967 resultados para INNATE IMMUNE-SYSTEM
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Para estudar a resposta imune inata produzida especificamente no interior do SNC em desenvolvimento, evitando a influencia do sistema imune, empregamos modelo de infeccao viral induzida pela inoculacao intracerebral do virus da dengue em camundongos neonatos. Oito camundongos lactentes de dois dias de idade da espécie Mus musculus e variedade suica albina foram inoculados por via intracerebral com homogenado cerebral infectado com a especie Flavivirus (DENV3 genotipo III). Outro conjunto de animais foi utilizado como controle (nao infectado) e inoculado com igual volume de homogenado cerebral nao infectante e mantidos nas mesmas condicoes dos infectados. Decorridos 7 dias apos a infeccao os camundongos doentes foram sacrificados e tiveram seus cerebros processados para imunomarcacao de astrocitos e microglias. Quantificou-se a resposta imune glial no stratum lacunosum molecular (Lac Mol), radiatum (Rad) e pyramidale (Pir) de CA1-2 do hipocampo e na camada molecular do giro denteado (GDMol) usando o fracionador optico para estimar o numero de microglias e astrocitos em animais infectados e controles. Intensa astrocitose reativa e intensa ativacao microglial foram encontradas em animais neonatos com sinais clinicos de meningoencefalite. Entretanto, embora tenham sido maiores as estimativas do numero de microglias ativadas nos infectados (Inf) do que nos animais controles (Cont) nas camadas GDMol (Inf: 738,95 } 3,07; Cont: 232,73 } 70,38; p = 0,0035), Rad (Inf: 392,49 } 44,13; Cont: 62,76 } 15,86; p = 0,0004), em relacao ao numero total de microglias (ativadas ou nao) apenas o stratum radiatum mostrou diferença significante (Inf: 6.187,49 } 291,62; Cont: 4.011,89 } 509,73; p = 0,01). Por outro lado apenas a camada molecular do giro denteado mostrou diferenca no numero de astrocitos (Inf: 8.720,17 } 903,11; Cont: 13.023,13 } 1.192,14; p = 0,02). Tomados em conjunto os resultados sugerem que a resposta imune inata do camundongo neonato a encefalite induzida pelo virus da dengue (sorotipo 3, genotipo III) esta associada a um maior aumento do numero de microglias do que de astrocitos reativos e essa mudanca e dependente da camada e da regiao investigada. As implicacoes fisiopatologicas desses achados permanecem por ser investigadas.
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Pós-graduação em Odontologia - FOAR
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Although melatonin is mainly produced by the pineal gland, an increasing number of extra-pineal sites of melatonin synthesis have been described. We previously demonstrated the existence of bidirectional communication between the pineal gland and the immune system that drives a switch in melatonin production from the pineal gland to peripheral organs during the mounting of an innate immune response. In the present study, we show that acute neuroinflammation induced by lipopolysaccharide (LPS) injected directly into the lateral ventricles of adult rats reduces the nocturnal peak of melatonin in the plasma and induces its synthesis in the cerebellum, though not in the cortex or hippocampus. This increase in cerebellar melatonin content requires the activation of nuclear factor kappa B (NF-κB), which positively regulates the expression of the key enzyme for melatonin synthesis, arylalkylamine N-acetyltransferase (AA-NAT). Interestingly, LPS treatment led to neuronal death in the hippocampus and cortex, but not in the cerebellum. This privileged protection of cerebellar cells was abrogated when G-protein-coupled melatonin receptors were blocked by the melatonin antagonist luzindole, suggesting that the local production of melatonin protects cerebellar neurons from LPS toxicity. This is the first demonstration of a switch between pineal and extra-pineal melatonin production in the central nervous system following a neuroinflammatory response. These results have direct implications concerning the differential susceptibility of specific brain areas to neuronal death.
