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Suzuki, Lisandra Akemi. « Resposta imune humoral na neurocisticercose ». [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308741.
Texte intégralRésumé :
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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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.
Texte intégralRésumé :
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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Patel, Ekta. « IgM antibodies enhance the phagocytosis of apoptotic cells by immature dendritic cells ». Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p1462525.
Texte intégralRésumé :
Thesis (M.S.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed May 8, 2009). Available via ProQuest Digital Dissertations. Includes bibliographical references (p. 45-47).
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Hesketh, Emily Ellen. « Apoptotic cell interaction with IgM antibodies and modulation of ischaemic tissue injury ». Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/15840.
Texte intégralRésumé :
Acute kidney injury (AKI) induced by renal ischaemia reperfusion injury (IRI) is characterised by renal failure, acute tubular necrosis (ATN), inflammation and microvascular congestion. Apoptotic cell administration reduces inflammation in experimental models of acute inflammation in the lung, joints and peritoneum. Preliminary data suggested that administration of 20x106 apoptotic thymocytes to mice 24-hours prior to renal IRI ameliorated renal function without affecting ATN 24-hours following IRI. This thesis attempted to validate these finding and explore underlying hypothetical mechanisms. These studies examined if functional protection was conferred by apoptotic cell modulation of (a) circulating IgM antibodies or (b) coagulation status leading to improved intrarenal microvascular blood flow. Pathogenic IgM antibodies bind ischaemic cardiac or skeletal muscle and the intestine leading to complement activation and worse injury. We examined IgM binding to human renal (HK-2) cells by flow cytometry and to ischaemic murine kidney tissue. H2O2 or Antimycin A treated HK-2 cells incubated with human serum (IgM source) exhibited no IgM binding. Medullary IgM deposition assessed by immunofluorescence was minimal following IRI. We also assessed IgM deposition by immunohistochemistry following hepatic IRI and discovered dramatic deposition. These data suggest that IgM antibodies exhibit differential binding to injured tissues and are not directly involved in renal IRI, but may have a role in hepatic IRI. To support our second hypothesis we studied apoptotic cell modulation of coagulation. A thrombin generation assay revealed that early apoptotic cell-treated mice exhibited delayed thrombin generation. Furthermore, in vitro studies confirmed direct apoptotic cell-platelet binding. To replicate apoptotic cell derived functional protection Balb/c mice underwent 20, 24 or 25-minutes of ischaemia to induce mild, moderate or severe kidney dysfunction. Renal function and injury was determined 24-hours following IRI by plasma creatinine measurement and ATN scoring. Unexpectedly, intravenous pretreatment of mice with apoptotic thymocytes conferred no protection. Indeed, apoptotic thymocytes further impaired renal function depending upon injury severity. Impairment of renal function was not secondary to increased microvascular congestion, inferred by fibrin and platelet deposition, neither increased ATN nor inflammation, assessed by neutrophil infiltration. These data indicate that apoptotic cell administration does not protect from subsequent renal IRI and that apoptotic cells are thus not inherently anti-inflammatory in all models of acute inflammation. Unable to replicate apoptotic cell derived functional protection we explored the binding of IgM antibodies to apoptotic cells which acts to facilitate dead cell clearance. We characterised IgM binding to non-apoptotic and apoptotic murine thymocytes and human Jurkat cells using flow cytometry, confocal and electron microscopy. We demonstrated specific IgM binding to a subset of late apoptotic cells. Electron microscopy indicated that IgM+ apoptotic cells exhibited marked plasma membrane disruption, suggesting that access to intracellular epitopes was required for IgM binding. Binding of IgM to permeabilised non-apoptotic and apoptotic cells suggested that IgM bound epitopes are ‘apoptosis independent’ such that IgM may bind any cell with profound plasma membrane disruption. Interestingly, permeabilised erythrocytes exhibited significant IgM binding thus supporting the importance of cell membrane epitopes. These data suggest that IgM may recognise and tag damaged nucleated cells or erythrocytes that exhibit significant cell membrane disruption.
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Ghouma, S. M. « An investigation of the function of human IgM and IgG antibodies recognizing P. falciparum erythrocyte membrane protein 1 (PfEMP1) ». Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3022830/.
Texte intégral
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Salgado, Rafael Moysés. « Avaliação do papel do soro imune de camundongos CD28KO (deficiente em IgG especifica) na interação in vivo e in vitro do T. cruzi Sylvio X10/4 com células da linhagem macrofágica ». Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-11072014-135353/.
Texte intégralRésumé :
As células da linhagem macrofágica são fundamentais na infecção por T. cruzi. Além do reconhecimento por PRRs, a interação com anticorpos e/ou complemento facilita a internalização. Avaliamos o papel in vivo e in vitro de IgM e IgG específicas na saída de parasitas Sylvio X10/4 do sangue, um clone miotrópico de T. cruzi que causa infecção sem parasitemia patente. Devido à sua saída espontânea, estudamos a remoção no sexto dia de infecção, momento em que a parasitemia subpatente aumenta. Camundongos foram infectados e tratados com soro normal (NMS), soro crônico (B6) e soro de animais CD28KO crônicos (que produzem somente IgM). O grupo tratado com soro de CD28KO apresentou uma remoção significativa, porém menos eficiente do que com soro crônico (B6). Tais resultados foram reproduzidos em estudo in vitro na invasão de macrófagos (derivados de medula óssea ou do peritônio) com os distintos tratamentos. Concluímos que os macrófagos são fundamentais na remoção dos parasitas e os anticorpos, não somente IgG, mas também os da classe IgM reforçam este processo.The cells of the macrophage lineage are essential for the infection by T. cruzi. Besides the recognition by PRRs, interaction with antibodies and/or complement facilitates internalization. We evaluated the role in vivo and in vitro of specific IgM and IgG in the blood output of parasites Sylvio X10/4, clone myotropic of T. cruzi which causes infection without patent parasitemia. Due to its spontaneous exit, we studied the removal on the sixth day of infection, when the parasitemia subpatent increases. Mice were infected and treated with normal mouse serum (NMS), chronic serum (B6) and serum from CD28KO chronic mice (which produce only IgM). The group treated with CD28KO serum showed a significant removal, but less efficiently than with chronic serum (B6). These results were reproduced in vitro study on the invasion of macrophages (derived from bone marrow or peritoneum) with these different treatments. We conclude that macrophages are essential in the removal of parasites and antibodies, not only IgG, but also IgM enhance this process.
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Voakes, Christy L. « Comparative analysis of serologic assays for the detection of antibodies to eastern equine encephalomyelitis virus in sentinel chickens ». [Tampa, Fla.] : University of South Florida, 2004. http://purl.fcla.edu/fcla/etd/SFE0000268.
Texte intégral
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Elfaitouri, Amal. « Development of Real-Time PCR Based Methods for Detection of Viruses and Virus Antibodies ». Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7320.
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Haller, Logan C. « Development of a micropshere-based immunoassay for the detection of IgM antibodies to West Nile virus and St. Louis Encephalitis virus in sentinel chicken sera ». [Tampa, Fla] : University of South Florida, 2006. http://purl.fcla.edu/usf/dc/et/SFE0001505.
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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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Sá, Maria Joana Giraldes Pereira Côrte-Real Corrêa de. « Natural IgM secretion in health and disease : genetic control and role in type 1 diabetes ». Doctoral thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2012. http://hdl.handle.net/10400.5/4232.
Texte intégralRésumé :
Tese de Doutoramento em Ciências Veterinárias, especialidade de Ciências Biológicas e BiomédicasGermline-encoded autoreactive natural antibodies (NAbs) of the IgM isotype are secreted and circulate as a result of basal immune system stimulation, and constitute an important first line of defense against microorganism invasion, bridging the innate and the adaptive immune responses. NAbs are mostly secreted by positively selected B1a cells, and have been claimed to have a protective role against autoimmunity. Nevertheless, NAbs binding to cell surface self-antigens could have implications in the initiation of autoimmunity. Article I focused on the genetic control of NAbs secretion in healthy mice. Importantly, interferon regulatory factor 4 (Irf4), a transcription factor required for plasma cell differentiation and antibody secretion, was identified as the most probable candidate for the control of homeostatic serum IgM levels in the mouse. Type 1 diabetes (T1D) is a complex autoimmune disease that develops spontaneously in humans and is pathogenically similar in the non-obese-diabetic (NOD) mouse model. B cells are necessary in the NOD diabetogenic process, and the presence of anti-pancreatic beta cell antibodies is the earliest manifestation of T1D. Article II revealed that NOD peritoneal cavity B1a cells are more prone to spontaneously secrete NAbs that recognize pancreatic beta cell autoantigens, which could promote T1D either by enhancing professional antigen presentation of islet antigens, by activating the complement cascade or by directly promoting beta cell damage and self-antigens release. The studies reported in article III have explored these possibilities and have proven that NAbs of NOD B1a cells origin could bind and directly induce oxidative stress on pancreatic beta cells. Moreover, these studies have shown that NOD B1a cells have a lower threshold for innate-like stimulation and have established a link between NOD B1a cells properties, NAbs specificities and impact of IgM binding on beta cells physiology. Finally, article IV provides evidence that early treatment with antibodies that evoke NOD B1a cells proliferation and differentiation into IgM secreting cells correlates with T1D precipitation. In conclusion, this thesis has shown that Irf4 is a critical player in the genetic network that controls IgM secretion in healthy individuals, and that in the NOD mouse model of T1D, a lower threshold for innate like stimulation of peritoneal cavity B1a cells contributes to a naturally increased state of B1a cells activation and autoreactive IgM secretion, determining the initiation and/or contributing to the fueling of beta cells autoimmunity.
