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1
Suzuki, Lisandra Akemi. "Resposta imune humoral na neurocisticercose". [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308741.
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Orientador: Claudio Lucio RossiTese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas
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Resumo: A neurocisticercose (NC) e uma importante causa de doença neurológica em muitos paises em desenvolvimento, incluindo o Brasil. O diagnostico clinico da NC e dificultado pelo polimorfismo e pela não especificidade dos sintomas. As tecnicas de neuroimagem e pesquisa de anticorpos específicos tem contribuído para o diagnostico da NC e uma melhor compreensão dos processos fisiopatológicos dessa infecção. O presente trabalho teve como objetivo avaliar, por meio de técnicas imunoenzimaticas (ELISA), a resposta imune humoral na NC, utilizando como preparações antigênicas o liquido vesicular (LV) e uma fração glicoproteica obtida do extrato bruto de cisticercos de Taenia solium (T. solium) com afinidade por lentil-lectina (fração Gp). Cinquenta e seis amostras de liquido cefalorraquidiano (LCR), 22 de pacientes com NC e 34 de pacientes com outros problemas neurológicos, foram utilizadas para a pesquisa de IgG e suas subclasses, com os seguintes resultados: IgG-LV: 100% de sensibilidade e especificidade; IgG1 -LV: 72,73% de sensibilidade e 100% de especificidade; IgG2-LV: 81,81% de sensibilidade e 100% de especificidade; IgG3-LV: 59,09% de sensibilidade e 97,06% de especificidade; IgG4-LV: 90,91% de sensibilidade e 97,06% de especificidade; IgG-fração Gp: 90,91% de sensibilidade e 97,06% de especificidade; IgG1-fração Gp: 59,09% de sensibilidade e 91,18% de especificidade; IgG2-fração Gp: 68,18% de sensibilidade e 94,12% de especificidade; IgG3-fração Gp: 36,36% de sensibilidade e 100% de especificidade; IgG4-fração Gp: 86,36% de sensibilidade e 100% de especificidade. Quarenta e sete amostras de LCR, 16 de pacientes com NC e 31 de pacientes com outros problemas neurológicos foram utilizadas para a pesquisa de IgE, com os seguintes resultados: IgE-LV e IgE-fração Gp: 93,75% de sensibilidade e 100% de especificidade. Cinquenta e sete amostras de soros, 22 de pacientes com NC, 18 de pacientes com outras infecções e 17 de pessoas presumivelmente sadias, foram utilizadas para a pesquisa da IgG e suas subclasses, IgE, IgA e IgM, com os seguintes resultados: IgG-LV: 100% de sensibilidade e especificidade; IgG1-LV: 86,36% de sensibilidade e 94,28% de especificidade; IgG2-LV: 90,91% de sensibilidade e 97,14% de especificidade; IgG3-LV: 86,36% de sensibilidade e 97,14% de especificidade; IgG4-LV: 100% de sensibilidade e de especificidade; IgG-fração Gp: 95,45% de sensibilidade e 100% de especificidade; IgG1-fração Gp: 63,64% de sensibilidade e 94,28% de especificidade; IgG2-fração Gp: 68,18% de sensibilidade e 97,14% de especificidade; IgG3-fração Gp: 54,54% de sensibilidade e 88,57% de especificidade; IgG4-fração Gp: 90,91% de sensibilidade e 100% de especificidade; IgELV: 90,91% de sensibilidade e 97,14% de especificidade; IgE-fração Gp: 86,36% de sensibilidade e 100% de especificidade; IgA-LV: 54,54% de sensibilidade e 94,28% de especificidade; IgA-fração Gp: 13,63% de sensibilidade e 100% de especificidade. Anticorpos IgM não foram detectados com as preparações de LV e fração Gp. Nossos resultados mostraram que, com ambas as preparações antigênicas, tanto em amostras de LCR quanto em amostras de soros, a maior positividade foi obtida na detecção de anticorpos das classes IgG e IgE, seguida da positividade da IgA. Anticorpos IgM não foram detectados em amostras de soros com reações de ELISA realizadas com LV e fração Gp. Com relação as subclasses da IgG, a IgG4 apresentou, tanto em amostras de LCR como em amostras de soros, valores de positividade e concentração iguais ou superiores as outras subclasses. As reações ELISA realizadas com LV mostraram sensibilidades iguais ou superiores aquelas obtidas com a fração Gp. Considerando a complexidade e o custo final da obtenção da fração Gp, o LV pode ser considerado mais adequado para a pesquisa de anticorpos em amostras de LCR e soros de pacientes com NC.
Abstract: Neurocysticercosis (NC) is an important cause of neurological disease in many developing countries, including Brazil. The clinical diagnosis of NC is hindered by the polymorphism and non-specificity of the symptoms. Neuroimaging techniques and detection of specific antibodies have contributed to the diagnosis of NC and a better understanding of the physiopathological processes of this infection. The purpose of this study was to evaluate the humoral immune response in NC by using immunoenzymatic techniques (ELISA) in which vesicular fluid (VF) and a glycoprotein fraction purified from a crude extract of Taenia solium cysticerci with affinity for lentil-lectin (fraction Gp) were used as antigenic preparations. Fifty-six cerebrospinal fluid (CSF) samples, 22 from patients with NC and 34 from patients with other neurological disorders, were assayed for IgG and IgG subclasses, with the following results: IgG-VF: 100% sensitivity and specificity, IgG1 - VF: 72.73% sensitivity and 100% specificity, IgG2 -VF: 81.81% sensitivity and 100% specificity, IgG3 -VF: 59.09% sensitivity and 97.06% specificity, IgG4 -VF: 90.91% sensitivity and 97.06% specificity, IgG-fraction Gp: 90.91% sensitivity and 97.06% specificity, IgG1- fraction Gp: 59.09% sensitivity and 91.18% specificity, IgG2-fraction Gp: 68.18% sensitivity and 94.12% specificity, IgG3 -fraction Gp: 36.36% sensitivity and 100% specificity, IgG4 - fraction Gp: 86.36% sensitivity and 100% specificity. Forty-seven CSF samples, 16 from patients with NC and 31 from patients with other neurological disorders, were assayed for IgE, with the following results: IgE-VF and IgE-fraction Gp: 93.75% sensitivity and 100% specificity. Fifty-seven serum samples, 22 from patients with NC, 18 from patients with other infections and 17 from presumably healthy individuals, were assayed for IgG, IgG subclasses, IgE, IgA and IgM, with the following results: IgG-VF: 100% sensitivity and specificity, IgG1-VF: 86.36% sensitivity and 94.28% specificity, IgG2 -VF: 90.91% sensitivity and 97.14% specificity, IgG3 -VF: 86.36% sensitivity and 97.14% specificity, IgG4 -VF:100% sensitivity and specificity, IgG-fraction Gp: 95.45% sensitivity and 100% specificity, IgG1- fraction Gp: 63.64% sensitivity and 94.28% specificity, IgG2 -fraction Gp: 68.18% sensitivity and 97.14% specificity, IgG3 -fraction Gp: 54.54% sensitivity and 88.57% specificity, IgG4 - fraction Gp: 90.91% sensitivity and 100% specificity, IgE-VF: 90.91% sensitivity and 97.14% specificity, IgE-fraction Gp: 86.36% sensitivity and 100% specificity, IgA-VF: 54.54% sensitivity and 94.28% specificity, IgA-fraction Gp: 13.63% sensitivity and 100% specificity. No specific IgM antibodies were detected with VF and fraction Gp antigenic preparations. These results show that with the two antigenic preparations the highest positivity in CSF and serum samples was obtained for IgG and IgE antibodies, followed by positivity for IgA. No IgM antibodies were detected in serum samples assayed with VF and fraction Gp. With regard to IgG subclasses, IgG4 positivity and concentration in CSF and serum samples were higher than or equal to the other subclasses. ELISA reactions done with VF showed equal or higher sensitivities than those obtained with fraction Gp. Considering the complexity and high cost of obtaining fraction Gp, VF could be more suitable for detecting specific antibodies in CSF and serum samples from patients with NC.
Doutorado
Ciencias Biomedicas
Doutor em Ciências Médicas
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Hjelm, Fredrik. "Early Immunostimulatory Effects of IgE- and IgG Antibodies". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7209.
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Renault, Neil. "Construction, method development and comparative testing of an 'All-Diet' protein microarray to measure IgA, IgM, IgG and IgE in human sera and milk". Thesis, University of Nottingham, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503929.
