Detalhes bibliográficos
| Ano de defesa: |
2015 |
| Autor(a) principal: |
Gassen, Rodrigo Benedetti
 |
| Orientador(a): |
Bonorino, Cristina Beatriz C.
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| Banca de defesa: |
Não Informado pela instituição |
| Tipo de documento: |
Dissertação
|
| Tipo de acesso: |
Acesso aberto |
| Idioma: |
por |
| Instituição de defesa: |
Pontifícia Universidade Católica do Rio Grande do Sul
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| Programa de Pós-Graduação: |
Programa de Pós-Graduação em Medicina/Pediatria e Saúde da Criança
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| Departamento: |
Faculdade de Medicina
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| País: |
Brasil
|
| Palavras-chave em Português: |
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| Área do conhecimento CNPq: |
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| Link de acesso: |
http://tede2.pucrs.br/tede2/handle/tede/5999
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Resumo: |
Introduction: Viruses cause diseases in humans and can cause epidemics and pandemics leading to death of thousands of people. When a virus infects the body, the immune system is activated to control the infection. The primary response against viruses consist mainly of cytotoxic CD8+ T cells and antibodies produced by B cells, however, both B and CD8 + T cells require auxiliary CD4 + T cells to generate an effective response. The production of antibodies needs a specific type helper cells, CD4 + follicular T cells (TFH). Both responses can generate memory, so in a second infection by the same virus strain can respond more efficient way. In these next two articles we discuss the TFH cell function towards viral response. First we produced an article that reviews all studies that performed a connection between this cell population and different viruses, such as HIV, HBV, EBV, LCMV and influenza. We next present an original article trying to unravel the mechanism by which the Respiratory Syncytial Virus (RSV) inhibits adequate humoral immune responses. Antibodies generated in RSV infections often have low affinity and little neutralizing activity, resulting in the accumulation of inflammatory immune complexes in the lower airways of children under 2 years of age. RSV can lead to death by bronchiolitis and pneumonia in approximately 50% of cases and increases the chance of developing asthma later in life. The TFH cells play an important role in helping B cells for class switching and the production of high affinity immunoglobulin. Objective: To understand the immunological mechanisms related to TFH cells in viral responses and investigate the mechanisms underlying the effect of RSV in decreasing antibody efficiency. Methods and Results: In the first article we reviewed Medline / Pubmed for original articles published from 2008 to 2014, using the terms "TFH" and "Virus" together. In the second article was conducted original research with animal models, focused on determining the interaction of RSV with the TFH cells. In our model, RSV was able to increase the amount of TFH cells in vitro, promoting their proliferation (Ki67) and death (Annexin-V). In vivo, RSV did not induce an increase in germinal centers and decreased the amount of IgG antibodies. We observed that RSV was capable of PD-L1 induction in dendritic cells as well in B cells. Conclusion: TFH cells are crucial for anti-viral humoral responses. Different types of viruses interact through varied mechanisms with the immune system. Our results suggest that the RSV induces PD-L1 in dendritic cells and B cells, and may be able to cause death by apoptosis in TFH cells, reducing the size of germinal centers and decreasing the amount of antibodies |
