand, that certain features may predispose to the development of the disorder. It is important to recognize these signs in order to guide further development in a more favorable direction. The results confirmed that cephalometry is a valid screening tool when assessing nasopharyngeal and retropalatal airway dimensions. Clinical examination of tonsillar size was found reliable when retroglossal airway size was evaluated. / Tiivistelmä Väitöskirjatyön tarkoituksena oli selvittää lasten unenaikaisten hengityshäiriöiden yhteyttä kasvojen ja leukojen kasvuun, purennan kehitykseen sekä ylempien hengitysteiden rakenteeseen. Lisäksi tutkittiin, kuinka luotettavasti hammaslääkäreiden käytössä olevin menetelmin pystytään arvioimaan lasten ahtautuneita ilmateitä. Tutkimusaineistossa oli mukana 70 lasta (36 tyttöä, 30 poikaa, ikä 4.2–11.9 vuotta), joilla diagnosoitiin unenaikainen obstruktiivinen hengityshäiriö vuosina 2000–2002. Lapsille tehtiin kliiniset tutkimukset oikojahammaslääkärin ja korva-, nenä- ja kurkkutautien erikoislääkärin toimesta sekä otettiin lateraalikallokuva ja hampaistosta kipsimallijäljennökset. Lisäksi ylempien hengitysteiden magneettitutkimus suoritettiin 36 lapselle eri pään asennoissa. Verrokkiryhmässä oli sama ikä- ja sukupuolijakauma kuin tutkimusryhmässä. Tulokset osoittivat, että unenaikaisista hengityshäiriöistä kärsivillä lapsilla horisontaalinen ylipurenta oli suurentunut, vertikaalinen ylipurenta oli pienentynyt, ylähammaskaari oli kapeampi ja alahammaskaari lyhyempi kuin terveillä verrokeilla. Alaetualueen ahtaus ja etualueen avopurenta olivat yleisempiä niillä lapsilla, joilla oli vaikeampiasteinen hengityshäiriö. Lasten unenaikaiset hengityshäiriöt liittyivät suurentuneeseen leukojen väliseen kokoepäsuhtaan, alaleuan avautuvaan kasvumalliin, pidempään ja paksumpaan pehmeään suulakeen, kieliluun alempaan asentoon, kohonneeseen pään asentoon sekä ahtaampiin nielun ilmatilan mittoihin verrattaessa terveisiin lapsiin. Häiriön vaikeusaste korreloi suurempiin poikkeamiin nielun mitoissa. Lapsilla, joilla todettiin unenaikainen hengityshäiriö, magneettitutkimukset osoittivat nielun olevan ahdas. Pään asennon vaikutukset ilmatien rakenteeseen poikkesivat unenaikaisista hengityshäiriöistä kärsivillä lapsilla. Saadut tulokset osoittivat, että hengitystapa voi vaikuttaa hampaiston, kasvojen ja leukojen rakenteiden kehitykseen. Tietyt kasvojen ja leukojen piirteet puolestaan saattavat altistaa häiriön kehittymiselle. On tärkeää tunnistaa nämä merkit, jotta kehitystä voidaan ohjata suotuisampaan suuntaan. Tutkimukset osoittivat, että kefalometrinen analyysi on luotettava arvioitaessa nenänielun sekä pehmeän suulaen takana olevan ilmatilan kokoa. Nielurisojen kliinisen koon arviointi on luotettava arvioitaessa alemman suunielun ilmatilan kokoa.