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Existing immunoglobulin (Ig) tests only give a limited picture of the immunological response to food antigens. Furthermore, existing tests require large volumes of sample, over a limited number of foods, are not amenable to a high sample through-put system and the results are limited to normally just one immunoglobulin class. In order to investigate the global immune response towards food products we have developed the "all diet" microarray concept. The "all-diet food protein microarray contains extracts of over 400 food ingredients that cover most of the food products found in the UK. Using this system we have retrospectively determined food specific IgE, IgA, IgG and IgM from 17 well characterized sera. The results were analyzed by multivariate techniques and parametric methods. The proof-of-concept of the ''all diet microarray to investigate the relationships between food antigen specificity and multiple Ig type was demonstrated here. The novelity of this protein microarray is the use of arrayed food samples sequentially extracted with detergent and chaotropic agents. The array system possesses many advantages over traditional systems such as requirement of low sample volume, high sensitivity and a global view of the immune response. Notwithstanding these potential advantages to clinical practices, these benefits remain yet to be demonstrated. The development of the technique will allow further expansion into areas of research such as conjugation of the microarray with sensitized human basophils and also immunoglobulin binding to extracts of parasites.
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Gilbert, Sophie. "Studies on feline IgE". Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/29776.
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Ten normal cats were immunised with Dermatophagoides farinae (DF) antigen and intradermal skin tests (IDSTs) were performed weekly. Sera from the latter were also assessed for DF-specific IgE by ELISA and PK tests. Detectable DF-specific IgE was induced in all of the 10 cats, however levels were found not to be correlated with the development of positive IDSTs nor with the levels of IgE as assessed by PK tests. Sera from 10 cats with symptoms consistent with atopy, from 15 normal household cats and from 11 laboratory maintained cats were assessed for allergen-specific IgE and IgG to DF by ELISA. Although DF-specific IgE was detectable in all the atopic cats, there was no significant difference between the levels in this group and in the clinically normal household cats. However levels in both these groups were significantly higher than those in the laboratory maintained cats. The influence of vaccination and endoparasitism on the IgE response to a food antigen was assessed in 34 cats. Seventeen kittens experimentally infected with T. cati and 17 parasite-free kittens were dosed with human serum albumin (HSA) daily for 3 weeks. Seven cats from both groups were given two injections of a live attenuated viral vaccine. The group of parasitised cats has significantly higher levels of HSA-specific IgE, IgG and IgA than did the group of parasite-free cats. Vaccinated cats had also higher levels than non vaccinated cats but only in the group of parasite-free cats. None of the cats developed clinical signs of food allergy.
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Ding, Zhoujie. "Feedback Enhancement of Immune Responses by IgE, IgM, and IgG3 Antibodies". Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-237337.
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Antibodies can enhance or suppress the immune responses against their specific antigens. This phenomenon is known as antibody-mediated feedback regulation. We have studied the mechanisms underlying IgE-, IgM-, and IgG3-mediated enhancement of immune responses in mouse models using intravenous immunization. We attempted to answer the following questions: 1) Which cell type presents IgE-complexed antigens to CD4+ T cells? 2) Is complement activation required for specific IgM to enhance antibody responses? 3) Does IgM enhance CD4+ T-cell responses? 4) How are IgG3-antigen complexes transported into B-cell follicles? We found that CD23+ B cells transporting IgE-antigen complexes into B-cell follicles were not required to prime the antigen-specific CD4+ T cells in vivo, whereas CD11c+ cells were indispensable. After examining the three most common subpopulations of CD11c+ cells in the spleen, we determined that it was CD8α- conventional dendritic cells migrating into the T-cell zone following immunization that presented IgE-complexed antigens to CD4+ T cells. Next, we showed that specific IgM from Cµ13 mice, which is unable to activate complement, failed to enhance either antibody or germinal center responses whereas wild-type IgM enhanced both responses. Therefore, specific IgM must activate complement to enhance humoral responses. In addition, wild-type IgM did not up-regulate CD4+ T-cell responses. Finally, we showed that IgG3-antigen complexes were transported by marginal zone B cells into B-cell follicles via binding to complement receptors 1 and 2 (CR1/2) on those cells. The immune complexes were captured by follicular dendritic cells as early as 2 h after immunization. Germinal center responses were also enhanced by IgG3. Using bone marrow chimeric mice, we found that CR1/2 expression was required on both marginal zone B cells and follicular dendritic cells to provide an optimal enhancement of antibody responses.
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Ashburn, David. "The relevance of IgA and IgE assays, IgG avidity and western blotting in the diagnosis of Toxoplasma infection". Thesis, University of Aberdeen, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361776.
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To improve diagnosis of Toxoplasma gondii in difficult patient groups, IgA- and IgE-immunosorbent agglutination assays (ISAGA), IgG avidity and Western blotting were developed and assessed. In the ISAGA, rabbit anti-human IgA or anti-human IgE (for the IgA-ISAGA and IgE-ISAGA respectively) was adsorbed onto microtitre plates; formaldehyde fixed tachyzoites were used to identify specific antibody. Both ISAGAs were specific; only 1/482 (0.2%) and 1/513 (0.19%) false positive results were recorded for the IgA and IgE-ISAGA respectively. Both were produced early in infection and were detected for up to 11 (IgA) and 10 (IgA) months. In the avidity ELISA, the performance of excretory/secretory, surface, cytoplasmic and mixed antigen was similar when tested with sera from patients with known duration of infection. Thirteen pregnant women were tested. Specific IgA was detected in all and so was not useful to time infection but specific IgE was absent in 5 women and may therefore have been useful to exclude recent infection. Specific IgE however, was not detected in one woman who seroconverted; detection of IgE may indicate severity of infection. High IgG avidity was measured in 4 patients and could have been useful in conjunction with IgE to exclude recent infection. In immunocompromised patients, IgA and IgE were detected with similar frequency to IgM, but their presence in some IgM negative patients makes them a useful addition to the repertoire of testing. High avidity in immunocompromised patients was not of use to improve diagnosis. Using Western blotting it was possible to differentiate between acute (< 4 months) and recent (4-10 months) infection. This test was less useful for timing infection of infection in pregnancy.
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Zimmer, Anja. "Futtermittel-spezifisches IgG und IgE vor und nach Eliminationsdiäten bei allergischen Hunden". Diss., lmu, 2012. http://nbn-resolving.de/urn:nbn:de:bvb:19-148673.
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Guerra, Fernanda Garcia. "Anticorpos igg e ige para auto-antígenos nucleares no lúpus eritematoso sistêmico". Instituto de Ciências da Saúde, 2005. http://repositorio.ufba.br/ri/handle/ri/21734.
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CNPq; PPGIM – UFBA
O Lúpus Eritematoso Sistêmico (LES) é uma doença reumática autoimune, classificada como uma reação de hipersensibilidade tipo III, que cursa com exuberante produção de auto-anticorpos de diferentes especificidades, e reação inflamatória crônica. O LES acomete predominantemente pessoas do sexo feminino, com prevalência de 5-50 casos/100.000. Contudo, estudos epidemiológicos têm mostrado diferenças raciais na prevalência e aspectos clínicos e laboratoriais do LES. Diferenças têm sido demonstradas principalmente na freqüência dos auto-anticorpos contra antígenos nucleares extraíveis (ENA, extractable nuclear antigens) e de anticorpos IgG anti-DNA fita dupla. Existem poucos dados sobre a prevalência destes auto-anticorpos em pacientes brasileiros, principalmente usando imunoensaios sensíveis. Assim, neste estudo foram investigadas as freqüências de anticorpos antinúcleo dos isotipos IgG e IgE com especificidade antigênica para as proteínas nucleares SSA, SSB, Sm e U1-RNP, além de anticorpos IgG anti-DNA fita dupla. Soros de 21 pacientes do sexo feminino e de 26 doadoras sadias, idade entre 15-65 anos foram inicialmente triados para a presença de anticorpos antinucleares IgG e IgE através de reação de imunofluorescência indireta (IFI, FAN-IgG e FAN-IgE) com células HEp-2. Anticorpos IgG anti-DNA fita dupla, e IgG e IgE anti-ENA foram investigados por técnica de ELISA (Enzyme-Linked Immunosorbent Assay) indireto, usando fase sólida coberta com os autoantígenos purificados. A concentração sérica de IgE foi determinada por ELISA de captura. Todos os soros dos pacientes com LES (100%) foram reativos no teste de FAN-IgG (mediana do título = 640), enquanto 15/21 (71%) amostras reagiram no teste de FAN-IgE. Anticorpos IgG anti-DNA fita dupla foram detectados em 12/21 (52%) soros (mediana do título = 777 UI/ml, sensibilidade de 35,5%). Quatorze soros reagiram em ELISA-IgG para anticorpos anti-ENA, apresentando as seguintes sensibilidades: anti-RNP = 40%; anti-SSA e anti-Sm = 20%, e anti SSB = 10,5%. Anticorpos IgE anti-ENA foram detectados em sete soros, apresentando o teste de ELISA-IgE uma sensibilidade de 2,5% para 13 anticorpos anti-SSA e SSB, e de 5,3% e 17,6% para anti-Sm e anti-RNP, respectivamente. Os testes de ELISA-IgE para anticorpos anti-Sm e anti-SSA mostraram 100% de especificidade, enquanto uma especificidade de 95% foi encontrada para os testes com anticorpos anti-SSB e anti-RNP. Um aumento na concentração de IgE sérica for observado em 6 (29%) das amostras (mediana = 426 UI/ml), existindo uma correlação positiva entre os títulos de FAN-IgG e IgG anti-RNP (r = 0.796, P = 0.002), entre os títulos de IgG e IgE anti-RNP (r = 0.594, P = 0.0045) e também entre IgE anti-RNP e IgE total (r = 0.680, P = 0.0007). Concluindo, a freqüência de FAN-IgG e anticorpos IgG anti- SSA, SSB e anti-Sm nos pacientes brasileiros com LES concordou com os resultados de outros estudos internacionais, existindo contudo uma forte predominância de anticorpos anti-RNP nestes indivíduos.
