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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2012.tde-30012013-105937
Document
Author
Full name
Luciana Thomaz
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Taborda, Carlos Pelleschi (President)
Correa, Benedito
Ferreira, Luis Carlos de Souza
Gaspari, Elizabeth Natal de
Santos, André Luis Souza dos
Title in Portuguese
Proteção ou exacerbação de anticorpos monoclonais gerados contra antígenos de Paracoccidioides brasiliensis na infecção experimental.
Keywords in Portuguese
Paracoccidioides brasiliensis
Anticorpos monoclonais
Fungos
Infecção experimental animal
Micologia
Abstract in Portuguese
Nesse trabalho avaliamos a proteção que o anticorpo monoclonal (AcM) contra CMH e contra Hsp60 fornecem aos animais infectados com as leveduras de Paracoccidioides brasiliensis e P. lutzii em modelo profilático. O tratamento com os AcMs de isotipos IgG2a e IgG2b foram protetores, induzindo a secreção das citocinas IL-12p70, IFN-g e TNF-a, padrão de resposta imune Th1. Nós mostramos por imunomarcação que moléculas de CMH e Hsp60 estão acessíveis na célula. E o anticorpo monoespecífico contra CMH e os anticorpos policlonais contra melanina, gerados nesse trabalho foram eficazes nos ensaios in vitro de proteção. Foram gerados anticorpos monoclonais contra glicoproteina extraída de Pb18, o AcM reconheceu, por imunomarcação, estruturas internas e a parede celular da levedura. Avaliamos um novo modelo de hospedeiro, com o uso da larva Galleria mellonella, o que pode servir de triagem e reduzir desta forma o uso excessivo de camundongos, as leveduras P. lutzii e H. capsulatum são letais para as larvas e evocam resposta celular que se organizam semelhante a um granuloma.
Title in English
Protection or exacerbation of monoclonal antibodies generated against antigens of Paracoccidioides brasiliensis in the experimental infection.
Keywords in English
Paracoccidioides brasiliensis
Animal experimental infection
Fungi
Monoclonal antibodies
Mycology
Abstract in English
In this work we evaluated the protection that the monoclonal antibody (MAb) against Hsp60 and against CMH provides the animals infected with the yeast Paracoccidioides brasiliensis and P. lutzii in prophylactic model. The treatment with the MAbs of IgG2a and IgG2b isotypes were protective, inducing the secretion of IL-12p70, IFN-g and TNF-a, Th1 pattern of immune response. We show by immunogold that Hsp60 and MHC molecules are accessible on the cell. And the monospecific antibody against HCM and polyclonal antibodies against melanin, generated in this study were effective in in vitro assays of protection. Monoclonal antibodies were generated glycoprotein extracted from Pb18, Mab recognized by immunogold, internal structures and cell wall material. Evaluated a new type of host, using the larvae Galleria mellonella, which can serve as a screening and reduce thus the overuse of mice, yeast P. lutzii and H. capsulatum are lethal to larvae and evoke cellular responses that are organized like a granuloma.
 
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Publishing Date
2013-03-21
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • SILVA, M. B., et al. Resistance of melanized yeast cells of P. brasiliensis to antimicrobial oxidants and inhibition of phagocytosis using carbohydrates and monoclonal antibody to CD18 [doi:10.1590/S0074-02762009000400019]. Memórias do Instituto Oswaldo Cruz [online], 2009, vol. 104, p. 644-648.
  • Thomaz, L., et al. Experimental paracoccidioidomycosis: alternative therapy with ajoene, compound from Allium sativum , associated with sulfamethoxazole/trimethoprim [doi:10.1080/13693780701651681]. Medical Mycology (Oxford. Print) [online], 2008, vol. 46, p. 113-118.
  • THOMAZ, Luciana, et al. Galleria mellonella as a model host to study Paracoccidioides lutzii and Histoplasma capsulatum [doi:10.4161/viru.23047]. Virulence [online], 2013, vol. 4, p. 139-146.
  • DIAS, L. S., et al. Monoclonal antibody to heat shock protein 60 induces a protective immune response against experimental Paracoccidioides lutzii. In 27 Congresso Brasileiro de Microbiologia, Natal - RN, 2013. 27 Congresso Brasileiro de Microbiologia., 2013. Resumo.
  • SILVA, Cássia Jacqueline da, et al. Bioactive lipids in paracoccidioidomycosis: induction of specific antibodies that increase yeast cell phagocytosis. In 107 General Meeting - American Society for Microbiology, Toronto, 2007. 107 General Meeting - American Society for Microbiology., 2007. Abstract.
  • Thomaz, L., et al. Utilização do ajoene no controle da paracoccidioidomicose experimental. In 24 Congresso Brasileiro de Microbiologia, Brasilia, 2007. 24 Congresso Brasileiro de Microbiologia., 2007. Resumo.
  • THOMAZ, Luciana, et al. A monoclonal antibody to glucosylceramide of Paracoccidioides brasiliensis enhances the antifungal action of macrophages. In XI International Meeting on paracoccidioidomycosis, Taubaté, 2011. XI International Meeting on Paracoccidioidomycosis., 2011. Resumo.
  • THOMAZ, Luciana, et al. Carbohydrate compositon of the cell wall from seven Paracoccidioides brasiliensis strains. In XI International Meeting on paracoccidioidomycosis, Taubaté, 2011. XI International Meeting on Paracoccidioidomycosis., 2011. Resumo.
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