Resveratrol, a polyphenol abundant in peanuts, red wine and the skin of grapes, has been shown to have anti-cancer, anti-oxidant and anti-inflammatory activities, and may also have beneficial effects on allergic infla...Resveratrol, a polyphenol abundant in peanuts, red wine and the skin of grapes, has been shown to have anti-cancer, anti-oxidant and anti-inflammatory activities, and may also have beneficial effects on allergic inflammation. We investigated the effects of resveratrol on human mast cell activation in comparison to the anti-allergy drug tranilast. In LAD2 mast cells, both resveratrol and tranilast inhibited degranulation induced by the mast cell activators substance P, IgE/anti-IgE, and compound 48/80. Resveratrol inhibition was immediate, preventing degranulation when added simultaneously to physiological stimuli, and the effect was sustained for up to 24 hrs. The inhibitory effect was not cAMP dependent, but may be attributable to calcium modulation, as resveratrol, and to a lesser extent tranilast, prevented substance P-induced increases in intracellular calcium. Resveratrol attenuated substance P-induced TNF and MCP-1 production and inhibited IgE-mediated release of cysteinyl leukotrienes, whereas tranilast was ineffective. Furthermore, both resveratrol and tranilast reduced expression of the high affinity IgE receptor, FcεRI, on LAD2 cells. The effects of resveratrol on mast cell activation were more marked in human primary CD34+-derived mast cells (HuMC), and the polyphenol was significantly more efficacious than tranilast in these cells. In conclusion, resveratrol inhibited key aspects of human mast cell activation to physiological stimuli, and was comparable, if not more efficacious than the anti-allergy drug tranilast. Thus, resveratrol may be an effective therapeutic agent for the treatment of allergic disease.展开更多
It has long been known that protein antigen conjugated with polyethylene glycol (PEG), a nonimmunogenic artificial polymer, induces immune tolerance of antigen-specific Th cells. However, the mechanism of this toleran...It has long been known that protein antigen conjugated with polyethylene glycol (PEG), a nonimmunogenic artificial polymer, induces immune tolerance of antigen-specific Th cells. However, the mechanism of this tolerance induction remains unknown. In this study, the response and differentiation of ovalbumin (OVA)-specific CD4+ Th cells upon exposure to tolerogenic PEG conjugate of OVA (PEG-OVA) were studied. Na?ve OVA-specific Th cells from OT-II mice were labeled with carboxyfluorescein succinimidyl ester (CFSE), transferred into histocompatible C57BL/6 mice, and then subsequently stimulated with either tolerogenic PEG-OVA or with OVA. Upon stimulation with tolerogenic PEG-OVA in vivo, these cells showed a robust proliferative response comparable to that observed by stimulation with OVA. Nevertheless, upon prolonged exposure to PEG-OVA, OVA-specific Th cells became anergic, showing a markedly reduced capacity to respond, and to produce IL-2 and other cytokines when stimulated with antigenic OVA323-339 peptide in vitro. There was also a significant reduction of the frequency of clonotypic TCR Vα2+CD4+ T cells in the spleens of OT-II mice treated with PEG-OVA. These features of response of na?ve OVA-specific Th cells upon sustained exposure to PEG-OVA were quite analogous to those reported for the same cells transferred into mice with systemic expression of the transgenic OVA gene. The highly enhanced stability in the circulation that was observed for PEG-OVA was likely the basis of its tolerogenic capacity.展开更多
Context: One of the treatment strategies for atopic diseases is to skew immune response away from Th2 dominance by using Mycobacterial strains. Objective: We wanted to find out whether M. vaccae administration to preg...Context: One of the treatment strategies for atopic diseases is to skew immune response away from Th2 dominance by using Mycobacterial strains. Objective: We wanted to find out whether M. vaccae administration to pregnant mice had any preventive effect on the offsprings in the development of a murine asthma model. Materials and Methods: Pregnant BALB/c mice were divided into two groups;first group received heat-killed M. vaccae subcutaneously on 12th day of pregnancy and the latter group received PBS. After delivery, newborn mice of each group were further divided into two subgroups as M. vaccae/Ovalbumin (OVA), M. vaccae/control, PBS/OVA and PBS/ control. To establish experimental murine asthma model, mice were intraperitoneally sensitized and challenged intratracheally with Ovalbumin. We analysed airway histopathology, bone marrow eosinophil progenitors and splenic cell cytokine profiles of the offsprings. Results: Comparison of offsprings in M. vaccae/OVA group were not different than PBS controls with respect to thicknesses of airway epithelium, basement membrane, subepithelial smooth muscles and number of hyperplasic goblet cells as well as bronchial associated lymphoid tissue density and eosinophil progenitors in the bone marrow. Comparison of M. vaccae/OVA group to asthma model revealed significant differences and lower levels of OVA-induced IL-5. Conclusions: We propose that immunization of pregnant BALB/c with M. vaccae could prevent histopathological alterations in the airways related to the asthma model and down-regulates IL-5 secretion from splenocytes of offsprings.展开更多
A plant fermentation was carried out by Yeast and Lactobacilli against single cellular algae (f-Chlorella). These materials were proved by as safe in animal safety experiment. We sought to look into changes of immune-...A plant fermentation was carried out by Yeast and Lactobacilli against single cellular algae (f-Chlorella). These materials were proved by as safe in animal safety experiment. We sought to look into changes of immune-competent cells that commonly utilized f-Chlorella including after administration of immno-suppressed animals. The effects by f-Chlorella on the regurational effect to the host were measured. Our results showed that f-Chlorella regulated the level of lymphocytes, while conventional-Chlorella worked to adjust the level of granulocytes. In our clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio was obtained as neutral in the peripheral blood. In rodents, immune-compromised host as well as normal animal were prepared with cancer chemotherapeutic agent (Mytomycin-C), and then tried to rescue the immune-competent rebel. Our observations showed that both Chlorella derivatives regulated in number and functions. The effect was more prominent in f-Chlorella than that of conventional one. We discussed the significance and mechanism of f-Chlorella on the level of leukocyte subsets in number and function. These effects were considered to bring the potential elevation of antibody secreting cell by the localized heamolysis in gel method. We also proposed an idea that exhibited tonic effects were brought via activating the complement components in the serum. Moreover, we tried to access further to the anti-oxidative activities of this f-Chlorella. This modification brought to the significant lifted up for immune competent cells and anti-oxidative activity for phagocytic cells.展开更多
