Introdução: O lúpus eritematoso sistêmico (LES) é uma doença autoimune caracterizada por uma alteração no sistema imunológico e uma inflamação crônica. O exercício físico agudo e crônico têm sido apontados como uma estratégia capaz de atenuar os acometimentos da doença e os fatores de risco cardiovasculares em pacientes com LES. Entretanto, ainda não se sabe se o exercício físico poderia piorar o quadro inflamatório e imunológico de pacientes com LES em remissão (LESREM) e atividade da doença (LESATIV). Objetivos: Avaliar o efeito agudo e crônico do exercício aeróbio na resposta das citocinas (IFN-y, IL-10, IL-6 e TNF-alfa) e receptores solúveis de TNF (sTNFR1 e sTNFR2) séricos e na expressão gênica em leucócitos circulantes de pacientes com LESREM e LESATIV. Métodos: A resposta das citocinas e dos sTNFRs às sessões agudas de exercício moderado (~50% do VO2pico) e intenso (~70% do VO2pico) foram avaliadas em 11 pacientes com LESATIV, 12 pacientes com LESREM e 10 controles saudáveis (GC), os quais foram pareados por sexo, idade e índice de massa corporal. A resposta da expressão gênica em leucócitos circulantes à sessão aguda intensa de exercício foi avaliada em quatro voluntárias por grupo (LESATIV, LESREM e GC). O treinamento aeróbio (12 semanas, 2x/semana, 30 a 50 minutos, FC entre os limiares ventilatórios) foi realizado por oito pacientes com LESREM. As citocinas e os sTNFRs foram avaliados por multiplex e a expressão gênica pelo método de PCRarray, com subsequente análise bioinformática. Resultados: Em resposta a sessão aguda moderada de exercício não houve alteração na resposta das citocinas e receptores solúveis de TNF (P > 0,05), com exceção da redução da IL-6 e do sTNFR1 na recuperação nos grupos LESATIV e GC (P < 0,05), respectivamente. Após o exercício agudo intenso, apenas o sTNFR1 reduziu durante a recuperação (P < 0,05) no grupo LESREM. No GC, a IL-10, o TNF-alfa, o sTNFR1 e o sTNFR2 permaneceram inalterados (P > 0,05), enquanto o IFN-y reduziu ao final do exercício (P = 0,05) e a IL-6 apresentou um aumento transitório ao final do exercício (P = 0,028). No grupo LESATIV, houve um aumento transitório da IL-10, IL-6 e TNF-alfa (P < 0,05), porém, todos os valores estavam normalizados 24 horas após o término da sessão. A análise da expressão gênica mostrou que uma sessão aguda de exercício intenso pode modular a expressão de genes nos leucócitos circulantes. Ao final da sessão intensa de exercício, houve uma redução da expressão de genes relacionados a citocinas e seus receptores, bem como da via dos receptores do tipo toll e da JAK/STAT nos três grupos do estudo, porém, com uma menor quantidade de genes alterados nos grupos LESREM e LESATIV comparados ao GC. Em resposta ao treinamento aeróbio, o grupo LESREM apresentou uma redução da concentração basal do sTNFR2 (P = 0,025) e uma tendência para redução da IL-10 (P = 0,093). Além disso, a área sob a curva (ASC) da resposta da cinética da IL-10 às sessões agudas moderada e intensa de exercício reduziram após o treinamento aeróbio (P < 0,05). As ASCs da IL-10, IL-6, TNF-alfa e sTNFR1 em resposta a sessão moderada de exercício não reduziram, mas alcançaram os valores do GC (P > 0,05). Conclusão: As sessões agudas de exercício moderado e intenso não exacerbam o quadro inflamatório em pacientes com LESREM e LESATIV. Adicionalmente, uma sessão intensa de exercício parece modular a expressão gênica em leucócitos circulantes de pacientes com LESREM e LESATIV, porém, em menor quantidade comparados ao GC. Por fim, o treinamento aeróbio parece reduzir o milieu inflamatório em pacientes com LESREM / Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an altered immune system and a chronic inflammation. Acute and chronic