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Vitamin D: The Immunologic Role and its Effect on Human Pathophysiology 维生素D:免疫作用及其对人体病理生理的影响
Pub Date : 2015-05-05 DOI: 10.3844/AJISP.2015.10.16
W. Whalen, Edward Cook, N. Chakraborty
There are several reasons why understanding the role of vitamin D in the immune system is worthy of widespread attention. Our knowledge of the immune system is crucial for understanding human health and disease. New ideas for vitamin D and life style in the twenty-first century build directly on our understanding of immunology-from the development of new immune-based cancer drugs to advancing treatments for common diseases, such as autoimmunity and allergies. The scientists and physicians must be inspired to tackle the vast array of unmet immunological needs and the application of old theories-the effectiveness of vaccines, for example-can benefit largely from our understanding of Vitamin D and its role in immunology. The role of immune system is to seek out and destroy dangerous bacteria, viruses, fungi and uncontrolled tumor (cancer) growth. Its activities connect with other body systems and influences, our metabolism and hormone levels and controls how well we feel. Nutrition and our mental health are all connected to our ability to fight infections and abnormal cell growth. In this article we will mainly focus on Vitamin D and its immunological effects on pulmonary disease, tuberculosis and cancer.
了解维生素D在免疫系统中的作用值得广泛关注,有几个原因。我们对免疫系统的了解对于理解人类健康和疾病至关重要。21世纪关于维生素D和生活方式的新想法直接建立在我们对免疫学的理解之上——从开发新的基于免疫的癌症药物到推进常见疾病的治疗,如自身免疫和过敏。必须激励科学家和医生解决大量未满足的免疫学需求,并应用旧理论——例如疫苗的有效性——这在很大程度上得益于我们对维生素D及其在免疫学中的作用的理解。免疫系统的作用是寻找和摧毁危险的细菌、病毒、真菌和不受控制的肿瘤(癌症)的生长。它的活动与其他身体系统和影响,我们的新陈代谢和激素水平,并控制我们的感觉。营养和我们的心理健康都与我们抵抗感染和异常细胞生长的能力有关。在本文中,我们将主要关注维生素D及其对肺部疾病、结核病和癌症的免疫作用。
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引用次数: 0
Effects of Short Term in vitro Stress Hormone Exposure on Regulatory T Cell Number and Function in Asthma 短期体外应激激素暴露对哮喘患者调节性T细胞数量和功能的影响
Pub Date : 2015-04-24 DOI: 10.3844/AJISP.2015.1.9
K. Rehm, G. Marshall
Asthma is characterized by alterations in the immune system, including regulatory T cells (Treg). Further alterations in Treg numbers and/or function caused by stress hormones may be a contributing factor in asthma pathogenesis. We compared Treg populations and the effects of Dexamethasone (DEX, a laboratory analog of cortisol) on Treg cell number and function in patients with asthma and a control group. We isolated Peripheral Blood Mononuclear Cells (PBMC) from asthma patients (n = 7) and normal controls (n = 8) and quantified CD4+, CD4+CD25hi and CD4+CD25hiFoxP3+ T cells by flow cytometry. To determine the effects of in vitro stress hormones on Treg number and function, we incubated PBMC with 10-9 M, 10-8 M and 10-7 M DEX for 24 h and then CD4+CD25hiFoxP3+ Treg were quantified by flow cytometry. To assess function, CD4+CD25+ were separated and added to cultures of bead-stimulated CD4+CD25- cells and proliferation was measured and compared to the CD4+CD25- cultures incubated with beads alone. The asthma group had significantly fewer CD4+CD25hi and CD4+CD25hiFoxP3+ cells than the control group. DEX significantly decreased Treg number in the control group but not in the asthma group. DEX had no effect on CD4+CD25+ function in either group and the suppressive capacity of the CD4+CD25+ cells was no different between the asthma group and the normal control group. These data suggest that while asthmatics have fewer Treg than normal controls, their function does not differ. These data also suggest that Treg from asthmatics may be less susceptible to the effects of stress hormones.