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Bracher, Marguerite. "IgE in immunotherapy of cancer". Thesis, King's College London (University of London), 2006. https://kclpure.kcl.ac.uk/portal/en/theses/ige-in-immunotherapy-of-cancer(08abceea-54a8-436c-9504-24742d57538d).html.
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Karnowski, Alexander. "Post-transcriptional regulation of IgE". [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10990069.
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Kirak, Oktay. "Eliminierung IgE-positiver B Lymphozyten mit Hilfe eines rekombinanten bispezifischen anti-IgE/anti-CD3 Antikörpers". Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-122571.
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Ledin, Anna. "More or Less IgE : Therapeutic Vaccines, Adjuvants and Genes and Their Effect on IgE Levels". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4254.
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Housden, Jonathan E. M. "Lys 352 in human IgE is a major effector determinant residue in IgE-CD23 interaction". Thesis, University of Sheffield, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.443882.
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Yahya, Mohd Norhakim. "Analysis of the IgE network : inhibition of CD23-mediated IgE upregulation and CD21/C3d interaction". Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:bc5ff165-2d2c-4e4f-a0e9-5651cacd2ddf.
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Allergic reactions are mainly mediated by the interactions between the IgE and its ligands, amongst them CD23 and CD21 in what is termed the IgE network. CD23 is involved in upregulating IgE expression by forming a trimolecular complex with CD21 and IgE on the B-cell surface, resulting in the specific activation of IgE-positive B cells. CD21 also interacts with C3d and is a bridge between the innate and the immune system. A crystal structure of the interaction has been solved (Szakonyi et al., 2001) but was controversial because it contradicted previous biochemical analyses. The aims of this thesis were to use various biophysical techniques to study the interactions between the molecules in the IgE network and its possible inhibition. Part 1: Characterisation of a phage display-derived peptide that inhibit IgE binding to CD23 A peptide was previously derived using phage display technology and tested for binding ability to CD23 using SPR and ITC. Subsequent NMR experiments were performed to identify the binding site, followed by characterization of its derivatives. Crystallisation of CD23 with the peptide and soaking with its truncated tripeptide, NWP, were also attempted. Part 2: Characterisation of CD23 and its interaction with its ligands X-ray crystallography was undertaken to solve the structure of derCD23 in complex with a phage display-derived peptide (Part1) followed by crystal soaking with a truncated tripeptide, NWP. However, a reproducible, high-resolution wild type derCD23 structure was determined at 1.9 Å. A comparison of the binding behaviour between the monomeric derCD23 and a trimeric CD23 construct was carried out in order to see the effect of oligomerisation upon IgE binding. Using the known interaction map as well as a crystal structure, the possible interacting residues between CD23 and IgE were examined. The characterisation of the CD23/CD21 interaction was continued from previous efforts in order to confirm that the binding epitope of CD23 for CD21 lies within the C-terminus of CD23. Characterisation of the interactions of CD23/IgE/FcεRI was performed to examine these multimolecular interactions and possible regulatory mechanisms in mast cell degranulation. It was shown that CD23 can form multimeric complexes with IgE-Fc that bind to FcεRI with higher apparent affinity than IgE-Fc alone, which may lead to increases in mast cell degranulation. It was also found that the IgE bound on FcεRI still binds to CD23 although with a lower binding capacity, presumably due allosteric changes. The binding of CD23 with a monoclonal antibody IDEC-152 was also characterised using SPR and NMR spectroscopy. It was proposed that IDEC-152 might interfere with the trimerisation site of CD23 thus reducing its affinity for IgE. A thermofluor assay was developed and optimised for potential screening of compounds that bind to derCD23 using a qPCR machine, which may be useful to screen compounds that bind to CD23 as part of future drug discovery project. Crystallisation of the derCD23/CD21 and IgE/triCD23/CD21 complexes was also attempted as part of ongoing crystallisation projects. Part 3: The interaction between C3d and CD21 The interaction between C3d and CD21 is believed to be a bridge between the innate and adaptive immune response, and is thought to be pivotal in the initiation of autoimmune disease. Following from previous studies on this interaction, further characterisations were performed using NMR and ITC to confirm the involved sites on CD21 (SCR1-2) in binding to C3d. Several potential salt bridges have been identified so far, allowing a high-resolution docked structure of the C3d/CD21 complex.
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Muntwyler, Jeannette. "Specific antibodies against a recombinant equine IgE heavy chain fragment recognizing native horse serum IgE /". [S.l.] : [s.n.], 1997. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Griot-Wenk, Monika. "Charakterisierung von IgE beim Hund mit Ausblick auf die Bedeutung von IgE bei chronischen idiopathischen Gastroenteropathien /". Bern : [s.n.], 2000. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Zwahlen, Roger Arthur Stucki Marco Viktor. "Basophil histamine release and leukotriene production in response to anti-IgE and Anti IgE-receptor antibodies /". Basel : Karger, 1996. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Vernersson, Molly. "The rise and fall of IgE". Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2597.
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Immunoglobulin E (IgE) occurs exclusively in mammals and is one of five immunoglobulin (Ig) classes found in man. Unlike other isotypes, IgE is best known for its pathological effects, whereas its physiological role remains somewhat elusive.
To trace the emergence of IgE and other post-switch isotypes we have studied Ig expression in two monotreme species, the duck-billed platypus (Ornithorhynchus anatinus) and the short-beaked echidna (Tachyglossus aculeatus), leading to the cloning of IgE, two IgG isotypes in platypus and echidna IgE. The presence of IgE and the conservation of the overall structure in all extant mammalian lineages indicates an early appearance in mammalian evolution and a selective advantage of structural maintenance. Furthermore, both of the two highly divergent platypus γ-chains have three constant domains. Hence, the major evolutionary changes that gave rise to the IgE and IgG isotypes of present day mammals occurred before the separation of monotremes from the marsupial and placental lineages, estimated to have occurred 150-170 million years ago.
As the central mediator in atopic allergy, IgE is a prime target in the development of preventive treatments. This thesis describes an active immunization strategy that has the potential to reduce IgE to a clinically significant extent. The active vaccine component is a chimeric IgE molecule, Cε2-Cε3-Cε4. The receptor-binding target domain, Cε3, is derived from the recipient species, whereas the flanking domains, acting both as structural support and to break T-cell tolerance, are derived from an evolutionarily distant mammal. Vaccination of ovalbumin-sensitized rats resulted in a substantial reduction in total IgE in three out of four strains, accompanied by a significant reduction in skin-reactivity upon allergen challenge. No cross-linking activity was observed and the response to vaccination was reversible with time. The apparent safety and efficacy of the vaccine suggest that active immunization against IgE has the potential to become a therapeutic method for humans.
Furthermore, the cloning and expression of the pig (Sus scrufa) ε-chain will facilitate the development of sensitive and specific assays for pig IgE, thus increasing the possibilities of using the pig model in future studies of IgE-mediated reactions.
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Thienes, Cortlandt Paul. "Studies on the regulation of IgE". Thesis, King's College London (University of London), 1998. https://kclpure.kcl.ac.uk/portal/en/theses/studies-on-the-regulation-of-ige(7b8d519e-0c0e-4a5a-80d8-5ba000d104ec).html.
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Koers, Alexander Magnus Maria. "Radiolabelling and biodistribution of IgE antibodies". Thesis, King's College London (University of London), 2015. http://kclpure.kcl.ac.uk/portal/en/theses/radiolabelling-and-biodistribution-of-ige-antibodies(08a7505b-018b-4bf9-a23f-d31b2432d07a).html.
