Mestrado em Medicina Tropical e Saúde Pública (IPTSP)
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Item Polimorfismo Alélico do receptor FcyRIIA na Leishmaniose Tegumentar Americana(Universidade Federal de Goiás, 2007-02-13) OLIVEIRA, Cristina Rodrigues de; SILVEIRA, Lucimeire Antonelli da; http://lattes.cnpq.br/1252319967725429The FcγRIIA, receptor for the Fc portion of IgG, expressed by macrophages, neutrophils, platelets and dendritic cells, bind to the subclasses of IgG with variable affinity, that can be influenced by the polymorphism in the gene that encodes this receptor. The substitution of the amino acid arginine (R) for histidine (H), in the 131 position, defines three allelic patterns, the homozygote H/H, R/R and the heterozygote H/R, conferring to the FcγRIIA H/H131 a greater affinity to the IgG2 and IgG3 subclasses. This can result in different responses to diverse pathogens. Studies show the importance of Fcγ receptors on the macrophage infection by amastigote forms of Leishmania sp, in addition to those for the complement (CR3) and for mannose (MR). Besides that, genetic factors related to the hosts are involved in the immune response to the leishmaniasis, among them, the FcγRs. Until this time, we haven t found studies relating the receptor FcγRIIA to the leishmaniasis in humans. This way, this work consists in analyzing the allelic polymorphism in the gene that encodes the FcRIIA in individuals with American Tegumentary Leishmaniasis (ATL), evaluate if this polymorphism would be a genetic fact of susceptibility or resistance for this disease, if this would be influencing in the development of the different clinical forms of the ATL, as well in the healing process of the lesions. The FcγRIIA H/R131 polymorphism was analyzed in 88 blood samples of individuals with leishmaniasis and in 98 samples of healthy individuals (control group), using PCR, amplifying a segment of the gene that encodes the FcRIIA, followed by allele-specific enzymatic digestion and agarose gel eletrophoresis 3%. These results showed that the genotypic and allelic distribution of the FcγRIIA H/R131 were similar in the patients with leishmaniasis and in the control group, as well in patients with different clinical forms of the ATL. Concerning the resolution time of the disease, among the patients that had their lesions healed within one month of treatment or after this period, there was a predominance of the alleles R and H, respectively, however these differences were not significant. This way, our study suggests that the allelic polymorphism of the FcγRIIA H/R131 possibly is not a genetic factor of host that is associated to the protection or pathogenesis in the American Tegumentary Leishmaniasis.Item Participação das células Th1, Th17 e T reguladoras no desenvolvimento da tu-berculose ativa(Universidade Federal de Goiás, 2010-11-19) SILVA, Bruna Daniella de Souza; KIPNIS, André; http://lattes.cnpq.br/4434965360286741; KIPNIS, Ana Paula Junqueira; http://lattes.cnpq.br/1252262903952987Tuberculosis (TB) is a disease that afflicts mankind catastrophically, causing millions of new cases and deaths worldwide. It is estimated that one third of the world population is infected with the TB bacillus, Mycobacterium tuberculosis. Currently, the major challenges in TB control are the iden-tification of latent individuals, who are have increased chances to become ill, and the effective treat-ment of individuals with active disease. Understanding the immunology of this disease is of crucial importance for the development of new diagnostic tests and vaccines to combat this disease effec-tively. In order to elucidate the cellular immune response in tuberculosis, we evaluated the subpopu-lations of TCD4+ Th1, Th17 and T regulatory cells of patients with active pulmonary tuberculosis and rheumatoid arthritis against the recombinant antigen GLcB of M. tuberculosis. Peripheral blood mononuclear cells were obtained from twenty one patients with active pulmonary tuberculosis, re-cruited at Anuar Auad Hospital, twenty five patients with rheumatoid arthritis (RA), eleven individu-als with latent tuberculosis (TST+) and twelve healthy subjects (TST-). These cells were cultured, stimulated with antigen recombinant GLcB and Th1, Th17 and T regulatory subsets cells