RESUMO Secreção de IgM natural na saúde e na doença: controlo genético e papel na diabetes tipo 1 - Os autoanticorpos naturais (NAbs) da classe IgM existem no organismo na ausência de imunização e constituem uma primeira linha de defesa fundamental contra infecções. Os NAbs são secretados maioritariamente por células B1a e a sua ligação a autoantigénios na superfície celular pode ter implicações para a iniciação de autoimunidade. O trabalho descrito no artigo I focou-se na compreensão do controlo genético da secreção de NAbs em murganhos saudáveis. Este estudo identificou o interferon regulatory factor 4 (Irf4), um factor de transcrição necessário para a diferenciação de plasmócitos e secreção de anticorpos, como o candidato mais provável para o controlo da homeostasia dos níveis de IgM circulante no murganho. A diabetes tipo 1 (T1D) é uma doença autoimune complexa que se desenvolve espontaneamente nos humanos e que tem uma patogenia semelhante no murganho NOD (non-obese-diabetic). Os linfócitos B são necessários para o processo diabético do NOD, em que a presença de anticorpos anti-células beta pancreáticas é uma das manifestações mais precoces. O artigo II revelou que as células B1a da cavidade peritoneal do NOD têm uma elevada predisposição para secretarem NAbs que reconhecem autoantigénios de células beta pancreáticas e que podem promover o desenvolvimento de T1D quer pelo aumento da apresentação de autoantigénios, quer pela activação da cascata do sistema de complemento, quer pela indução directa de danos nas células beta pancreáticas. A investigação descrita no artigo III provou que os NAbs secretados por células B1a do NOD têm a capacidade de se ligarem e induzirem stress oxidativo nas células beta do pâncreas. Estes estudos revelaram ainda que as células B1a do NOD têm um limiar reduzido para activação inata e estabeleceram uma relação entre as propriedades das células B1a do NOD, as especificidades dos NAbs e o impacto da ligação de IgM na fisiologia das células beta. Finalmente, o artigo IV evidenciou que a indução de proliferação e diferenciação das células B1a em células secretoras de IgM contribui para o início da T1D. Esta tese demonstrou que o Irf4 é um factor de transcrição com um papel fundamental no controlo da secreção de IgM em animais saudáveis e que, no murganho NOD, as células B1a da cavidade peritoneal têm um menor limiar para estimulação inata, que contribui para o seu estado de activação e para a secreção de IgM autoreactiva, determinando a iniciação e/ou contribuindo para a progressão da diabetes tipo 1.
Fundação para a Ciência e Tecnologia; Instituto Gulbenkian da Ciência
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Koga, Rosemary de Carvalho Rocha. « ASPECTOS CLÍNICOS E SOROLÓGICOS DE INDIVÍDUOS COM SINAIS E SINTOMAS DE FEBRE CHIKUNGUNYA ». Pontifícia Universidade Católica de Goiás, 2017. http://tede2.pucgoias.edu.br:8080/handle/tede/3664.
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Introduction: Chikungunya fever (FCHIK) is a disease of abrupt onset, transmitted by arthropod mosquitoes intermediate hosts of the Chikungunya virus (CHIKV). The illness has a significant impact on the quality of life of the affected person. Since a disease causes intense and prolonged symptoms of polyarthralgia and myalgia, it requires health care, during a recovery, more than other arboviruses. The objective of this study was to study clinicians and clinicians suggestive of FCHIK, residing in the States of Amapá and Goiás, aiming to correlate the results of laboratory tests with the presented symptomatology. Materials and methods: The study was carried out at the Center for Immunological Studies and Research of the Pontifical Catholic University of Goiás, Goiânia, and in Emergency Care Units in the cities of Macapá, Oiapoque and Santana-AP. The study population consisted of 80 individuals with suspected FCHIK and for investigators of inflammatory markers, the control group consisted of 20 blood samples from healthy donors from Goiana Central de Serologia e Imunohematologia. Viral RNA extraction was performed, followed by RNA detection by Real-Time Polymerase Chain Reaction. In addition to ELISA for detection of IgM and IgG against Chikungunya virus. Participants symptoms were correlated with serology and Creactive protein (CRP), which was evaluated in healthy subjects and in people with FCHIK. Results: No data presented for detection of viral RNA by RT-qPCR for CHIKV, but three samples were positive in this technique for zika virus and one for dengue subtype 1 (DENV1). In an enzyme-linked immunosorbent assay, 26 samples were positive for IgG and 3 for IgM. Regarding the stage of the disease, 10 were in the acute phase, 04 in the subacute phase and 12 in the chronic phase. Correlated the results of the serology with a symptomatology it was observed that the acute phase, all have fever, 90% headache, 70% arthralgia and 60% edema. (100%), myalgia and edema (75%). (100%), arthralgia (92%) and myalgia (75%). When comparing participants with negative serology, n = 54, the most prevalent symptoms were rash, headache, fever, and arthralgia. The CRP levels in individuals infected with more than four symptoms were higher when compared with healthy individuals. Conclusion: The study focused on people with a clinical picture characteristic of FCHIK. The most common symptom in the three phases presented for arthralgia, followed by edema and myalgia, a fever was frequent only in the acute phase. All participants were negative in the evaluation of viral RNA by RT-qPCR for CHIKV, for the virus has a short duration in the body, and this methodology is limited to the time of symptom onset and sample collection, DENV and ZIKV. IG G. Those with negative serology for CHIKV, despite taking into account the joints, symptoms common to other arboviruses. CRP levels have been shown to be high relative to healthy subjects.
Introdução: A Febre Chikungunya (FCHIK) é uma doença de início abrupto, transmitida por mosquitos artrópodes hospedeiros intermediários do vírus Chikungunya (CHIKV). A enfermidade representa um significativo impacto na qualidade de vida da pessoa afetada. Uma vez que a doença causa sintomas intensos e prolongados de poliartralgia e mialgia, requerendo atenção de saúde, durante a recuperação, mais do que outras arboviroses. Objetivou-se estudar aspectos clínicos e sorológicos de indivíduos apresentando quadro clínico sugestivo de FCHIK, residentes nos Estados de Amapá e Goiás, visando correlacionar os resultados de testes laboratoriais com a sintomatologia apresentada. Materiais e métodos: O estudo foi realizado no Núcleo de Estudos e Pesquisa Imunológica da Pontifícia Universidade Católica de Goiás, em Goiânia, e em Unidades de Pronto Atendimento de Saúde das cidades de Macapá, Oiapoque e Santana-AP. A população de estudo foi constituída de 80 indivíduos com suspeita de FCHIK e para comparar os marcadores inflamatórios, o grupo controle foi constituído de 20 amostras de sangue de doadores saudáveis da Central Goiana de Sorologia e Imunohematologia. Foi realizada a extração do RNA viral, seguido de detecção do RNA por meio de Reação em Cadeia de Polimerase em Tempo Real. Além de ELISA para detecção de IgM e IgG específicos para o CHIKV. Os sintomas dos participantes foram correlacionados com o resultado da sorologia e da proteína C reativa (PCR), que foi avaliada em indivíduos saudáveis e em pessoas com FCHIK. Resultados: Nenhuma amostra apresentou limiar de detecção do RNA viral por RT-qPCR para CHIKV, porém três amostras foram positivas nessa técnica para vírus zika (ZIKV) e uma para dengue subtipo 1 (DENV1). Em ensaio imunoenzimático, 26 amostras foram positivas para IgG e 3 dessas para IgM. Em relação ao estágio da doença, 10 encontravam-se em fase aguda, 04 em fase subaguda e 12 em fase crônica. Correlacionados os resultados da sorologia com a sintomatologia observou-se que os de fase aguda, todos tiveram febre, 90% cefaleia, 70% artralgia e 60% edema. Enquanto que, os de fase subaguda tiveram: artralgia e cefaleia (100%), mialgia e edema (75%). Os de fase crônica tiveram edema (100%), artralgia (92%) e mialgia (75%). Quando comparados os participantes com sorologia negativa, n=54, os sintomas mais apresentados foram exantema, cefaleia, febre e artralgia. Os níveis de PCR nos indivíduos infectados e que apresentavam mais de quatro sintomas foram maiores quando comparados com indivíduos saudáveis. Conclusão: O estudo focou em pessoas com quadro clínico característico para FCHIK. O sintoma mais comum nas três fases apresentadas foi a artralgia, seguido de edema e mialgia, a febre foi frequente somente na fase aguda. Todos os participantes foram negativos na avaliação do RNA viral por RT-qPCR para CHIKV, pois o vírus tem uma curta duração no organismo, e esta metodologia é limitada ao tempo de início dos sintomas e coleta de amostra, ainda assim foi encontrado RNA viral do DENV e ZIKV. Alguns participantes foram positivos para sorologia IgG. Aqueles com sorologia negativa para CHIKV, apesar de terem dor nas articulações, tinham sintomas comuns a outras arboviroses. Os níveis de PCR demonstraram-se elevados em relação aos indivíduos saudáveis.