Elderly individuals, especially those with pre-existing conditions like type 2 diabetes mellitus (T2DM), have a high risk for developing severe cases of COVID-19. The aim of this work was to characterize the alteratio...Elderly individuals, especially those with pre-existing conditions like type 2 diabetes mellitus (T2DM), have a high risk for developing severe cases of COVID-19. The aim of this work was to characterize the alterations of blood immune cells (BIC) in patients with symptomatic COVID-19 and confirmed SARS-CoV-2 infection, ≥60 years and who needed hospitalization in the Centro de Salud Hospital of Tucuman, Argentina, during the second peak of the pandemic in Argentina. Ten patients were enrolled from December 2020 to May 2021. Blood samples were taken at the time of admission (day 0) and five days after (day 5) for routine laboratory tests and the characterization of BIC by flow cytometry. Most of the patients were men (70%) aged between 60 and 78 years. The 70% of patients had T2DM while 50% had arterial hypertension. At day 0, all the patients had increased neutrophils and inflammatory markers (C reactive protein and D-dimers) and reduced numbers of lymphocytes, HLA-DR<sup>hi</sup> monocytes, CD16<sup>+</sup>CD56<sup>+</sup> NK cells, CD3<sup>+</sup>HLA<sup>−</sup>DR<sup>+</sup>CD25<sup>+</sup> cells, CD4<sup>+</sup> and CD8<sup>+</sup> T cells in blood. Patients received a standard treatment for COVID-19 care (O<sub>2</sub>, corticosteroids and antibiotics). The hospital treatment normalized the levels of BIC (day 5) in 30% of patients who were those with no comorbidities. In patients with T2DM, BIC recovery was variable. In T2DM patients who required administration of plasma (30%), prolonged O<sub>2</sub> therapy (40%) or referral to the intensive care unit (10%) significant reductions of CD16<sup>+</sup>CD56<sup>+</sup>, CD3<sup>+</sup>HLA<sup>−</sup>DR<sup>+</sup>CD25<sup>+</sup>, CD4<sup>+</sup> and CD8<sup>+</sup> cells were observed between days 0 and 5. In line with previous studies, our results show that absolute counts of major lymphocyte subsets in blood are significantly and substantially decreased during the course of severe COVID-19 disease in elderly patients. These BIC alterations may persist despite clinical care in elderly patients with T2DM. Further studies are needed to investigate the utility of early lymphocyte subset measurements as prognostic biomarkers of disease severity, mortality, and response to treatment in COVID-19 elderly patients with T2DM.展开更多
Interleukin-10 (IL-10) mediates an anti-inflammatory response that is executed through the expression of IL-10-induced genes. Certain IL-10-induced genes, exemplified by TNIP3, are induced by IL-10 only in conjunction...Interleukin-10 (IL-10) mediates an anti-inflammatory response that is executed through the expression of IL-10-induced genes. Certain IL-10-induced genes, exemplified by TNIP3, are induced by IL-10 only in conjunction with a pro-inflammatory signal. We sought to characterize the mechanism whereby IL-10 and Toll-like receptor signals synergized to induce expression of genes like TNIP3 inmacrophages. Stimulation with IL-10 and lipopolysaccharide (LPS) synergistically induced an increase in the transcription rate of TNIP3, while having no effect on its mRNA stability. This transcriptional mechanism proved to be generalizable to 14 other genes that also were synergistically induced by IL-10 and LPS in monocytes/macrophages. Although all of the genes had this synergistic transcriptional regulation in common, they could be divided into three subsets based on their differential requirements for de novo protein synthesis and kinetics of expression: namely, primary response genes, early secondary response genes, and late secondary response genes. This coordinated and temporal pattern of transcriptional regulation in response to IL-10 and LPS was conserved in both human and mouse monocytes/macrophages, and it was associated with differential dependencies on PI3K and JNK signaling pathways. These results underscore the complex nature of the IL-10-induced transcriptional response that occurs specifically in LPS-triggered macrophages.展开更多
The immune system operates as a complex organization with distinct roles and functions. Excitingly we recognized the similarities between the cellular dynamics of the immune system and our lives, activities, and behav...The immune system operates as a complex organization with distinct roles and functions. Excitingly we recognized the similarities between the cellular dynamics of the immune system and our lives, activities, and behaviors. Observing the immune system can guide how to respond to various daily situations, including when to react, tolerate, or ignore. Recognizing this analogy between our lives and the immune system should motivate us to adopt a wisdom-based approach when investigating the mechanisms and future discoveries related to this system and to deepen our understanding of this complex system with newfound respect. In this context, the present review examines several integral biological processes of the immune system by drawing parallels between them and human life, activities, and behaviors to learn how we must behave based on the insights offered by this complex organization. The literature search was conducted in international databases such as PubMed/MEDLINE and Google Scholar search engine using English equivalent keywords from 1998 up to April 2023. The search strategy used the following subject heading terms: Immune system, analogy, human life, cellular dynamics, memory, tolerance, and ignorance. In conclusion, the immune system is a complex organization comprising various cells interacting within specific sites and networks, communicating, drawing experiences, and learning how to tolerate certain conditions that make it share certain similarities with human life.展开更多
DPPD (Rv0061) is a difficult to express protein of Mycobacterium tuberculosis that elicits strong and specific delayed type hypersensitiv-ity reactions in humans infected with M. tuber-culosis. Therefore DPPD is a mol...DPPD (Rv0061) is a difficult to express protein of Mycobacterium tuberculosis that elicits strong and specific delayed type hypersensitiv-ity reactions in humans infected with M. tuber-culosis. Therefore DPPD is a molecule that can improve the specificity of the tuberculin skin test, which is widely used as an aid for the di-agnosis of tuberculosis. However, a pitfall of our initial studies was that the DPPD molecule used to perform the skin tests was engineered as fu-sion molecule with another Mycobacterium protein. This approach was used because no expression of DPPD could be achieved either as a single molecule or as a fusion protein using a variety of commercially available expression systems. Here, we report the production and purification of rDPPD using a synthetic gene engineered to contain E. coli codon bias. The gene was cloned into pET14b expression vector, which was subsequently used to transform Rosetta 2(DE3)pLysS or BL-21(DE3)pLysS host cells. The recombinant protein was over-ex- pressed after induction with IPTG and its puri-fication was easily achieved at levels of 5 – 10 mg/l of bacterial broth cultures. The purified protein was confirmed to be DPPD by Mass Spectroscopy sequencing analysis. Moreover, purified rDPPD stimulated peripheral blood mononuclear cells of PPD positive blood do-nors to produce high levels of IFN-γ, thus con-firming that this molecule is biologically active. Because of the DPPD gene is restricted to the tuberculosis-complex organisms of Mycobacte-rium genus, this highly purified molecule should be useful for the identification of indi-viduals sensitized with tubercle展开更多
Introduction: In the Americas, Brazil contributes 91.63% of the total cases and the state of Pará still has high endemia for leprosy. Objective: To analyze the performance of a rapid test for the diagnosis and ep...Introduction: In the Americas, Brazil contributes 91.63% of the total cases and the state of Pará still has high endemia for leprosy. Objective: To analyze the performance of a rapid test for the diagnosis and epidemiological surveillance of leprosy in endemic areas. Methods: The sample consisted of 70 MB multibacillary leprosy (MB) patients, 63 paucibacillary (PB) patients, and 80 intradomiciliary consanguineous contacts (ICSCO) of patients. A rapid test with a 15-minute reading was applied using two prototypes: prototype 1, double test with trisaccharide antigen (NT-P-BSA) at 1a. line (83.2 ng/test) and disaccharide antigen (ND-O-BSA) at 2a. (83.2 ng/test), both with a flow of 0.08 μL/mm with a 10 μC membrane, anti-IgM conjugate with a flow of 0.040 μL/mm and a Tris-Triton and prototype 2 runner buffer with MIX antigen (trisaccharide + disaccharide) in the same concentrations and conditions of prototype 1. Results: The comparison of the MIX test positivity rate and the disaccharide or trisaccharide doublet test across all samples was statistically significant, demonstrating that the MIX test had higher seropositivity rates compared to the ND-O-BSA or NT-P-BSA. It was demonstrated that the MIX test showed a good performance, with 25.39% of the PB patients negative for the disaccharide and trisaccharide duplet test, but positive for MIX. Conclusions: These data suggest the potential for further optimizing the performance by adding other synthetic antigens to the MIX antigens.展开更多