physical exercise has been emerged as a strategy to attenuate the disease outcomes and the cardiovascular risk factors in SLE patients. However, it is not known yet if physical exercise could dysregulate the inflammatory process and immune system in active (SLEACTIVE) and inactive SLE patients (SLEINACTIVE). Aims: to assess the effects of acute and chronic aerobic exercise training on the serum cytokines (IFN-y, IL-10, IL-6 e TNF-?) and soluble TNF receptors (sTNFR1 and sTNFR2) levels and in the gene expression of circulating leukocytes in SLEACTIVE and SLEINACTIVE patients. Methods: Cytokines and sTNFRs responses to acute moderate (~50% of VO2peak) and intense (~70% of VO2peak) aerobic exercise were assessed in 11 SLEACTIVE patients, 12 SLEINACTIVE patients and 10 healthy controls (HC), who were matched for age, sex and body mass index. Leucocytes gene expression responses to acute intense exercise were assessed in four subjects of each group (SLEACTIVE, SLEINACTIVE, and HC). Aerobic exercise training (12 weeks, twice a week, 30 to 50 minutes, HR between ventilatory thresholds) was performed by eight SLEINACTIVE patients. Cytokines and sTNFRs were assessed by multiplex technique and the gene expression by a PCRarray method, followed by bioinformatics analysis. Results: In response to an acute moderate exercise there were no significant differences in cytokines and sTNFRs (P > 0.05), except for the reduction in IL-6 and sTNFR1 during recovery in SLEACTIVE and HC (P < 0.05), respectively. After acute intense exercise, only sTNFR1 levels reduced during recovery (P < 0.05) in the SLEINACTIVE. In HC group, IL-10, TNF-?, sTNFR1 and sTNFR2 remained unchanged (P > 0.05), while IFN-y reduced at the end of exercise (P = 0.05) and IL-6 increased transitorily at the end of exercise (P = 0.028). In the SLEACTIVE group, there was a transitory increase in IL-10, IL-6 and TNF-alfa (P < 0.05), however, all cytokines were normalized 24 hours after the end of exercise. The analyses of gene expression showed that an acute intense aerobic exercise can modulate the gene expression in circulating leukocytes. At the end of acute intense exercise, there was a down-regulation of cytokines-cytokines receptor genes, and in the genes involved in the toll-like receptors and JAK/STAT pathways, however, with fewer genes altered in the SLEACTIVE and SLEINACTIVE groups compared with HC. In response to aerobic exercise training, SLEINACTIVE showed a reduction in the baseline sTNFR2 levels (P = 0.025) and a tendency to decrease in IL-10 levels (P = 0.093). Moreover, area under the curve (AUC) of the IL-10 kinetics to acute moderate and intense aerobic exercise reduced after the aerobic exercise training (P < 0.05). The AUCs of IL-10, IL-6, TNF-alfa and sTNFR1 in response to acute moderate exercise did not reduce, but reached the HC values (P > 0.05). Conclusion: Acute moderate and intense aerobic exercise did not exacerbate the inflammatory process in SLEINACTIVE and SLEACTIVE patients. Additionally, acute intense aerobic exercise seems to modulate the gene expression in leukocytes of SLEINACTIVE and SLEACTIVE patients, however, in fewer genes than in HC group. Finally, the aerobic exercise training seems to reduce milieu inflammatory in SLEINACTIVE patients

