968 resultados para Chronic lymphoproliferative disorders. Immunophenotyping. Immune system lymphoma
Resumo:
Malaria causes important functional alterations of the immune system, but several of them are poorly defined. To evaluate thoroughly the natural killer cell cytotoxicity in patients with malaria, we developed a technique capable to assess both the dynamics and the kinetics of the process. For the kinetics assay, human peripheral blood mononuclear cells were previously incubated with K562 cells and kept in agarose medium, while for the dynamics assay both cells were maintained in suspension. NK activity from patients with vivax malaria presented a kinetics profile faster than those with falciparum malaria. NK cytotoxicity positively correlated with parasitemia in falciparum malaria. The dynamics of NK cytotoxicity of healthy individuals was elevated at the beginning of the process and then significantly decreased. In contrast, malaria patients presented successive peaks of NK activity. Our results confirmed the occurrence of alteration in NK cell function during malaria, and added new data about the NK cytotoxicity process.
S100, CD68, and MHC class II molecule expression in cervical high- and low-grade HPV-induced lesions
Resumo:
INTRODUCTION: Some human papillomavirus (HPV) types are involved in malignant processes in the cervical epithelium, with 99% of cases attributed to oncogenic HPV infection. This study aimed to detect S100, CD68, and major histocompatibility complex class II (MHC-II) molecules in cervical uterine epithelial samples in patients with high- and low-grade lesions induced by HPV. METHODS: Fifty-eight samples from patients who were confirmed positive or negative for high-risk oncogenic HPV DNA, had histopathological diagnosis of cervical intraepithelial neoplasia (CIN) of grades I, II, or III, or were negative for intraepithelial lesion or malignancy were subjected to immunohistochemistry reaction to S100 protein, CD68, and MHC-II (HLA-DR alpha chain). RESULTS: The presence of MHC-II predominated in samples exhibiting histopathological alterations (p < 0.05). S100 detection was more numerous in carcinoma samples (CIN III) (75%). Presence of this protein correlated significantly (p < 0.05) with histopathological findings and viral load. CONCLUSIONS: A small expression of CD68 was observed, which may be explained by the observation in our study having been made on random microscopic fields and not on specific areas. The findings, such as the presence of S100 protein and MHC-II expression in samples with histological alterations, could suggest that the immune system fails to control HPV replication at the early stages of infection. Further studies with larger prospective data are necessary to confirm this result.
Resumo:
INTRODUCTION: The innate immune response is the first mechanism of protection against Trypanosoma cruzi, and the interaction of inflammatory cells with parasite molecules may activate this response and modulate the adaptive immune system. This study aimed to analyze the levels of cytokines and chemokines synthesized by the whole blood cells (WBC) and peripheral blood mononuclear cells (PBMC) of individuals seronegative for Chagas disease after interaction with live T. cruzi trypomastigotes. METHODS: IL-12, IL-10, TNF-α, TGF-β, CCL-5, CCL-2, CCL-3, and CXCL-9 were measured by ELISA. Nitrite was determined by the Griess method. RESULTS: IL-10 was produced at high levels by WBC compared with PBMC, even after incubation with live trypomastigotes. Production of TNF-α by both PBMC and WBC was significantly higher after stimulation with trypomastigotes. Only PBMC produced significantly higher levels of IL-12 after parasite stimulation. Stimulation of cultures with trypomastigotes induced an increase of CXCL-9 levels produced by WBC. Nitrite levels produced by PBMC increased after the addition of parasites to the culture. CONCLUSIONS: Surface molecules of T. cruzi may induce the production of cytokines and chemokines by cells of the innate immune system through the activation of specific receptors not evaluated in this experiment. The ability to induce IL-12 and TNF-α contributes to shift the adaptive response towards a Th1 profile.
Resumo:
While most of those infected with hepatitis C virus (HCV) are asymptomatic or only develop liver manifestations, a significant percentage evolves with autoimmune and lymphoproliferative disorders, resulting in a clinical condition called HCV syndrome. This work involving case studies of six patients with hepatitis C and varied skin manifestation aimed to report skin lesions occurring with HCV infection and its treatment. Skin manifestations in hepatitis C have been based on epidemiological studies. This justifies the need for studies that correlate HCV infection and its treatment with skin manifestations.