Introdução: Dentre as alterações da má-oclusão dentária na primeira dentição, destaca-se a mordida cruzada posterior, a qual consiste numa relação de sobressaliência vestibular inversa dos dentes superiores com seus antagonistas inferiores. O crescimento das estruturas faciais é composto de múltiplas atividades funcionais inter-relacionadas por diferentes componentes da cabeça e pescoço. A respiração nasal é um dos elementos de atividade funcional. Se houver obstrução nas vias aéreas superiores, haverá adaptações funcionais na direção de crescimento das estruturas do esqueleto da face. A hiperplasia das tonsilas faríngeas e/ou palatinas associadas são uma das causas mais comuns de obstrução respiratória. Objetivos: investigar a prevalência da mordida cruzada posterior em crianças de 3 a 6 anos de idade e associá-la ao padrão respiratório; verificar se houve associação desta má-oclusão com o tipo da hiperplasia das tonsilas palatinas associadas ou não com tonsilas faríngeas; realizar uma análise comparativa em crianças respiradoras orais e respiradoras nasais na idade categorizada 3-4 anos e 5-6 anos nos seguintes aspectos: distâncias da largura dos arcos por meio das distâncias intercaninos e intermolares da maxila e mandíbula. Casuística e Métodos: Participaram deste estudo 53 crianças, meninos e meninas com hiperplasia das tonsilas faríngea e/ou palatinas provenientes do ambulatório da Divisão da Clínica Otorrinolaringológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, com indicação de adenoamigdalectomia ou adenoidectomia. Os pacientes foram submetidos a exame físico otorrinolaringológico, além de fibronasofaringoscopia ou Raios- X de Cavum. O grupo controle foi de 41 crianças sem queixas de obstrução respiratória levantada por questionários dirigidos aos pais, oriundas de escolas do município de Itapetininga-SP. Todas as crianças foram avaliadas por um cirurgião dentista que mensurou a largura dos arcos dentários diretamente na boca por meio de um paquímetro digital. Resultados: A mordida cruzada posterior esteve presente em 9,57% do total da amostra. A prevalência do cruzamento posterior no grupo de estudo foi de 15,09% e, no grupo controle, 2,13%. Foram encontradas nos diferentes tipos de hiperplasia linfoide as seguintes frequências de cruzamento posterior: palatina isolada (16,67%); faríngea isolada (25%); e palatina e faríngea associada (7,41%). A largura dos arcos dentais no grupo de estudo, apesar de não apresentar relevância estatística quando comparado com o grupo controle na idade de 3-4 anos, mostrou-se com as maiores médias. Já na idade de 5-6 anos, mostrou-se com as menores médias. Conclusões: A prevalência de mordida cruzada em respiradores orais é 15,09%. Observou-se uma tendência associativa da mordida cruzada posterior nas crianças do grupo de estudo. Na associação do tipo de obstrução respiratória com a presença do cruzamento posterior, não houve diferença estatística. Quanto à análise da largura dos arcos dentais em relação à idade categorizada, verificou-se, no grupo controle, uma diferença estatisticamente significante da idade de 5-6 anos em relação à idade 3-4 anos. Esta diferença, porém, não foi encontrada no grupo de estudo / Introduction: Among the alterations of dental malocclusion in the first dentition, the posterior crossbite stands out, which consists of a relation of vestibular reverse overjet of superior teeth with their inferior antagonists. The growth of facial structures consists of multiple functional activities interrelated by different components of the head and the neck. Breathing through the nose is one of the elements of functional activity. If there is obstruction in the superior airway, there will be functional adaptations in the growth direction of face skeleton structures. The hyperplasia of the adenoids and/or associate palatine tonsils is one of the most common causes of airway obstruction. Objectives: Probe the prevalence of posterior crossbite in children from 3 to 6 years old and associate it to the respiratory pattern; verify if there is association of such malocclusion with the etiology of hyperplasia of palatine tonsils associate or not with hyperplasia of the adenoids; carry out a comparative analysis in children who breathe through their mouth and nose at the categorized age of 3-4 years old and 5-6 years old in the following aspects: arch width distances by means of maxillary and mandibular intercanine and intermolar distances. Casuistry and Methods: A total of 53 children took part in the study herein, boys and girls with hyperplasia of the adenoids and/or associate palatine tonsils coming from the ambulatory of the Division of Otorhinolaryngology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, with indication of tonsillectomy or adenoidectomy. The patients have been submitted to an otorhinolaryngological physical examination, in addition to nasal fiber pharyngoscopy or Cavum x-ray. The control group consisted of 41 children with no complaints of airway obstruction surveyed by questionnaires forwarded to their parents, children coming from schools of the municipality of Itapetininga, State of São Paulo. All children have been evaluated by a dental surgeon who has measured their dental arch width directly in the mouth by means of a digital calliper. Results: The posterior crossbite was present in 9.57% out of the total of the sample. The prevalence of posterior cross in the study group was 15.09% and, in the control group, 2.13%. The following frequencies of posterior cross have been found in different etiologies of lymphoid hyperplasia: isolated palatine (16.67%); isolated pharynx (25%); and associated