Although the proteomics and its applications in detecting autoimmune diseases are a prominently discussed issue, this review will focus particularly some prominent aspects regarding clinical utility of these technique...Although the proteomics and its applications in detecting autoimmune diseases are a prominently discussed issue, this review will focus particularly some prominent aspects regarding clinical utility of these techniques in prognosis, diagnosis, and treatment of these diseases. The impact of immunofluorescent techniques, enzyme immunoassays and use of proteomics biomarkers in the characterization of the auto immune diseases is briefly discussed. The necessity of adopting existing technologies of protein chemistry, predisposition testing, targeted monitoring and prevention of diseases through nutrition coupled with lifestyle changes will be focused as modern diagnostic tools in realizing the changeover from isolated medicine to personalized medicine. Use of biological fluids, in order to identify low abundance proteins as biomarkers in detecting autoimmune diseases is attempted in the study of serum/plasma proteomics.展开更多
Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missin...Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missing from the rodent endometrium. Interestingly, CD62L (L-selectin)-deficient BALB/c mice delivered significantly higher numbers of viable offspring than wild type controls via mechanisms yet to be defined. Methods: Nulliparous CD62L-deficient (8-10-week-old, n = 25) or wild type (n = 18) females were mated with 43 age-matched males. Animals were sacrificed at gestational day (GD) 9.5. Tissue samples were analyzed by immunostaining and flow cytometry. Results: Mating wild type and CD62L-deficient BALB/c mice revealed that the increased birth rate was due to the CD62L deficiency in females. Flow cytometric analysis demonstrated significant differences in the number of natural killer (NK) cells present in the uterus of pregnant CD62L- deficient mice compared to controls. Immunohistochemistry confirmed NK cell accumulation at the fetal-maternal interface. Discussion: Uterine NK cells have been shown to peak at GD 8-10 at the fetal-maternal interface. NK cells might regulate mouse fertility rates by facilitating development of the maternal spiral arteries, thereby stimulating the formation of larger vessels that facilitate intrauterine survival, however, their role is not obligate to spiral artery development. Conclusions: Diminished CD62L expression modified immune cell trafficking into the uterus of pregnant mice generating a microenvironment primarily dominated by NK cells resulting in improved embryonic survival rates.展开更多
The C-type lectin MGL is a pathogen recognition receptor, expressed by dendritic cells (DCs) and macrophages (Mfs), able to bind GalNAc (Tn) carrying structures. This receptor also recognized Tn-TAAs that were interna...The C-type lectin MGL is a pathogen recognition receptor, expressed by dendritic cells (DCs) and macrophages (Mfs), able to bind GalNAc (Tn) carrying structures. This receptor also recognized Tn-TAAs that were internalized, processed and presented by DCs to T cells and it acted as an adjuvant on DCs, highlighting its possible application in anti-cancer vaccination. In this work, we found that this receptor present a seasonal modulation: its expression is higher in winter rather than in summer. The percentage of MGL+ donors displayed a negative trend that dropped to 33% during the summer and increased up to 100% in winter. This modulation could be also ascribed to the circa-annual variation of glucocorticoids, in fact MGL is up-regulated in presence of dexamethasone in vitro. The seasonal variation of this receptor could be an important point in the field of tumor vaccination strategies.展开更多
Introduction: HIV infection is a public health issue. Developing countries are facing the challenge of patient populations that remain undiagnosed and under-served in combined antiretroviral treatment (cART) leading t...Introduction: HIV infection is a public health issue. Developing countries are facing the challenge of patient populations that remain undiagnosed and under-served in combined antiretroviral treatment (cART) leading to opportunistic infections. Lymph node tuberculosis is one of the most common. His firm diagnosis is not always easy in resources limited country. Case Presentation: We report a case of a 35-year-old woman known HIV for the past 10 years but not on treatment. She presented with a four-month history of fatigue, weight loss and pain in the right flank. The diagnosis of lymph node tuberculosis, hepatitis c virus infection and sickle cell disease was done. After 6 months of treatment, there was a favourable clinical evolution. Conclusion: This case report highlights the necessity to screen for opportunistic and non-opportunistic co-infection in HIV infected patient.展开更多
The B7 family member B7-H3 is broadly expressed in many tissue and tumor types. B7-H3 expression is induced on some immune cells;however, its immunological function remains controversial, because both immunoenhancing ...The B7 family member B7-H3 is broadly expressed in many tissue and tumor types. B7-H3 expression is induced on some immune cells;however, its immunological function remains controversial, because both immunoenhancing and immunoinhibitory effects have been reported in human and mouse systems. We have previously reported the following: 1) murine B7-H3 specifically bound to Triggering receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2, TREML2), a member of the TREM family of receptors;and 2) the B7-H3:TLT-2 pathway up-regulated T cell responses. However, the expression and function of human TLT-2 has not yet been clarified. A recent study found no evidence to support the existence of an interacttion between human B7-H3 and TLT-2. In this study, we demonstrated that human B7-H3 binds to TLT-2 and augments T cell responses. Human and mouse B7-H3Ig chimeric proteins cross-interacted with both human and mouse species of TLT-2-transduced cells. Human TLT-2 was expressed on freshly isolated, peripheral blood B cells and monocytes, and subpopulations of CD4+ and CD8+ T cells. Human TLT-2 expression on T cells did not correlate with na?ve or memory phenotypes and was diminished after culture, despite the presence of mitogenic stimuli. Constitutive TLT-2 expression on monocytes was also down-regulated after culture. Human B7-H3 transfectants augment IL-2 production from TLT-2-transduced T cell hybridomas, and IFN-γ production from peripheral blood CD4+ and CD8+ T cells. The enhanced responses were inhibited by the addition of anti-TLT-2 mAbs, suggesting TLT-2-mediated costimulatory effect. Our results demonstrate the existence of a functional interaction between human B7-H3 and TLT-2, and the restricted expression of TLT-2 on T cells and monocytes.展开更多