A tolerância imunológica é a propriedade essencial do sistema imune que controla as reações patológicas contra antígenos do próprio. O timo é visto como o principal órgão envolvido com a indução de tolerância aos antígenos próprios que são expressos pelas células tímicas (tolerância central), enquanto que a indução de tolerância aos antígenos relacionados a outros tecidos (TRAs) tem sido atribuída aos mecanismos de tolerância extratímica (tolerância periférica). Entretanto, a evidência da expressão de TRAs de órgãos e tecidos parenquimais no timo pelas células medulares epiteliais (mTECs) de camundongos e de humanos a qual foi referida como expressão gênica promíscua (PGE) reforçou a concepção de tolerância central de TRAs. O controle molecular dessa expressão tem sido atribuído ao gene Aire (Auto immune regulator) que é um regulador de transcrição. No presente estudo, procurou-se retratar a expressão gênica promíscua no timo de camundongos NOD (Non Obese Diabetic) por meio da análise da expressão gênica em grande escala, ou seja, descrevendo seu transcriptoma usando a tecnologia de cDNA microarrays. Para a análise dos dados utilizamos programas de bioinformática dedicados a microarrays bem como dados de bancos para a caracterização da PGE e susceptibilidade genética ao diabetes melitus do tipo 1 (DM-1). Três conjuntos de resultados puderam ser evidenciados. No primeiro conjunto observou-se a ocorrência da PGE de antígenos tecidos/órgãos parenquimatosos (TRAs) em timos recém removidos e em in vitro em cultura ATOC de camundogos NOD pré-autoimunes e autoimunes (diabéticos). O segundo conjunto de resultados consistiu na análise do efeito da inativação do transcrito de gene Aire na expressão gênica do timo de camundongos NOD in vitro em cultura ATOC. Finalmente, no último conjunto de dados, demonstrou-se que certos genes de TRAs com expressão promíscua, se encontram em regiões cromossômicas de susceptibilidade ao DM - 1 (idds). Como três deles (Il-4, Cd4 e Cdk4) são diretamente relacionados com a patogenia do DM-1 em camundongos foi possível estabelecer um paralelo entre PGE e susceptibilidade genética. / Immunologic tolerance is an essential property of the immune system, which controls immune reactions directed against the body self components. The thymus is seen as the main organ involved with the tolerance induction to self antigens, which are expressed by the thymic cells (central tolerance), while the tolerance induction to the diverse other peripheral tissues and organs is attributed to extra thymic mechanisms (peripheral tolerance). Nevertheless, the evidence for the expression of peripheral tissue related antigens (TRAs) in the thymus by the medullary thymic epithelial cells (mTECs) of mice and humans, which have been termed to as promiscuous gene expression (PGE), has contributed to the concept of central tolerance to TRAs. The molecular control of such gene expression has been attributed to the Aire (autoimmune regulator) gene, which plays a role as a transcriptional regulator. In the present study, we searched to picture PGE in the thymus of NOD (non obese diabetic) mice by means of high throughput gene expression, analyzing the transcriptome by the cDNA microarray method. To analyzing data we used bioinformatics programs dedicated to microarrays and specialized data banks to characterize PGE and genetic susceptibility to type 1 diabetes mellitus (DM-1). Studying pre and autoimmune NOD mice, we evidentiate three sets of results. In the first set, it was observed the occurrence of PGE of parenchymal tissue/organs antigens (TRAs) in fresh thymuses and in thymuses cultured in vitro in adult thymus organ cultures (ATOC). The second set of results consisted in the analysis of the effect of in vitro (ATOC) Aire gene silencing on PGE. Finally, in the third data set, we demonstrated that certain promiscuously expressed genes are positioned in DM-1 genetic susceptibility chromosomal regions (idds). As three of such genes (IL4, Cd4 and Cdk4) are directly associated to the DM-1 pathogenesis in mice, it was possible to establishing a parallel between PGE in the thymus and genetic susceptibility to this autoimmune disease.