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Antibodies used for cancer treatment and immune therapy have, to date, been of the IgG class. Efficacy might be improved by using the IgE class of antibodies as these have higher affinity for their Fc-receptors. IgE has a greater tissue penetration and longer half-life in tissue and IgE bound to IgE-receptor-expressing effector cells is thought to actively infiltrate tumours. IgE has not been subject of in vivo imaging studies to date. Objectives: The aim was to radiolabel both anti-CSPG4-IgE and MOV18-IgE, and their IgG counterparts targeted to the same antigen, while maintaining the functionality of the antibodies; and subsequently, to compare IgE with IgG in in vivo imaging and biodistribution studies in a disease model. Methods: IgE’s and their antigen-matched IgG counterparts were engineered against two different tumour antigens. Tumour models were developed to assess targeting in vivo and imaging and biodistribution studies using radiolabelled IgE were carried out. Six antibodies were engineered for comparison: MOv18-IgE and -IgG antibody targeted against the folate receptor alpha (FR ) expressed on ovarian cancer cells; A MOv18-IgE and -IgG chimeric rat/mouse were engineered for evaluation in a new syngeneic immunocompetent rat model to mimic the immunotherapeutic antibody (human/mouse chimeric MOv18-IgE and -IgG) planned for a clinical study; and a second antibody, anti-CSPG4-IgE, targeted against the chondroitin sulfate proteoglycan 4 (CSPG4), expressed in melanoma cancer was compared to its IgG counterpart. The antibodies were analysed in a NOD/SCID xenograft mouse model with splenic engraftment of human peripheral blood lymphocytes. All antibodies were labelled with 111In using the same bifunctional chelator and labelling conditions (p-SCN-CHX-A"-DTPA) and radiolabelled with 111In at room temperature. Functional assays using FACS were carried out to assure binding to the target and high- and low-affinity Fc-binding to Fc"R expressing immune effector cells. NanoSPECT/CT imaging and biodistribution studies were used to determine targeting and clearance of IgE in vivo. Results: 111In-CHX-A"-DTPA-IgE and -IgG antibodies were labelled with high efficiency (>98%). Binding of the conjugated antibody to the target antigen and Fc"R expressing immune effector cells was identical to that of the native antibody. IgE showed a higher liver uptake in biodistribution (up to 75% ID IgE vs 5% ID IgG 8 h post injection) compared with the IgG counterpart as well as more than 10 times faster blood clearance where as IgG showed prolonged half-life (2.5 days) in blood. Tumour-to-blood and tumour-to-muscle ratios of IgE and IgG showed significant (tbr: P<0.05; tmr: P<0.0005) differences. Conclusion: Similar conjugation and radiolabelling of all antibodies as well as the in vivo assessment allowed the evaluation of targeting, biodistribution and clearance of IgE compared with its IgG counterpart. Observed characteristics of IgE like the rapid blood clearance and the higher liver uptake were found to be fundamentally different compared to its IgG counterpart and suggest a different and mostly unknown mode of action.
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Pachlopnik, Jana Maria. "Antigen induced conformational change in IgE /". [S.l.] : [s.n.], 1998. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Helbling, Arthur. "IgE-vermittelte Allergien: Ursache und Diagnostik /". [Bern] : [Universität Bern], 2000. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Palhas, Priscila Botelho. "IgE para ácaros, barata e Ascaris lumbricoides: impacto na IgE total e implicações para o desenvolvimento de alergia e asma". Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17138/tde-19072018-095431/.
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A imunoglobulina E (IgE) tem papel central na patogênese das doenças alérgicas. É parte da resposta do tipo 2, e as citocinas IL-4 e IL-13 são essenciais para que haja produção deste isotipo de imunoglobulina. Produção de IgE é também induzida por parasitas intestinais, particularmente helmintos. O objetivo do presente estudo foi avaliar a contribuição de IgE específica para ácaros, barata, gato, cachorro e para o parasita Ascaris lumbricoides sobre os níveis de IgE total entre crianças de áreas distintas no Brasil. Anticorpos IgE para ácaros Dermatophagoides pteronyssinus e Blomia tropicalis; barata Blattella germanica; gato; cachorro; e A. lumbricoides foram medidos usando o sistema ImmunoCAP, e comparados à IgE total no soro de 150 crianças de 3-6 anos de idade vivendo na cidade de Natal, endêmica para parasitoses intestinais, e de 54 crianças de 3-6 anos de idade com asma e/ou rinite, vivendo em Ribeirão Preto. Níveis de IgE total foram significantemente mais elevados em crianças de Natal quando comparados aqueles em crianças de Ribeirão Preto (média geométrica 630,9 kU/L, faixa 19,6-63.290 kU/L; e 398,1 kU/L, faixa 35,7-4.803 kU/L, respectivamente). Entre as 150 crianças de Natal, 52(34,6%) apresentaram IgE positiva para D.pteronyssinus; 70(46,6%) para B.tropicalis; 45(30%) para barata; 19(12,6%) para gato; 17(11,3%) para cachorro; e 125(83,3%) para A.lumbricoides. Entre as 54 crianças com asma e/ou rinite de Ribeirão Preto, 41(75,9%) apresentaram IgE positiva para D.pteronyssinus; 34(62,9%) para B.tropicalis; 22(40,7%) para barata; 11(20,3%) para gato; 12(22,2%) para cachorro. Embora estas crianças fossem negativas para parasitas à inclusão no estudo, 22(40,7%) tinham IgE para A.lumbricoides. Anticorpos IgE para A. lumbricoides foram mais elevados entre crianças de Natal, quando comparados a IgE para alérgenos inalantes (p<0,01). Níveis de IgE para D. pteronyssinus entre crianças de Ribeirão Preto foram mais altos que IgE para outros inalantes e A.lumbricoides (p<0,01). Em Natal, a porcentagem de IgE para A. lumbricoides em relação à IgE total foi maior em comparação a IgE para D.pteronyssinus e B.germanica (mediana 0,41%; 0,08%; e 0,04% respectivamente, p<0,01). Em Ribeirão Preto, a porcentagem de IgE para D.pteronyssinus e para B.tropicalis em relação à IgE total foi maiorem comparação a IgE para A.lumbricoides e barata (mediana 9,8%; 0,6%; 0,3%; e 0,2%, respectivamente, p<0,05). Regressão linear revelou que a associação mais forte foi para IgE para A.lumbricoides com IgE total em Natal (R²=0,56; p<0,01); associação significante foi também observada para IgE para ácaros com IgE total em Ribeirão Preto (R2=0,35; p<0,01 para D.pteronyssinus; R2=0,33; p<0,01 para B.tropicalis, respectivamente). Nossos resultados demonstraram que anticorpos IgE para ácaros contribuem fortemente para a IgE total entre crianças com asma e/ou rinite, vivendo em uma área de baixa taxa de infecções parasitárias em nosso meio. Por outro lado, entre crianças vivendo em uma área em que parasitas são encontrados em abundância, infecções parasitárias induzem uma forte resposta IgE policlonal, e anticorpos IgE específicos para parasita, além de ácaros, barata, gato e cachorro representam uma modesta proporção da IgE total. A especificidade desta IgE, e os efeitos a longo prazo desta resposta cedo na vida, permanecem desconhecidos.Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases. It is part of the type 2 response, and the cytokines IL-4 and IL-13 are essential for the production of this immunoglobulin isotype. IgE production is also induced by intestinal parasites, particularly helminths. The aim of the present study was to evaluate the contribution of specific IgE to mites, cockroach, cat, dog and parasite Ascaris lumbricoides on total IgE levels among children living in different areas in Brazil. IgE antibodies to mites Dermatophagoides pteronyssinus and Blomia tropicalis; cockroach Blattella germanica; cat; dog; and A. lumbricoides were measured using the ImmunoCAP system and compared to total serum IgE of 150 children 3-6 year-old living in the city of Natal, endemic for intestinal parasites, and 54 children 3-6 years of age with asthma and /or rhinitis, living in Ribeirão Preto. Total IgE levels were significantly higher in children from Natal as compared to those among children in Ribeirão Preto (geometric mean 630,9 kU/L, range 19,6-63.290 kU/L; e 398,1 kU/L, range 35,7-4.803 kU/L, respectively). Among the 150 children from Natal, 52(34.6%) presented IgE positive to D.pteronyssinus; 70(46.6%) to B. tropicalis; 45(30%) to cockroach; 19 (12.6%) to cat; 17(11.3%) to dog; and 125(83.3%) to A. lumbricoides. Among the 54 children with asthma and /or rhinitis from Ribeirão Preto, 41(75.9%) had IgE positive to D.pteronyssinus; 34(62.9%) to B.tropicalis; 22(40.7%) to cockroach; 11(20.3%) to cat; 12(22.2%) to dog. Although these children were negative for parasites at inclusion in the study, 22(40.7%) had IgE to A.lumbricoides. IgE antibodies to A.lumbricoides were higher among children from Natal, as compared to IgE to inhalant allergens (p<0.01). IgE levels to D.pteronyssinus among children living in Ribeirão Preto were higher than IgE to other inhalants and A.lumbricoides (p<0.01). In Natal, the percentage of IgE to A.lumbricoides in relation to total IgE was higher in comparison to IgE to D.pteronyssinus e B.germanica (median 0.41%, 0.08%, and 0.04% respectively, p<0.01). In Ribeirão Preto, the percentage of IgE to D.pteronyssinus and to B.tropicalis in relation to total IgE was higher in comparison to IgE to A.lumbricoides and cockroach (median 9.8%, 0,6%, 0.3%, and 0.2%, respectively, p <0.05). Linear regression analysis revealed that the strongest association was for IgE to A.lumbricoides with total IgE in Natal (R²=0.56, p<0.01); significantassociation was also observed for IgE to mites with total IgE in Ribeirão Preto (R2=0.35, p<0.01 for D. pteronyssinus, R2=0.33, p<0.01 for B.tropicalis, respectively). Our results demonstrated that IgE antibodies to mites contribute strongly to total IgE among children with asthma and /or rhinitis, living in an area of low parasite infection rates in our country. On the contrary, among children living in an area where parasites are found in abundance, parasitic infections induce a strong polyclonal IgE response, and IgE antibodies specific for parasite, and also for mites, cockroaches, cat and dog represent a modest proportion of total IgE. The specificity of these IgE antibodies and the implications of this response occurring early in life remain unknown.