Resumo:
RESUMO: A prevalncia das doenas atpicas tem vindo a aumentar, em especial ao nvel dos pases ocidentalizados. Vrios fatores tm sido apontados para justificar este aumento de prevalncia,destacando-se o reduzido tamanho das famlias, o elevado uso de antibiticos, a melhoria das condies sanitrias, bem como a diminuio quer das infees de helmintas, quer da contaminao orofecal. Alguns estudos tm tambm avaliado a influncia do ambiente pr-natal no desenvolvimento de atopia e asma. Da anlise da literatura, parece inegvel a importncia deste perodo para o desenvolvimento do sistema imunitrio. Neste mbito, a transmisso de atopia descendncia em mulheres atpicas, e concretamente com asma alrgica, poder ser moldada desde este perodo. A possibilidade de identificar marcadores de risco precoces para o desenvolvimento de atopia poder ser o primeiro passo para o desenvolvimento de estratgias de preveno para os indivduos em risco. Este trabalho pretendeu abordar o sistema imunitrio materno de forma a enriquecer a sua caraterizao desde o terceiro trimestre da gravidez at ao fim do puerprio. Para alm da explorao de perfis celulares e citocnicos maternos (nos quais se incluiu sobretudo a avaliao de diferentes populaes de clulas T e B, com funes efetoras e reguladoras), foi tambm considerada a sua eventual relao com o desenvolvimento de atopia nas crianas. Foram recrutadas 135 mulheres com critrios para serem includas num dos 4 grupos do estudo: grvidas atpicas GA (n=24), no grvidas atpicas NGA (n=32), grvidas saudveis GS (n=44) e no grvidas saudveis NGS (n=35). Foram caraterizadas por Citometria de Fluxo populaes de leuccitos e linfcitos, com particular interesse nos perfis maturativos de linfcitos T e B, bem como nas subpopulaes de clulas T e B reguladoras. Foi ainda efetuada uma anlise funcional, para avaliar a capacidade de produo de citocinas pelos linfcitos T e B. Foram igualmente avaliadas as concentraes de citocinas sricas por ensaios imunoenzimticos. Estes parmetros imunolgicos maternos foram acompanhados desde o terceiro trimestre de gestao, at depois do puerprio (primeiras 6 semanas ps parto), e aos seis meses de idade, foi efetuada uma avaliao clnica das crianas. As mulheres no grvidas atpicas apresentaram contagens celulares mais elevadas para a generalidade das populaes leucocitrias e linfocitrias (em relao a mulheres no grvidas saudveis). Destaca-se ainda uma maior presena de eosinfilos nas mulheres NGA (p=0,0009; teste de Mann-Whitney U), que tinham igualmente os seus compartimentos linfocitrios T e B mais ricos em clulas de memria, em relao s mulheres NGS. Para os perfis de regulao, verificou-se que as clulas T reguladoras se encontravam percentualmente aumentadas (p0,003; teste de Mann-Whitney U), tal omo as clulas T produtoras de IL10 aps estimulao (p0,03; teste de Mann-Whitney U) em mulheres NGA. Tambm se observou uma maior expresso de Foxp3 (p=0,0002; teste de Mann-Whitney U), e ainda a diminuio dos nveis sricos de IFN- nas mulheres NGA (p=0,0019; teste de Mann-Whitney U), em relao a mulheres NGS. De um modo geral, as alteraes verificadas nos parmetros imunolgicos de mulheres grvidas atpicas no terceiro trimestre da gravidez foram semelhantes s observadas em mulheres grvidas saudveis. Comparadas com mulheres NGA, nas mulheres grvidas atpicas ocorreu uma alterao substancial da frmula leucocitria, com um importante incremento de neutrfilos (p<0,0001; teste de Mann-Whitney U) e diminuio dos valores das restantes populaes leucocitrias. A diminuio nas contagens de linfcitos totais estendeu-se a grande parte das subpopulaes linfocitrias caraterizadas. Nos compartimentos linfocitrios T e B foi possvel observar uma diminuio das subpopulaes de clulas de memria. Verificou-se igualmente na gravidez uma menor expresso de Foxp3 em mulheres GA (p<0,0001; teste de Mann-Whitney U) e ainda menos clulas B CD24HiCD38Hi circulantes (p=0,0012; teste de Mann-Whitney U). Ocrreu ainda uma diminuio relativa das clulas T CD4 produtoras de IFN- em mulheres GA (p0,024; teste de Mann-Whitney U), e uma maior presena de clulas T CD8 produtoras de IL17 (p=0,0172; teste de