In einer prospektiven, randomisierten, doppelblinden, Placebo-kontrollierten Cross-over-Studie wurden hämodynamische und immunologische Effekte einer dreitägigen adjunktiven Therapie mit niedrig dosiertem Hydrocortison (HC) (100 mg Bolus + 10 mg/Stunde) bei 40 Patienten im septischen Schock untersucht. Die Therapie mit HC führte zum Anstieg des mittleren arteriellen Drucks und des systemischen Gefäßwiderstands sowie zur Reduktion des Herzzeitvolumens und der Herzfrequenz, die pulmonalvaskulären Widerstände blieben unverändert. Die Nitrit/Nitrat-Plasmaspiegel (Stickstoffmonoxid-Synthese) und der Katecholaminverbrauch nahmen ab. Die Immunreaktionen waren komplex: Abnahme proinflammatorischer (Interleukin-(IL)-6, 8) und antiinflammatorischer (IL-10, lösliche Tumor-Nekrosefaktor-Rezeptoren) Mediatoren, Anstieg proinflammatorischer Zytokine (IL-12 und Interferon-?), Reduktion der Endothel- (E-Selektin) und Granulozytenaktivierung (CD11b, CD64), Reduktion der T-Helfer- und Suppressorzellzahl und der eosinophilen und basophilen Granulozyen, die Monozytenzahl stieg an und die neutrophilen Granulozyten sowie die Gesamtleukozytenzahl blieben unverändert. Parameter der unspezifischen (Respiratory Burst, Phagozytose) und der spezifischen Immunreaktion (HLA-DR auf Monozyten, Antigenpräsentation) wurden nicht oder nicht wesentlich supprimiert, die Phagozytosefähigkeit von Monozyten nahm zu. Eine Beendigung der HC-Therapie führte zu ausgeprägten hämodynamischen und immunologischen Rebound-Phänomenen. Die Wirkung von niedrig dosiertem HC im septischen Schock kann daher als kreislaufstabilisierend und immunmodulatorisch charakterisiert werden, Zeichen einer ausgeprägten Immunsuppression fanden sich nicht. / In a prospective, double-blind, randomised, placebo-controlled cross-over study, hemodynamic and immune effects of a three-day adjunctive treatment with low doses of hydrocortisone (HC) (100 mg bolus followed by 10 mg per hour) were investigated in forty patients with septic shock. HC-therapy induced a rise of mean arterial pressure and systemic vascular resistance and a decline of cardiac index and heart rate without altering pulmonary vascular resistance. Both, nitrite/nitrate levels (nitric oxide formation) and cathecholamine requirement were reduced. Immune responses were complex and included: reduction of proinflammatory (interleukin-(IL)-6, 8) and antiinflammatory (IL-10, soluble tumor necrosis factor receptors) mediators, an increase of proinflammatory cytokines (IL-12 and interferon-?), a reduction of endothelial (E-selectin) and granulocyte activation (CD11b, CD64), and a decrease of T-helper and suppressor cells as well as eosinophil and basophil granulocytes; monocytes increased and total granulocyte and leukocyte counts remained unaltered. Parameters of innate (respiratory burst, phagocytosis) and adaptive immune responses (HLA-DR-expression on monocytes, antigen presentation) were not essentially affected, monocyte phagocytosis rather increased. HC-withdrawal induced marked hemodynamic and immunologic rebound effects. In conclusion, effects of low dose HC-therapy in septic shock is characterised by hemodynamic stabilisation and immunomodulation, without inducing severe immunosuppression.

