Navegando por Palavras-chave "innate immunity"
Agora exibindo 1 - 8 de 8
Resultados por página
Opções de Ordenação
- ItemSomente MetadadadosInterplay between parasite cysteine proteases and the host kinin system modulates microvascular leakage and macrophage infection by promastigotes of the Leishmania donovani complex(Elsevier B.V., 2006-01-01) Svensjo, E.; Batista, P. R.; Brodskyn, C. I.; Silva, R.; Lima, APCA; Schmitz, V; Saraiva, E.; Pesquero, J. B.; Mori, MAS; Muller-Esterl, W.; Scharfstein, J.; Universidade Federal do Rio de Janeiro (UFRJ); Ctr Pesquisa Goncalo Moniz; Universidade Federal de São Paulo (UNIFESP); Univ FrankfurtKinins, the vasoactive peptides proteolytically liberated from kininogens, were recently recognized as signals alerting the innate immune system. Here we demonstrate that Leishmania donovani and Leishmania chagasi, two etiological agents of visceral leishmaniasis (VL), activate the kinin system. Intravital microscopy in the hamster cheek pouch showed that topically applied promastigotes induced macromolecular leakage (FITC-dextran) through postcapillary venules. Peaking at 15 min, the parasite-induced leakage was drastically enhanced by captopril (Cap), an inhibitor of angiotensin-converting enzyme (ACE), a kinin-degrading metallopeptidase. the enhanced microvascular responses were cancelled by HOE-140, an antagonist of the B, bradykinin receptor (13,R), or by pre-treatment of promastigotes with the irreversible cysteine proteinase inhibitor N-methylpiperazine-urea-Phe-homoPhe-vinylsulfone-benzene (N-Pip-hF-VSPh). in agreement with the above-mentioned data, the promastigotes vigorously induced edema in the paw of Cap-treated J129 mice, but not Cap-B2R-/(-) mice. Analysis of parasite-induced breakdown of high molecular weight kininogens (HK), combined with active site-affinity-labeling with biotin-N-Pip-hF-VSPh, identified 35-40 kDa proteins as kinin-releasing cysteine peptidases. We then checked if macrophage infectivity was influenced by interplay between these kinin-releasing parasite proteases, kininogens, and kinin-degrading peptidases (i.e. ACE). Our studies revealed that full-fledged B2R engagement resulted in vigorous increase of L. chagasi uptake by resident macrophages. Evidence that inflammatory macrophages treated with HOE-140 became highly susceptible to amastigote outgrowth, assessed 72 h after initial macrophage interaction, further suggests that the kinin/B2R activation pathway may critically modulate inflammation and innate immunity in visceral leishmaniasis. (c) 2005 Elsevier SAS. All rights reserved.
- ItemSomente MetadadadosLower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease(Wiley-Blackwell, 2009-12-01) Ndhlovu, L. C.; Snyder-Cappione, J. E.; Carvalho, Karina Inacio [UNIFESP]; Leal, F. E.; Loo, C. P.; Bruno, F. R.; Jha, A. R.; Devita, D.; Hasenkrug, A. M.; Barbosa, H. M. R. [UNIFESP]; Segurado, A. C.; Nixon, D. F.; Murphy, E. L.; Kallas, Esper Georges [UNIFESP]; Univ Calif San Francisco; Blood Syst Res Inst; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. the majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.
- ItemSomente MetadadadosThe role of HiTI, a serine protease inhibitor from Haematobia irritans irritans (Diptera : Muscidae) in the control of fly and bacterial proteases(Elsevier B.V., 2005-09-01) Azzolini, S. S.; Sasaki, S. D.; Campos, ITN; Torquato, RJS; Juliano, M. A.; Tanaka, A. S.; Universidade Federal de São Paulo (UNIFESP)Blood-sucking arthropods are vectors responsible for the transmission of several pathogens and parasites to vertebrate animals. the horn fly Haematobia irritans irritans (Diptera: Muscidae) and the tick Boophilus microplus are important hematophagous ecto-parasites that cause losses in cattle production. A serine protease inhibitor from a thorax extract of the fly H. irritans irritans (HiTI) was previously isolated, characterized and cloned. in the present study we described the expression, purification, and characterization of the recombinant HiTI (rHiTI) and its possible role in the control of different endogenous and bacterial proteases. rHiTI was successfully expressed using the pPIC9 expression vector with a yield of 4.2 mg/L of active rHiTI. the recombinant HiTI purified by affinity chromatography on trypsin-Sepharose had a molecular mass of 6.53 kDa as determined by LS-ESI mass spectrometry and inhibition constants (Kis) similar to those of native HiTI for bovine trypsin and human neutrophil elastase of 0.4 and 1.0 nM, respectively. Purified rHiTI also showed inhibitory activity against the trypsin-like enzyme of H. i. irritans using its possible natural substrates, fibrinogen and hemoglobin; and also inhibited the OmpT endoprotease of Escherichia coli using fluorogenic substrates. the present results confirm that HiTI may play a role in the control of fly endogenous proteases but also suggest a role in the inhibition of pathogen proteases. (c) 2005 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Sistema imunitário - parte II: fundamentos da resposta imunológica mediada por linfócitos T e B(Sociedade Brasileira de Reumatologia, 2010-10-01) Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Souza, Alexandre Wagner Silva de [UNIFESP]; Cruvinel, Wilson de Melo [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.