Differential contributions of the glycosylphosphatidylinositol (GPI)-anchor and GPI-anchored proteins (GPI-AP) to signalling remain poorly understood. Here we show that GPI-AP deficient murine clones produce on averag...Differential contributions of the glycosylphosphatidylinositol (GPI)-anchor and GPI-anchored proteins (GPI-AP) to signalling remain poorly understood. Here we show that GPI-AP deficient murine clones produce on average 18 and 181-fold more IL-2 mRNA and protein, respectively, upon T cell receptor (TCR) stimulation, in a cell-intrinsic fashion. This phenotype is formally attributed to a mutation within the transferase complex that predicates the initial step in GPI-anchor biosynthesis. Conditional disruption of the transferase complex enabled the generation of primary GPI-AP deficient CD4<sup>+</sup> T cells, which produce on average 10- and 23-fold more IL-2 mRNA and protein, respectively, upon TCR stimulation. Conditional disruption of the transamidase complex yields GPI-sufficient, GPI-AP deficient primary CD4<sup>+</sup> T cells. TCR stimulation of these cells yields levels of IL-2 mRNA and protein ranging from 1 - 3 and 3-fold, respectively, of controls. These results provide the first evidence of a profound impact of GPI in the regulation of TCR signalling.展开更多
Introduction: Studies that have investigated autoimmune thyroid disease in newly diagnosed type 1 diabetic children are few and reported prevalence rate ranges between 4.5 - 29.4 percent. Considering the effect of age...Introduction: Studies that have investigated autoimmune thyroid disease in newly diagnosed type 1 diabetic children are few and reported prevalence rate ranges between 4.5 - 29.4 percent. Considering the effect of age, ethnic origin, and disease duration on the prevalence of autoimmune thyroid disease in diabetic subjects, we decided to investigate the thyroid autoimmunity in newly diagnosed type 1 diabetic children in our area of residence (North-WestIran). Methods: This cross-sectional study was carried out between 2008 and 2010. All of the children with newly diagnosed type 1 diabetes mellitus (T1DM) presenting to the outpatient pediatric- endocrinology clinic of Tabriz University of Medical Sciences (the only university-affiliated clinic for pediatric-endocrinology in North-west Iran), were investigated for serum levels of anti- TPO, anti-Tg and TSH. Results: The study group included 99 children [mean age 7.75 ± 3.21 years (range 1.2 - 14), 45 boys (45.5%) and 54 girls (54.5%)]. About 9% of patients were seropositive for anti thyroid antibodies and females were affected more than males. The mean TSH level of subjects above 12 years of age (3.5 ± 2) was significantly (p = 0.037) higher than those below this age. Conclusion: Autoimmune thyroid disease and even hypothyroidism may accompany T1DM at its presenting time in children. This finding is more common in girls especially those above 12 years of age.展开更多
<b>Background: </b>COVID-19 produced by SARS-CoV-2 infection has spread worldwide. There is a growing need for immunological assays to detect viral specific antibodies or viral antigen. Current standard of...<b>Background: </b>COVID-19 produced by SARS-CoV-2 infection has spread worldwide. There is a growing need for immunological assays to detect viral specific antibodies or viral antigen. Current standard of diagnosis is reverse-transcriptase polymerase chain reaction (RT-PCR) in nasopharyngeal swabs. However serological tests can be used to determine previous exposure to the virus and complement the diagnosis. IgM and IgG SARS-CoV-2 specific antibodies can be detected as early as one week after infection and assays can be useful to test large groups of individuals. This work revised the available information concerning assays that detect antibodies and antigens for SARS-CoV-2. <b>Methods:</b> Three sources of information were used: technical data sheets (TDS) web pages of the company’s products and published articles in Pubmed with reference to the use of diagnostic kits. All the information was revised until April 5<sup>th</sup> 2020. <b>Results: </b>There were 226 tests coming from 20 countries mainly from China. TDS were found only in 50 (22.1%). Most assays detect specific antibodies (n 180) based on immunochromatography methods (n 110) and use blood-derived samples (n 105). Assays for antibodies detection measured mainly IgM/IgG (n 112) and the most common procedure time was <20 min (n 83). Internal control referred as sensitivity and specificity was found only in 18.6% (n 42) of the assays. The majority of the tests are currently for<i> in vitro</i> diagnosis (IVD). A total 165 articles were found on PubMed 15 were included and only 4 used the commercial kits reviewed. <b>Conclusions: </b>Due to the urgency of producing diagnostic tests for SARS-CoV-2 there is a broad offer of kits. Many tests need additional information for their application. The data collected may be useful in the selection of assays but more and higher quality information is needed.展开更多
Background: Parasitic worms evade immune responses, and interactions between diseases can cause altered immunologic outcomes compared to what usually occurs with single infections. These interactions may influence vac...Background: Parasitic worms evade immune responses, and interactions between diseases can cause altered immunologic outcomes compared to what usually occurs with single infections. These interactions may influence vaccine and chemotherapeutic efficacy. Schistosoma mansoni and Plasmodium falciparum are co-endemic in Uganda and are the leading parasitic causes of public health problems across sub-Saharan Africa. Objectives: The overall aim was therefore, to elucidate the impact of S. mansoni infection on protective T helper immune responses on P. falciparum and S. mansoni co-infection. Methodology: This study evaluated the T helper immune responses in individuals with independent S. mansoni infection, independent P. falciparum infection, co-infection and non-infection in school attending children in a co-endemic area along Lake Victoria shores, Uganda. Immune responses were categorized into Th1, Th2, and Th17 based on unique cytokine(s) produced by the T helper subpopulation in ex vivo. Kato Katz thick smears and circulating cathodic antigen tests were performed for S. mansoni screening, whereas thick and thin blood smear techniques were performed for P. falciparum screening. Results: We observed an up regulated Th1 T helper subpopulation in independent P. falciparum infections compared to the uninfected group. Suboptimal T helper immune responses were detected in independent S. mansoni infections characterized by significantly down regulated Th1 (Z = -1.425, p = 0.0313) response in comparison to the non-infected group. Suboptimal T helper immune responses were also recorded in the co-infected individuals characterized by significantly down regulated Th1 (Z = -3.260, p = 0.0273) and Th2 (Z = -1.180, p = 0.0078) responses compared to independent P. falciparum. Conclusions: S. mansoni infection is a major contributor of a reduced effective T helper immune response against P. falciparum in P. falciparum and S. mansoni co-infection.展开更多
Objective: To estimate the potential impact of an HIV/AIDS Vaccine in Kenya. Design: The Kenyan HIV/AIDS epidemic was modeled using the most current data from national sources including epidemiology and behavioral sur...Objective: To estimate the potential impact of an HIV/AIDS Vaccine in Kenya. Design: The Kenyan HIV/AIDS epidemic was modeled using the most current data from national sources including epidemiology and behavioral surveillance. The model’s baseline projection was validated against adult HIV prevalence at antenatal clinics and general population surveys. The model was used to analyze the effects of scaling up current prevention programs and adding potential HIV vaccines with varying levels of effectiveness and coverage. Results: Even with full scale-up of currently available prevention, care and treatment programs, new infections will continue to burden Kenya. The introduction of a partially effective AIDS vaccine could significantly alter the trajectory of the epidemic. Conclusion: The game changing impact that an AIDS vaccine could have on the AIDS epidemic in Kenya under-scores the importance of sustaining political support and financial investment to accelerate HIV/AIDS vaccine research and development.展开更多