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Dendritic cells play a central role in the regulation of immunological reactivity. The existence of functionally specialized populations of dendritic cells in the skin is a consequence of qualitatively different attacks on our organism. slanDCs are human inflammatory dendritic cells that are characterized by the specific expression of the carbohydrate 6-sulfo LacNAc (slan). After phenotypic maturation, slanDCs are capable of producing very high amounts of proinflammatory mediators such as IL-12, TNF-, IL-1 and IL-23. Recent data describe a potential role of slanDCs in a number of different diseases like psoriasis, lupus erythematosus, and tumors, thus opening up new areas of research on their respective pathogenesis. Furthermore, a slanDC-specific targeting system has been developed as a basis for direct therapeutic manipulation. Future challenges of slanDC research include deepening our understanding of the significance of slanDCs in the regulation of adaptive and innate immune responses, as well as translating this knowledge into therapeutic options.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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The main function of the immune system is the defense against infection, being composed by the leukocytes that modulate the immune response, which can be innate or adaptive. The physical exercise can causes positive or negative alterations in the total or relative number of leukocytes. When the exercise has a low or moderate intensity it`s considered beneficial for improving the function of the cells responsible for the defense and to reduce the risk of infectious illnesses. The type 2 diabetes is related to an incapacity of the body in rightly respond to insulin, associated to an resistance to its actions. The purpose of this research was to make a study of the immune system characteristics, as well as the type 2 diabetes and the relation among both and the physical exercise. So, it was analyzed a group of type 2 diabetics coming from Diabetics House of Franca -SP, treated through a program of mix physical training. Two collections of blood were pre and post training program for the pair comparable of the participants. It was found positive alterations of the subpopulations of leukocytes that show a probable improvement of the immunological state what allows us to suggest about a possible improvement of the immunological activity, what would be measured by the activation of these cells forward to an inflammatory/infectious condition. So, we suggest that future studies involving diabetes, immune system and physical exercise be encouraged.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Immune thrombocytopenic purpura (ITP) is a common hematological disorder in the childhood, and it is one of the most common forms of autoimmune disease in pediatric patients. The ITP basis is a primary dysfunction of the immune system. This study aimed to analyze the genetic polymorphisms of the Fc gamma receptors IIA and IIIA. The genetic polymorphisms of the Fc receptors gamma IIA (131H/R) and gamma RIIIA (158V/F) were analyzed by polymerase chain reaction-restriction fragment length polymorphism technique. Odds ratio and 95% confidence interval were calculated by chi(2) test. Homozygous polymorphic genotype for the Fc gamma RIIIA was significantly more frequent among patients compared with controls (odds ratio = 0.27; 95% confidence interval, 0.09-0.80; P = 0.03). There was no statistical difference between the ITP group and the controls in the analysis of combinations of alleles of the high-affinity Fc receptor, but the ITP individuals with this combination had a lower duration of disease (P = 0.01). Genetic polymorphisms in immune system genes can be important for ITP pathogenesis and disease outcome.
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Aims: Development of effective immune-based therapies for patients with non-small-cell lung carcinoma (NSCLC) depends on an accurate characterization of complex interactions that occur between immune cells and the tumour environment. Methods and results: Innate and adaptive immune responses were evaluated in relation to prognosis in 65 patients with surgically excised NSCLC. Immunohistochemistry and morphometry were used to determine the abundance and distribution of immune cells. We found low numbers of immune cells and levels of cytokines in the tumour environment when compared with surrounding parenchyma. Smoking was associated inversely with the adaptive immune response and directly with innate immunity. We observed a prominent adaptive immune response in squamous cell carcinomas (SCC) but greater innate immune responses in adenocarcinomas and large cell carcinomas. Cox model analysis showed a low risk of death for smoking <41 packs/year, N-0 tambour stage, squamous carcinoma, CD4(+) > 16.81% and macrophages/monocytes >4.5%. Collectively, the data indicate that in NSCLC there is not a substantive local immune cell infiltrate within the tumour. Conclusion: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.