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Champy-Tixier, Anne-Sophie. « Extraction, purification, and structurala nalysis of glycosylated natural products, mimetics of native antigens involved in an immune response ». Thesis, Bourgogne Franche-Comté, 2018. http://www.theses.fr/2018UBFCE003/document.
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Cette these en cotutelle entre le Laboratoire Peptlab de l’Université de Florence en Italie et le Laboratoire de Pharmacognosie de l’Université de Bourgogne Franche-Comté en France, porte sur l’extraction, la purification et l’élucidation structurale de saponines d’origine végétale en tant que mimétiques d’antigènes impliqués dans une réponse immunitaire. L’étude phytochimique de cinq espèces végétales appartenant à trois familles différentes, Fabaceae : Wisteria frustecens, Wisteria floribunda “macrobotrys”, Wisteria floribunda “rosea”, Caprifoliaceae : Weigela florida “rumba” et Polygalaceae : Polygala acicularis, a conduit à l’isolement de seize glycosides triterpéniques naturels parmi lesquelles six sont de structure nouvelle, une a été isolée sous sa forme native pour la première fois, et neuf déjà répertoriées dans la littérature. Les composés ont été isolés grâce à l’utilisation de différentes méthodes chromatographiques. Leurs structures ont été élucidées en utilisant principalement la RMN 2D et la spectrométrie de masse. Parmis ces seize molécules, six ont été sélectionnées pour être testées en tant que mimétiques d’antigènes impliqués dans une réponse immunitaire. De plus, un flavonoïde glycosylé extrait de Sophora japonica et un acide triterpénique commercial, l’acide ursolique, ont eux aussi été choisis comme mimétiques d’antigènes. Des tests immunochimiques (ELISA) ont été réalisés afin d’évaluer leur potentiel en tant que mimétiques d’antigènes dans le sang de patients atteints de sclérose en plaque ou du syndrome de Rett. Le taux IgM dans le sérum des patients atteints de sclérose en plaque ou du syndrome de Rett a été mesuré et comparé à celui de donneurs sains. Concernant la sclérose en plaque, les résultats sont peu significatifs concernant le potentiel des saponines en tant que mimétiques d’antigènes. Mais dans le cas du syndrome de Rett des résultats intéressants et surprenants ont été obtenus. En effet, l’hypothèse de départ était l’implication de la partie glycosylée dans la reconnaissance d’autoanticorps. Pour le syndrome de Rett, l’acide ursolique, qui est un aglycone, démontre une grande efficacité dans la reconnaissance d’IgM. Par contre, un triterpène glycosylé démontre lui aussi une efficacité semblable. Les résultats obtenus sont donc à analyser afin d’établir des relations structure/activité fiablesThis PhD in co-direction between the Peptlab Laboratory of the University of Firenze (Italy) and the Laboratory of Pharmacognosy of the University of Bourgogne Franche-Comté (France), deals with extraction, purification and structural elucidation of saponins from plants as mimetic antigens involved in an immune response. The phytochemical study of five species from three different families, Wisteria frustecens, Wisteria floribunda “macrobotrys” and Wisteria floribunda “rosea” from Fabaceae, Weigela florida “rumba” from Caprifoliaceae, and Polygala acicularis from Polygalaceae, allowed us to isolate sixteen natural glycosides: six with new structures, one analyzed for the first time in its native form, and nine which have been already described in the literature. These compounds were isolated using various chromatographic methods, and their structures were elucidated using mainly 2D NMR and mass spectrometry. From the isolated glycosides, six were selected and tested as mimetics of native antigens involved in the immune response. Moreover, one flavonoid glycoside extracted from Sophora japonica, and one commercial triterpenic acid, ursolic acid, were also chosen as mimetics of native antigens. Immunoenzymatic assays (ELISA) were performed for each compound to evaluate their potential as mimetics of native antigens of multiple sclerosis and Rett syndrome. The IgM levels in sera of patients affected by multiple sclerosis and Rett syndrome were measured and compared to normal blood donors. Concerning multiple sclerosis, no significant results were obtained for saponins, but in the case of Rett syndrome, interesting and surprising results were obtained. Indeed, the first hypothesis was that the glycosyl part of the molecule could be relevant for antibody recognition. In the case of Rett syndrome ursolic acid, an aglycone without any glycosidic part, demonstrated a good efficiency in IgM recognition. On the other hand, one triterpenic glycoside showed similar results. These results were discussed to define possible structure/activity relationships
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Torres, Leuridan Cavalcante. « Avaliação da imunocompetência de portadores da síndrome de Rubinstein-taybi ». Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-01092008-192345/.
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A síndrome de Rubinstein-Taybi (RTS, OMIM 180849) é uma doença autossômica dominante caracterizada por dismorfismos craniofaciais típicos, polegares e háluces alargados, infecções respiratórias recidivantes, retardo mental e de crescimento. RTS está associada com mutação no gene CREBBP. Na avaliação da imunocompetência de 17 portadores de RTS, observaram-se algumas alterações na resposta imune inata e adaptativa: leucocitose persistente, neutrófilos com desgranulopoiese, elevada concentração sérica de IgM e IgG1, produção normal de anticorpos contra antígenos protéicos e anti-polissacarídeos, elevados valores absolutos de células B totais, B \"naive\", B de memória, subpopulação B1 e de linfócitos B com IgM de membrana, e elevado percentual de apoptose de linfócitos B. DTH negativo para três antígenos e baixa resposta linfoproliferativa para antígenos protéicos. Diante do exposto, concluímos que os pacientes RTS apresentam alterações em vários mecanismos da resposta imune e principalmente, na imunidade humoral. Portanto, com este trabalho foi possível identificar as principais alterações imunológicas destes pacientes, e com isso, caracterizar quais os defeitos da resposta imune que pode estar associada com gene CREBBP.Rubinstein-Taybi syndrome (RTS, OMIM 180849) is a dominant Mendelian disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, mental retardation and growth and recurrent respiratory infections. RTS is classically associated with CREBBP gene mutations, but recently, p300 gene mutations were reported in three individuals. In imunonocompetence investigation of a group of 17 patient of the RTS, we found that the patients really show alterations in more than one arm of the immune response. The main alterations were found in: a) innate immunity, patients have defects in the distribution of the granules citoplasmatic and partial absence of F-actin filament part of its polymorphonuclear cells. In addition, some patients had decreased phagocytic activity, b) humoral immunity: elevated serum IgM antibodies and IgG1 subclass, normal production of antibodies for protein antigens and antipolysaccharide, high absolute values of B cell total, B \"naive\", B memory, subpopulation B1 and B lymphocytes with the membrane IgM, and high percentage of apoptosis of B lymphocytes; c) cellular immunity: delayed hypersensitivity skin tests negative for three antigens and low lymphoproliferative response to protein antigens. Values reduced percentage of CD45RA+ , CD45RO+ T cells and high doublepositive CD45RA+/CD45RO +) T cell. Ahead of the severe recurrent respiratory infections that affect the patients with RTS, and of the evaluation of immunocompetence of these patients, we find that they have several alterations in mechanisms of immune response and mainly in humoral immunity. Therefore, with this study was to identify the major immunological alterations of these patients, and with this, which characterize the main defects of the immune response of the patients RTS that can is associated with gene CREBBP.