Background: We previously showed that MyD88 knocked out mice were protected from death due to B. cenocepacia pneumonia implying that a toll-like receptor(s) (TLR) was involved in mediating death. The aim of the presen...Background: We previously showed that MyD88 knocked out mice were protected from death due to B. cenocepacia pneumonia implying that a toll-like receptor(s) (TLR) was involved in mediating death. The aim of the present study was to determine which TLR(s) was involved in triggering the inflammatory response responsible for the pathogenesis. We specifically focus on the TLRs 4 and 5, as these two receptors are the main ones involved in the recognition of P. aeruginosa, a flagellated Gram-bacterium similar to B. cenocepacia. Methods: Mice were infected intratracheally with a suspension of B. ceno-cepacia. Animals were then observed daily for signs of morbidity. Alternatively, bronchoalveolar lavages (BAL) were collected at different time points to further determine cytokine con-centrations and the number of CFU of B. ceno-cepacia. Results: The data clearly indicate that the innate immune response of the host to B. cenocepacia lung infection was due to TLR4 that senses the pathogen while TLR5 does not do so in vivo. As with the MyD88-/- strain, TLR4-/- mice were protected from death and cytokine and chemokine synthesis to infection were reduced. The only paradoxical observation was the reduced pathogen burden in the case of TLR4-/- mice compared to the enhanced (but transient) pathogen burden observed with MyD88-/- mice, suggesting that another TLR was involved in bacterial clearance. Conclusion: The data clearly demonstrate a deleterious implication of TLR4 in the host to B. cenocepacia lung infection.展开更多
文摘Resveratrol, a polyphenol abundant in peanuts, red wine and the skin of grapes, has been shown to have anti-cancer, anti-oxidant and anti-inflammatory activities, and may also have beneficial effects on allergic inflammation. We investigated the effects of resveratrol on human mast cell activation in comparison to the anti-allergy drug tranilast. In LAD2 mast cells, both resveratrol and tranilast inhibited degranulation induced by the mast cell activators substance P, IgE/anti-IgE, and compound 48/80. Resveratrol inhibition was immediate, preventing degranulation when added simultaneously to physiological stimuli, and the effect was sustained for up to 24 hrs. The inhibitory effect was not cAMP dependent, but may be attributable to calcium modulation, as resveratrol, and to a lesser extent tranilast, prevented substance P-induced increases in intracellular calcium. Resveratrol attenuated substance P-induced TNF and MCP-1 production and inhibited IgE-mediated release of cysteinyl leukotrienes, whereas tranilast was ineffective. Furthermore, both resveratrol and tranilast reduced expression of the high affinity IgE receptor, FcεRI, on LAD2 cells. The effects of resveratrol on mast cell activation were more marked in human primary CD34+-derived mast cells (HuMC), and the polyphenol was significantly more efficacious than tranilast in these cells. In conclusion, resveratrol inhibited key aspects of human mast cell activation to physiological stimuli, and was comparable, if not more efficacious than the anti-allergy drug tranilast. Thus, resveratrol may be an effective therapeutic agent for the treatment of allergic disease.
文摘It has long been known that protein antigen conjugated with polyethylene glycol (PEG), a nonimmunogenic artificial polymer, induces immune tolerance of antigen-specific Th cells. However, the mechanism of this tolerance induction remains unknown. In this study, the response and differentiation of ovalbumin (OVA)-specific CD4+ Th cells upon exposure to tolerogenic PEG conjugate of OVA (PEG-OVA) were studied. Na?ve OVA-specific Th cells from OT-II mice were labeled with carboxyfluorescein succinimidyl ester (CFSE), transferred into histocompatible C57BL/6 mice, and then subsequently stimulated with either tolerogenic PEG-OVA or with OVA. Upon stimulation with tolerogenic PEG-OVA in vivo, these cells showed a robust proliferative response comparable to that observed by stimulation with OVA. Nevertheless, upon prolonged exposure to PEG-OVA, OVA-specific Th cells became anergic, showing a markedly reduced capacity to respond, and to produce IL-2 and other cytokines when stimulated with antigenic OVA323-339 peptide in vitro. There was also a significant reduction of the frequency of clonotypic TCR Vα2+CD4+ T cells in the spleens of OT-II mice treated with PEG-OVA. These features of response of na?ve OVA-specific Th cells upon sustained exposure to PEG-OVA were quite analogous to those reported for the same cells transferred into mice with systemic expression of the transgenic OVA gene. The highly enhanced stability in the circulation that was observed for PEG-OVA was likely the basis of its tolerogenic capacity.
文摘Context: One of the treatment strategies for atopic diseases is to skew immune response away from Th2 dominance by using Mycobacterial strains. Objective: We wanted to find out whether M. vaccae administration to pregnant mice had any preventive effect on the offsprings in the development of a murine asthma model. Materials and Methods: Pregnant BALB/c mice were divided into two groups;first group received heat-killed M. vaccae subcutaneously on 12th day of pregnancy and the latter group received PBS. After delivery, newborn mice of each group were further divided into two subgroups as M. vaccae/Ovalbumin (OVA), M. vaccae/control, PBS/OVA and PBS/ control. To establish experimental murine asthma model, mice were intraperitoneally sensitized and challenged intratracheally with Ovalbumin. We analysed airway histopathology, bone marrow eosinophil progenitors and splenic cell cytokine profiles of the offsprings. Results: Comparison of offsprings in M. vaccae/OVA group were not different than PBS controls with respect to thicknesses of airway epithelium, basement membrane, subepithelial smooth muscles and number of hyperplasic goblet cells as well as bronchial associated lymphoid tissue density and eosinophil progenitors in the bone marrow. Comparison of M. vaccae/OVA group to asthma model revealed significant differences and lower levels of OVA-induced IL-5. Conclusions: We propose that immunization of pregnant BALB/c with M. vaccae could prevent histopathological alterations in the airways related to the asthma model and down-regulates IL-5 secretion from splenocytes of offsprings.
文摘A plant fermentation was carried out by Yeast and Lactobacilli against single cellular algae (f-Chlorella). These materials were proved by as safe in animal safety experiment. We sought to look into changes of immune-competent cells that commonly utilized f-Chlorella including after administration of immno-suppressed animals. The effects by f-Chlorella on the regurational effect to the host were measured. Our results showed that f-Chlorella regulated the level of lymphocytes, while conventional-Chlorella worked to adjust the level of granulocytes. In our clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio was obtained as neutral in the peripheral blood. In rodents, immune-compromised host as well as normal animal were prepared with cancer chemotherapeutic agent (Mytomycin-C), and then tried to rescue the immune-competent rebel. Our observations showed that both Chlorella derivatives regulated in number and functions. The effect was more prominent in f-Chlorella than that of conventional one. We discussed the significance and mechanism of f-Chlorella on the level of leukocyte subsets in number and function. These effects were considered to bring the potential elevation of antibody secreting cell by the localized heamolysis in gel method. We also proposed an idea that exhibited tonic effects were brought via activating the complement components in the serum. Moreover, we tried to access further to the anti-oxidative activities of this f-Chlorella. This modification brought to the significant lifted up for immune competent cells and anti-oxidative activity for phagocytic cells.