L’infarctus du myocarde reste aujourd’hui une pathologie fréquente et grave, en dépit des progrès thérapeutiques réalisés au cours des deux dernières décennies. Une recherche fondamentale et clinique intense a permis de mieux appréhender le rôle crucial de la réponse immunitaire au cours de cette pathologie. La réponse inflammatoire post-ischémique est ambivalente puisque nécessaire à la détersion de la zone infarcie et à la consolidation de la cicatrice cardiaque, mais également délétère car impliquée dans le remodelage ventriculaire et capable d’augmenter la taille de l’infarctus. TREM-1 est un récepteur amplificateur de la réponse immunitaire innée. Sa modulation pharmacologique par un peptide de synthèse, LR12, permet de limiter l’amplitude de la réponse inflammatoire sans l’inhiber complètement. A travers différents modèles expérimentaux, nous avons pu montrer que la modulation de TREM-1 au cours de l’infarctus est bénéfique en termes de contractilité cardiaque, de taille d’infarctus et de remodelage ventriculaire. Le mécanisme d’action principal passe par les neutrophiles, dont l’infiltration au sein du myocarde infarci est nettement atténuée. TREM-1 apparait désormais comme une cible thérapeutique prometteuse dans le combat contre l’infarctus et l’insuffisance cardiaque post-ischémique / Despite improvements in therapeutic management of acute myocardial infarction, the prevalence of this deadly condition remains high. Intensive research has raised the critical and ambivalent role of immune response after myocardial infarction. Optimal healing requires an inflammatory reaction for debris removal and scar formation, but unrestrained immune response leads to infarct expansion and maladaptive remodeling. TREM-1 is an immune-receptor that acts as an amplifier of the innate immune response. Blockade of TREM-1 activation by a short inhibitory peptide, LR12, protects from inflammatory hyper-responsiveness. Through various experimental models, we show that TREM-1 modulation improves outcome after myocardial infarction (infarct size, heart function, ventricular remodeling), with significant impact on neutrophils recruitment within the myocardium. TREM-1 could constitute a new therapeutic target in the fight against myocardial infarction and post-ischemic heart failure

The purpose of this research is to validate various forms of mathematical modeling of glioblastoma multiforme (GBM) expressed as differential equations, numerically. The first work was involved in the numerical solution of the reaction-convection model, efficacy of which is expressed in terms of survival time. It was calculated using simple numerical scheme for the standard-of-care treatment in clinics which includes surgery followed by the radiation and chemotherapy. Survival time using all treatment options increased significantly to 57 weeks compared to that of surgery close to 14 weeks. It was also observed that survival time increased significantly to 90 weeks if tumor is totally resected. In reaction-diffusion model using simple numerical scheme, tumor cell density patterns due to variation in patient specific tumor parameters such as net proliferation rate and diffusion coefficient were computed. Significant differences were observed in the patterns while using dominant diffusion and proliferation rate separately. Numerical solution of the tumor growth model under the anti-angiogenic therapy revealed some impacts in optimum tumor growth control however it was not significant. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

There is compelling evidence that smokers are less responsive to vaccination. We reported that both therapeutic and prophylactic vaccines fail to protect and cure animals from disease due to negative effects of nicotine on DCs’ ability to generate effector T cells. We have been investigating whether vaccine formulated with TLR agonist(s) could potentially overcome the immunosuppressive effects of nicotine on human DC-NK cross-talk essential for effector T cell generation. Monocyte-derived DCs and nicDCs were stimulated with individual and combined TLR agonists prior to co-culture with purified T cells. The phenotypes and cytokine profiles of T cell were assessed using Flow Cytometry and ELISA, respectively. We found nicDCs cultured with TLR-8/7 alone or in combination with TLR-3 produce quantitatively and qualitatively similar IFN-γ producing effector T cells when compared to control DCs. Our data suggest that the addition of appropriate TLR agonist to vaccine formulation could potentially overcome the immunosuppression seen in smokers, thereby containing the spread of infectious disease to vulnerable population / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015 / FAU Electronic Theses and Dissertations Collection

Células dendríticas (DCs) são células do sistema imunológico muito importantes no processo de indução de imunidade, capazes de conectar respostas imunes inata e adquirida e levar à ativação de células T e B. Recentemente demonstrou-se que é possível direcionar antígenos diretamente para as DCs in vivo através da administração de baixas doses de uma proteína recombinante híbrida fusionada a um anticorpo monoclonal específico para receptores presentes na superfície destas células. Dois dos anticorpos monoclonais utilizados tem a capacidade de ligar-se aos receptores endocíticos DEC205 e DCIR2 presentes na superfície de duas sub-populações distintas de DCs.Construiu-se anticorpos híbridos em fusão com os genes que codificam a proteína MSP-119 presente na superfície das formas merozoítas de P.yoelii e P.vivax. Ensaios de imunização mostraram que o anticorpo anti-DEC fusionado a qualquer das duas proteínas foi capaz de induzir principalmente uma resposta imune celular quando administrado na presença de diferentes adjuvantes. Já a resposta imune humoral foi modulada dependendo de várias combinações. / Dendritic cells (DCs) are cells of the immune system very important in the process of induction of immunity. They are able to connect innate and acquired immune responses and lead to activation of T and B cells. Recently it was shown that it is possible to target antigens directly to DCs in vivo by the administration of low doses of a recombinant hybrid protein consisting of a monoclonal antibody specific for receptors present on the surface of these cells fused with the antigen of interest. When these hybrid antibodies were injected in animals in the presence of a DC maturation stimulus, strong immune response against different antigens was obtained. Two of the monoclonal antibodies used have the ability to bind to either the DEC205 or the DCIR2 endocytic receptors present on the surface of two distinct DC sub-populations. In this work, we constructed hybrid antibodies fused with the sequence encoding the MSP-119 protein present on the surface P. yoelii and P. vivax merozoites. Most antibodies were successfully produced and maintained their ability to bind to their respective receptors. Immunization trials showed that the anti-DEC antibody fused to any of the two proteins was able to induce mainly a cellular immune response when administered in the presence of adjuvants. On the other hand, the humoral immune response depends of some combinations.