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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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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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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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Sheoran, Abhineet Subhash. « Characterisation of the subisotypes of equine IgG ». Thesis, University of Cambridge, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243195.
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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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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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Lastra, German Carlos. « The role of agalactosyl IgG in rheumatoid arthritis ». Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245581.
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Longman, Emma. « Investigating the solution conformations of IgG subclass monoclonal antibodies ». Thesis, University of Nottingham, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415692.
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Rosa, Marguerita Evangelho da. « Production and purification of IgY antibodies with antimicrobial properties ». Master's thesis, Universidade de Aveiro, 2017. http://hdl.handle.net/10773/22545.
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Mestrado em Biotecnologia - Biotecnologia Industrial e AmbientalA Aquacultura tem recebido especial destaque nos últimos anos como alternativa às atividades de pesca tradicional, atualmente restritas pelos limites legais de captura. Neste sentido, têm-se desenvolvido novas técnicas de modo a aumentar o lucro e o rendimento das atividades associadas à aquacultura. No entanto, a sobre-exploração de espécies, poluição, surgimento de doenças e o aumento de microorganismos resistentes a antibióticos, surgem como consequências deste desenvolvimento. Vibrio anguillarum é uma bactéria Gram-negativa que causa infeções em peixes de sistemas de aquacultura e que origina perdas económicas significativas. Estas infeções são normalmente tratadas com recurso a agentes antimicrobianos, tais como antibióticos. No entanto, a prevalência de bactérias resistentes a estes compostos destaca a necessidade crucial de desenvolvimento de estratégias terapêuticas alternativas. O uso de anticorpos, nomeadamente a imunoglobulina Y (IgY) produzidas em aves poedeiras e purificado a partir de gemas de ovos é uma abordagem promissora para o controlo de infeções por V. anguillarum na aquacultura. O atual trabalho centrou-se no desenvolvimento de anticorpos IgY específicos contra os determinantes de virulência associados a V. anguillarum como uma estratégia antimicrobiana capaz de melhorar a produtividade dos sistemas de aquacultura. Neste são apresentados resultados da produção, purificação e caracterização de anticorpos IgY de galinha e codorniz contra antigénios (extratos celulares, frações da membrana externa e péptidos do canal TolC) de V. anguillarum. Aves hiperimunes foram produzidas com sucesso para cada antigénio e foram purificadas as respetivas frações específicas de IgY (> 95% de pureza). Por fim, estudou-se o potencial antimicrobiano dos anticorpos anti-extrato celular de V. anguillarum por ensaios de crescimento bacteriano que revelaram um efeito bacteriostático promissor com 50% de inibição. Em suma, e face aos resultados obtidos, os anticorpos podem ser usados como agentes antimicrobianos alternativos para combater e prevenir infeções por V. anguillarum em sistemas de aquacultura.
Aquaculture has received remarkable attention in recent years as an alternative to traditional fishing activities, currently restricted by fishing quotas. New techniques have therefore been developed to increase production and profit of aquaculture activities. However, over-exploitation, pollution, appearance of infectious diseases and antimicrobial resistance, have emerged as concerning consequences of such development. Vibrio anguillarum is a Gram-negative bacterium causing fish infections in aquaculture systems and leading to significant economic losses. These infections are usually treated with antibiotics; however, the prevalence of bacteria resistant to such drugs urges the development of alternative therapeutic strategies. The use of antibodies, namely avian Immunoglobulin Y (IgY) purified from bird egg yolks, is a promising approach for the control of V. anguillarum infections in aquaculture. The current work focused on the development of specific IgY antibodies against virulence determinants associated to V. anguillarum, envisaging an antimicrobial strategy capable of improving the productivity of aquaculture systems. In this work, the production, purification and characterization of chicken and quail IgY antibodies against V. anguillarum antigens are presented. Whole-cell extracts, outer-membrane fractions and outer-membrane TolC channel peptides were used as antigens in independent protocols to elicit target-specific V. anguillarum antibodies. Hyperimmune birds were successfully generated for each antigen and respective target-specific IgY fractions were purified (>95% purity) from selected bird eggs for downstream studies. Finally, the antimicrobial potential of anti-whole-cell V. anguillarum antibodies was studied by bacterial growth assays, revealing a promising bacteriostatic effect, with 50% of bacterial growth inhibition. In summary, and according to the results obtained, such antibodies can be used as alternative antimicrobial agents to prevent and combat infections by V. anguillarum in aquaculture systems.
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Joyce, Christopher Francis. « The production and functional assessment of IGA monoclonal antibodies ». Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46374.
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Ferreira, Thalita Lopes. « Avaliação da ação neutralizante e da reatividade de anticorpos IgA e IgG anti-rotavírus SA-11 em soro de adultos saudáveis ». Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-15092011-105733/.
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O rotavírus é a principal causa de diarréia em crianças em todo o mundo. Infecta também adultos, mas não há dados completos sobre a sua incidência nesse grupo nem sobre o papel de anticorpos preexistentes na proteção contra o vírus. O objetivo do trabalho foi avaliar a presença de anticorpos IgA e IgG anti-rotavírus SA-11, por ELISA, em amostras de soro de adultos saudáveis e sua ação neutralizante frente ao vírus, em ensaios de neutralização. Por Immunoblotting foi avaliado o reconhecimento de proteínas virais pelos anticorpos séricos. Observou-se que os títulos das amostras foram muito variáveis, sendo os de IgG superiores aos de IgA. Todas as amostras mostraram-se capazes de neutralizar o vírus em diferentes níveis, porém não foi possível estabelecer uma correlação com os títulos de anticorpos. Foi observado que anticorpos da classe IgG reconhecem mais proteínas virais que os da classe IgA. Este trabalho pode ser considerado mais um passo na elucidação do papel dos anticorpos séricos IgA e IgG anti-rotavírus na infecção em adultos.Rotavirus has been considered the leading cause of diarrhea in children worldwide. The virus also infects adults but there is no conclusive data neither on the incidence of infection on this group nor on the role of pre-existing antibodies. The aim of the work was to evaluate the presence of anti-rotavirus SA-11 IgA and IgG by ELISA in serum samples of healthy adults and the serum neutralizing ability against the virus by neutralization assays. Immunoblotting was used to evaluate viral proteins recognition by serum antibodies. The antibody titers were extremely variable where IgG titers are greater than IgA ones. All samples were able to neutralize the virus in different levels but it was not possible to establish a correlation between antibody titers and neutralization ones. Immunoblotting assays revealed that IgG antibodies recognize more viral proteins than IgA did. This work can be considered a valuable step for elucidating the role of serum anti-rotavirus IgG and IgA antibodies in adults infection.
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MacIntyre, Elizabeth A. « Activation of human haemopoietic cells via Fc receptors for IgG ». Thesis, University of Newcastle Upon Tyne, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241359.
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Ehrenstein, Michael Randolph. « Production and analysis of human monoclonal IgG anti-DNA antibodies ». Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309101.
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Sallam, Jamal A. « Intestinal humoral immunity in man : IgA and anti-salmonella antibodies ». Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20766.
Texte intégralRésumé :
Studies of gut immunity must be carried out on intestinal fluid and jejunal biopsies. Recent work from Edinburgh has shown that the use of Whole Gut Lavage (WGL) technique is a non-invasive, direct and reliable method of obtaining intestinal fluids. My thesis describes the use of WGL technique in a variety of studies on gastro-intestinal mucosal immunity. The effect of the newly licensed oral live typhoid vaccine Ty21a on gut immunity was investigated in a group of 22 healthy British volunteers. Later on, the intestinal immune responses to naturally acquired Salmonella infection were investigated in a group of patients who had had the infection within the preceding 12 months. Results obtained in these studies were compared with results obtained from healthy individuals, patients with inflammatory bowel disease (IBD) and African children from Sierra Leone. I investigated further the effect of heavy smoking and non-smoking in healthy volunteers on gut immunity and the effect of administration of the live oral vaccine Ty21a on the intestinal mucosal immune responses of smokers and non-smokers. I also studied agglutinating antibodies in WGL fluids and sera. Patients with a variety of GI diseases and patients who had had Salmonella infection were tested against a panel of 11 Salmonella antigens using a modified Widal test in microtitration plates. In the course of the above studies, I found that there were patients who had very low or absent intestinal IgA but had normal levels of IgA in the serum. Therefore, I investigated further this phenomenon by counting plasma cells in the lamina propria of intestinal biopsies from patients with "intestinal IgA deficiency" and normal controls using image analysis.
29
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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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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Dahlbom, Ingrid. « The Significance of IgG Antibodies against Tissue Transglutaminase in Coeliac Disease ». Doctoral thesis, Uppsala University, Department of Genetics and Pathology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8424.