palatine and pharynx (7.41%). The dental arch width in the study group, in spite of not presenting statistical relevance when compared to the control group at the age of 3-4 years old, was shown with the highest averages. On the other hand, at the age of 5-6 years old, lowest averages were shown. Conclusions: The prevalence of crossbite in children who breathe through their mouth is of 15.09%. An associated trend of posterior crossbite in children of the study group has been observed. In the association of the type of airway obstruction with the presence of posterior cross, there was no statistical difference. As per the dental arch width analysis in regards to the categorized age, in the control group, a statistically significant difference was verified at the age of 5-6 years old regarding the age of 3-4 years old. Such difference, however, was not found in the study group

Introdução: Dentre as alterações da má-oclusão dentária na primeira dentição, destaca-se a mordida cruzada posterior, a qual consiste numa relação de sobressaliência vestibular inversa dos dentes superiores com seus antagonistas inferiores. O crescimento das estruturas faciais é composto de múltiplas atividades funcionais inter-relacionadas por diferentes componentes da cabeça e pescoço. A respiração nasal é um dos elementos de atividade funcional. Se houver obstrução nas vias aéreas superiores, haverá adaptações funcionais na direção de crescimento das estruturas do esqueleto da face. A hiperplasia das tonsilas faríngeas e/ou palatinas associadas são uma das causas mais comuns de obstrução respiratória. Objetivos: investigar a prevalência da mordida cruzada posterior em crianças de 3 a 6 anos de idade e associá-la ao padrão respiratório; verificar se houve associação desta má-oclusão com o tipo da hiperplasia das tonsilas palatinas associadas ou não com tonsilas faríngeas; realizar uma análise comparativa em crianças respiradoras orais e respiradoras nasais na idade categorizada 3-4 anos e 5-6 anos nos seguintes aspectos: distâncias da largura dos arcos por meio das distâncias intercaninos e intermolares da maxila e mandíbula. Casuística e Métodos: Participaram deste estudo 53 crianças, meninos e meninas com hiperplasia das tonsilas faríngea e/ou palatinas provenientes do ambulatório da Divisão da Clínica Otorrinolaringológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, com indicação de adenoamigdalectomia ou adenoidectomia. Os pacientes foram submetidos a exame físico otorrinolaringológico, além de fibronasofaringoscopia ou Raios- X de Cavum. O grupo controle foi de 41 crianças sem queixas de obstrução respiratória levantada por questionários dirigidos aos pais, oriundas de escolas do município de Itapetininga-SP. Todas as crianças foram avaliadas por um cirurgião dentista que mensurou a largura dos arcos dentários diretamente na boca por meio de um paquímetro digital. Resultados: A mordida cruzada posterior esteve presente em 9,57% do total da amostra. A prevalência do cruzamento posterior no grupo de estudo foi de 15,09% e, no grupo controle, 2,13%. Foram encontradas nos diferentes tipos de hiperplasia linfoide as seguintes frequências de cruzamento posterior: palatina isolada (16,67%); faríngea isolada (25%); e palatina e faríngea associada (7,41%). A largura dos arcos dentais no grupo de estudo, apesar de não apresentar relevância estatística quando comparado com o grupo controle na idade de 3-4 anos, mostrou-se com as maiores médias. Já na idade de 5-6 anos, mostrou-se com as menores médias. Conclusões: A prevalência de mordida cruzada em respiradores orais é 15,09%. Observou-se uma tendência associativa da mordida cruzada posterior nas crianças do grupo de estudo. Na associação do tipo de obstrução respiratória com a presença do cruzamento posterior, não houve diferença estatística. Quanto à análise da largura dos arcos dentais em relação à idade categorizada, verificou-se, no grupo controle, uma diferença estatisticamente significante da idade de 5-6 anos em relação à idade 3-4 anos. Esta diferença, porém, não foi encontrada no grupo de estudo / Introduction: Among the alterations of dental malocclusion in the first dentition, the posterior crossbite stands out, which consists of a relation of vestibular reverse overjet of superior teeth with their inferior antagonists. The growth of facial structures consists of multiple functional activities interrelated by different components of the head and the neck. Breathing through the nose is one of the elements of functional activity. If there is obstruction in the superior airway, there will be functional adaptations in the growth direction of face skeleton structures. The hyperplasia of the adenoids and/or associate palatine tonsils is one of the most common causes of airway obstruction. Objectives: Probe the prevalence of posterior crossbite in children from 3 to 6 years old and associate it to the respiratory pattern; verify if there is association of such malocclusion with the etiology of hyperplasia of palatine tonsils associate or not with hyperplasia of the adenoids; carry out a comparative analysis in children who breathe through their mouth and nose at the categorized age of 3-4 years old and 5-6 years old in the following aspects: arch width distances by means of maxillary and mandibular intercanine and intermolar distances. Casuistry and Methods: A total of 53 children took part in the study herein, boys and girls with hyperplasia of the adenoids and/or associate palatine tonsils coming from the ambulatory of the Division of Otorhinolaryngology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, with indication of tonsillectomy