Avaliação da resposta imune específica de células TCD8+ e citocinas na tuberculose humana

Detalhes bibliográficos
Ano de defesa: 2015
Autor(a) principal: Silva, Bruna Daniella de Souza lattes
Orientador(a): Junqueira-Kipnis, Ana Paula lattes
Banca de defesa: Junqueira-Kipnis, Ana Paula, Bocca, Anamélia Lorenzetti, Souza, Menira Borges de Lima Dias e, Fonseca, Simone Gonçalves da, Stefani, Mariane Martins de Araújo
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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spelling 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). 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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
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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.
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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
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collection Repositório Institucional da UFG
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http://repositorio.bc.ufg.br/tede/bitstreams/982733ac-252f-4c28-951a-12385ac0cfc5/download
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repository.name.fl_str_mv Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)
repository.mail.fl_str_mv tasesdissertacoes.bc@ufg.br
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