Texte intégralRésumé :
Coeliac disease (CD) is a multifactorial disease of the small intestine. In genetically predisposed individuals the, ingestion of cereals leads to a remodulation of the mucosal architecture, and the production of autoantibodies against tissue transglutaminase (tTG). The treatment is a lifelong gluten-free diet.
The diagnostic procedure relies on the examination of a small-bowel biopsy that displays villous atrophy. A spectrum of clinical manifestations is associated with CD, ranging from overt enteropathy to atypical and silent symptoms. Approximately 1% of the general population has CD, and the majority is undiagnosed. Although most patients with active CD can be detected by the assessment of elevated IgA-tTG, some patients lack these antibodies. Moreover, individuals with IgA-deficiency cannot be identified by means of IgA serology.
The aim of this thesis was to investigate the clinical utility of IgG-tTG for the detection and follow-up of subjects with active CD. The included studies showed that IgG-tTG was highly prevalent in IgA-deficient and IgA-competent patients with CD, whereas non-CD patients rarely had these antibodies. During a gluten-free diet, IgG-tTG decreased, demonstrating that IgG-tTG can be used to follow the patient’s adherence such a diet. Furthermore, 10% of healthy IgA deficient blood donors had elevated IgG-tTG, indicating that they had silent CD.
In IgA-competent subjects, high IgG-tTG levels correlated with a severe mode of CD and profound mucosal deterioration, suggesting that IgG-tTG might be involved in the disease progression. Moreover, we found that although a considerable percentage of IgA-competent patients lack IgG-tTG, the presence of these antibodies in conjunction with high levels of IgA-tTG was highly predictive of a severe small-intestine villous atrophy. It was also demonstrated that IgG-tTG normalisation coincided with clinical remission in IgA-competent CD patients on a gluten-free diet.
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Epp, Alexandra [Verfasser]. « Murine sialylated IgG1 antibodies prevent IgG-dependent allergic reactions / Alexandra Epp ». Lübeck : Zentrale Hochschulbibliothek Lübeck, 2017. http://d-nb.info/1137537140/34.
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Yannakis, John. « Development of IgY antibodies in egg yolk against ß-casomorphin-7 ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq21227.pdf.
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Mietzner, Brun Henning. « IgG memory B cell antibodies in patients with systemic lupus erythematosus ». Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2009. http://dx.doi.org/10.18452/16078.
Texte intégralRésumé :
Die beständige Autoantikörperproduktion in Patienten mit Systemischem Lupus Erythematodes (SLE) suggeriert die Existenz eines autoreaktiven humoralen Gedächtnisses; die Häufigkeit selbstreaktiver Gedächtnis-B-Zellen in SLE wurde jedoch noch nicht ermittelt. Unter normalen Umständen exprimieren neu gebildete B-Zellen im Knochenmark Autoantikörper mit hoher Frequenz, darunter auch antinukleäre Antikörper. Diese autoreaktiven B Zellen unterliegen einer strengen Überwachung an zwei Kontrollpunkten für Selbsttoleranz, einer im Knochenmark und einer in der Peripherie. Im Gegensatz dazu steht SLE mit einem Defekt in Zusammenhang, der die Etablierung von B-Zell-Toleranz an diesen beiden Kontrollpunkten verhindert und somit einer hohe Anzahl selbstreaktiver naiver B-Zellen in der Peripherie. Das Ziel dieser Studie war die Bestimmung der molekularen Eigenschaften und Reaktivitäten von IgG Gedächtnis-B-Zell-Antikörpern in SLE. Mittels einer Einzelzell-PCR basierten Methode wurden 200 monoklonale Antikörper von einzelnen IgG+ Gedächtnis-B-Zellen vier unbehandelter SLE Patienten kloniert. Die generelle Häufigkeit an polyreaktiven und HEp-2 selbstreaktiven Antikörpern in dieser Population war vergleichbar mit der in gesunden Vergleichspersonen. 15% der Antikörper aus IgG+ Gedächtnis-B-Zellen eines Patienten mit Serum-Autoantikörpertitern derselben Spezifität waren hochreaktiv und spezifisch gegen die SLE-assoziierten löslichen Kernantigene Ro52 und La; nicht jedoch in den übrigen drei Patienten oder gesunden Vergleichspersonen. Die Keimbahnkonfigurationen dieser Antikörper gegen Kernantigen waren nicht-selbstreaktiv oder polyreaktiv mit schwacher Ro52-Bindung und untermauern die Theorie, dass somatische Mutationen zur Reaktivität und Spezifität von Autoantikörpern beitragen. Die Häufigkeitsvarianz, mit der Gedächtnis-B-Zellen SLE-assoziierte Antikörper exprimieren, legt nahe, dass dies eine wichtig Variable für den Erfolg von Therapien sein kann, die diese Population beseitigen.Persistent autoantibody production in patients with systemic lupus erythematosus (SLE) suggests the existence of autoreactive humoral immunological memory, but the frequency of self-reactive memory B cells in SLE has not been determined. Under normal circumstances, autoantibodies including antinuclear antibodies (ANAs) are frequently expressed by newly generated B cells in the bone marrow, but these autoreactive B cells are tightly regulated at two checkpoints for self-tolerance, in the bone marrow and the periphery, before maturation into naïve immunocompetent B cells. In contrast, SLE is associated with a failure to establish B cell tolerance at the two checkpoints leading to high numbers of autoreactive naïve B cells in the periphery. The aim of this study was to determine the molecular features and reactivities of IgG memory B cell antibodies expressed in SLE. A single-cell PCR based strategy was applied that allowed the cloning of the Ig heavy and Ig light chain genes of a single purified B cell and the in vitro expression of 200 recombinant monoclonal antibod-ies from single IgG+ memory B cells of four untreated SLE patients. The overall frequency of polyreactive and HEp-2 self-reactive antibodies in this compartment was similar to healthy controls (HC). 15% of IgG memory B cell antibodies were highly reactive and specific for SLE-associated extractable nuclear antigens (ENAs) Ro52 and La in one patient with serum autoantibody titers of the same specificity but not in the other three patients or healthy individuals. The germline forms of the ENA antibodies were non-self-reactive or polyreactive with low binding to Ro52 supporting the idea that somatic mutations contribute to autoantibody specificity and reactivity. Heterogeneity in the frequency of memory B cells expressing SLE-associated autoantibodies suggests that this variable may be important in the outcome of therapies that ablate this compartment.
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Xu, Hui. « Modulation of B cell access to antigen by passively administered antibodies : an explanation for antibody feedback regulation ? » Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-302780.
Texte intégralRésumé :
Antibody responses can be up- or down-regulated by passive administration of specific antibody together with antigen. Depending on the structure of the antigen and the antibody isotype, responses can be completely suppressed or enhanced up to a 1000-fold of what is seen in animals immunized with antigen alone. IgG suppresses primary antibody responses against erythrocytes. Suppression works well in mice lacking Fc-receptors for IgG, C1q, C3, or complement receptor 1 and 2 (CR1/2). Here, we demonstrate that IgG anti-NP given to mice together with NP-conjugated sheep erythrocytes, suppresses the generation of NP-specific extra-follicular antibody-secreting cells, NP-specific germinal center B cells, induction of memory and long-lived plasma cells. IgG increases antigen clearance but this does not explain the suppressed antibody response. It is demonstrated that IgG-mediated suppression of IgG responses is epitope specific, suggesting that epitope masking is the dominant explanation for IgG-mediated suppression of antibody responses. Both IgE and IgG3 can enhance antibody responses against soluble antigens. IgE-antigen complexes bind to recirculating B cells expressing CD23, an Fc-receptor for IgE. Thirty minutes after intravenous administration, IgE-antigen is found in splenic follicles. Subsequently, germinal center responses, antigen-specific T cell proliferation, and antibody responses are enhanced. We show that also antigen conjugated to anti-CD23 can bind to CD23+ B cells and be transported to splenic follicles. CD11+ spleen cells, rather than CD23+ B cells, present IgE-antigen complexes to T cells. Here, it is demonstrated that CD8α− conventional dendritic cells is the CD11c+ cell population presenting IgE-antigen to T cells. IgG3-mediated enhancement is dependent on CR1/2. We find that IgG3-antigen complexes, administered intravenously to mice, bind to marginal zone B cells via CR1/2. These cells then transport IgG3-antigen into splenic follicles and deposit antigen onto follicular dendritic cells. Mice treated with FTY720, a drug which dislocates marginal zone B cells from the marginal zone, impairs this transport. Studies in bone marrow chimeric mice show that CR1/2 on both B cells and follicular dendritic cells are crucial for IgG3-mediated enhancement. In summary, these observations suggest that antibodies can feedback regulate antibody responses by modulating the access of antigen to the immune system.