文摘Elderly individuals, especially those with pre-existing conditions like type 2 diabetes mellitus (T2DM), have a high risk for developing severe cases of COVID-19. The aim of this work was to characterize the alterations of blood immune cells (BIC) in patients with symptomatic COVID-19 and confirmed SARS-CoV-2 infection, ≥60 years and who needed hospitalization in the Centro de Salud Hospital of Tucuman, Argentina, during the second peak of the pandemic in Argentina. Ten patients were enrolled from December 2020 to May 2021. Blood samples were taken at the time of admission (day 0) and five days after (day 5) for routine laboratory tests and the characterization of BIC by flow cytometry. Most of the patients were men (70%) aged between 60 and 78 years. The 70% of patients had T2DM while 50% had arterial hypertension. At day 0, all the patients had increased neutrophils and inflammatory markers (C reactive protein and D-dimers) and reduced numbers of lymphocytes, HLA-DR<sup>hi</sup> monocytes, CD16<sup>+</sup>CD56<sup>+</sup> NK cells, CD3<sup>+</sup>HLA<sup>−</sup>DR<sup>+</sup>CD25<sup>+</sup> cells, CD4<sup>+</sup> and CD8<sup>+</sup> T cells in blood. Patients received a standard treatment for COVID-19 care (O<sub>2</sub>, corticosteroids and antibiotics). The hospital treatment normalized the levels of BIC (day 5) in 30% of patients who were those with no comorbidities. In patients with T2DM, BIC recovery was variable. In T2DM patients who required administration of plasma (30%), prolonged O<sub>2</sub> therapy (40%) or referral to the intensive care unit (10%) significant reductions of CD16<sup>+</sup>CD56<sup>+</sup>, CD3<sup>+</sup>HLA<sup>−</sup>DR<sup>+</sup>CD25<sup>+</sup>, CD4<sup>+</sup> and CD8<sup>+</sup> cells were observed between days 0 and 5. In line with previous studies, our results show that absolute counts of major lymphocyte subsets in blood are significantly and substantially decreased during the course of severe COVID-19 disease in elderly patients. These BIC alterations may persist despite clinical care in elderly patients with T2DM. Further studies are needed to investigate the utility of early lymphocyte subset measurements as prognostic biomarkers of disease severity, mortality, and response to treatment in COVID-19 elderly patients with T2DM.
文摘Interleukin-10 (IL-10) mediates an anti-inflammatory response that is executed through the expression of IL-10-induced genes. Certain IL-10-induced genes, exemplified by TNIP3, are induced by IL-10 only in conjunction with a pro-inflammatory signal. We sought to characterize the mechanism whereby IL-10 and Toll-like receptor signals synergized to induce expression of genes like TNIP3 inmacrophages. Stimulation with IL-10 and lipopolysaccharide (LPS) synergistically induced an increase in the transcription rate of TNIP3, while having no effect on its mRNA stability. This transcriptional mechanism proved to be generalizable to 14 other genes that also were synergistically induced by IL-10 and LPS in monocytes/macrophages. Although all of the genes had this synergistic transcriptional regulation in common, they could be divided into three subsets based on their differential requirements for de novo protein synthesis and kinetics of expression: namely, primary response genes, early secondary response genes, and late secondary response genes. This coordinated and temporal pattern of transcriptional regulation in response to IL-10 and LPS was conserved in both human and mouse monocytes/macrophages, and it was associated with differential dependencies on PI3K and JNK signaling pathways. These results underscore the complex nature of the IL-10-induced transcriptional response that occurs specifically in LPS-triggered macrophages.
文摘The immune system operates as a complex organization with distinct roles and functions. Excitingly we recognized the similarities between the cellular dynamics of the immune system and our lives, activities, and behaviors. Observing the immune system can guide how to respond to various daily situations, including when to react, tolerate, or ignore. Recognizing this analogy between our lives and the immune system should motivate us to adopt a wisdom-based approach when investigating the mechanisms and future discoveries related to this system and to deepen our understanding of this complex system with newfound respect. In this context, the present review examines several integral biological processes of the immune system by drawing parallels between them and human life, activities, and behaviors to learn how we must behave based on the insights offered by this complex organization. The literature search was conducted in international databases such as PubMed/MEDLINE and Google Scholar search engine using English equivalent keywords from 1998 up to April 2023. The search strategy used the following subject heading terms: Immune system, analogy, human life, cellular dynamics, memory, tolerance, and ignorance. In conclusion, the immune system is a complex organization comprising various cells interacting within specific sites and networks, communicating, drawing experiences, and learning how to tolerate certain conditions that make it share certain similarities with human life.
文摘DPPD (Rv0061) is a difficult to express protein of Mycobacterium tuberculosis that elicits strong and specific delayed type hypersensitiv-ity reactions in humans infected with M. tuber-culosis. Therefore DPPD is a molecule that can improve the specificity of the tuberculin skin test, which is widely used as an aid for the di-agnosis of tuberculosis. However, a pitfall of our initial studies was that the DPPD molecule used to perform the skin tests was engineered as fu-sion molecule with another Mycobacterium protein. This approach was used because no expression of DPPD could be achieved either as a single molecule or as a fusion protein using a variety of commercially available expression systems. Here, we report the production and purification of rDPPD using a synthetic gene engineered to contain E. coli codon bias. The gene was cloned into pET14b expression vector, which was subsequently used to transform Rosetta 2(DE3)pLysS or BL-21(DE3)pLysS host cells. The recombinant protein was over-ex- pressed after induction with IPTG and its puri-fication was easily achieved at levels of 5 – 10 mg/l of bacterial broth cultures. The purified protein was confirmed to be DPPD by Mass Spectroscopy sequencing analysis. Moreover, purified rDPPD stimulated peripheral blood mononuclear cells of PPD positive blood do-nors to produce high levels of IFN-γ, thus con-firming that this molecule is biologically active. Because of the DPPD gene is restricted to the tuberculosis-complex organisms of Mycobacte-rium genus, this highly purified molecule should be useful for the identification of indi-viduals sensitized with tubercle
文摘Introduction: In the Americas, Brazil contributes 91.63% of the total cases and the state of Pará still has high endemia for leprosy. Objective: To analyze the performance of a rapid test for the diagnosis and epidemiological surveillance of leprosy in endemic areas. Methods: The sample consisted of 70 MB multibacillary leprosy (MB) patients, 63 paucibacillary (PB) patients, and 80 intradomiciliary consanguineous contacts (ICSCO) of patients. A rapid test with a 15-minute reading was applied using two prototypes: prototype 1, double test with trisaccharide antigen (NT-P-BSA) at 1a. line (83.2 ng/test) and disaccharide antigen (ND-O-BSA) at 2a. (83.2 ng/test), both with a flow of 0.08 μL/mm with a 10 μC membrane, anti-IgM conjugate with a flow of 0.040 μL/mm and a Tris-Triton and prototype 2 runner buffer with MIX antigen (trisaccharide + disaccharide) in the same concentrations and conditions of prototype 1. Results: The comparison of the MIX test positivity rate and the disaccharide or trisaccharide doublet test across all samples was statistically significant, demonstrating that the MIX test had higher seropositivity rates compared to the ND-O-BSA or NT-P-BSA. It was demonstrated that the MIX test showed a good performance, with 25.39% of the PB patients negative for the disaccharide and trisaccharide duplet test, but positive for MIX. Conclusions: These data suggest the potential for further optimizing the performance by adding other synthetic antigens to the MIX antigens.
