Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana
Ano de defesa: | 2015 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Goiás
|
Programa de Pós-Graduação: |
Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)
|
Departamento: |
Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.bc.ufg.br/tede/handle/tede/5147 |
Resumo: | Millions of people die every year due to tuberculosis (TB), an infectious disease that have effective treatment, can be prevented and is curable. One of the greatest problems faced by this disease is the latent infection (LTBI), where individuals do not manifest clinical symptoms, is a reservoir of the causing agent, Mycobacterium tuberculosis (Mtb), and can reactive the disease at any time during their life span. Moreover, TB can affect any organ in the body, such as the skin, causing extrapulmonary TB, a rare form of TB, the TB skin. Some of these forms may be more severe than pulmonary TB, causing serious consequences to the patient, contributing to the high mortality rate of this disease. In this context, understanding the immunological events related to the interaction between pathogen and host the development of active disease or latent infection is a crucial point that can contribute to the control of TB. Thus, the objectives of this study were to evaluate the specific immune response of CD8+ T cells and cytokines in cutaneous tuberculosis, latent and active pulmonary TB. Thirty six patients with pulmonary TB, one patient with cutaneous TB and 36 healthy controls, classified as LTBI (N = 13) or negative (TST-, N = 23) by the tuberculin skin test were recruited and the peripheral blood mononuclear cells, plasma and sera from those individuals were collected to perform flow cytometry, ELISA and multiplex bead array analysis. It was observed that patients with active pulmonary TB presented TCD8+ cells with a regulatory profile, expressing IL-10 and TGF-β in a direct relation to the bacillary load. The same profile was observed in the individual with cutaneous TB, an extra-pulmonary form of TB. The findings observed in this studyco nclude that Mtb can modulate CD8+ T cell response in lung and skin tuberculosis, demonstrating the importance of studies assessing the immune interaction between the pathogen and the host. |
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Junqueira-Kipnis, Ana Paulahttp://lattes.cnpq.br/1252262903952987Kipnis, Andrehttp://lattes.cnpq.br/4434965360286741Junqueira-Kipnis, Ana PaulaBocca, Anamélia LorenzettiSouza, Menira Borges de Lima Dias eFonseca, Simone Gonçalves daStefani, Mariane Martins de Araújohttp://lattes.cnpq.br/1980334089792650Silva, Bruna Daniella de Souza2016-01-28T09:49:33Z2015-02-13SILVA, Bruna Daniella de Souza. Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana. 2015. 110 f. Tese (Mestrado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2015.http://repositorio.bc.ufg.br/tede/handle/tede/5147Millions of people die every year due to tuberculosis (TB), an infectious disease that have effective treatment, can be prevented and is curable. One of the greatest problems faced by this disease is the latent infection (LTBI), where individuals do not manifest clinical symptoms, is a reservoir of the causing agent, Mycobacterium tuberculosis (Mtb), and can reactive the disease at any time during their life span. Moreover, TB can affect any organ in the body, such as the skin, causing extrapulmonary TB, a rare form of TB, the TB skin. Some of these forms may be more severe than pulmonary TB, causing serious consequences to the patient, contributing to the high mortality rate of this disease. In this context, understanding the immunological events related to the interaction between pathogen and host the development of active disease or latent infection is a crucial point that can contribute to the control of TB. Thus, the objectives of this study were to evaluate the specific immune response of CD8+ T cells and cytokines in cutaneous tuberculosis, latent and active pulmonary TB. Thirty six patients with pulmonary TB, one patient with cutaneous TB and 36 healthy controls, classified as LTBI (N = 13) or negative (TST-, N = 23) by the tuberculin skin test were recruited and the peripheral blood mononuclear cells, plasma and sera from those individuals were collected to perform flow cytometry, ELISA and multiplex bead array analysis. It was observed that patients with active pulmonary TB presented TCD8+ cells with a regulatory profile, expressing IL-10 and TGF-β in a direct relation to the bacillary load. The same profile was observed in the individual with cutaneous TB, an extra-pulmonary form of TB. The findings observed in this studyco nclude that Mtb can modulate CD8+ T cell response in lung and skin tuberculosis, demonstrating the importance of studies assessing the immune interaction between the pathogen and the host.A tuberculose (TB) é uma doença causada por Mycobacterium tuberculosis, principal agente etiológico da TB humana. Milhões de pessoas morrem todo ano em decorrência da TB, doença infecciosa que tem prevenção, tratamento e cura. Um dos maiores problemas enfrentados com essa doença é a infecção latente (TBIL), onde o indivíduo não manifesta os sintomas clínicos e constitui um reservatório da bactéria, podendo desenvolver a doença ativa em qualquer momento. Além disso, a TB pode afetar qualquer órgão do corpo, como por exemplo, a pele, causando uma forma rara de TB extrapulmonar, a TB cutânea. Algumas dessas formas podem ser mais severas que a TB pulmonar, trazendo consequências graves ao paciente, contribuindo para o alto índice de mortalidade dessa enfermidade. Nesse contexto, entender os eventos imunológicos relacionados à interação entre patógeno e o hospedeiro no desenvolvimento da doença ativa ou da infecção latente é um ponto crucial que pode contribuir para o controle da TB. Diante disso, os objetivos desse trabalho foram avaliar a resposta imune específica de células TCD8+ e citocinas na tuberculose cutânea, latente e pulmonar ativa. Para isso, foram recrutados 36 pacientes com TB pulmonar ativa, 01 paciente com TB cutânea e 36 controles sadios classificados quanto à prova tuberculínica em indivíduos com infecção latente (TBIL = 13) ou não (PT-=23). Foram obtidas, de todos os pacientes, as células mononucleares do sangue periférico, o plasma e o soro para realização dos ensaios de citometria de fluxo e ELISA. Foi observado que os pacientes com TB pulmonar ativa apresentam um perfil regulador de células TCD8+ específicas, com expressão de IL-10 e TGF-β relacionados com a carga bacilar quando comparado aos indivíduos com TBIL e controles sadios PT negativa. Esse mesmo perfil também foi observado e descrito no caso clínico do paciente com TB cutânea. Diante de todos os achados observados nesse trabalho podemos concluir que Mtb pode modular a resposta de células TCD8+ na tuberculose pulmonar e cutânea, demonstrando a importância de estudos que avaliem a interação imunológica entre o patógeno e o hospedeiro tais como este.Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-01-28T09:47:26Z No. of bitstreams: 2 Tese - Bruna Daniella de Souza Silva - 2015.pdf: 3849700 bytes, checksum: 267d28b0d91fc274ddb5bfd83ed08e5b (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-01-28T09:49:33Z (GMT) No. of bitstreams: 2 Tese - Bruna Daniella de Souza Silva - 2015.pdf: 3849700 bytes, checksum: 267d28b0d91fc274ddb5bfd83ed08e5b (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2016-01-28T09:49:33Z (GMT). No. of bitstreams: 2 Tese - Bruna Daniella de Souza Silva - 2015.pdf: 3849700 bytes, checksum: 267d28b0d91fc274ddb5bfd83ed08e5b (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2015-02-13Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttp://repositorio.bc.ufg.br/tede/retrieve/25468/Tese%20-%20Bruna%20Daniella%20de%20Souza%20Silva%20-%202015.pdf.jpgporUniversidade Federal de GoiásPrograma de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessTuberculoseCélulas TCD8+Citometria de fluxoBaciloscopiaTuberculose cutâneaTuberculosisTCD8+ cellsFlow cytometryBacillary loadCutaneous tuberculosisCIENCIAS DA SAUDE::MEDICINAAvaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humanaEvaluation of specific immune response of TCD8+ cells and cytokines in human tuberculosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis6085308344741430434600600600600-7769011444564556288-9693694523087866272075167498588264571reponame:Biblioteca Digital de Teses e Dissertações da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana |
dc.title.alternative.eng.fl_str_mv |
Evaluation of specific immune response of TCD8+ cells and cytokines in human tuberculosis |
title |
Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana |
spellingShingle |
Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana Silva, Bruna Daniella de Souza Tuberculose Células TCD8+ Citometria de fluxo Baciloscopia Tuberculose cutânea Tuberculosis TCD8+ cells Flow cytometry Bacillary load Cutaneous tuberculosis CIENCIAS DA SAUDE::MEDICINA |
title_short |
Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana |
title_full |
Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana |
title_fullStr |
Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana |
title_full_unstemmed |
Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana |
title_sort |
Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana |
author |
Silva, Bruna Daniella de Souza |
author_facet |
Silva, Bruna Daniella de Souza |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Junqueira-Kipnis, Ana Paula |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1252262903952987 |
dc.contributor.advisor-co1.fl_str_mv |
Kipnis, Andre |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/4434965360286741 |