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Zhang, Jie Wei. "Investigation of IgE and IgG epitopes on ovomucoid using egg-white allergic patients' sera". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ40451.pdf.
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Huang, Xinyuan [Verfasser]. "Evolution of serum IgE and IgG antibodies to 35 molecules in childhood / Xinyuan Huang". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2019. http://d-nb.info/1179778111/34.
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Mancardi, David. "Rôles pro-inflammatoires des RFcγIV murins, et de leurs deux équivalents fonctionnels humains, les RFcγI et les RFcεI(αγ)". Paris 6, 2009. http://www.theses.fr/2009PA066504.
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Un nouveau RFc, nommé RFcγIV, a été récemment cloné. Ce sont des RFc activateurs murins pour les IgG2 exprimés par les macrophages et les neutrophiles. Ils n’existent pas chez l’homme. Nous avons caractérisé des propriétés biologiques de ces RFc et recherché s’ils avaient des équivalents fonctionnels humains. Nous avons mis en évidence une interaction de faible affinité entre les RFcγIV et les IgE. Cette interaction participe à l’induction d’une inflammation pulmonaire. Dans des modèles d’inflammation dépendante des IgG, les RFcγIV sont capables d’induire une arthrite auto-immune et des chocs anaphylactiques systémiques. L’ensemble de ce travail met en évidence de nouvelles fonctions des RFcγIV, et des cellules qui les expriment, dans des réactions in vivo induites à la fois par des IgE et par des IgG. Deux RFc humains, les RFcγI et les RFcεI(αγ) pourraient, chez l’homme, jouer le rôle que jouent les RFcγIV chez la souris.
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Bowles, Sandra Lyn. "An investigation of IgE regulation by recombinant soluble IgE receptors and co-receptors in human cell culture models". Thesis, Nelson Mandela Metropolitan University, 2010. http://hdl.handle.net/10948/1231.
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Type I hypersensitivities are mediated by the IgE antibody. The effector functions and synthesis of IgE result from interactions with a network of proteins that include a high affinity (FcRIα) and a low affinity (CD23, FcRII) Fc receptor in conjunction with the B lymphocyte receptor, CD21. CD23 is a multifunctional type II transmembrane protein that binds its known ligands through its ectodomain either as a membrane-bound or soluble receptor generated in vivo by specific proteolytic cleavages. IgE production is primarily regulated by interactions between IgE, CD23 and CD21. Despite its importance for development of strategies to limit hypersensitivity, precise information about the molecular interactions remains limited. During this study, I engineered, expressed and purified from bacteria three soluble human CD23 fragments that are normally formed in vivo and shed from the cell surface (1) derCD23, amino acids 156-298 (2) sCD23, amino acids 150-321 and (3) the entire ectodomain, exCD23, amino acids 48-321 to examine the comparative binding of recombinant human CD21 SCR 1-2 and native human IgE to these fragments. Gel filtration HPLC revealed that derCD23 and sCD23 were monomeric whereas exCD23 assembled as a heterogeneous mixture that included trimers and monomers. At the concentrations utilized, CD23 fragments sCD23 and exCD23 bound CD21 with similar affinity, whereas interaction between derCD23 and CD21 was minimal when analyzed by surface plasmon resonance (SPR) spectroscopy. These findings suggest that penultimate “tail” amino acids between 298 and 321 stabilize CD21 attachment, although it cannot be ruled out, the region between Met 150 and Ser 156 may also play a role in binding CD21 SCR 1-2. In contrast, there is a progressive increment in the affinity of soluble fragments (exCD23>sCD23>derCD23) for IgE, upon increasing length of the proximal CD23 “stalk” domain. These findings highlight the differences in both the structural basis and affinity of the three physiological fragments of human CD23 for the ligands CD21 and IgE and underscore the complexity of CD23-mediated regulatory networks. It was found that B-cells only make up ~5% of the PBMC population, and that these cells were able to be activated, via STAT-6 phosphorylation, to enter class switch recombination (CSR) by the addition of switch factors (IL-4 and anti-CD40). Titration experiments dictated that 25 ng/mL of CD23 was the most efficient concentration to up-regulate IgE synthesis in PBMCs; furthermore, soluble CD23 proteins were incubated with PBMCs in the presence and absence of CD21 SCR 1-2 to investigate the effect that these recombinant proteins have on IgE synthesis. Results showed that the influence of recombinant proteins (both CD23 and CD21) on IgE synthesis was slight. It was shown that while derCD23 had no significant effect, monomeric sCD23 down-regulated, and the mixture of monomeric and oligomeric exCD23 up-regulated IgE synthesis. On addition of CD21 SCR 1-2 to the cells switched and treated with soluble CD23, it was found that in both cases for sCD23 and exCD23, IgE synthesis was increased, while for derCD23, there was no noticeable difference in IgE synthesis. This confirmed previous data showing the lack of binding between derCD23 and CD21 SCR 1-2. The exact binding site for CD21 on the CD23 molecule is unknown, and incompletely represented in the NMR and crystal structures. It is thought that CD21 binds to the C-terminal tail section, not present in derCD23. It is therefore likely that only a negative-feedback mechanism operates with derCD23 to regulate IgE synthesis. Further investigation of the binding of CD23 fragments to SCR 5-8 of CD21 and the effect of this on IgE synthesis may lead to a potential therapeutic role for derCD23 in the treatment of allergic disease. Data accumulated in this study suggests that investigating the modulation of oligomeric state and thus the activity of soluble CD23 fragments may be important in the construction of new regulators of IgE synthesis.
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Luz, Johanna Da. "Aspects of N-glycosylation in human IgE /". Stockholm : [Karolinska institutets bibl.], 2002. http://diss.kib.ki.se/2002/91-7349-130-6.
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Quinn, Phyllis Mary. "The structure and function of IgE-tailpiece". Thesis, University of Nottingham, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444655.
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Corfield, Gaynor Christa. "The regulation and characterization of porcine IgE". Thesis, University of Bristol, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319081.
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Neiss, Anne-Catherine. "La regulation de la production des ige". Strasbourg 1, 1987. http://www.theses.fr/1987STR10767.
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Asai, Koichi. "Regulation of mast cell survival by IgE". Kyoto University, 2002. http://hdl.handle.net/2433/149705.
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Yu, Yan. "Anti-IgE autoantibodies in bee venom allergy /". [S.l.] : [s.n.], 1991. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Machado, Fernando Osni. "Tabagismo materno e IgE no cordão umbilical". reponame:Repositório Institucional da UFSC, 1995. http://repositorio.ufsc.br/xmlui/handle/123456789/76218.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciencias da SaudeMade available in DSpace on 2012-10-16T08:22:12Z (GMT). No. of bitstreams: 0Bitstream added on 2016-01-08T19:26:34Z : No. of bitstreams: 1 101681.pdf: 3505184 bytes, checksum: 09b9d59fd408db6c1062007e4db0090b (MD5)
Objetivo: Analisar a influência do tabagismo materno nos níveis de IgE do sangue do cordão umbilical dos recém nascidos (RN). Local: O estudo desenvolveu-se na Maternidade Escola da UFSC (Maternidade Carmela Dutra) em Florianópolis, Santa Catarina. Sujeitos: Investigou-se 492 RN e respectivos pais e mães. Métodos: Colheu-se sangue do cordão umbilical dos RN para análise laboratorial de imunoglobulina E, pela técnica de enzima imuno ensaio (ABBOTT IgE EIA). As mães foram também questionadas em relação ao uso de tabaco e fatores outros relativos à gravidez. Para analisar a influência das três variáveis independentes (antecedentes alérgicos maternos, paternos e tabagismo materno), utilizamos o modelo de análise de variância múltipla. Resultados: Os RN de mães certamente alérgicas tiveram, em média, níveis de IgE mais elevados que aqueles de mães não alérgicas. Tabagismo materno foi o mais importante fator determinante de elevação dos níveis de IgE no cordão umbilical. Diminuir o número de cigarros/dia, durante a gravidez, não excluiu o efeito do tabaco sobre a IgE no cordão umbilical. Os RN de mães ex-fumantes apresentaram o mesmo comportamento daqueles de mães não fumantes, em relação à IgE. Conclusões: Nossos resultados demonstraram que o tabagismo materno está associado a níveis elevados de IgE no sangue do cordão umbilical. A abolição do tabagismo durante a gravidez, permitiu observar a eliminação deste efeito.