or adenoidectomy. The patients have been submitted to an otorhinolaryngological physical examination, in addition to nasal fiber pharyngoscopy or Cavum x-ray. The control group consisted of 41 children with no complaints of airway obstruction surveyed by questionnaires forwarded to their parents, children coming from schools of the municipality of Itapetininga, State of São Paulo. All children have been evaluated by a dental surgeon who has measured their dental arch width directly in the mouth by means of a digital calliper. Results: The posterior crossbite was present in 9.57% out of the total of the sample. The prevalence of posterior cross in the study group was 15.09% and, in the control group, 2.13%. The following frequencies of posterior cross have been found in different etiologies of lymphoid hyperplasia: isolated palatine (16.67%); isolated pharynx (25%); and associated palatine and pharynx (7.41%). The dental arch width in the study group, in spite of not presenting statistical relevance when compared to the control group at the age of 3-4 years old, was shown with the highest averages. On the other hand, at the age of 5-6 years old, lowest averages were shown. Conclusions: The prevalence of crossbite in children who breathe through their mouth is of 15.09%. An associated trend of posterior crossbite in children of the study group has been observed. In the association of the type of airway obstruction with the presence of posterior cross, there was no statistical difference. As per the dental arch width analysis in regards to the categorized age, in the control group, a statistically significant difference was verified at the age of 5-6 years old regarding the age of 3-4 years old. Such difference, however, was not found in the study group

Gedächtnis-B-Zellen und Plasmazellen sind essentielle Komponenten der protektiven Immunität. Die Mechanismen ihrer Induktion, ihres Überlebens und der Gedächtnis-B-Zellreaktivierung sind allerding bisher nur unvollständig verstanden. Um unser Wissen diesbezüglich zu erweitern, wurden in der vorliegenden Arbeit zum einen Charakteristika von Primär- und Sekundärimmunantworten nach Immunisierung mit Keyhole Limpet Hemocyanin (KLH) untersucht und zum anderen das Vorkommen sowie der Phänotyp humaner Gedächtnis-B-Zellen in verschiedenen lymphatischen Geweben analysiert. Die primäre parenterale KLH Immunisierung führte auf serologischer und zellulärer Ebene zu einer Reihe unerwarteter Ergebnisse, welche u. a. das Auftreten von IgA Antikörpern und die gleichzeitige Präsenz von hoch- und wenig mutierten primären Plasmablasten beinhalteten. Die Untersuchung der Gedächtnis-B-Zellverteilung in verschiedenen lymphatischen Geweben ergab den größten Gedächtnis-B-Zellpool in der Milz. Blut-, Tonsillen-, Knochenmarks- und Milz-Gedächtnis-B-Zellen wiesen nur wenige phänotypische Unterschiede auf. Einer davon war die CD69 Expression auf tonsillären ruhenden Gedächtnis-B-Zellen, was darauf hindeutet, dass tonsilläre Gedächtnis-B-Zellen tatsächlich sessil sein könnten. Die hier erhaltenen Ergebnisse stellen neue Erkenntnisse über bisher unbeschriebene Mechanismen bei parenteralen Immunantworten wie zum Beispiel die Induktion von IgA Antikörpern sowie die potentielle Rekrutierung kreuzreaktiver Gedächtnis-B-Zellen dar. Es bleibt zu klären, wie die Reaktivierung solcher Gedächtnis-B-Zellen reguliert ist. Derartiges Wissen wäre insbesondere für Therapien von Erkrankungen des Immunsystems, wie Autoimmunität, von Bedeutung. Das potentiell patrouillierende Verhalten der Gedächtnis-B-Zellen ist ein markanter Unterschied zu den nischenabhängigen sessilen Plasmazellen und deutet weitestgehend darauf hin, dass Gedächtnis-B-Zellen nicht auf derartige Nischen angewiesen sind. / Memory B cells (mBC) and antibodies are major mediators of protective immune responses yet the mechanisms of their induction, maintenance and mBC reactivation are poorly understood. Therefore, to enhance knowledge in this regard this study comprehensively characterized a human primary and secondary B cell immune response to Keyhole Limpet Hemocyanin (KLH). Secondly, mBC maintenance was investigated by a systematic analysis of mBC presence, frequency and phenotype within different lymphoid organs. Parenteral primary KLH immunization yielded unexpected results on the serological and B cellular level, including KLH-specific IgA antibody induction, the simultaneous presence of low and highly mutated circulating KLH-specific primary plasmablasts and only little clonal overlap between the primary, memory and secondary KLH-specific B cell repertoires. With respect to the organ distribution of human mBC, the spleen was identified as a major mBC reservoir. Splenic, tonsillar, bone marrow and blood mBC pools exhibited a largely comparable phenotype. Yet, we found tonsillar mBC to express CD69. Due to their resting state tonsillar mBC could therefore constitute a tissue resident cell population. The observations described allow insights into hitherto unknown potential mechanisms behind primary immune responses, i.e. prominent IgA induction by parenteral challenge and inclusion of cross-reactive mBC. The so far unclear regulatory players involved deserve future investigation, as such knowledge may be crucial for therapeutic interventions in immune system disorders. Furthermore, strikingly different to the resident plasma cells in the bone marrow, mBC appear to distribute between lymphoid organs and continuously recirculate in peripheral blood indicative of their potential permanent screening activities, suggesting that human mBC do not require one dedicated niche for their principle survival.