Mann-Whitney U), em relao ao observado em mulheres NGA. Depois do puerprio, no compartimento T de mulheres do grupo GA, verificou-se um aumento das populaes de clulas de memria. Em comparao com a gravidez, aps o puerprio o compartimento B, apresentou nas mulheres GA um aumento significativo da subpopulao de clulas B de transio (p<0,0001; teste de Wilcoxon). Verificou-se, igualmente em mulheres GA aps o puerprio, uma maior expresso de Foxp3 nas clulas T reguladoras (p<0,0001; teste de Wilcoxon) e o aumento das populaes de clulas T circulantes produtoras de IFN- (p0,0234; teste de Wilcoxon). As modulaes das populaes T e B desde a gravidez at depois do puerprio ocorreram de forma semelhante nas mulheres dos grupos GA e GS. Apesar de as mulheres GA manterem um perfil imunolgico prximo do das mulheres GS depois do puerprio, aconteceu tambm neste perodo um processo de reaproximao ao perfil observado nas mulheres NGA. As mulheres GA com manifestaes de risco para atopia na descendncia (comparadas com mulheres GA sem manifestaes de risco para atopia na descendncia at aos 6 meses de vida) apresentaram uma maior proporo de clulas T e menor proporo de clulas B, percentagens mais elevadas de clulas T CD8 de memria efetoras, de clulas B de transio e de clulas B CD24HiCD38Hi, e contagens mais baixas de clulas B de memria. Na avaliao destes parmetros como marcadores de risco para o desenvolvimento de atopia verificou-se que o parmetro com melhor desempenho foi a percentagem de clulas B de transio, com uma Odds-Ratio de 54,0 [IC 95%: 4,2-692,9; (p=0,0005)], sensibilidade de 90,0% [IC 95%: 55,5 99,8] e especificidade de 85,7% [IC 95%: 57,2 98,2]. Este estudo foi pioneiro em Portugal, e no mundo, no que se refere ao acompanhamento do compartimento linfocitrio B circulante, abordando o seu perfil de maturao, e em particular as clulas B com funes reguladoras, desde a gravidez at ao fim do puerprio, em mulheres atpicas e no atpicas. A este nvel, encontram-se estudos na literatura a documentar a alterao do compartimento B durante a gravidez. O presente trabalho reporta agora que alteraes, como a diminuio do nmero de clulas B em circulao, so impostas tambm na mulher atpica. Em suma, demonstrou-se a existncia de um perfil imunolgico caraterstico em mulheres atpicas, que sofre alteraes significativas durante a gravidez, tendendo os parmetros imunolgicos a normalizar aps o puerprio. O compartimento T, para o qual a literatura mais rica em estudos e abordagens, demonstrou tambm neste trabalho oscilaes caratersticas entre o perodo pr e ps-natal. Verificaram-se sobretudo variaes nos compartimentos de clulas T de memria, sem grandes alteraes ao nvel das clulas Treg no que se refere sua presena em circulao. Apenas a registar a menor expresso de Foxp3 nas clulas Treg durante a gestao observada em mulheres atpicas, tal como em mulheres saudveis (como tambm j foi relatado em estudos anteriores). Apesar de muitos dos dados se encontrarem em concordncia com a literatura, quer no que se refere s subpopulaes de clulas de memria, quer no que se refere s clulas Treg, tambm se encontram resultados discordantes, por exemplo documentando variaes numricas nas clulas Treg em circulao em mulheres atpicas e mulheres atpicas grvidas. A importncia de harmonizar protocolos e fentipos, parece crucial na abordagem de estudos futuros. Ao nvel do risco para a atopia na descendncia de mulheres atpicas, acrescentou-se ainda a possibilidade de definir marcadores no invasivos para a criana, em particular as clulas B de transio. Estas clulas, cuja maior presena em circulao no recm-nascido foi recentemente associada com manifestaes alrgicas subsequentes, so agora apontadas j na mulher atpica, grvida do terceiro trimestre, como um elemento de risco para o desenvolvimento de atopia. Os marcadores de risco descritos, para alm de facilmente poderem vir a ser englobados no mbito dos normais rastreios maternos durante a gravidez, apresentam ainda a vantagem da precocidade do diagnstico, permitindo no s a possibilidade de preveno ps-natal, mas estendendo esta possibilidade ao perodo gestacional.