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Balbino, Bianca. "Characterizing the role of IgG antibodies in anaphylaxis". Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS024.
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L'anaphylaxie est la manifestation clinique la plus sévère de l’allergie. Il est couramment admis que chez l’homme, l’anaphylaxie est médiée par les anticorps de type IgE. Cependant, des données chez la souris indiquent que les IgG peuvent également contribuer à l’anaphylaxie. Le but de ma thèse a été de mieux comprendre comment les IgG induisent l’anaphylaxie. Dans un premier temps, nous avons démontré que les IgG murines induisent l’anaphylaxie en activant le récepteur FcγRIII à la surface des macrophages, ce qui aboutit à la libération de PAF. Nous avons ensuite voulu savoir si les IgG humaines peuvent également induire des chocs anaphylactiques. L’anticorps thérapeutique Omalizumab (IgG1 humanisée anti-IgE) induit des chocs anaphylactiques chez certains patients. Nous avons démontré que Omalizumab forme des complexes immuns qui peuvent activer les récepteurs FcγRs et induire des chocs anaphylactiques dans des souris exprimants les FcγRs humains (hFcγRKI). Nous avons ensuite développé une version mutante d’Omalizumab incapable de lier les FcγRs et démontré que cet anticorps bloque les IgE sans induire d’anaphylaxie. Finalement, nous avons développé un nouveau modèle humanisé d’anaphylaxie aux arachides dans lequel les souris hFcγRKI sont sensibilisées avec des IgG de patients allergiques aux arachiques. Nos données préliminaires indiquent que les IgG peuvent induire l’anaphylaxie dans ce modèle. De manière surprenante, l’anaphylaxie est augmentée dans des souris n’exprimant aucun FcγR. Nous étudions actuellement le(s) mécanisme(s) responsables de cet effet, et notamment l’implication de la voie du complément et le rôle du récepteur inhibiteur FcγRIIBAnaphylaxis is a severe and potentially fatal allergic reaction. The current paradigm in humans states that anaphylaxis is triggered by allergen-specific IgE antibodies (Abs). Several reports in mice indicate that IgG Abs can also trigger anaphylaxis. The goal of my thesis was to better understand the pathways through which IgG mediate anaphylaxis. We first evaluated this in an adjuvant-free mouse model of active systemic anaphylaxis. We observed a contribution of the 'classical’ pathway mediated by IgE, FcγRI, mast cells and histamine. However, anaphylaxis was largely mediated by an ‘alternative’ pathway driven by IgG, FcγRIII, macrophages and PAF. We then examined whether human IgG can also trigger anaphylaxis. Omalizumab, an IgG1 anti-IgE mAb, has been reported to induce adverse events, including anaphylaxis. We found that Omalizumab forms immune complexes with IgE that engage FcγRs and induce both skin inflammation and anaphylaxis when injected into mice expressing all human FcγRs (hFcγRKI). We then developed an Fc-engineered version of Omalizumab which cannot bind FcγRs, and demonstrated that this Ab is as potent as Omalizumab at blocking IgE-mediated allergic reactions, but does not induce FcγR-mediated anaphylaxis. Finally, I describe ongoing work in a new model of peanut anaphylaxis in which hFcγRKI mice are sensitized with IgG from allergic subjects. Preliminary data indicate that these IgG induce anaphylaxis in this model; Surprisingly, anaphylaxis is increased in mice deficient for all FcγRs. We are now investigating the mechanism(s), in particular the implication of the complement pathway, and the role of the inhibitory receptor FcγRIIB
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Montagnac, Guillaume. "Etude du rôle du récepteur de faible affinité aux IgE, CD23, dans le transport transépithélial de complexes IgE/allergènes". Paris 5, 2005. http://www.theses.fr/2005PA05N11S.
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Le récepteur de faible affinité aux IgE (CD) est impliqué dans le transport transépithélial de complexes IgE / allergène. Au niveau intestinal, ce transport est à l'origine du déclenchement allergique. Mon travail de thèse a visé à étudier le rôle du CD23 dans ce processus. Nous avons établi que les cellules épithéliales intestinales murines expriment la forme CD23b ainsi qu'une nouvelle forme épissée, bDELTA5, dont l'expression est induite par la sensibilisation in vivo. La régulation de l'internalisation du CD23 murin est complexe, faisant intervenir des domaines intra et extracellulaires. Nous avons ensuite déterminé que la forme CD23b peut prendre en charge la transcytose de complexes IgE/allergène tandis que bDELTA5 peut transporter des IgE libres. Les études que nous avons menées en parallèle chez l'homme suggèrent que le CD23 y joue un rôle similaire bien que les modalités régulant l'endocytose et la transcytose soient différentesThe low affinity receptor for IgE (CD23) has been implicated in the transepithelial transport of IgE/allergen complexes. This transport is known to induce allergic reactions in sensitized animals. The purpose of my thesis was to characterize the precise role of CD23 in this process. We first establish that mouse intestinal epithelial cells express CD23b. A new CD23b derived splice form, bDELTAS, is also expressed upon sensitization. We found that that endocytosis regulation of CD23 is complex involving both extra and intracellular domains of the receptor. We then showed that classical CD23b transports IgE/allergen complexes while bDELTA5 mediates free IgE transcytosis. Studies in human revealed that CD23 plays a similar role in this species but that endocytosis and transcytosis regulation are here very different
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Dupuy, Michèle. "Intérêt des IgE et de IgA anti-toxoplasma gondii dans le diagnostic sérologique de la toxoplasmose". Bordeaux 2, 1993. http://www.theses.fr/1993BOR23036.
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Renner, Eleonore D. "Klinisch-genetische Definition des Hyper-IgE-Syndroms (HIES)". Diss., lmu, 2002. http://nbn-resolving.de/urn:nbn:de:bvb:19-1763.
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Stöberl, Christian. "Gene-Targeting zur Herstellung einer IgE überexprimierenden Maus". Diss., lmu, 2003. http://nbn-resolving.de/urn:nbn:de:bvb:19-10405.
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Nilsson, Caroline. "Cytokine profiles, infections and IgE sensitisation in childhood /". Stockholm : Department of Clinical Science and Education, Södersjukhuset : Sachs' Children's Hospital : Karolinska institutet, 2006. http://diss.kib.ki.se/2006/91-7140-720-0/.
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Shi, Jianguo. "Interaction of human CD23 with IgE and CD21". Thesis, King's College London (University of London), 1997. https://kclpure.kcl.ac.uk/portal/en/theses/interaction-of-human-cd23-with-ige-and-cd21(373685f2-b918-4cae-9404-c10d226ff134).html.
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Smith, Susan Jayne. "The molecular pathology of human autoanti-IgE antibodies". Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294568.
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DONADINI, VERONIQUE. "Regulation de la synthese des ige : donnees recentes". Strasbourg 1, 1993. http://www.theses.fr/1993STR15047.
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Lai, Catherine Li. "Regulatory Immune Mechanisms in IgE-Mediated Food Allergies". Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/27352.
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Background
Egg allergy is an IgE-mediated food allergy affecting 10% of Australian infants. Two Australian early egg introduction trials were conducted – Beating Egg Allergy Trial (BEAT) and Start Time of Egg Protein to Prevent Egg Allergy (STEP). Both studies showed significant induction of egg-specific IgG4 that was associated with early egg consumption. IgG4 is associated with tolerance induction. However, the mechanisms of tolerance acquisition are still poorly understood but may involve regulatory T and B cells.
Aims
To examine the antigen‑specific and non‑specific immune cell subsets in at‑risk infants from primary prevention trials for egg allergy. The capacity of naïve CD4+ T cells to differentiate into T helper subsets in food allergic children was evaluated.
Methods
Cells from BEAT and STEP cohorts were used to examine ovalbumin-specific Tregs, Bregs, Th1 and Th2 cells as well as general phenotyping on T helper subsets, regulatory B cells and innate lymphoid cells. Egg-specific sIgE and sIgG4 was also used to assess correlations with cellular data. From another cohort of food allergic children with age-matched controls, cells were examined for activated CD14+ monocyte cytokines and the differentiation potential of naïve CD4+ T cells.
Results
Early egg introduction and clinical tolerance to egg were associated with the expansion of ovalbumin‑specific Treg and Bregs in infants at risk of developing allergies. The impairment in Th1 and Treg differentiation in food allergic children parallels early dysregulation of T helper development in food allergic infants. Additionally, pro‑inflammatory tendencies of monocytes are persistent in food allergic children.