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Rosek, Alyssa. « Expression of Epstein-Barr virus proteins and their detection by IgG antibodies ». OpenSIUC, 2018. https://opensiuc.lib.siu.edu/theses/2460.
Texte intégralRésumé :
Epstein-Barr virus, or EBV, is a human herpesvirus that is nearly universally present in most of the human population. The infection rate in adults is quickly approaching an astonishing 95% worldwide. While the most common clinical manifestation of EBV infection is infectious mononucleosis, there are multiple malignancies strongly associated with the virus, such as nasopharyngeal carcinoma (NPC). A contemporary problem in public health is the scarcity of markers to predict the development of EBV-associated malignancies, which prevents a possible cure or a suitable treatment. Of the approximately 85 proteins that the virus expresses, EBV serological tests rely on detection of antibodies against only three antigens: BFRF3 (viral capsid antigen or VCA), BMRF1 (early antigen or EA), and BKRF1 (nuclear antigen or NA). Antibodies against two of these antigens, VCA and NA, are produced by almost all EBV carriers for their entire lifetime, and so detection of these antibodies can make it difficult to differentiate between non-cancerous EBV carriers and EBV-associated cancer patients. To address this problem, the project aimed to identify a set of markers to diagnose NPC and treat it. To test this, 3 EBV genes were cloned with a 3X FLAG-tag into a mammalian expression vector, then expressed and detected by immunoblotting with a monoclonal FLAG antibody and each of the 9 human serum samples used in this study. Our results were generally inconclusive, and further studies are warranted to explore possible diagnostic and prognostic biomarkers.
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Mills, Ross Jack. « Autoantibodies in ILD : detection and association of anti-Hsp72 IgG complexes in IPF ». Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/29615.
Texte intégralRésumé :
Background Idiopathic pulmonary fibrosis (IPF) is one of a number of interstitial lung diseases (ILDs) that result in extensive and chronic pulmonary fibrosis. In IPF pathology, immunological dysfunction has been identified as a contributing factor to the ongoing fibrotic process, implicating cells and mechanisms of both the innate and humoral immune response. Due to the complex and diverse range of cells and mediators involved in IPF, the pathology is still poorly understood. Evidence of complement activation through the classical pathway in IPF lungs implies a role for IgG in the pathology. The active IgG in IPF may be autoreactive in nature, as IgG that target antigens of alveolar epithelial cells have been. Two autoantibodies in IPF, anti-periplakin IgG and anti-Hsp72 IgG, have been associated with poorer prognoses in IPF patients. The association of anti-Hsp72 IgG with IPF patient outcomes has not been validated and little work has been done to study the underlying mechanisms of autoantibodies in IPF pathogenesis. Hypothesis Anti-Hsp72 IgG is associated with poorer outcomes in IPF, and may induce alveolar macrophages to exhibit a pro-fibrotic phenotype. Aims The aims were to: Optimise an ELISA for anti-Hsp72 IgG detection and determine any association of anti-Hsp72 IgG with IPF patient outcomes Determine the location of anti-Hsp72 IgG producing cells and detect if Hsp72-IgG complexes are present in IPF patients’ lungs Explore a potential underlying pro-fibrotic mechanism through which anti-Hps72 IgG modulates macrophage function. Results The presence of anti-Hsp72 IgG was determined in ILD patient and healthy control bronchoalveolar lavage fluid (BALf) and serum. A novel anti-Hsp72 IgG ELISA was developed and optimised and then compared against a commercial anti-Hsp72 IgGAM ELISA which became available during the PhD. Progression in IPF was defined by a decrease of ≥10% vital capacity (VC) over twelve months. Serum anti-Hsp72 IgG(AM) did not associate with changes in VC over 12 months. In contrast, BALf anti-Hsp72 IgG(AM) concentrations were elevated in IPF non-progressors. Patients with high BALf anti-Hsp72 IgGAM, had improved survival compared patient with low anti-Hsp72 IgGAM (adjusted HR 0.39, 95% CI 0.16-0.92; p=0.032) In contrast there was no association between anti-Hsp72 IgG and survival. Detection of anti-Hsp72 IgG subtypes in the serum and BALf of IPF patients revealed no significant difference in anti-Hsp72 IgG subtype detection levels between progressors and non-progressors. BALf anti-Hsp72 IgG1 levels were associated with a significantly lower rate of decline in VC over twelve months than patients with no detectable anti-Hsp72 IgG1. The presence of Hsp72-IgG complexes was confirmed by detection in purified IgG from IPF patient BALf. Immuno-histological detection of C4d deposition in the lungs of IPF patients coincided in areas of Hsp72 expression in alveolar epithelium. Summary These findings do not validate serum and-Hsp72 IgG as a biomarker for IPF. They support a role for anti-Hsp72 IgG in IPF, but associate with decreased rates of lung function decline and increased patient survival. Data also suggests that the decreased rate of decline may be related to specific anti-Hsp72 IgG subtype expression. The immune-histological data further suggests that anti-Hsp72 IgG may be targeting Hsp72 expressed by lung epithelium. Therefore these findings support a role for immunological dysfunction in IPF, but further work is required to determine the underlying mechanism.
38
Baruah, Kavitha. « Structural biology of IgG Fc glycoforms ». Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:def683d3-aa06-41d9-9f28-29d21258bebe.
Texte intégralRésumé :
The conserved N-linked glycosylation site on the Fc domain of IgG1 antibodies is essential for maintaining a functionally active conformation of the antibody. Different glycoforms of the Fc exhibit widely different effector functions. Similarly, therapeutic antibodies, with engineered glycosylation, exhibit altered binding to cellular Fc receptors (FcRs). Here, X-ray crystallographic structures were obtained for biosynthetic intermediate glycoforms of human IgG1 Fc bearing: unprocessed oligomannose-type, intermediate hybrid-type, and mature complex-type glycans. The fully processed Fc protein crystallised in an “open” conformation with glycans forming canonical stabilising interactions on the protein surface. Analysis of the biosynthetic intermediates revealed that these stabilising hydrophobic protein-glycan interactions are formed only after processing by Golgi -mannosidase II. Mutagenesis of hydrophobic residues on Fc disrupted crucial protein-glycan interactions resulting in the selective destabilization of the 3-arm of the glycan chain with the 6-arm closely matching that seen for the native structure. However, carbohydrate analysis of released glycans shows increased processing on both arms indicating a more accessible and flexible glycan in the mutant structure suggesting that the crystallographic structure of these antibody glycans represents a minor low-energy conformation. The importance of Fc glycosylation is highlighted by endoglycosidases which eliminate Fc effector function. The crystallographic structure of enzymatically deglycosylated IgG Fc revealed a significant collapse of the of Cγ2 domains resulting in a ‘closed’ quaternary conformation, incompatible with Fc receptor binding. This provides a structural explanation for immune deactivating properties of endoglycosidases including those under preclinical development for the treatment of antibody-mediated immune pathology. One such bacterial endoglycosidase, Endo S, was studied further and revealed a specificity for complex-type glycans of the type found on IgG but no hydrolytic activity towards an engineered IgG Fc with oligomannose-type glycans. Introduction of both the engineered monoclonal IgG and endoglycosidase in serum led to a dramatic increase in FcR binding as the competitive binding of serum IgG for FcRs was selectively eliminated. This approach is a general technique for boosting the effector signal of therapeutic antibodies.
39
Hart, Felix Andreas Wolfgang [Verfasser]. « Elucidating the potential of IgA antibodies for cancer immunotherapy / Felix Andreas Wolfgang Hart ». Berlin : Freie Universität Berlin, 2016. http://d-nb.info/1108270905/34.
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Gao, Bin. « Studies of the IgE receptor using sequence-specific peptides, antibodies and other probes ». Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281710.
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Hoare, Jennifer Anne. « The production and evaluation of IgA monoclonal antibodies directed against Eimeria tenella sporozoites ». Thesis, University of Liverpool, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.303735.
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Siman, Isabella Lima. « Atividade bloqueadora de anticorpos IgG específicos purificados de soros de pacientes atópicos a ácaros sobre a reatividade de IgE a Dermatophagoides pteronyssinus por ELISA inibição ». Universidade Federal de Uberlândia, 2013. https://repositorio.ufu.br/handle/123456789/12772.