哮喘的特点是免疫系统的改变,包括调节性T细胞(Treg)。应激激素引起的Treg数量和/或功能的进一步改变可能是哮喘发病的一个促成因素。我们比较了哮喘患者和对照组Treg细胞的数量和功能,以及地塞米松(Dexamethasone,一种皮质醇的实验室类似物)对Treg细胞数量和功能的影响。我们从哮喘患者(n = 7)和正常对照(n = 8)中分离外周血单核细胞(PBMC),用流式细胞术定量CD4+、CD4+CD25hi和CD4+CD25hiFoxP3+ T细胞。为了确定体外应激激素对Treg数量和功能的影响,我们用10-9 M、10-8 M和10-7 M DEX孵育PBMC 24 h,然后用流式细胞术定量CD4+CD25hiFoxP3+ Treg。为了评估其功能,分离CD4+CD25+并将其添加到珠状细胞刺激的CD4+CD25-细胞中,并测量其增殖情况,并与单独用珠状细胞孵育的CD4+CD25-细胞进行比较。哮喘组CD4+CD25hi和CD4+CD25hiFoxP3+细胞明显少于对照组。DEX在对照组显著降低Treg数量,在哮喘组无显著降低。DEX对两组患者CD4+CD25+功能均无影响,哮喘组与正常对照组对CD4+CD25+细胞的抑制能力无差异。这些数据表明,虽然哮喘患者的Treg比正常人少,但它们的功能并没有什么不同。这些数据还表明,哮喘患者的Treg可能不太容易受到应激激素的影响。
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引用次数: 0
HELICOBACTER INFECTION AND ALLERGY IN MAJORITY AND ROMA POPULATION IN THE CZECH REPUBLIC 捷克共和国大多数人和罗姆人的幽门螺杆菌感染和过敏
Pub Date : 2014-12-24 DOI: 10.3844/AJISP.2014.166.172
R. Josef, V. Vaclav, Král Vlastimil, Svozil Vladimir, Pohořská Jitka, S. Ivana, S. Hana, Rajnohova Dobiasova Lucie
In our paper we decided to evaluate the hypothesis about the relation between living conditions, infection with Helicobacter pylori and development of allergic problems. Two groups of children, one from the Roma population and one from the majority population, were chosen for this study. Comparing the levels of total IgE and specific IgE antibodies, IgA and IgG Helicobacter pylori antibodies in both populations, we found significant differences in all tested aspects. We conclude that changes in lifestyle together with changes in improvements in living conditions and reduction of risk factors can significantly influence the health conditions of thepopulation and overall quality of life.
在我们的论文中,我们决定评估关于生活条件、幽门螺杆菌感染和过敏问题发展之间关系的假设。本研究选择了两组儿童,一组来自罗姆人,另一组来自大多数人。比较两种人群中总IgE和特异性IgE抗体、IgA和IgG幽门螺杆菌抗体的水平,我们发现在所有测试方面都有显著差异。我们的结论是,生活方式的改变以及生活条件的改善和风险因素的减少可以显著影响人口的健康状况和整体生活质量。
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引用次数: 1
To NET or not to NET 使用。NET还是不使用。NET
Pub Date : 2014-12-03 DOI: 10.3844/AJISP.2014.174.175
J. Jablonska
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引用次数: 14
DUAL ROLES OF CANCER CELL-EXPRESSED IMMUNOGLOBULINS IN CANCER IMMUNOLOGY 癌细胞表达的免疫球蛋白在癌症免疫学中的双重作用
Pub Date : 2014-10-02 DOI: 10.3844/AJISP.2014.156.165
Gregory Lee, Cheng-Yuan Huang, S. Liu, C. Chien, S. Chow
While the expression of immunoglobulins and T cell receptors on cancer cells has been well-established for decades, the potential roles and mechanisms of action of these cancerous antigen receptors have not been fully elucidated. A monoclonal antibody designated as RP215, which reacts specifically with the carbohydrate-associated epitope located on the heavy chain region of cancerous immunoglobulins and T cell receptors, was used as a unique probe to study the roles of antigen receptors in the immunology of cancer cells. Through extensive cell-based biological and immunological studies, it was found that both anti-antigen receptors and RP215 demonstrated similar actions on the gene regulations involved in the growth/proliferation of cancer cells, as well as on toll-like receptors involved in innate immunity. In addition, RP215-specific cancerous immunoglobulins are believed to capture or neutralize circulating antigen/antibodies which may be harmful to cancer cells within the human body. In contrast to normal B and T cells and their respective receptors in the conventional immune system, cancer cells co-express both immunoglobulins and T cell receptors and immune protection