----------------------------ABSTRACT: The prevalence of atopic diseases has been increasing, especially in Westernized countries. Several factors have been suggested to justify this increase in prevalence, as the small size of families, the high use of antibiotics, the improvement in sanitation conditions, as well as the reduction of both helminth infections, and orofecal contamination. A few studies have adressed the influence of prenatal environment on the development of atopy and asthma. From literature, it seems undeniable the importance of the prenatal period for the development of the immune system. In this context, the transmission of atopy to the progeny in atopic women, and specifically in women with allergic asthma, can be modulated from this period on. The ability to detect early risk markers for the development of atopic diseases may be the first step in the development of prevention strategies for individuals at risk. This study aimed to approach the maternal immune system in order to enrich its characterization from the third trimester of pregnancy until the end of the puerperium period. In addition to the evaluation of the maternal cellular profiles (in which, mostly, diferente populations of T and B cells with effector and regulatory functions were included) and citokines, the relation between these profiles and the development of atopy in the progeny was also assessed. 135 women were recruited for this study, and fullfiled the inclusion criteria necessary to be included in one of the four groups preset: atopic pregnant women - GA (n = 24), atopic nonpregnant women - NGA (n = 32), healthy pregnant women - GS (n = 44) and healthy nonpregnant women - NGS (n = 35). Populations of leukocytes and lymphocytes, and particularty maturation profiles of T and B lymphocytes, as well as subpopulations of T and B cells with regulatory functions, were characterized by flow cytometry. Functional assays were also performed, to assess the ability of cytokine production by T and B lymphocytes. Serum cytokine concentrations were assessed as well by enzymatic immunoassays. These maternal imune parameters were monitored since the third trimester of pregnancy until the end of the puerperium period (first six weeks after delivery). A clinical evaluation of all the newborn children was performed at the age of six months. Non-atopic pregnant women presented higher cell counts for most leukocyte and lymphocyte populations (compared to healthy non-pregnant women). We should also highlight the increased presence of eosinophils in NGA women (p = 0,0009; Mann-Whitney U test). Again compared to NGS women, NGA women showed increased memory cells within the circulating T and B lymphocyte compartments. Considering the regulatory profiles, NGA women presented higher percentages of regulatory T cells (p0,003; Mann-Whitney U test) and IL10 producing T cells after stimulation (p0,03; Mann Whitney U), as well as increased expression of Foxp3 (p = 0,0002; Mann-Whitney U test), and also decreased serum levels of IFN- (p = 0,0019; test Mann-Whitney U test) compared to NGS women. In general, the changes observed in immune parameters of atopic pregnant women in the third trimester of gestation were similar to those observed in healthy pregnant women. Comparing pregnant and non-pregnant atopic women, an important change in leukocyte subsets was observed, with a significant increase of neutrophils (p <0,0001; Mann-Whitney U test) and the consequent diminution of the remaining leukocyte populations in the GA group. The decrease in total lymphocyte counts was extended to most of the lymphocyte subsets characterized. It was possible to detect a decrease in memory cell subsets within the T and B lymphocyte compartments, also. During pregnancy, a lower expression of Foxp3 was reported in GA women (p <0,0001; Mann-Whitney U test) and, besides, lesser CD24HiCD38Hi B cells were present in circulation in these women, compared to NGA women (p = 0,0012; Mann-Whitney U test). There was still a decrease in the percentages of IFN--producing CD4 T cells in GA women (p0,024; Mann-Whitney U test) and a greater