Texte intégralRésumé :
One of the purposes of allergen-specific immunotherapy (SIT) is to modulate the humoral
immune response against allergens with significant increases in allergen-specific IgG1 and
IgG4 levels. These antibodies are associated with blocking activity by preventing IgE binding
to allergen and leading to reduced inflammatory responses. This study aimed to investigate in
vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to D.
pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were obtained
from atopic sera and irrelevant IgG from non-atopic sera. IgG antibodies were purified by
ammonium sulfate precipitation followed by Protein-G affinity chromatography and evaluated
with regards to purity by SDS-PAGE and immunoreactivity by slot-blot and immunoblot
assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretical
profile after salting-out precipitation showed an enrichment of high molecular weight proteins
in the precipitated fraction and strongly stained bands in the ligand fraction after
chromatography, compatible with molecular weight of human IgG. It was detected strong
immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific
IgG fraction was capable to significantly reduce levels of IgE anti-Dpt, resulting in 35-51%
inhibition of IgE reactivity to Dpt in atopic patient sera. Allergen-specific IgG antibodies
purified using available and standardized methodology are able to inhibit IgE reactivity to Dpt
allergen extract. In addition to the clinical symptoms improvement (subjective parameter),
this approach reinforces that the intermittent measurement of serum allergen-specific IgG
antibodies will be an important objective laboratorial parameter that will help specialists to
follow their patients under SIT.Uma das propostas da imunoterapia alérgeno específica é a de modular a resposta imune humoral contra alérgenos, com aumento significativo nos níveis de IgG1 e IgG4 específicos. Esses anticorpos estão associados com uma atividade bloqueadora, impedindo a ligação de anticorpos IgE ao alérgeno e levando a uma redução nas respostas inflamatórias. Esse estudo objetivou investigar a atividade bloqueadora, in vitro, de anticorpos IgG específicos sobre a reatividade de IgE a D. pteronyssinus (Dpt) em soros de pacientes atópicos. Anticorpos IgG específicos foram obtidos de soros de pacientes atópicos, e IgG irrelevante a partir de soros de não atópicos, e depois purificados por precipitação com sulfato de amônio, seguido de cromatografia de afinidade em Proteina G-agarose. A pureza desses anticorpos foi avaliada por SDS-PAGE, a imunoreatividade por ensaios de slot-blot e immunoblot, e a atividade bloqueadora por ELISA inibição. O perfil eletroforético, após precipitação com sulfato de amônio, mostrou um enriquecimento de proteínas de alto peso molecular na fração precipitada,e bandas fortemente coradas na fração ligante após a cromatografia, compatíveis com o peso molecular de IgG humana. Foi detectada uma forte imunoreatividade para IgG, leve para IgA, e nenhuma reatividade para IgE e IgM. A Fração IgG específica foi capaz de reduzir significantemente os níveis de IgE anti-Dpt, resultando em 35-51% de inibição da reatividade de IgE a Dpt em pools de soros de pacientes atópicos. Anticorpos IgG específicos purificados, através de uma metodologia disponível e padronizada, são capazes de inibir a reatividade de IgE ao extrato alergênico Dpt. Além da melhoria da sintomatologia clínica, considerada um parâmetro subjetivo, essa abordagem reforça que a avaliação intermitente de anticorpos IgG alérgeno-específicos pode ser uma ferramenta importante, auxiliando especialistas a acompanharem seus pacientes em processo de imunoterapia específica.
Mestre em Ciências da Saúde
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Sandin, Anna. « Development of allergy, salivary IgA antibodies and gut microbiota in a Swedish birth cohort ». Doctoral thesis, Umeå universitet, Pediatrik, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1627.
Texte intégralRésumé :
The increasing prevalence of allergic diseases in affluent societies has been associated with changes in microbial exposure early in life and a less diverse gut flora. The objective of this thesis was to assess the development of allergic sensitisation and symptoms during the first four years of life in a non-selected birth cohort in relation to environmental factors, family history, gut microbiota and salivary IgA antibodies. The cohort comprised all 1,228 infants living in a Swedish county who were born over a one-year period. The parents replied to questionnaires, and 817 children (67 %) were skin prick tested both at 1 and 4 years of age. Saliva (n=279), faecal (n=139) and blood (n=253) samples were collected at 1 year of age from children with a positive skin prick test at 1 year and from a sample of children with a negative skin prick test. Faecal samples were also obtained from 53 children at 4 years of age. Dog keeping during infancy was associated with a decreased risk of sensitisation to pollen and late-onset wheezing at age 4, and the reduced odds ratios persisted after adjustment for heredity and avoidance measures, OR 0.3, 95% CI 0.1-0.9 and OR 0.5, 95% CI 0.2-1.0, respectively. In contrast, early dog keeping was associated with an increased risk of earlyonset transient wheezing but only in children with parental asthma (OR 2,8, 95% CI 1.3-6.4). Levels of short chain fatty acids (SCFAs) in faeces were assessed both at 1 and 4 years of age and related to the development of sensitisation and symptoms. The levels of acetic (p<.01) and propionic (p<.01) acids decreased from one to four years of age, whereas valeric acid (p<.001) increased which is in line with a more complex gut microbiota with age. Allergic children, compared with non-allergic children, had lower levels of i-butyric, i-valeric and valeric acid in faeces both at 1 and 4 years of age. Low levels of secretory IgA (SIgA) in saliva were associated with wheezing but only in sensitised children. In children with positive SPT to at least one allergen both at 1 and 4 years of age and in children with circulating IgE antibodies to egg or cat at one year of age, those who developed late-onset wheezing had lower levels of SIgA than those who did not, p=.04 and p=.02 respectively. Of 9 children with levels of SIgA in the upper quartile and persistent sensitisation, none developed wheezing, compared with 10/20 children with lower levels, (p=. 01). Having older siblings, more than three infections during infancy, at least one smoking parent and male gender were all associated with high levels (in the upper quartile) of total IgA and SIgA. The findings in this thesis indicate that the microbial load early in life could affect the development of allergy. A functional assessment of the gut flora demonstrated differences between allergic and non-allergic children both at 1 and 4 years of age. Salivary IgA was associated with infections during infancy, and high levels of secretory IgA protected from symptoms in sensitised children. Finally, dog keeping in infancy may offer protection from allergy, but the mechanism is uncertain.
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Heß, Constanze Verfasser], et Roland [Akademischer Betreuer] [Lauster. « Induction and Function of Antigen-specific Sialylated IgG Antibodies / Constanze Heß. Betreuer : Roland Lauster ». Berlin : Universitätsbibliothek der Technischen Universität Berlin, 2011. http://d-nb.info/1014756871/34.
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SILVA, SANDRA R. da. « Producao de duplo anticorpo para radioimunoensaio (Antissoro de carneiro anti-igG de coelho) ». reponame:Repositório Institucional do IPEN, 1993. http://repositorio.ipen.br:8080/xmlui/handle/123456789/10340.
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Made available in DSpace on 2014-10-09T12:37:32Z (GMT). No. of bitstreams: 0Made available in DSpace on 2014-10-09T14:03:10Z (GMT). No. of bitstreams: 1 05175.pdf: 2805276 bytes, checksum: 2afc72fc3d3ca38375a373de3e5aa8cb (MD5)
Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
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Falanga, Yves. « Role of Fyn and Lyn in IgG-mediate immune responses ». VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/2874.
Texte intégralRésumé :
Anaphylaxis is a rapid, life-threatening hypersensitivity reaction. Until recently, it was mainly attributed to histamine released by mast cells activated by allergen crosslinking (XL) of FcεRI-bound allergen-specific IgE. However, recent reports established that anaphylaxis could also be triggered by basophil, macrophage and neutrophil secretion of platelet activating factor subsequent to FcγR stimulation by IgG/Ag complexes. I have investigated the contribution of Fyn and Lyn tyrosine kinases to FcγRIIb and FcγRIII signaling in the context of IgG-mediated passive systemic anaphylaxis (PSA). I found that mast cell IgG XL induced Fyn, Lyn, Akt, Erk, p38 and JNK phosphorylation. Additionally, IgG XL of mast cells, basophils and macrophages resulted in Fyn- and Lyn-regulated mediator release in vitro. FcγR–mediated activation was enhanced in Lyn-deficient (KO) cells, but decreased in Fyn KO cells, compared to wild type cells. More importantly, Lyn KO mice displayed significantly exacerbated PSA features while no change was observed for Fyn KO mice, compared to wild type littermates. Intriguingly, this work establishes that mast cells account for the majority of serum histamine in IgG-induced PSA. Taken together, these findings establish pivotal roles for Fyn and Lyn in the regulation of PSA and highlight their unsuspected functions in IgG-mediated pathologies.
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Knevelman, C. A. « An evaluation of bioprocess development approaches for the precipitation-based purification of IgG monoclonal antibodies ». Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1334500/.