were eva-luated by flow cytometry. It was found that patients with active pulmonary tuberculosis have a high-er response of Th1 (8.21.9), Th17 (3.92.1) and T regulatory (2.81.2) antigen-specific recombi-nant GLcB when compared with individuals with latent infection (Th17=2.81.3; Treg=3.11.2) and healthy controls (Th17=1.40.8; Treg=0.60.3). Individuals with latent infection have only a signifi-cant percentage of Th1 cells specific (4.61.1) to GLcB when compared to controls (1.71.0). RA Patients that developed tuberculosis had immune response similar to those with only TB. Given these results, we conclude that the Th1 cells, Th17 and regulatory T cells are directly involved in active disease.Item Avaliação de resposta imunológica aguda de camundongos c57bl/6 e balb/c frente à infecção por mycobacterium massiliense(Universidade Federal de Goiás, 2009-02-11) SOUSA, Eduardo Martins de; KIPNIS, André; http://lattes.cnpq.br/4434965360286741; KIPNIS, Ana Paula Junqueira; http://lattes.cnpq.br/1252262903952987Atypical mycobacteria are microorganism s appart from the etiological agents responsible for tuberculosis and leprosy. They are currently considered as emerging pathogens associated with simple surgical procedures, and are resistant to conventional antibiotics. The atypical mycobacterial infections is responsible for three in every 10 thousand people per year, but the incidence has been increasing as the number of individuals infected with HIV also increases. The low virulence of atypical mycobacteria associates its pathogenicity to decreased resistance of the host, and consequently it is necessary to better understand the interaction between host and microorganism. The cellular and humoral immune response of BALB/c mice and C57BL/6 mice infected with M. massiliense isolated from an outbreak of hospitals in the city of Goiania was evaluated. The isolate of M. massiliense used in this study was able to infect immunocompetent mice, which completely controlled the bacterial load before the 30 days of infection. The mechanisms by which these animals cleared the mycobacteria were: production of NO by peritoneal macrophages, presence of specific IgG1 and induction of mRNA for inflammatory cytokines, as well as regulatory cytokines in inflammation.Item Caracterização Genotípica do HIV-1 em Pacientes dos Estados do Tocantins e Mato Grosso(Universidade Federal de Goiás, 2008-03-12) VIEGAS, ângela Alves; STEFANI, Mariane Martins de Araújo; http://lattes.cnpq.br/5581414958714905Introduction: There are limited HIV-1 genetic diversity studies performed in Central West and North Brazil subjects. Objectives: To characterize the HIV-1 genetic diversity in the gag region of patients from the States of Tocantins (TO) and Mato Grosso (MT). Material and Methods: 130 patients infected with HIV-1 were recruited from 2003 to 2006, at the regional Public Health Central Laboratories (LACEN) from TO (n=70) e MT (n=60). The HIV-1 genetic diversity in the gag region was investigated by heteroduplex mobility analysis HMA (HMA gag kits/AIDS Reagent Program/ NIH/ USA). For the gag region the Nested-PCR was performed employing the primers H1G777/ H1P02 and H1gag1584/ g17. HIV-1 subtypes references were amplified using the primers of Nested-PCR second round. HMA gag consists in the migration analysis of the hybrid formed by HIV-1 subtypes references and patient samples after polyacrylamide gel electrophoresis (5%). Results: Males were 60% of the study population in TO and 48,3% in MT. The median age was 34 years (21 l71 years) in TO and 35.5 years (4 64 years) in MT. The risk exposure categories of this study group were: sexual exposure (TO: 72.9%, MT: 93.3%), parenteral risk (TO: 4.3%, MT: 3.4%) and vertical case (MT: 1.4%). The HIV-1 subtypes identified by HMA gag were: B (TO: 82.8%, MT: 50.0%), F (TO: 7.8%, MT: 5.6%), C (TO: 4.7%, MT: 11.1%), B/D (TO: 4.7%, MT: 31.5%) and B/F (MT: 1.8%). Subtype B was predominant among men, women and all risk exposure categories. Conclusions: The genetic diversity analysis of HIV-1 isolates from TO and MT pointed subtype B as the prevalent. The most prevalent second form in TO was subtype F and in MT was subtype C. These results contribute to the genetic molecular mapping of the HIV-1 gag region in the Central West and North Brazil.