As células dendríticas (DCs) são críticas no processo de indução de imunidade e tolerância periférica. Estas células apresentam inúmeros receptores em sua superfície e podem ser classificadas em diferentes subpopulações de acordo com a expressão dos mesmos. Anticorpos monoclonais dirigidos contra diferentes receptores celulares vêm sendo utilizados com sucesso no tratamento de patologias como câncer. Nos últimos dez anos, demonstrou-se que é possível enviar antígenos diretamente para o receptor DEC205 presente na superfície das DCs. Quando isso acontece na ausência de estímulo inflamatório, o resultado é a indução de tolerância imunológica. Quando o antígeno é enviado a estas mesmas células na presença de um estímulo inflamatório, o resultado é a indução de uma forte resposta imunológica. Geramos um anticorpo <font face=\"Symbol\">aDEC205 em fusão com a proteína 2 de superfície dos amastigotas (ASP-2) de Trypanosoma cruzi e estudamos o efeito da administração deste anticorpo in vivo na presença de diferentes adjuvantes em duas linhagens distintas de camundongos. Observamos que ambas as linhagens de camundongos não foram capazes de gerar anticorpos, mas a resposta imune celular foi suficiente para reduzir a parasitemia quando desafiados com tripomastigotas cepa Y de Trypanosoma cruzi. Camundongos A/J foram capazes de mediar apresentação cruzada. Mapeamos um peptídeo que é reconhecido por camundongos BALB/c. Camundongos imunizados com Poly (I:C) como estímulo de maturação mostrou-se superior ao CpG. / As part of the innate immune system, dendritic cells (DCs) are critical in the process of induction of immunity and peripheral tolerance. These cells offer many receptors on their surface and can be classified in different subsets according to the expression there of. Monoclonal antibodies directed against different cellular receptors have been used successfully to treat diseases such as cancer. In the last ten years has been demonstrated that antigen can be sent directly to the receiver DEC205 present on the surface of DCs in vivo. When this happens in the absence of concomitant inflammatory stimulus, the result is the induction of immunological tolerance. Moreover, when the antigen is sent to the same cells in the presence of an inflammatory stimulus, the result is to induce a strong immune response. In this study we generated an antibody <font face=\"Symbol\">aDEC205 fusion protein with the amastigote surface protein 2 (ASP-2) from Trypanosoma cruzi and study the effect of administration of this antibody in vivo in the presence of different adjuvants in two distinct strains of mice. We observed that both strains of mice were unable to generate antibodies, but cellular immune response was sufficient to reduce the parasitemia when challenged with trypomastigotes Y strain of Trypanosoma cruzi. The mice A/J were able to mediate cross-presentation. In contrast, we mapped a peptide that is recognized by BALB/c mice. In counterpart mice immunized with Poly (I:C) as maturation stimuli was superior to CpG.

