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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2011.tde-26102011-170611
Document
Author
Full name
Sheyla Inés Castillo Méndez
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Lima, Maria Regina D'Imperio (President)
Keller, Alexandre de Castro
Mauro, Eliana Faquim de Lima
Peçanha, Ligia Maria Torres
Rodrigues, Mauricio Martins
Title in Portuguese
Estudo dos mecanismos envolvidos na ativação policlonal dos linfócitos B durante a fase aguda da infecção pelo Plasmodium chabaudi AS.
Keywords in Portuguese
Plasmodium
Infecções por protozoários
Linfócitos B
Malária
Abstract in Portuguese
A resposta imune ao P. chabaudi se caracteriza pela ativação policlonal de linfócitos B na fase aguda da doença, que resulta em uma intensa produção de anticorpos IgM e IgG de baixa afinidade e autoanticorpos. Apesar de esses anticorpos contribuírem para o controle da infecção, pode retardar a geração de anticorpos de alta afinidade que garantem a destruição dos parasitas e a proteção contra infecções subseqüentes. O nosso objetivo foi caracterizar os mecanismos envolvidos na ativação policlonal dos linfócitos B na infecção pelo P. chabaudi AS. Os nossos resultados mostraram que a cooperação T-B e importante nessa fase da infecção. Os ensaios in vitro mostraram que os linfócitos T da fase aguda da infecção são capazes de estimular linfócitos B naives, aumentando a expressão do CD69 e induzindo proliferação e produção de anticorpos. A molécula de classe II do MHC é importante na ativação policlonal dos linfócitos B, aumentando a expressão do CD69 e induzindo a proliferação de anticorpos, devido ao seu envolvimento na ativação dos linfócitos T. Assim, moléculas como CD28, CD40L e ICOS são importantes na ativação, proliferação e produção de anticorpos.
Title in English
Polyclonal antibody induction mechanisms during the acute phase of Plasmodium chabaudi AS malaria.
Keywords in English
Plasmodium
B lymphocytes
Malaria
Protozoan infections
Abstract in English
Polyclonal B cell activation is a feature of the early spleen B cell response to human and murine malaria, which results in intense production of parasite low-affinity IgM and IgG and autoantibodies. Although this response may contribute for the initial parasite control, it may also hinder the generation of high-affinity IgG that guarantees parasite elimination and protection against secondary infections. To characterize the mechanism involved in the polyclonal B cell response to P. chabaudi AS, we have analyzed in vivo and in vitro the role of several molecules known to be involved in antibody production. According to our in vivo results, this response depends on the cooperation of CD4+ T cells with B cells. The in vitro assays shows that the expression of MHC class II molecules is crucial for B cell activation in terms of CD69 expression, proliferation and antibody production, apparently due to their requirement for T cell activation. Signaling pathways mediated by the co-stimulatory receptor CD28, CD40L and ICOS has a central role for B cell proliferative response and antibody production. This study may help to clarify the molecular basis of polyclonal B cell activation induced during acute malaria.
 
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Publishing Date
2011-10-26
 
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