is exercised by unique mechanisms. For example, these cancer cell-expressed antigen receptors display a lack of class switching, limited hyper-mutation, aberrant glycosylations and a strong influence on the toll-like receptors of cancer cells. Therefore, it is hypothesized that both normal and cancerous immune systems may co-exist and operate simultaneously within the human body. The balance of these two immune factors for respective surveillance and protection may be relevant to the outcome of cancer immunotherapy in humans. A potential therapeutic strategy is being developed by using RP215 as a drug candidate to target cancer cells based on these observations.
虽然免疫球蛋白和T细胞受体在癌细胞上的表达已经建立了几十年,但这些癌性抗原受体的潜在作用和作用机制尚未完全阐明。一种被命名为RP215的单克隆抗体,可以与位于癌性免疫球蛋白和T细胞受体重链区域的糖相关表位发生特异性反应,作为一种独特的探针来研究抗原受体在癌细胞免疫学中的作用。通过广泛的基于细胞的生物学和免疫学研究,发现抗抗原受体和RP215对参与癌细胞生长/增殖的基因调控以及参与先天免疫的toll样受体的作用相似。此外,rp215特异性癌性免疫球蛋白被认为可以捕获或中和可能对人体内癌细胞有害的循环抗原/抗体。与常规免疫系统中正常的B细胞和T细胞及其受体不同,癌细胞同时表达免疫球蛋白和T细胞受体,免疫保护通过独特的机制发挥作用。例如,这些癌细胞表达的抗原受体表现出缺乏类转换、有限的超突变、异常的糖基化和对癌细胞的toll样受体的强烈影响。因此,假设正常免疫系统和癌变免疫系统可能在人体内共存并同时运作。这两种免疫因子在各自的监测和保护方面的平衡可能与人类癌症免疫治疗的结果有关。基于这些观察结果,人们正在开发一种潜在的治疗策略,即使用RP215作为靶向癌细胞的候选药物。
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引用次数: 6
IMMUNOLOGY IN BRAZIL: CHALLENGES AND OPPORTUNITIES FOR YOUNG SCIENTISTS 巴西的免疫学:青年科学家的挑战和机遇
Pub Date : 2014-09-26 DOI: 10.3844/AJISP.2014.173.173
C. Panis
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引用次数: 0
PREVALENCE OF AUTOANTIBODIES REVEALS A PREDOMINANT SMA AND ANCA-PR3/MPO PATTERN IN HIV INFECTION AND SMA IN HAV-INFECTED CHILDREN 自身抗体的流行揭示了HIV感染和已感染儿童中主要的sma和anca-pr3 / mpo模式
Pub Date : 2014-09-18 DOI: 10.3844/AJISP.2014.144.155
L.M. Navarta, C. Espul, N. Acosta-Rivero
Hepatitis A Virus (HAV) and Human Immunodeficiency Virus (HIV) have been associated with development of autoantibodies and autoimmune manifestations in children. Autoimmune Hepatitis (AIH) is particularly aggressive in children/adolescents with a more severe outcome. Thus, studying the mechanisms of virus-related autoimmune disorders in children is a relevant topic of research. We aimed to study the prevalence of autoantibodies in plasma of children infected with either HAV or HIV comparing to healthy children. The relationship bet ween the presence of autoantibodies and biochemical markers of hepatic damage was also investigated. De tection of autoantibodies (SMA) was associated with HAV infection with a prevalence of 35%. Similar levels of hepatic enzymes were observed in sera of HAV-infected patients with reactivity against autoa ntigens as compared to those without autoantibodies . On the other hand, HIV infection showed broader aut oantibodies reactivities than HAV-infected patients and was associated with SMA (18%), ANCA (20%), ANCA-PR3 (15%) and ANCA-MPO (13%). Moreover, either RF or ANA was detected in 8% of HIV-infected children. Prevalence of autoantibodies was not associated with either gender or age of inf ected children. A high prevalence of SMA was observed in HAV- and HIV-infected patients. As HAV and SMA may persit in some patients and AIH can develop in susceptible children, it is recommen ded a follow up of virus infected patients. Since ANCA-PR3 and ANCA-MPO have been shown to be pathogenic, proinflammatory and associated with symptomatic HIV infection, further studies are requ ired to determine the role of these autoantibodies in the pathogenesis associated with viral infection in children.