presence of IL17-producing CD8 T cells (p = 0,0172; Mann-Whitney U test), compared to the levels observed in NGA women. At the end of the puerperium, there was an increase in memory cell subpopulations within the T cell compartment of GA women. Compared with the pregnancy evaluation, after puerperium, the B cell compartment showed a significant increase in the transitional subpopulation (p<0,0001; Wilcoxon test), in GA women. Moreover, after puerperium, GA women exhibited a greater expression of Foxp3 in Treg cells (p <0,0001; Wilcoxon test) and there was an increase in circulating IFN--producing T cells (p0,0234; Test Wilcoxon). The modulations of T and B cell subpopulations from pregnancy until the end of puerperium were similar in women of GA and GS groups. Although at the end of puerperium, GA women still kept an immune profile close the one observed in GS women, at this time point, there were also signs of rapprochement between the immune profiles observed in women of GA and NGA groups. GA women with atopic manifestations in the offspring (compared to GA women without atopic manifestations in the offspring at the age of 6 months) presented higher proportions of T cells and lower proportions of B cells, higher percentages of effector memory CD8 T cells, transitional B cells and CD24HiCD38Hi B cells, and, finally, lower absolute counts of memory B cells. In the evaluation of these parameters as risk markers for the development of atopy, the parameter which presented the best performance was the percentage of transitional B cells, with an Oddsratio of 54,0 [95% CI: 4,2 to 692,9; (p = 0,0005)], sensitivity of 90,0% [95% CI: 55,5 to 99,8] and a specificity of 85,7% [95% CI: 57,2 to 98,2]. This study was a pioneer in Portugal, and in the world, in what concerns the monitoring of the circulating B cell compartment, addressing not only the maturation profile, but, in particular, B cells with regulatory functions, from pregnancy untill after puerperium, in atopic and non-atopic women. Literature presents evidence of a typical change in circulating B cells during pregnancy. This study now reports that changes, such as the decrease in the number of circulating B cells,/ are also imposed by pregnancy in atopic woman. In brief, it demonstrated the existence of a characteristic immune profile in atopic women, which undergoes significant alterations during pregnancy, tending to normalize after the puerperium. As for the T cell compartment, for which the literature is richer in studies and approaches, this study also showed characteristic fluctuations between the pre- and postnatal periods. There were variations mostly in the memory subsets within the T cell compartment, without major changes in regulatory T cells regarding their presence in circulation. Only the expression of Foxp3 in Treg cells presented lower levels during pregnancy, in both atopic and healthy women (as previously reported in other studies). Although much of the data now reported are in agreement with literature, regarding either memory cell subsets or regulatory T cells, there are also conflicting results, for example documenting changes in the numbers of regulatory T cells circulating in atopic pregnant and atopic non-pregnant women. The importance of harmonizing protocols and phenotypes seems crucial for the establishement of future studies. Considering the risk for atopy in the offspring of atopic women, this study added the possibility to define non-invasive markers for the child, in particular transitional B cells. These cells, whose greater presence in circulation in newborns has recently been associated with subsequent allergy development, are here identified in atopic pregnant women in the third trimester of gestation as a risk factor in the development of atopy in their progeny. The risk factors described, besides having the capacity to easily become integrated within the normal maternal screening protocols during pregnancy, also have the advantage of an early diagnosis, allowing not only the possibility of postnatal prevention but extending this possibility to the prenatal period.