A imunidade inata que o mosquito apresenta tenta combater os patógenos dentro do organismo do mosquito impedindo que este seja transmitido para outros hospedeiros. A resposta celular apresenta três diferentes processos: fagocitose, encapsulamento e formação nodular, todos estes processos buscam eliminar os patógenos. Peptídeos antimicrobianos fazem parte da resposta humoral do mosquito, sendo codificados por genes e secretados por diversos tipos celulares. Um peptídeo novo pouco conhecido descoberto em Anopheles gambiae, a gambicina, demonstrou bons resultados no combate de parasitas. Na infecção por Plasmodium galleceum, não há diferença significativa na expressão deste peptídeo entre o grupo controle e infectado nos intervalos analisados. Na infecção por vírus dengue, sorotipo 2, a gambicina não apresenta diferença significativa no intervalo de 24 horas após a infecção, quando comparamos grupo controle e infectado, nos intervalos de 7 dias e 14 dias após a infecção, a expressão da gambicina é maior no grupo controle quando comparemos com o grupo infectado. / Innate immunity presents a mosquito tries to combat the pathogens inside the body of the mosquito preventing it from being transmitted to other hosts. The cellular response has three different processes: phagocytosis, encapsulation and nodule formation, all these processes seek to eliminate pathogens. Antimicrobial peptides are part of the humoral response mosquito being encoded by genes and secreted by several cell types. A little known new peptide discovered in Anopheles gambiae, the gambicina showed good results in controlling pests. In Plasmodium infection galleceum, there is no significant difference in the expression of this peptide between the control group and infected in the analyzed intervals. In infection with dengue virus serotype 2, the gambicina no significant difference within 24 hours after infection when comparing the control group and infected at intervals of 7 days and 14 days after infection, the expression is higher in gambicina control group when compare to the infected group.

Linfomas pertencem a um grupo de neoplasias que tem em comum a origem em células linforreticulares, sendo a forma anatômica gastrointestinal a mais prevalente na espécie felina. A maioria dos animais responde inicialmente ao tratamento, contudo, sabe-se que o desequilíbrio no sistema imune, de modo geral, pode facilitar a ocorrência e a disseminação das neoplasias. Para equilibrar a atividade do sistema imune, as células com função regulatória (Tregs) são fundamentais e por isso, alvo de diversas pesquisas isoladamente ou associadas a outros marcadores, como a IL-17A e o CD8, já que tanto as Tregs quanto os linfócitos Th17 originam-se de uma mesma célula T progenitora. Assim, alterações na relação Treg/Th17 podem levar à supressão na produção de linfócitos T CD8, invertendo a relação Tregs/CD8. Também há indícios de que as Tregs alterem a função efetora de células T contra neoplasias em seres humanos e em cães. Foram objetivos deste estudo avaliar as características do linfoma gastrointestinal em felinos, a proliferação celular por meio do índice mitótico e do marcador Ki-67, a expressão imunoistoquímica de CD4, CD8, CD25 (IL-2R), FOXP3 e IL-17A e correlacionar a expressão desses marcadores com o tipo celular, imunofenótipo, resposta ao tratamento e sobrevida global. Para análise estatística foram utilizados os testes de Mann-Whitney, Kruskal-Wallis, Quiquadrado de Pearson, de correlação de Spearman e a curva Kaplan-Meyer. Dos 47 gatos, 85% apresentaram a forma linfocítica de células T, com mediana de sobrevida de 24 meses; 15% apresentaram a forma linfoblástica de células B ou T, com mediana de sobrevida de 5 meses. A expressão de Ki-67 foi mais evidente naqueles pacientes com linfoma linfoblástico de células B ou T se comparado ao linfocítico de células T, com mediana de 40,5% e 8,2%, respectivamente e p=0,002. Na análise dos marcadores do sistema imune, não foi observada marcação de IL-2R. Não houve diferença significante na expressão de IL-17 e FOXP3 entre os tipos celulares e imunofenótipo, bem como não houve correlação entre FOXP3 e IL-17 e entre FOXP3 