- ItemAcesso aberto (Open Access)Sistema imunitário: Parte I. Fundamentos da imunidade inata com ênfase nos mecanismos moleculares e celulares da resposta inflamatória(Sociedade Brasileira de Reumatologia, 2010-08-01) Cruvinel, Wilson de Melo [UNIFESP]; Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Souza, Alexandre Wagner Silva de [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Pontifícia Universidade Católica de Goiás cursos de Medicina e BiomedicinaThe immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.
- ItemAcesso aberto (Open Access)Sistema imunitário: parte III. O delicado equilíbrio do sistema imunológico entre os pólos de tolerância e autoimunidade(Sociedade Brasileira de Reumatologia, 2010-12-01) Souza, Alexandre Wagner Silva de [UNIFESP]; Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Cruvinel, Wilson de Melo [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Pontifícia Universidade Católica de Goiás cursos de Medicina e BiomedicinaThe immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ
- ItemSomente MetadadadosStructure-activity relationship studies of gomesin: Importance of the disulfide bridges for conformation, bioactivities, and serum stability(Wiley-Blackwell, 2006-01-01) Fazio, M. A.; Oliveira, V. X.; Bulet, P.; Miranda, MTM; Daffre, S.; Miranda, A.; Universidade Federal de São Paulo (UNIFESP); Bernex; Universidade de São Paulo (USP)Gomesin is an antimicrobial peptide isolated from hemocytes of the Brazilian spider Acanthoscurria gomesiana that contains two disulfide bridges Cys(2-15)/Cys(6-11) and presents a beta-hairpin structure. To investigate the role of the disulfide bridges on gomesin conformation, bioactivities, and serum stability, structure-activity relationship (SAR) studies were conducted. Initially, gomesin and variants lacking one or both disulfide bridges were synthesized. CD studies showed that the gomesin structure is very rigid independently of the solvent enviromnent. On the other hand, the linearized analogues adopted secondary structures according to the environment, while the monocyclic disulfide-bridged peptides had a tendency to adopt a turn structure. the absence of one or both bridges resulted in a decrease in the antimicrobial and hemolytic activities. in addition, serum stability studies revealed that, contrasting to gomesin that was stable even after 48 h of incubation, the linearized analogues were rapidly degraded. the replacement of the disulfide bounds by lactam bridges led to monocyclic and bicyclic compounds. SAR studies indicated that the monocyclic lactam-bridged analogues tend to assume a alpha-helical structure being less potent, hemolytic, and serum stable than the wild-type gomesin. On the other hand, the bicyclic lactam/disulfide-bridged analogues displayed a similar conformation and degradation kinetics identical to gomesin. However, the antimicrobial activity appeared to be dependent on the lactam bridge position and size. These findings indicated that (i) the secondary structure plays a pivotal role for the full activity of gomesin; (ii) the antimicrobial and hemolytic activities of gomesin are correlated events; (iii) while at least one of the disulfide bridges is needed for the maintenance of a significant antimicrobial activity of gomesin, both bridges are required for high serum stability and optimal conformation; and finally (iv) the best analogue obtained was the bicyclo (2-15,6-11)[Glu(2), Cys(6.11), Lys(15) J-Gm since it is as stable and potent as gomesin. (c) 2005 Wiley Periodicals, Inc.
- ItemAcesso aberto (Open Access)Variable contexts and levels of hypermutation in HIV-1 proviral genomes recovered from primary peripheral blood mononuclear cells(Elsevier B.V., 2008-06-20) Kijak, Gustavo H.; Janini, Luiz Mário Ramos [UNIFESP]; Tovanabutra, Sodsai; Sanders-Buell, Eric; Arroyo, Miguel Angel; Robb, Merlin L.; Michael, Nelson L.; Birx, Debora L.; McCutchan, Francine E.; Henry M Jackson Fdn Advancement Mil Med; Universidade Federal de São Paulo (UNIFESP); Walter Reed Army Inst ResAPOBEC-mediated cytidine cleamination of HIV-1 genomes during reverse transcription has been shown to be a potent mechanism of host restriction for HIV-1 infection ex vivo and in vitro. However, this defense system can be overcome by the viral protein Vif. Unlike other mechanisms of host restriction, the APOCEC-Vif interaction leaves an imprint on integrated proviruses in the form of G-A hypermutation. in the current work we systematically studied levels, contexts, and patterns of HIV-1 hypermutation in vivo. the analysis of 24 full-genome HIV-1 sequences retrieved from primary PBMCs, representing infections with several HIV-1 clades, and the inclusion of 7 cognate pairs of hypermutated/non-hypermutated sequences derived from the same patient sample, provided a comprehensive view of the characteristics of APOBEC-mediated restriction in vivo. Levels of hypermutation varied nearly 5-fold among the studied proviruses. GpG motifs were most frequently affected (22/24 proviruses). Levels of hypermutation varied across the genome. the reported twin peak pattern of hypermutation was observed in 18/24 hypermutants, but the remainder exhibited singular non-conforming patterns. These data suggest considerable complexity in the interplay of host restriction and viral defense during HIV-1 infection. (c) 2008 Elsevier Inc. All rights reserved.