Texte intégralRésumé :
This thesis investigates bioprocess development approaches for the precipitation-based purification of IgG monoclonal antibodies (mAb) from clarified cell culture supernatant. A high throughput platform using microgram quantities of IgG was developed for the rapid identification and selection of suitable conditions for precipitation of IgG from a complex feedstock. The most effective conditions were then assessed in an ultra scale-down (USD) device run with 60 mL of material in order to characterise the precipitates in terms of their particle size distribution (PSD), morphology, strength and density with the aim of predicting likely precipitation and centrifugation separation performance upon scale-up. The influence of the physiochemical environment on precipitation was investigated and the effectiveness of the USD device in predicting laboratory scale and pilot scale performance was also evaluated. A high throughput micro-scale approach conducted in a 96 microwell plate format was developed for scouting favourable precipitation conditions. Optical measurements were used to locate suitable conditions. Turbidity was measured by absorbance at 600 nm as a rapid measure of the solids content and to monitor the progress of precipitation. Coupled with high throughput analytical techniques including Protein A HPLC and capillary SDS electrophoresis, the strategy for rapid process screening was defined. The capacity of this system to deliver rapid process understanding was then illustrated by applying it to the full factorial investigation of Polyethylene Glycol (PEG) precipitation for an IgG mAb as a function of antibody concentration, precipitant concentration and pH. Results showed that PEG concentrations required for maximum yield and purity were dependent on the IgG concentration. A window of operation was defined for all mAb concentrations tested where PEG concentrations of 12 to 20 %w/v, pH 8.0 gave desirable levels of yield and purity. The effect of reactor conditions on the IgG precipitate characteristics generated from batch precipitations at USD scale showed a marked dependence of PSD on mixing, IgG concentration, PEG concentration, and PEG addition rate. The results also showed that particle strength and density were a factor of aging time, PEG concentration and mixing intensity. Data on scale-up from USD to lab (330 mL) and pilot (7 to 8 L) scales indicated that the trends and parameters identified at USD scale were important at large scale. Scale-up based on the local energy dissipation rate of the impeller region and the ratio of circulation time to feed addition time was shown to allow accurate prediction of large scale performance from USD scale. A USD rotating shear device providing feed material to a laboratory batch centrifuge allowed successful prediction of pilot plant scale clarification performance using the equivalent settling area theory. Expectatedly, preliminary analysis of the bulk re-solubilised precipitates following the precipitation step showed that the level of impurity clearance achieved did not match the performance of traditional Protein A affinity chromatography. However, integrating the precipitation step into a generic antibody purification platform and substituting the Protein A chromatography capture step with a precipitation step demonstrated the potential of precipitation albeit purity and yield of the final purified product was lower than the process incorporating a Protein A capture step. Nevertheless, this work indicated that further development activities would be required in order to use precipitation in the biopharmaceutical manufacture of mAbs. The use of precipitation for antibody recovery could potentially reduce costs associated with downstream operations, increase plant throughput and manage large intermediate process volumes associated with high titre high volume mAb production processes. Furthermore, such a development and scale-up approach could reduce the timelines for bioprocess design and development to facilitate faster drug to clinic initiatives. In conclusion, this study has demonstrated that micro-scale and ultra scale-down evaluation methods can be used successfully to predict precipitation conditions for use at laboratory and pilot scales. Rapid development of precipitation conditions can allow this unit operation to be used for a range of recombinant proteins (including mAbs) with associated reductions in cost of manufacturing.
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Hedqvist, Camilla. « Lyophilization of specific IgY antibodies against Pseudomonas Aeruginosa used as therapy for Cystic fibrosis patients ». Thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-227236.
Texte intégralRésumé :
Pseudomonas Aeruginosa is a common gram-negative bacterium present in the environment. It causes severe infections in immunosuppressed patients. Cystic fibrosis patients are especially at risk of being infected with Pseudomonas Aeruginosa. Ongoing studies are preformed to find alternative therapies to antibiotics, due to increased resistance. One new treatment is intake of specific IgY antibodies against Pseudomonas Aeruginosa as an oral therapy. The problem today is that IgY solutions must be kept frozen until consumed. In this study we examined the possibility to freeze-dry specific IgY antibodies without losing any activity or specificity of the antibodies. This would be more convenient of patients, as well as it makes transportation and storage easier. The methods used were ELISA for control of activity, western blot analysis and SDS-PAGE gel for control of specificity. Three different batches of the IgY anti-Pseudomonas Aeruginosa solution were tested. The results showed that no loss in activity occurred that would affect clinical outcome or change of specificity in the antibodies after freeze-drying appears. This indicates that it is possible to replace the liquid antibody to a freeze-dried powder.
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Hsu, Hsing-Ho Vasha. « Prevalence Of Igg Antibodies To Encephalitozoon Cuniculi, Toxoplasma Gondii, And Sarcocystis Neurona In Domestic Cats ». Thesis, Virginia Tech, 2010. http://hdl.handle.net/10919/44421.
Texte intégralRésumé :
Encephalitozoon cuniculi, Toxoplasma gondii and Sarcocystis neurona are intracellular parasites that infect a wide range of mammalian host species including domestic cats. The prevalence of antibodies to these parasites in cats was examined using an indirect immunofluorescence antibody assay. E. cuniculi targets the kidneys of rabbits but the prevalence of disease in cats is unknown. Chronic kidney disease (CKD) is a common cause of illness in cats. T. gondii is a widespread parasite of cats; however, it is not considered a major causative agent of CKD. The first hypothesis was that E. cuniculi and T. gondii are unrecognized causes of chronic kidney disease in domestic cats. Serum and plasma samples were examined for protozoal antibodies from 232 feline patients at the VMRCVM Teaching Hospital. Thirty-six of the 232 samples met the IRIS criteria for CKD. Antibodies to E. cuniculi were found in 15 samples, 4 of which came from cats with CKD. Antibodies to T. gondii were found in 63 samples; 10 cats of the 63 had CKD. These were not significantly different from cats with no CKD and the null hypothesis was rejected.
Domestic cats, armadillos, raccoons and skunks are intermediate hosts (IH) for S. neurona while opossums are the definitive host (DH). The seroprevalence of S. neurona was examined in domestic cats from Virginia and Pennsylvania. The second hypothesis was that domestic cats are important IH for S. neurona transmission. A low seroprevalence was found in 32 of the 441 cats and the null hypothesis was rejected.Master of Science in Life Sciences
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Weinberg, Justin B. « Competitive IgG Adsorption on Protein A Chromatography Resins and Improving Resin Performance with PEGylated Ligands ». Research Showcase @ CMU, 2017. http://repository.cmu.edu/dissertations/1075.
Texte intégralRésumé :
Protein A (ProA) chromatography is a bioseparations technique employed throughout the biopharmaceutical industry for the selective capture and purification of IgG-class monoclonal antibodies (mAbs) and Fc-fusion proteins. The rapid growth of mAbs as commercial therapeutics has motivated the need for improved, efficient, and high-throughput purification processes during manufacturing. In direct response, the work presented in thesis aims to 1) increase the scientific community’s understanding of IgG adsorption behavior on ProA chromatography resins and 2) improve the performance of ProA chromatography with ligands that are chemically modified using polyethylene glycol (PEGylated). The results of this thesis suggest that IgG molecules of varying binding strength, or varying elution pH, are capable of competing for binding sites on ProA chromatography resins in simultaneous or sequential adsorption. The competitive phenomenon derives from variance in IgG binding strength, or IgG elution pH, due to differences in sub-class behavior as well as secondary IgG binding interactions with the ProA ligand. Competition is readily apparent in the adsorption of human polyclonal IgG, which has a wide variety of IgG sub-classes and binding epitopes. Additionally, the results presented in this thesis suggest that ProA chromatography resins with PEGylated ligands are a viable path to increase resin robustness and real-world chromatographic selectivity. It is demonstrated that ligand PEGylation can increase resistance to proteolytic digestion, mitigate impurity interactions with mAbs that are bound to ProA, and increase process selectivity against Chinese Hamster Ovary host cell proteins by up to 37%. However, resins with large volumes of conjugated PEG significantly decrease IgG static binding capacity and decrease the available pore space for diffusion, resulting in losses in dynamic binding capacity and productivity. Lighter modifications appear to avoid losses in dynamic binding capacity, however, they do not appear to be effective at mitigating impurity interactions with mAbs that are bound to ProA, which is key to increasing process selectivity. PEGylation of ProA also universally increases the elution pH of IgG molecules by weakening the binding interaction. This last result opens another path of viability for PEGylated ProA ligands for purification of mAbs of Fc-fusion proteins that are sensitive to low pH environments.