e CD8. Considerando somente os casos de linfoma linfocítico de células T, na análise do padrão de remissão parcial (n=12) versus completa (n=27), constatou-se diferença significante quanto à sobrevida (p&lt;0,0001) e CD8 (p&#61;0,015). Na análise de sobrevida, o tratamento com L-asparaginase, clorambucil e prednisolona, os níveis de albumina sérica iguais ou maiores que 2,5g/dL e o ganho de peso no início do tratamento foram preditores de maior tempo de sobrevida. Pode-se concluir que o linfoma linfocítico de células T foi o mais prevalente na espécie felina, envolvendo principalmente o intestino delgado e com um tempo mediano de sobrevivência de 24 meses; a expressão de ki-67 foi melhor marcador para determinar a proliferação celular se comparada ao índice mitótico; a expressão de FOXP3 foi baixa e não se relacionou à resposta terapêutica e ao tempo de sobrevida. Na análise específica dos casos de linfoma linfocítico de células T, não houve correlação entre FOXP3/IL-17 e FOXP3/CD8, enquanto que a baixa expressão de CD8 correlacionou-se a maior sobrevida naqueles pacientes em remissão completa / Lymphomas belong to a group of neoplasia that have in common the origin in lymphoreticular cells, and gastrointestinal is the most prevalent anatomical form in feline species. Most animals initially respond to treatment, however, it is known that the imbalance in the immune system generally may facilitate the occurrence and spread of tumors. To balance the activity of immune system, cells with regulatory function (Treg) are essential and therefore the target of many researches, alone or in combination with other markers such as IL-17A and CD8, as well Tregs as Th17 lymphocytes originate from a same progenitor T-cell. Thus, the relation between Treg / Th17 is important since changes in this relation can lead to suppressed production of CD8&#43; T lymphocytes, inverting the relation Treg/CD8. There is also evidence that Tregs alter the effector function of T cells against tumors in human beings and dogs. The objectives of this study was to evaluate the characteristics of gastrointestinal (GI) lymphoma in cats, cell proliferation by mitotic index and Ki-67 marker, immunohistochemical expression of CD4, CD8, CD25 (IL-2R), FOXP3 and IL-17A and correlate the expression of these markers on the cell-type, immunophenotype, response to treatment and overall survival. Statistical analysis was performed by Mann-Whitney test, Kruskal-Wallis test, Pearson\'s Chi-squared test, Spearman correlation and Kaplan-Meier curve. Of the 47 cats, 85% showed lymphocytic T cells, with a median survival of 24 months; and 15% had lymphoblastic B or T cells, with a median survival of 5 months. Ki-67 expression was most evident in patients with lymphoblastic B- or T-cell lymphoma compared to lymphocytic T cell lymphoma, with a median of 40.5% and 8.2%, respectively and p &#61 0.002. In the analysis of immune system markers, immunostaing was not observed IL-2R. There was no significant difference in IL-17A and FOXP3 expression between cell-type and immunophenotypes, as well as no correlation between FOXP3 and IL-17A and between FOXP3 and CD8. Considering only the cases of lymphocytic T-cell lymphoma, there was a significant difference in survival time (p <0.0001) and CD8 expression (p &#61; 0.015) considering partial (n &#61; 12) versus complete remission (n &#61; 27). In survival analysis, treatment A (L-asparaginase, chlorambucil and prednisolone), as well as serum albumin levels equal or higher than 2.5g/dL and weight gain after 30 days of treatment were predictive of increased survival time. As conclusion, lymphocytic T-cell lymphoma was more prevalent in feline species, mainly involving the small intestine and with a median survival of 24 months. Ki-67 expression was better marker to determine cell proliferation than mitotic index. FOXP3 expression was low and did not correlate to therapeutic response and survival time in GI lymphoma. In the specific analysis of lymphocytic T-cell lymphoma, there was no correlation between FOXP3/IL-17A and FOXP3/CD8, while low CD8 expression was correlated with increased survival in patients in complete remission