Resumo:
Many viruses have developed numerous strategies to recruit and take advantage of cellular protein degradation pathways to evade the cellular viral immune system. One such virus is the Kaposis Sarcoma associated herpesvirus (KSHV), first discovered in Kaposis Sarcoma lesions found in AIDS patients. Latency-Associated Nuclear Antigen (LANA) is a KSHV multifunctional protein responsible for tethering viral DNA to the chromosome ensuring maintenance and segregation of the viral genome during cell division. Besides its main role of viral maintenance, LANA also physically interacts with several host proteins to modulate cell functions. One such function is to recruit the EC5S ubiquitin-ligase complex by interacting with Elongin BC complex and Cullin 5 protein, which in turn ubiquitinate substrates such as NF-B and p53 to allow persistent viral infection. Like any other post-translation modifications, ubiquitination is reversible through deubiquitination enzymes (DUBs). LANA also interacts with ubiquitin specific protease 7 (USP7), a deubiquitination enzyme involved in regulation of several proteins including p53. Interaction with USP7 is made through a conserved peptide motif, which is also present in LANA. This work addresses the role of LANA in the recruitment and modulation of the ubiquitination and deubiquitination pathways. Despite the continued efforts in uncovering new LANA interacting partners to form a functional EC5S ubiquitin-ligase complex, only MHV-68 LANA interacted directly with Elongin BC, other interactions were not direct and may require a linker protein. On the other hand, LANA interaction with USP7 was able to be analysed by X-ray structure determination. In addition to a conserved P/AxxS motif, a novel Glutamine (Gln) residue from KSHV LANA was shown to make a specific interaction with USP7. This Gln residue is also present in other herpesvirus protein and hence it might be a conserved motif within herpesviruses.
Resumo:
Cancer remains as one of the top killing diseases in first world countries. Its not a single, but a set of various diseases for which different treatment approaches have been taken over the years. Cancer immunotherapy comes as a new breath on cancer treatment, taking use of the patients immune system to induce anti-cancer responses. Dendritic Cell (DC) vaccines use the extraordinary capacity of DCs antigen presentation so that specific T cell responses may be generated against cancer. In this work, we report the ex vivo generation of DCs from precursors isolated from clinical-grade cryopreserved umbilical cord blood (UCB) samples. After the thawing protocol for cryopreserved samples was optimized, the generation of DCs from CD14+ monocytes, i.e., moDCs, or CD34+ hematopoietic stem cells (HSCs), i.e, CD34-derived DCs, was followed and their phenotype and function evaluated. Functional testing included the ability to respond to maturation stimuli (including enzymatic removal of surface sialic acids), Ovalbumin-FITC endocytic capacity, cytokine secretion and T cell priming ability. In order to evaluate the feasibility of using DCs derived from UCB precursors to induce immune responses, they were compared to peripheral blood (PB) moDCs. We observed an increased endocytosis capacity after moDCs were differentiated from monocyte precursors, but almost 10-fold lower than that of PB moDCs. Maturation markers were absent, low levels of inflammatory cytokines were seen and T cell stimulatory capacity was reduced. Sialidase enzymatic treatment was able to mature these cells, diminishing endocytosis and promoting higher T cell stimulation. CD34-derived DCs showed higher capacity for both maturation and endocytic capacity than moDCs. Although much more information was acquired from moDCs than from CD34-derived DCs, we conclude the last as probably the best suited for generating an immune response against cancer, but of course much more research has to be performed.
Resumo:
Natural killer cells are increasingly being considered an important component of innate resistance to viruses, but their role in HIV infection is controversial. Some investigators have found that natural killer cells do not confer a protective effect during the progression of HIV disease, whereas others have shown that natural killer cells may be protective and retard the progression of the disease, either through their lytic activity or by a chemokine-related suppression of HIV replication. In this study, we analyzed functional alterations in the activity of natural killer cells during HIV-1 infection using a natural killer cells activity assay with K562 cells as targets. RESULTS: Our results show that the activity of natural killer cells decreases only in the advanced phase of HIV infection and when high (40:1) effector cell-target cell ratios were used. The depression at this stage of the disease may be related to increased levels of some viral factors, such as gp120 or gag, that interfere with the binding capacity of natural killer cells, or to the decreased production of natural killer cells -activity-stimulating cytokines, such as IFN-a and IL-12, by monocytes, a subset of cells that are also affected in the late stage of HIV infection. The data suggest that decreased natural killer cells cell activity may contribute to the severe impairment of the immune system of patients in the late stages of HIV infection.