甲型肝炎病毒(HAV)和人类免疫缺陷病毒(HIV)与儿童自身抗体和自身免疫表现的发展有关。自身免疫性肝炎(AIH)在儿童/青少年中尤其具有侵袭性,其后果更为严重。因此,研究儿童病毒相关自身免疫性疾病的机制是一个相关的研究课题。我们的目的是研究与健康儿童相比,感染HAV或HIV的儿童血浆中自身抗体的患病率。研究了自身抗体的存在与肝损伤生化指标之间的关系。自身抗体(SMA)检测与甲型肝炎感染相关,患病率为35%。与无自身抗体的患者相比,在对自身抗原有反应性的甲型肝炎患者血清中观察到相似的肝酶水平。另一方面,HIV感染表现出比hav感染患者更广泛的抗体反应性,并且与SMA(18%)、ANCA(20%)、ANCA- pr3(15%)和ANCA- mpo(13%)相关。此外,在8%的艾滋病毒感染儿童中检测到RF或ANA。自身抗体的流行与感染儿童的性别或年龄无关。在HAV和hiv感染患者中观察到SMA的高患病率。由于HAV和SMA可能在某些患者中持续存在,而AIH可能在易感儿童中发展,因此建议对病毒感染患者进行随访。由于ANCA-PR3和ANCA-MPO已被证明具有致病性、促炎性并与症状性HIV感染相关,因此需要进一步研究确定这些自身抗体在儿童病毒感染相关发病机制中的作用。
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引用次数: 2
THE IMMUNOMODULATORY EFFECTS OF PROBIOTIC BACTERIA ON PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMCS) OF ALLERGIC PATIENTS 益生菌对过敏患者外周血单个核细胞的免疫调节作用
Pub Date : 2014-09-10 DOI: 10.3844/AJISP.2014.116.130
Somaya M. El Sheikh, M. Shalaby, R. Hafez, Wafaa S. Metwally, Yassin El-Ayoty
Allergic diseases represent major health burden. An allergic reaction is characterized by a disrupted Thelper 1⁄T-helper 2 balance toward a preferential allergen specifically induced TH2 cytokine profile, causing allergic inflammation Probiotic bacteria ha ve various benificial effects in many pathologic situation. Studies have shown that the bacteria pre sent in the intestinal micro flora play a role in t he TH1/TH2 balance and its modulation can promote the control of infectious and immune processes. Testing the effects of probiotic bacteria on TH1/TH2 cytoki ne production by peripheral blood mononuclear cells of allergic patients and control subjects. This study included 24 patients allergic to date pollen and 16 healthy control subjects. PBMC of both groups were separated and cultured for 72 h with date pollen allergen (home-made) in the presence or absence of Lactobacillus rhamnosus ATCC 7469 (Living and dead) and Cphycocyanin (extracted from Spirulina platensi s). The cell culture supernatants were collected to measure Interlukin 4 and Interferon gamma by quantitative E LISA. Incubation of PBMCs of allergic patients with living Lactobacillus rhamnosus ATCC 7469 showed marked reduction in IL4 production (median IL4 concentarion = 3.9 pg.) compared to PBMCs callenged with pollen alone (mediam IL4 conentration = 52.6 pg). When PBMC were incubated with living Lactobacillus rhamnosus in absence of allergen significant increase in and IFN γ (median concentration = 42.75 pg.) was obtained, c ompared to PBMC challenged with allergen alone (median = 22.8 pg). When PBMCs