dc.contributor.referee1.fl_str_mv |
Junqueira-Kipnis, Ana Paula |
dc.contributor.referee2.fl_str_mv |
Bocca, Anamélia Lorenzetti |
dc.contributor.referee3.fl_str_mv |
Souza, Menira Borges de Lima Dias e |
dc.contributor.referee4.fl_str_mv |
Fonseca, Simone Gonçalves da |
dc.contributor.referee5.fl_str_mv |
Stefani, Mariane Martins de Araújo |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1980334089792650 |
dc.contributor.author.fl_str_mv |
Silva, Bruna Daniella de Souza |
contributor_str_mv |
Junqueira-Kipnis, Ana Paula Kipnis, Andre Junqueira-Kipnis, Ana Paula Bocca, Anamélia Lorenzetti Souza, Menira Borges de Lima Dias e Fonseca, Simone Gonçalves da Stefani, Mariane Martins de Araújo |
dc.subject.por.fl_str_mv |
Tuberculose Células TCD8+ Citometria de fluxo Baciloscopia Tuberculose cutânea |
topic |
Tuberculose Células TCD8+ Citometria de fluxo Baciloscopia Tuberculose cutânea Tuberculosis TCD8+ cells Flow cytometry Bacillary load Cutaneous tuberculosis CIENCIAS DA SAUDE::MEDICINA |
dc.subject.eng.fl_str_mv |
Tuberculosis TCD8+ cells Flow cytometry Bacillary load Cutaneous tuberculosis |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::MEDICINA |
description |
Millions of people die every year due to tuberculosis (TB), an infectious disease that have effective treatment, can be prevented and is curable. One of the greatest problems faced by this disease is the latent infection (LTBI), where individuals do not manifest clinical symptoms, is a reservoir of the causing agent, Mycobacterium tuberculosis (Mtb), and can reactive the disease at any time during their life span. Moreover, TB can affect any organ in the body, such as the skin, causing extrapulmonary TB, a rare form of TB, the TB skin. Some of these forms may be more severe than pulmonary TB, causing serious consequences to the patient, contributing to the high mortality rate of this disease. In this context, understanding the immunological events related to the interaction between pathogen and host the development of active disease or latent infection is a crucial point that can contribute to the control of TB. Thus, the objectives of this study were to evaluate the specific immune response of CD8+ T cells and cytokines in cutaneous tuberculosis, latent and active pulmonary TB. Thirty six patients with pulmonary TB, one patient with cutaneous TB and 36 healthy controls, classified as LTBI (N = 13) or negative (TST-, N = 23) by the tuberculin skin test were recruited and the peripheral blood mononuclear cells, plasma and sera from those individuals were collected to perform flow cytometry, ELISA and multiplex bead array analysis. It was observed that patients with active pulmonary TB presented TCD8+ cells with a regulatory profile, expressing IL-10 and TGF-β in a direct relation to the bacillary load. The same profile was observed in the individual with cutaneous TB, an extra-pulmonary form of TB. The findings observed in this studyco nclude that Mtb can modulate CD8+ T cell response in lung and skin tuberculosis, demonstrating the importance of studies assessing the immune interaction between the pathogen and the host. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-02-13 |
dc.date.accessioned.fl_str_mv |
2016-01-28T09:49:33Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
SILVA, Bruna Daniella de Souza. Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana. 2015. 110 f. Tese (Mestrado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2015. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/5147 |
identifier_str_mv |
SILVA, Bruna Daniella de Souza. Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana. 2015. 110 f. Tese (Mestrado em Medicina Tropical e Saúde Pública) - Universidade Federal de Goiás, Goiânia, 2015. |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/5147 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
6085308344741430434 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 |
dc.relation.department.fl_str_mv |
-7769011444564556288 |
dc.relation.cnpq.fl_str_mv |
-969369452308786627 |
dc.relation.sponsorship.fl_str_mv |
2075167498588264571 |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
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Universidade Federal de Goiás (UFG) |
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UFG |
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UFG |
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Biblioteca Digital de Teses e Dissertações da UFG |
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Biblioteca Digital de Teses e Dissertações da UFG |
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Biblioteca Digital de Teses e Dissertações da UFG - Universidade Federal de Goiás (UFG) |
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tesesdissertacoes.bc@ufg.br ||tesesdissertacoes.bc@ufg.br |
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