Conclusion
The expansion of regulatory immune cells may contribute towards tolerance acquisition to food allergens during infancy. The intrinsic alterations of naïve CD4+ T cell and antigen presenting cell traits may underlie the propensity for Th2 development and impaired Treg induction in food allergic children.
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Ilkow, Veronica Franciszka. "Engineering IgE antibodies and CD23 for therapeutic discovery". Thesis, King's College London (University of London), 2018. https://kclpure.kcl.ac.uk/portal/en/theses/engineering-ige-antibodies-and-cd23-for-therapeutic-discovery(54f73d64-5c16-42c4-9dea-42855873eeb6).html.
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Immunoglobulin E (IgE) is fundamental to the allergic response and the functions of IgE are mediated by its Fc region binding to two receptors, FcεRI and CD23 (FcεRII). The interaction of IgE with other proteins have complicated our investigations of the unique role each receptor plays. To solve this, a small-scale library of IgE-Fc proteins was designed with two key positions, one at each receptor-binding site mutated. The unpredictable allosteric nature of IgE prevents rational engineering approaches, thus the design of a membrane-bound IgE-Fc-GFP-tagged protein allowed for the generation of a membrane-surface display library of stable cell lines. A FACS selection assay identified IgE-Fc proteins with weakened binding to a single IgE-receptor, which serves as a proof-of-principle for this concept. Additional studies into human CD23 and the differences between it and murine CD23 revealed additional levels of regulation for IgE-binding not seen in other species and this is due to its unique properties. Human CD23 is an unusual antibody receptor, being a calcium dependent (C-type) lectin that has lost its carbohydrate binding capability. Ca2+ binds to and increases CD23’s affinity for IgE, and one of two Ca2+ binding sites usually present in C-type lectins is absent in human but present in murine CD23. To understand if the loss of the second Ca2+ binding site has led to a regulatory gain/loss of function in human CD23, a panel of CD23 mutant proteins with increasingly ‘mouse-like’ sequences was generated. The insertion of the second Ca2+ binding site was verified by HSQC-NMR whilst molecular dynamic simulations provided a means of understanding the flexibility of the proteins. It revealed that binding of two Ca2+ ions tethers the soluble CD23 loops into position in the most mouse-like mutant protein, limiting possible conformations for IgE binding. Complementary Biacore experiments indicated that higher calcium binding affinity may have come at a cost of weakened IgE binding, as data in the presence and absence of Ca2+ showed decreased binding affinities of the proteins for human IgE. This regulatory difference between murine and human soluble CD23 could inform the development of CD23/IgE inhibitor therapeutics for the treatment of allergy.
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Worm, Margitta. "Mechanismen der CD40/IL-4-abhängigen IgE-Regulation". Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2000. http://dx.doi.org/10.18452/13716.
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IgE ist das Schlüsselmolekül Typ-I allergischer Erkrankungen.. Die Produktion von IgE wird durch die Interaktion des Oberflächenmoleküls CD40 auf B-Zellen mit seinem Liganden (CD40L), dass von aktivierten T-Zellen exprimiert wird, sowie über Signale durch die Zytokine IL-4 oder IL-13 von B-Zellen produziert. Die CD40/IL-4-abhängige IgE-Produktion in vitro kann einerseits als Modell zum Verständnis der Entstehung allergischer Erkrankungen eingesetzt werden; andererseits können potenziell therapeutisch wirksame Substanzen untersucht werden. Untersuchungen zum Verständnis allergischer Erkrankungen zeigen, dass LTa nach CD40/IL-4-Stimulation von humanen B-Zellen vermehrt produziert wird und dies in autokriner Weise zu einer Steigerung der CD40/IL-4-vermittelten Proliferation und IgE-Produktion führt. Darüberhinaus wurde eine vermehrte Produktion von LTa bei allergischen Patienten nachgewiesen, so dass eine funktionelle Relevanz von LTa in der Pathogenese allergischer Erkrankungen zu vermuten ist. Die Arbeiten zu den intrazellulären Mechanismen der LTa-Induktion nach CD40/IL-4-Stimulation demonstrieren, dass sowohl der Transkriptionsfaktor NF-kB als auch verschiedene Proteinkinasen hier eine wesentliche Rolle spielen. Untersuchungen mit Hilfe des CD40/IL-4-abhängigen Systems bei humanen B-Zellen, die einen therapeutischen Einsatz zur Behandlung allergischer Erkrankungen haben könnten, zeigen, dass Retinoide aber auch Vitamin D zu einer erheblichen Hemmung der IgE-Produktion in- vitro führen.IgE plays a key role for the development of type I related allergic diseases. Production of IgE by B cells is induced by the interaction of the surface molecule CD40 with its natural ligand (CD40L), which is expressed on activated T cells and signals which are provided by the cytokines IL-4 or IL-13. This model can be used for studies either to understand the development of allergic diseases or to investigate novel therapeutic approaches. In the context of the understanding the development of allergic diseases the present work shows that LTa is produced by B cells after CD40+IL-4 stimulation and that increased production of LTa results in enhanced CD40+IL-4 mediated B cell proliferation and IgE synthesis. Furthermore an increased production of LTa was shown in allergic patients indicating the potential role of LTa in allergic diseases. Analysis of the gene regulation of LTa after CD40 stimulation revealed an important role of the transcription factor NF-kB and showed the role of different protein kinases at the intracellular level. Studies using the CD40+IL-4 system in vitro which may have a therapeutical impact revealed that vitamin A and vitamin D are potent inhibitors of IgE production in vitro. Taken together the present work shows new mechanisms of CD40+IL-4 mediated IgE synthesis and also offers new potential therapeutical approaches of allergic diseases.
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Lindner, Juliane. "Immunmodulation der IgE-Produktion durch autokrine Calcitriol-Synthese". Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2017. http://dx.doi.org/10.18452/17768.
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Aktuelle Studien legen nahe, dass ein niedriger Vitamin D-Status assoziiert mit steigenden Breitengraden, mit dem Auftreten von Autoantikörpern und damit einhergehenden Autoimmunerkrankungen positiv korreliert. Trifft UV-B-Strahlung auf die Haut, entsteht aus 7-Dehydrocholesterol nach enzymatischen Prozessen in Leber und Niere, die bioaktive Form von Vitamin D, 1α,25-Dihydroxyvitamin D3 (Calcitriol). Den finalen Stoffwechselschritt katalysiert die 1α-Hydroxylase CYP27B1. Die biologische Wirkung von Calcitriol wird über dessen Bindung an den nukleären Vitamin D-Rezeptor vermittelt, was letztlich zur Transkription der Zielgene führt. Die T-Zell-abhängige Sensibilisierung von Vitamin D-defizienten Cyp27b1-KO- und Wildtyp-Tieren mit Ovalbumin zeigte verstärkte humorale Immunantworten mit erhöhten Konzentrationen von Gesamt- sowie spezifischem IgG1, IgE und IgA bei den Cyp27b1-KO-Mäusen. Die Untersuchung der Leukopoese der Cyp27b1-KO-Tiere zeigte, dass die untersuchten lymphatischen Organe verminderte Gesamtzellzahlen gegenüber Wildtyp-Tieren aufwiesen. Die Präsenz und Verteilung in den jeweiligen Zellkompartimenten offenbarte keine wesentlichen Abweichungen zwischen Cyp27b1-KO- und Wildtyp-Mäusen. In einem Krankheitsmodell mit dem Helminthen Heligmosomoides polygyrus bakeri fielen die Cyp27b1-KO-Tiere durch dem Wildtyp gegenüber erhöhten Gesamt- sowie spezifischen IgE-Werten auf. Zwischen beiden Genotypen zeigten sich keine Unterschiede bei parasitologischen Parametern wie der Wurmlast, der Eianzahl pro Gramm Faeces sowie der Fekundität. Die Ergebnisse dieser Arbeit bestätigen, dass endogen-produziertes Vitamin D einen Einfluss auf die Funktionsweise von Lymphozyten hat. Dies äußert sich in verstärkten IgE-abhängigen Immunantworten bei Cyp27b1-KO-Tieren. In einem Parasiteninfektionsmodell wurden erneut verstärkte IgE-Antworten beobachtet, jedoch waren keine pathophysiologischen Konsequenzen in Bezug auf die Wurmabwehr nachweisbar.Current studies demonstrate that low vitamin D levels associated with higher latitudes correlate with the occurrence of autoantibodies and linked diseases. Following UV-B radiation of the skin, numerous enzymatic reactions in liver and kidneys causes 7-dehydrocholesterol to turn into the bioactive 1α,25-dihydroxyvitamin D3 (calcitriol). The final and crucial step is thereby performed by the enzyme CYP27B1, an 1α-hydroxylase. The effect of calcitriol is mediated through binding to the vitamin D receptor, resulting in the transcription of target genes. T cell-dependent sensitization of Cyp27b1-wildtype and Cyp27b1-KO mice with ovalbumin revealed an increased humoral immune response in Cyp27b1-KO mice reflected by elevated concentrations of total and specific IgG1, IgE and IgA. Analysis of the leukopoiesis showed a diminished total cell count in bone marrow, thymus, spleen and peritoneal cavity in Cyp27b1-KO compared to Cyp27b1-wildtype mice. However, appearance and distribution of the analyzed cell compartments were comparable. A disease model using the intestinal nematode Heligmosomoides polygyrus bakeri demonstrated enhanced secretion of total and specific IgE in Cyp27b1-KO mice, which confirmed our previous findings. However, this showed no effect on parasite rejection, as seen in comparable results for worm burden, eggs per gram faeces and fecundity of female worms in Cyp27b1-wildtype and Cyp27b1-KO mice. Our work verified the role of endogenous vitamin D for lymphocyte development revealed by increased IgE-dependent immune responses in Cyp27b1-KO mice. Infection with H.p. bakeri confirmed enhanced IgE-responses, however, these results revealed no benefit in parasite clearance.
