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Mémoire de Maîtrise
DOI
10.11606/D.42.2011.tde-21032012-161654
Document
Auteur
Nom complet
Icaro Matioli Barbosa
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2011
Directeur
Jury
Boscardin, Silvia Beatriz (Président)
Ferreira, Karen Spadari
Marinho, Claudio Romero Farias
Titre en portugais
Direcionando as proteínas MSP-119 de Plasmodium vivax e Plasmodium yoelii para células dendríticas in vivo: análise das respostas imunes celular humoral.
Mots-clés en portugais
Plasmodium vivax
Plasmodium
Células dendríticas
Imunologia celular
Malária
Sistema imune
Resumé en portugais
Células dendríticas (DCs) são células do sistema imunológico muito importantes no processo de indução de imunidade, capazes de conectar respostas imunes inata e adquirida e levar à ativação de células T e B. Recentemente demonstrou-se que é possível direcionar antígenos diretamente para as DCs in vivo através da administração de baixas doses de uma proteína recombinante híbrida fusionada a um anticorpo monoclonal específico para receptores presentes na superfície destas células. Dois dos anticorpos monoclonais utilizados tem a capacidade de ligar-se aos receptores endocíticos DEC205 e DCIR2 presentes na superfície de duas sub-populações distintas de DCs.Construiu-se anticorpos híbridos em fusão com os genes que codificam a proteína MSP-119 presente na superfície das formas merozoítas de P.yoelii e P.vivax. Ensaios de imunização mostraram que o anticorpo anti-DEC fusionado a qualquer das duas proteínas foi capaz de induzir principalmente uma resposta imune celular quando administrado na presença de diferentes adjuvantes. Já a resposta imune humoral foi modulada dependendo de várias combinações.
Titre en anglais
Targeting Plasmodium vivax and Plasmodium yoelii MSP-119 proteins to dendritic cells in vivo: analysis of cellular and humoral immune responses.
Mots-clés en anglais
Plasmodium vivax
Plasmodium
Cellular immunology
Dendritic cells
Immune system
Malaria
Resumé en anglais
Dendritic cells (DCs) are cells of the immune system very important in the process of induction of immunity. They are able to connect innate and acquired immune responses and lead to activation of T and B cells. Recently it was shown that it is possible to target antigens directly to DCs in vivo by the administration of low doses of a recombinant hybrid protein consisting of a monoclonal antibody specific for receptors present on the surface of these cells fused with the antigen of interest. When these hybrid antibodies were injected in animals in the presence of a DC maturation stimulus, strong immune response against different antigens was obtained. Two of the monoclonal antibodies used have the ability to bind to either the DEC205 or the DCIR2 endocytic receptors present on the surface of two distinct DC sub-populations. In this work, we constructed hybrid antibodies fused with the sequence encoding the MSP-119 protein present on the surface P. yoelii and P. vivax merozoites. Most antibodies were successfully produced and maintained their ability to bind to their respective receptors. Immunization trials showed that the anti-DEC antibody fused to any of the two proteins was able to induce mainly a cellular immune response when administered in the presence of adjuvants. On the other hand, the humoral immune response depends of some combinations.
 
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Date de Publication
2012-05-25
 
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