文摘Although the proteomics and its applications in detecting autoimmune diseases are a prominently discussed issue, this review will focus particularly some prominent aspects regarding clinical utility of these techniques in prognosis, diagnosis, and treatment of these diseases. The impact of immunofluorescent techniques, enzyme immunoassays and use of proteomics biomarkers in the characterization of the auto immune diseases is briefly discussed. The necessity of adopting existing technologies of protein chemistry, predisposition testing, targeted monitoring and prevention of diseases through nutrition coupled with lifestyle changes will be focused as modern diagnostic tools in realizing the changeover from isolated medicine to personalized medicine. Use of biological fluids, in order to identify low abundance proteins as biomarkers in detecting autoimmune diseases is attempted in the study of serum/plasma proteomics.
文摘Background: L-selectin (CD62L) is a cell surface adhesion molecule recently shown to play a critical role in determining endometrial receptivity and implantation in humans. By contrast, the L-selectin ligand is missing from the rodent endometrium. Interestingly, CD62L (L-selectin)-deficient BALB/c mice delivered significantly higher numbers of viable offspring than wild type controls via mechanisms yet to be defined. Methods: Nulliparous CD62L-deficient (8-10-week-old, n = 25) or wild type (n = 18) females were mated with 43 age-matched males. Animals were sacrificed at gestational day (GD) 9.5. Tissue samples were analyzed by immunostaining and flow cytometry. Results: Mating wild type and CD62L-deficient BALB/c mice revealed that the increased birth rate was due to the CD62L deficiency in females. Flow cytometric analysis demonstrated significant differences in the number of natural killer (NK) cells present in the uterus of pregnant CD62L- deficient mice compared to controls. Immunohistochemistry confirmed NK cell accumulation at the fetal-maternal interface. Discussion: Uterine NK cells have been shown to peak at GD 8-10 at the fetal-maternal interface. NK cells might regulate mouse fertility rates by facilitating development of the maternal spiral arteries, thereby stimulating the formation of larger vessels that facilitate intrauterine survival, however, their role is not obligate to spiral artery development. Conclusions: Diminished CD62L expression modified immune cell trafficking into the uterus of pregnant mice generating a microenvironment primarily dominated by NK cells resulting in improved embryonic survival rates.
文摘The C-type lectin MGL is a pathogen recognition receptor, expressed by dendritic cells (DCs) and macrophages (Mfs), able to bind GalNAc (Tn) carrying structures. This receptor also recognized Tn-TAAs that were internalized, processed and presented by DCs to T cells and it acted as an adjuvant on DCs, highlighting its possible application in anti-cancer vaccination. In this work, we found that this receptor present a seasonal modulation: its expression is higher in winter rather than in summer. The percentage of MGL+ donors displayed a negative trend that dropped to 33% during the summer and increased up to 100% in winter. This modulation could be also ascribed to the circa-annual variation of glucocorticoids, in fact MGL is up-regulated in presence of dexamethasone in vitro. The seasonal variation of this receptor could be an important point in the field of tumor vaccination strategies.
文摘Introduction: HIV infection is a public health issue. Developing countries are facing the challenge of patient populations that remain undiagnosed and under-served in combined antiretroviral treatment (cART) leading to opportunistic infections. Lymph node tuberculosis is one of the most common. His firm diagnosis is not always easy in resources limited country. Case Presentation: We report a case of a 35-year-old woman known HIV for the past 10 years but not on treatment. She presented with a four-month history of fatigue, weight loss and pain in the right flank. The diagnosis of lymph node tuberculosis, hepatitis c virus infection and sickle cell disease was done. After 6 months of treatment, there was a favourable clinical evolution. Conclusion: This case report highlights the necessity to screen for opportunistic and non-opportunistic co-infection in HIV infected patient.
文摘The B7 family member B7-H3 is broadly expressed in many tissue and tumor types. B7-H3 expression is induced on some immune cells;however, its immunological function remains controversial, because both immunoenhancing and immunoinhibitory effects have been reported in human and mouse systems. We have previously reported the following: 1) murine B7-H3 specifically bound to Triggering receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2, TREML2), a member of the TREM family of receptors;and 2) the B7-H3:TLT-2 pathway up-regulated T cell responses. However, the expression and function of human TLT-2 has not yet been clarified. A recent study found no evidence to support the existence of an interacttion between human B7-H3 and TLT-2. In this study, we demonstrated that human B7-H3 binds to TLT-2 and augments T cell responses. Human and mouse B7-H3Ig chimeric proteins cross-interacted with both human and mouse species of TLT-2-transduced cells. Human TLT-2 was expressed on freshly isolated, peripheral blood B cells and monocytes, and subpopulations of CD4+ and CD8+ T cells. Human TLT-2 expression on T cells did not correlate with na?ve or memory phenotypes and was diminished after culture, despite the presence of mitogenic stimuli. Constitutive TLT-2 expression on monocytes was also down-regulated after culture. Human B7-H3 transfectants augment IL-2 production from TLT-2-transduced T cell hybridomas, and IFN-γ production from peripheral blood CD4+ and CD8+ T cells. The enhanced responses were inhibited by the addition of anti-TLT-2 mAbs, suggesting TLT-2-mediated costimulatory effect. Our results demonstrate the existence of a functional interaction between human B7-H3 and TLT-2, and the restricted expression of TLT-2 on T cells and monocytes.
文摘Differential contributions of the glycosylphosphatidylinositol (GPI)-anchor and GPI-anchored proteins (GPI-AP) to signalling remain poorly understood. Here we show that GPI-AP deficient murine clones produce on average 18 and 181-fold more IL-2 mRNA and protein, respectively, upon T cell receptor (TCR) stimulation, in a cell-intrinsic fashion. This phenotype is formally attributed to a mutation within the transferase complex that predicates the initial step in GPI-anchor biosynthesis. Conditional disruption of the transferase complex enabled the generation of primary GPI-AP deficient CD4<sup>+</sup> T cells, which produce on average 10- and 23-fold more IL-2 mRNA and protein, respectively, upon TCR stimulation. Conditional disruption of the transamidase complex yields GPI-sufficient, GPI-AP deficient primary CD4<sup>+</sup> T cells. TCR stimulation of these cells yields levels of IL-2 mRNA and protein ranging from 1 - 3 and 3-fold, respectively, of controls. These results provide the first evidence of a profound impact of GPI in the regulation of TCR signalling.