incubated with heat killed Lactobacillus rhamnosus either in presence or absence of the offending allergen, m arked reduction in IL4 production was obtained (median = 10.6, 3.6 pg respectively) compared to PBMC incubated with allergen alone (median = 52.6 pg). When PBMCs incubated with dead Lactobacillus rhamnosus , marked increase in IFN γ production was obtained (median = 49 pg) when compared to IFN γ production by PBMC challenged with allergen (median 22.8 pg). PBMCs challenged with PC in the presence or absence of al lergen showed marked decrease of IL4 production (median = 19.8, 17 pg respectively) when compared to PBMC incubated with the offending allergen alone (median = 52.6 pg). PBMCs incubated with PC showed significant increase of and IFN γ production (median= 319.6 pg) when compared to PBMC incubated with the offending allergen alone (median = 22.8 pg). Conclusion Lactobacillus rhamnosus ATCC 7469 and C-phycocyanin (extracted from Spirulina platensi s) inversed the TH1: TH2 polarization in allergic patients and could be a pr omissing line of treatmen.
过敏性疾病是主要的健康负担。过敏反应的特征是TH2细胞因子的平衡被打乱,从而导致过敏性炎症。益生菌在许多病理情况下都有各种有益的作用。研究表明,肠道菌群中存在的细菌在TH1/TH2平衡中发挥作用,其调节可以促进感染和免疫过程的控制。检测益生菌对过敏患者和对照组外周血单核细胞产生TH1/TH2细胞素的影响。本研究包括24例红枣花粉过敏患者和16例健康对照。两组PBMC分别与自制的红叶花粉过敏原在鼠李糖乳杆菌(Lactobacillus rhamnosus) ATCC 7469(活的和死的)和藻青蛋白(Spirulina platensi s提取的)存在或不存在的情况下培养72 h,收集细胞培养上清,采用定量E - LISA检测Interlukin 4和干扰素γ。用活鼠李糖乳杆菌ATCC 7469孵育过敏患者的PBMCs显示,与单独用花粉孵育的PBMCs(中等IL4浓度= 52.6 pg)相比,IL4的产生明显减少(中位数IL4浓度= 3.9 pg)。当PBMC与活鼠李糖乳杆菌一起孵育时,与单独处理过敏原(中位数= 22.8 pg)相比,PBMC中IFN γ显著增加(中位数= 42.75 pg)。当PBMC在存在或不存在过敏原的情况下加热杀死鼠李糖乳杆菌时,与单独使用过敏原孵育的PBMC(中位数= 52.6 pg)相比,IL4的产生明显减少(中位数分别为10.6和3.6 pg)。当PBMC与死鼠李糖乳杆菌孵育时,与用过敏原刺激的PBMC相比,IFN γ的产生量显著增加(中位数= 49 pg)(中位数为22.8 pg)。与单独孵育过敏原(中位数= 52.6 pg)的PBMC相比,在存在或不存在所有过敏原的情况下,PC刺激的PBMC的il - 4产量显著降低(中位数分别为19.8和17 pg)。与单独使用有害过敏原孵育的PBMC(中位数= 22.8 pg)相比,与PC孵育的PBMC显示显著增加和IFN γ产生(中位数= 319.6 pg)。结论鼠李糖乳杆菌ATCC 7469和c -藻蓝蛋白(从螺旋藻中提取)可逆转过敏患者的TH1: TH2极化,可能是治疗过敏的有效途径。
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引用次数: 8
Glutathione: A possible link to autophagy in systemic lupus erythematosus 谷胱甘肽:与系统性红斑狼疮自噬的可能联系
Pub Date : 2014-09-03 DOI: 10.3844/AJISP.2014.114.115
D. Shah, S. Nath
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引用次数: 3
β1,3-GLUCAN ANTICANCER EFFICACIES AND SYNERGIES: A REVIEW β1,3-葡聚糖的抗癌作用及其协同作用综述
Pub Date : 2014-09-03 DOI: 10.3844/AJISP.2014.131.143
S. Jenny, V. Vaclav, A. Michael