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Yenagi, V. A. "GENERATION OF A TRANSGENIC FCRI-KO/ HIGH IGE-PRODUCER MOUSE TO ELUCIDATE THE ROLE OF IGE IN TUMOR SURVEILLANCE". Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/221195.
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Immunoglobulin E (IgE) is a powerful elicitor of anti-parasitic immunity and play a key role in pathophysiology of allergic reactions.IgE antibodies acts by engaging both high and low affinity receptors, FcεRI and CD23. Since the 1960s a number of epidemiological studies have investigated the potential association between a history of allergy and risk of malignancy. In this direction studies were planned by redirecting the power of the IgE system towards tumors, and to evaluate if it can trigger powerful anti-tumor cytotoxic activities. Previously in our laboratory,mouse and human IgE have been used as vaccines adjuvants,highlighting the importance of IgE:FcεRI interaction in establishment of strong allergy-like inflammatory response at tumor site,with induction of adaptive antitumor immune response and memory. Based on these results and Epidemiological studies relating possible link between allergies and cancer protection, we decided to study the involvement of endogenousIgE with antitumor specific IgE effect in vivo making use of high IgE producing(KN1-HyperIgE) and IgE knock out transgenics and two different tumor cell lines (TS/A-LACK and N2C), upon challenge we were able to note that tumor growth was seen in IgE knock out mice, wild type control mice and CD-23 knock out mice, however there was a striking tumor protection effect in KN1-HyperIgE mice. The results from in vitro studies showed presence of tumor specific IgE antibodies in serum of only in KN1-high IgE producing group indicating the role of IgE mediated mechanism in antitumor protection. In order to prove the involvement of Endogenous IgE in antitumor protection observed in vivo, we investigated if Bone Marrow cells of KN1-HyperIgE producing mice when transplanted can induct protection in spontaneously tumor developing mice(HER-2/neuT),BMT experiments were performed using the bone marrow cells from HyperIgE mice failed to have delayed and/or desired antitumor effect in immunocompromised spontaneous tumor developing HER-2/neuT mice. To validate that indeed IgE is involved in tumor protection and this protection is mediated by its interaction with its high affinity receptor FcεRI, a new transgenic was generated by breeding KN1-HyperIgE and FcεRIα knock out mice to arrive at a Double mutant(DB) mice(phenotype being high IgE producing but lacking in functional high affinity receptor FcεRI). In experiment with tumor challenge, there was tumor protection in HyperIgE mice, but was lost in the double mutant mice inducting the role of high affinity receptor FcεRI in tumor protection. Even the in vitro results showed the release of antitumor specific IgE antibodies in KN1-high IgE producing as well as Double mutant group indicating that tumor protection lost in Double mutant mice is due to 5 absence of functional high affinity receptor FcεRI .In another experiment, depletion of CD8+ cells led to abolishment of tumor protection in Kn1-HyperIgE mice. The results from this thesis study clearly signify the role of IgE in antitumor mechanism and highlight the prominent role of IgE:FcεRI in induction of Tumor protection. It also points towards crucial role of CD8+cells in antitumor immunity, suggesting towards an IgE mediated cross presentation pathway for induction of TAA specific cytotoxic lymphocytes in antitumor response. Studies are ongoing to further elucidate the evolving role IgE mediated mechanism in the context of cancer.
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Zimmer, Anja [Verfasser] y Rafl [Akademischer Betreuer] Müller. "Futtermittel-spezifisches IgG und IgE vor und nach Eliminationsdiäten bei allergischen Hunden / Anja Zimmer. Betreuer: Rafl Müller". München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2012. http://d-nb.info/1027066127/34.
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Dantas, Val?ria Cristina Ribeiro. "IgA s?rica, secretora, IgE total e estado nutricional em crian?as com infec??es por enteroparasitas". Universidade Federal do Rio Grande do Norte, 2003. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13438.
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Previous issue date: 2003-03-21Infections for intestinal parasites are one of the main morbidade causes in humans and, its relationships with socioeconomic levels and hygiene conditions in countries in development are already very established. Many works, even so, they are being accomplished to elucidate the complex interactions among nutrition, these infections and answer imunol?gica, because it is seen that malnutrition commits the immunity increasing the susceptibilidade for infectious diseases and these for its time can harm the state human nutricional. It is known that sponge helm?nticos they stimulate synthesis of IgE so much policlonal as specific for the same ones and that IgA secretora, main imunoglobulina of defense of the mucous ones, can act against protozoa as the Giardia lamblia and against helmintos as Trichuris tichiura and Strongyloides stercorales. Some studies show that the malnutrition energy prot?ica influences in the production of these answers, but some authors show results divergentes. In this work it was evaluated the levels of total IgE, IgA s?rica and secretora, contagem of sanguine eosin?filos, levels of proteins s?ricas and state nutricional, in 103 children of low socioeconomic level, to discover a correlation between those and infection for enteroparasitas. They participated in the study children of both sexes, with age of 3 to 6 years, visitors of the same creche and residents in a neighborhood with precarious hygiene conditions and basic saneamento, in the city of Christmas. The obtained results showed that the faulty environmental and socioeconomic conditions favored to a high infection frequency for enteroparasitas, mainly Trichuris trichiura and Ascaris lumbricoides between the helmintos and Endolimax sleep and Gi?rdia lamblia among the protozoa. Light malnutrition without deficit prot?ico was observed in 30% of the children, which didn't also present significant deficiencies of IgA s?rica and secretora. The sponged children
Infec??es por parasitas intestinais s?o uma das principais causas de morbidade em humanos e, suas rela??es com n?veis s?cio-econ?micos e condi??es de higiene em pa?ses em desenvolvimento j? s?o bem estabelecidas. Muitos trabalhos, por?m, est?o sendo realizados para elucidar as complexas intera??es entre nutri??o, estas infec??es e resposta imunol?gica, pois ? visto que desnutri??o compromete a imunidade aumentando a susceptibilidade para doen?as infecciosas e estas por sua vez podem prejudicar o estado nutricional humano. Sabe-se que parasitas helm?nticos estimulam s?ntese de IgE tanto policlonal como espec?fica para ant?geno dos mesmos e que IgA secretora, principal imunoglobulina de defesa das mucosas, pode atuar contra protozo?rios como a Giardia lamblia e contra helmintos como Trichuris tichiura e Strongyloides stercorales. Alguns estudos mostram que a desnutri??o energ?tico prot?ica influencia na produ??o destas respostas, mas outros autores mostram resultados divergentes. Neste trabalho avaliou-se os n?veis de IgE total, IgA s?rica e secretora, contagem de eosin?filos sangu?neos, n?veis de prote?nas s?ricas e estado nutricional, em 103 crian?as de baixo n?vel s?cio-econ?mico, para se averiguar uma correla??o entre esses e infec??o por enteroparasitas. Participaram do estudo crian?as de ambos os sexos, com idade de 3 a 6 anos, freq?entadoras da mesma creche e residentes em um bairro com prec?rias condi??es de higiene e saneamento b?sico, na cidade do Natal. Os resultados obtidos mostraram que as deficientes condi??es ambientais e s?cio-econ?micas favoreceram a uma alta freq??ncia de infec??o por enteroparasitas, principalmente Trichuris trichiura e Ascaris lumbricoides entre os helmintos e Endolimax nana e Gi?rdia lamblia entre os protozo?rios. Desnutri??o leve sem d?ficit prot?ico foi observada em 30% das crian?as, as quais tamb?m n?o apresentaram defici?ncias significativas de IgA s?rica e secretora. As crian?as parasitadas apresentaram eosinofilia sangu?nea e n?veis s?ricos de IgE total elevados confirmando a importante participa??o das mesmas na resposta imune contra helmintos. Pode-se, portanto, sugerir que as crian?as apesar de poliparasitadas n?o estavam com sua resposta imune de mucosa contra parasitas, prejudicada, provavelmente por ainda n?o estarem intensamente infectados, como observado na contagem de ovos por grama de fezes e tamb?m por n?o terem seu estado nutricional gravemente comprometido