文摘Introduction: Studies that have investigated autoimmune thyroid disease in newly diagnosed type 1 diabetic children are few and reported prevalence rate ranges between 4.5 - 29.4 percent. Considering the effect of age, ethnic origin, and disease duration on the prevalence of autoimmune thyroid disease in diabetic subjects, we decided to investigate the thyroid autoimmunity in newly diagnosed type 1 diabetic children in our area of residence (North-WestIran). Methods: This cross-sectional study was carried out between 2008 and 2010. All of the children with newly diagnosed type 1 diabetes mellitus (T1DM) presenting to the outpatient pediatric- endocrinology clinic of Tabriz University of Medical Sciences (the only university-affiliated clinic for pediatric-endocrinology in North-west Iran), were investigated for serum levels of anti- TPO, anti-Tg and TSH. Results: The study group included 99 children [mean age 7.75 ± 3.21 years (range 1.2 - 14), 45 boys (45.5%) and 54 girls (54.5%)]. About 9% of patients were seropositive for anti thyroid antibodies and females were affected more than males. The mean TSH level of subjects above 12 years of age (3.5 ± 2) was significantly (p = 0.037) higher than those below this age. Conclusion: Autoimmune thyroid disease and even hypothyroidism may accompany T1DM at its presenting time in children. This finding is more common in girls especially those above 12 years of age.
文摘<b>Background: </b>COVID-19 produced by SARS-CoV-2 infection has spread worldwide. There is a growing need for immunological assays to detect viral specific antibodies or viral antigen. Current standard of diagnosis is reverse-transcriptase polymerase chain reaction (RT-PCR) in nasopharyngeal swabs. However serological tests can be used to determine previous exposure to the virus and complement the diagnosis. IgM and IgG SARS-CoV-2 specific antibodies can be detected as early as one week after infection and assays can be useful to test large groups of individuals. This work revised the available information concerning assays that detect antibodies and antigens for SARS-CoV-2. <b>Methods:</b> Three sources of information were used: technical data sheets (TDS) web pages of the company’s products and published articles in Pubmed with reference to the use of diagnostic kits. All the information was revised until April 5<sup>th</sup> 2020. <b>Results: </b>There were 226 tests coming from 20 countries mainly from China. TDS were found only in 50 (22.1%). Most assays detect specific antibodies (n 180) based on immunochromatography methods (n 110) and use blood-derived samples (n 105). Assays for antibodies detection measured mainly IgM/IgG (n 112) and the most common procedure time was <20 min (n 83). Internal control referred as sensitivity and specificity was found only in 18.6% (n 42) of the assays. The majority of the tests are currently for<i> in vitro</i> diagnosis (IVD). A total 165 articles were found on PubMed 15 were included and only 4 used the commercial kits reviewed. <b>Conclusions: </b>Due to the urgency of producing diagnostic tests for SARS-CoV-2 there is a broad offer of kits. Many tests need additional information for their application. The data collected may be useful in the selection of assays but more and higher quality information is needed.
文摘Background: Parasitic worms evade immune responses, and interactions between diseases can cause altered immunologic outcomes compared to what usually occurs with single infections. These interactions may influence vaccine and chemotherapeutic efficacy. Schistosoma mansoni and Plasmodium falciparum are co-endemic in Uganda and are the leading parasitic causes of public health problems across sub-Saharan Africa. Objectives: The overall aim was therefore, to elucidate the impact of S. mansoni infection on protective T helper immune responses on P. falciparum and S. mansoni co-infection. Methodology: This study evaluated the T helper immune responses in individuals with independent S. mansoni infection, independent P. falciparum infection, co-infection and non-infection in school attending children in a co-endemic area along Lake Victoria shores, Uganda. Immune responses were categorized into Th1, Th2, and Th17 based on unique cytokine(s) produced by the T helper subpopulation in ex vivo. Kato Katz thick smears and circulating cathodic antigen tests were performed for S. mansoni screening, whereas thick and thin blood smear techniques were performed for P. falciparum screening. Results: We observed an up regulated Th1 T helper subpopulation in independent P. falciparum infections compared to the uninfected group. Suboptimal T helper immune responses were detected in independent S. mansoni infections characterized by significantly down regulated Th1 (Z = -1.425, p = 0.0313) response in comparison to the non-infected group. Suboptimal T helper immune responses were also recorded in the co-infected individuals characterized by significantly down regulated Th1 (Z = -3.260, p = 0.0273) and Th2 (Z = -1.180, p = 0.0078) responses compared to independent P. falciparum. Conclusions: S. mansoni infection is a major contributor of a reduced effective T helper immune response against P. falciparum in P. falciparum and S. mansoni co-infection.
文摘Objective: To estimate the potential impact of an HIV/AIDS Vaccine in Kenya. Design: The Kenyan HIV/AIDS epidemic was modeled using the most current data from national sources including epidemiology and behavioral surveillance. The model’s baseline projection was validated against adult HIV prevalence at antenatal clinics and general population surveys. The model was used to analyze the effects of scaling up current prevention programs and adding potential HIV vaccines with varying levels of effectiveness and coverage. Results: Even with full scale-up of currently available prevention, care and treatment programs, new infections will continue to burden Kenya. The introduction of a partially effective AIDS vaccine could significantly alter the trajectory of the epidemic. Conclusion: The game changing impact that an AIDS vaccine could have on the AIDS epidemic in Kenya under-scores the importance of sustaining political support and financial investment to accelerate HIV/AIDS vaccine research and development.
文摘Background: We previously showed that MyD88 knocked out mice were protected from death due to B. cenocepacia pneumonia implying that a toll-like receptor(s) (TLR) was involved in mediating death. The aim of the present study was to determine which TLR(s) was involved in triggering the inflammatory response responsible for the pathogenesis. We specifically focus on the TLRs 4 and 5, as these two receptors are the main ones involved in the recognition of P. aeruginosa, a flagellated Gram-bacterium similar to B. cenocepacia. Methods: Mice were infected intratracheally with a suspension of B. ceno-cepacia. Animals were then observed daily for signs of morbidity. Alternatively, bronchoalveolar lavages (BAL) were collected at different time points to further determine cytokine con-centrations and the number of CFU of B. ceno-cepacia. Results: The data clearly indicate that the innate immune response of the host to B. cenocepacia lung infection was due to TLR4 that senses the pathogen while TLR5 does not do so in vivo. As with the MyD88-/- strain, TLR4-/- mice were protected from death and cytokine and chemokine synthesis to infection were reduced. The only paradoxical observation was the reduced pathogen burden in the case of TLR4-/- mice compared to the enhanced (but transient) pathogen burden observed with MyD88-/- mice, suggesting that another TLR was involved in bacterial clearance. Conclusion: The data clearly demonstrate a deleterious implication of TLR4 in the host to B. cenocepacia lung infection.