Resumo:
The immune system comprises of different cell types whose role is to protect us against pathogens. This thesis investigates a very important mechanism for our organism protection in a specific disorder: cross-presentation in Wiskott-Aldrich Syndrome (WAS). WAS is caused by loss-of-function mutations in the cytoskeletal regulator WASp and WAS patients suffer from eczema, thrombocytopenia, and immunodeficiency. X-linked neutropenia (XLN) is caused by gain-of-function mutations in WASp and XLN patients suffer from severe congenital neutropenia and immunodeficiency. This thesis was focused on the role of B and T lymphocytes and dendritic cells (DCs). This work will be divided into two main topics: 1) In the first part I studied the capacity of B cells to take up, degrade and present antigen. Moreover I studied the capacity of B cells to induce T cell proliferation. 2) In the second part, I studied T cell proliferation induced by dendritic cells. To increase our understanding about this mechanism, additional experiments were performed, including acidification capacity of CD8+ and CD8- DCs, reactive oxygen species (ROS) production since it is directly connected to acidification. These assays were measured by flow cytometry. Localization of Rac1 and Rac2 GTPases was assessed by confocal microscopy. Proliferation, acidification and ROS production assays were performed also with cells from X-linked neutropenia (XLN) mice. From this study we concluded that B cells cannot induce CD8+ T cell proliferation however they take up and present antigen. Moreover I have shown that increased cross-presentation by WASp KO DCs with ovalbumin is associated with decreased capacity to acidify endosomal compartment; and WASp KO CD8- DCs have increased Rac2 localization to the phagosome. XLN dendritic cells have similar acidification and ROS production capacity than wildtype cells. In conclusion, our data suggests that WASp regulates antigen processing and presentation in DCs.
Resumo:
Mesenchymal stem cells (MSCs) are considered to be immunologicallyprivileged. In a previous work when human adiposetissue-derived stem cells (hASCs) subcutaneously implantedin mice we did not identify an adverse host response1. Recently, itwas shown that tissue regeneration could benefit from the polarization of M2 macrophages subpopulations 2. In this study wehypothesised that undifferentiated hASCs and derived osteoblastsand chondrocytes are able to switch murine bone marrow-derivedmacrophages (mBMM s) into M2 phenotype, aiding tissue regeneration. Murine BMM s were plated in direct contact with undifferentiatedand osteo or chondro-differentiated hASCs for 4 h, 10 h,24 h and 72 h. The cytokine profile was analysed by qRT-PCRand the surface markers were detected by flow cytometry. Thedirect interaction of both cell types was observed by time lapsemicroscopy. The results showed that mBMM s polarized after contacting tissueculture polystyrene. This M2 phenotype was maintained along the experimentin direct contact with both undifferentiated and osteo orchondro-differentiated hASCs. This was confirmed by the expression ofIL-1, IL-10, IL-4, TNF-a and IFN-g (genetic profile) and surfacemarkers (CD206 + + , CD336 + + , MHC II + and CD86 + + ) detection.These data suggest the potential of hASCs in contemporary xenogenictissue engineering and regenerative medicine strategies, aswell as host immune system modulation in autoimmune diseases.
Resumo:
Lipocalin-2 (LCN2) is an acute-phase protein that, by binding to iron-loaded siderophores, acts as a potent bacteriostatic agent in the iron-depletion strategy of the immune system to control pathogens. The recent identification of a mammalian siderophore also suggests a physiological role for LCN2 in iron homeostasis, specifically in iron delivery to cells via a transferrin-independent mechanism. LCN2 participates, as well, in a variety of cellular processes, including cell proliferation, cell differentiation and apoptosis, and has been mostly found up-regulated in various tissues and under inflammatory states, being its expression regulated by several inducers. In the central nervous system less is known about the processes involving LCN2, namely by which cells it is produced/secreted, and its impact on cell proliferation and death, or in neuronal plasticity and behaviour. Importantly, LCN2 recently emerged as a potential clinical biomarker in multiple sclerosis and in ageing-related cognitive decline. Still, there are conflicting views on the role of LCN2 in pathophysiological processes, with some studies pointing to its neurodeleterious effects, while others indicate neuroprotection. Herein, these various perspectives are reviewed and a comprehensive and cohesive view of the general function of LCN2, particularly in the brain, is provided.