β1,3-glucans from fungi, cereals, seaweeds and bacte ria have been shown to possess favourable biologica l and anti-carcinogenic activities including upregula tion of phagocytosis, cytokine production enhanceme nt, superoxide and nitrite production; antibody secreti on and stimulation of signalling pathways associate d with proto-oncogene expression. However, human dietary supplements containing β1,3-glucans vary in efficacy due to glucan source, the lifecycle stage of the so urce at extraction, extraction methods, purity, concentration and combination with other immunomodulators. A review of efficacy of some commercially available β1,3-glucan products is presented. Three apparently efficacious products in which β1,3-glucan was the only immunomodulator were identified: Glucan #300®, Maitake Gold 404® (diluted Yukiguni Maitake MD Fraction®) and Betamune®. A trial of Maitake Gold 404® produced evidence of standardisation problems. It is recommended that Yu kiguni Maitake MD Fraction® (a more standardised alternative), Glucan #300® and Betamune® be comparatively trialled at optimal doses across immunological measures and tumor reduction. β1,3-glucans have been shown to be synergistic with conventional cancer therapies and monoclonal antibodies, as well as immunomodulators including vitamin C, transresveratrol, humic acids and Ashwagandha ( Withania somnifera ). Trialled commercially available products containing immunomodulator combinations have been shown to be inefficacious, apart from RVB300®, a β1,3-glucan/transresveratrol/vitamin C combination. The efficacies of various combinations of β1,3-glucans with other immunomodulators and the details of specific β1,3-glucan/monoclonal antibody synergies in treating particular cancer cell lines, require systematic elucidation.
来自真菌、谷物、海藻和细菌的β1,3-葡聚糖已被证明具有良好的生物活性和抗癌活性,包括上调吞噬作用、增强细胞因子的产生、超氧化物和亚硝酸盐的产生;与原癌基因表达相关的抗体分泌和信号通路的刺激。然而,含有β1,3-葡聚糖的人类膳食补充剂的功效因葡聚糖来源、提取时葡聚糖的生命周期阶段、提取方法、纯度、浓度以及与其他免疫调节剂的组合而异。对市售β1,3-葡聚糖产品的功效进行了综述。鉴定出三种明显有效的产品,其中β1,3-葡聚糖是唯一的免疫调节剂:葡聚糖#300®,舞茸金404®(稀释Yukiguni舞茸MD Fraction®)和Betamune®。Maitake Gold 404®的试验产生了标准化问题的证据。建议在免疫测量和肿瘤减少方面,以最佳剂量对玉竹舞茸MD分数®(一种更标准化的替代方案)、葡聚糖300®和Betamune®进行比较试验。β1,3-葡聚糖已被证明与常规癌症治疗和单克隆抗体,以及免疫调节剂,包括维生素C,白藜芦醇,腐殖酸和印度水芹(Withania somnifera)具有协同作用。除了RVB300®(一种β1,3-葡聚糖/白藜芦醇/维生素C的组合)外,市面上含有免疫调节剂组合的试验产品已被证明无效。β1,3-葡聚糖与其他免疫调节剂的各种组合的疗效,以及β1,3-葡聚糖/单克隆抗体在治疗特定癌细胞系中的特异性协同作用的细节,需要系统的阐明。
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引用次数: 9
期刊
American journal of immunology
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