Resumo:
BACKGROUND: An autoimmune disease is characterized by tissue damage, caused by self-reactivity of different effector mechanisms of the immune system, namely antibodies and T cells. All autoimmune diseases, to some extent, have implications for fertility and obstetrics. Currently, due to available treatments and specialised care for pregnant women with autoimmune disease, the prognosis for both mother and child has improved significantly. However these pregnancies are always high risk. The purpose of this study is to analyse the fertility/pregnancy process of women with systemic and organ-specific autoimmune diseases and assess pathological and treatment implications. METHODS: The authors performed an analysis of the clinical records and relevant obstetric history of five patients representing five distinct autoimmune pathological scenarios, selected from Autoimmune Disease Consultation at the Hospital of Braga, and reviewed the literature. RESULTS: The five clinical cases are the following: Case 1-28 years old with systemic lupus erythematosus, and clinical remission of the disease, under medication with hydroxychloroquine, prednisolone and acetylsalicylic acid, with incomplete miscarriage at 7 weeks of gestation without signs of thrombosis. Case 2-44 years old with history of two late miscarriages, a single preterm delivery (33 weeks) and multiple thrombotic events over the years, was diagnosed with antiphospholipid syndrome after acute myocardial infarction. Case 3-31 years old with polymyositis, treated with azathioprine for 3 years with complete remission of the disease, took the informed decision to get pregnant after medical consultation and full weaning from azathioprine, and gave birth to a healthy term new-born. Case 4-38 years old pregnant woman developed Behcet's syndrome during the final 15 weeks of gestation and with disease exacerbation after delivery. Case 5-36 years old with autoimmune thyroiditis diagnosed during her first pregnancy, with difficult control over the thyroid function over the years and first trimester miscarriage, suffered a second miscarriage despite clinical stability and antibody regression. CONCLUSIONS: As described in literature, the authors found a strong association between autoimmune disease and obstetric complications, especially with systemic lupus erythematosus, antiphospholipid syndrome and autoimmune thyroiditis.
Resumo:
Dissertao de mestrado integrado em Engenharia Biomdica (rea de especializao em Engenharia Clnica)
Resumo:
The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.
Resumo:
ABSTRACTIn fish farmings, diseases can be reduced by using immunostimulants. The aim of this study was to evaluate the immunostimulant potential of Mentha piperita in tambaqui fed with 0, 0.5, 1.0 and 1.5% of oil per kg of commercial fish feed. The fish were inoculated with Aeromonas hydrophila to challenge them. Hematological and biochemical parameters were determined after 30 days of feeding and seven days after the challenge. There was no mortality and M. piperita oil did not influence fish production parameters. However, blood hemoglobin concentration (Hb) increased in the fish fed with 0.5 and 1.5% of oil per kg of diet; albumin increased in those fed with 1.0%; cholesterol increased in all groups with oil; and triglycerides increased in those fed with 0.5%. After the bacterial challenge, the fish showed decreases in Hb when fed with diet enriched with 1.5% oil per kg of diet, in mean corpuscular volume with 1.0% and in mean corpuscular hemoglobin concentration with 0 and 1.5%. Protein levels increased in groups with 0 and 1.5% of oil and albumin when fed with 0 and 1.0%; cholesterol levels increased in the control group; and high levels of triglycerides were observed in the groups with 0, 0.5 and 1.5%. Thus, M. piperita essential oil promoted hematological alterations in tambaqui and can be recommended in diets containing up to 1.0% per kg, because of the minimal physiological modifications caused. However, additional studies are necessary to obtain more information regarding to the physiological effects of this immunostimulant.
