immune response

免疫应答
  • 文章类型: Journal Article
    石墨烯,由单层排列在蜂窝状晶格中的碳原子组成的二维材料,在各个领域显示出巨大的潜力,包括生物医学.说到疫苗开发,由于其独特的性质,石墨烯可以提供若干优点。石墨烯在疫苗开发中的潜在应用包括改进疫苗递送,佐剂性质,提高疫苗稳定性,改善免疫反应,和生物传感能力。尽管石墨烯在疫苗开发中提供了许多潜在的好处,它的使用也有一些缺点和挑战。尽管石墨烯显示出疫苗开发的潜力,克服与使用相关的挑战和限制对于充分发挥其在免疫领域的潜力至关重要。需要进一步的研究和开发努力来克服这些缺点并利用石墨烯用于改进的疫苗制剂。在这次审查中,我们重点介绍了石墨烯在疫苗开发中的优缺点。
    Graphene, a two-dimensional material consisting of a single layer of carbon atoms arranged in a honeycomb lattice, has shown great potential in various fields, including biomedicine. When it comes to vaccine development, graphene can offer several advantages due to its unique properties. Potential applications of graphene in vaccine development include improved vaccine delivery, adjuvant properties, improved vaccine stability, improved immune response, and biosensing capabilities. Although graphene offers many potential benefits in vaccine development, there are also some drawbacks and challenges associated with its use. Although graphene shows promising potential for vaccine development, overcoming the challenges and limitations associated with its use is critical to realizing its full potential in the field of immunization. Further research and development efforts are needed to overcome these drawbacks and take advantage of graphene for improved vaccine formulations. In this review, we focus on the advantages and disadvantages of graphene for vaccine development.
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  • 文章类型: Journal Article
    目的:据报道,Abscopal效应主要发生在转移性癌症中,指示尚未包括在放射治疗目标体积中的病变的放射照相响应。该反应被解释为对放射疗法产生的肿瘤特异性抗原的体液免疫反应。在这个案例研究中,我们介绍了第一个经组织学证实的多灶性低级别脑膜瘤,常规分割立体定向放疗(RT)后所有其他病灶自发消退.
    方法:两种定位,右额叶和右蝶眶,在最初诊断时切除了一名66岁的女性。1年后对大脑falx的进行性枕骨病变进行了RT。
    结果:常规磁共振成像(MRI)显示,放疗后1年未治疗病变的肿瘤体积略有减小,并在进一步随访期间持续。治疗后超过7年,MRI显示所有初始病变几乎完全响应。在常规分割的RT后,一名非典型脑膜瘤患者和另一名放射外科手术后颅内脑膜瘤患者中,发表了两份脑膜瘤的先前报告。
    结论:本病例研究支持仅局部治疗进行性或有症状的脑膜瘤病变,并仔细定期进行MRI监测以进行进一步评估的概念。目前尚不清楚潜在的主动干预措施来触发abscopal效应。应该支持对我们患者的这种有益作用的进一步研究。
    OBJECTIVE: Abscopal effects have been reported predominantly in metastatic cancers, indicating a radiographic response in a lesion that has not been included in the radiotherapy target volume. The response is interpreted as a humoral immune response to radiotherapy-generated tumour-specific antigens. In this case study, we present the first histologically confirmed multifocal low-grade meningioma with spontaneous regression of all other lesions after conventionally fractionated stereotactic radiotherapy (RT).
    METHODS: Two localisations, right frontal and right spheno-orbital, were resected at the time of the initial diagnosis in a 66-year-old woman. RT was performed 1 year later to a progressive occipital lesion at the cerebral falx.
    RESULTS: Regular magnetic resonance imaging (MRI) showed slightly decreasing tumour volume in untreated lesions 1 year after RT and continued during further follow-up. Up to > 7 years after treatment, MRI demonstrated an almost complete response of all initial lesions. Two prior reports with meningioma were published in one patient with an atypical meningioma after conventionally fractionated RT and another patient with an intracranial meningiomatosis after radiosurgery.
    CONCLUSIONS: This case study supports the concepts of treating only progressive or symptomatic meningioma lesions locally and careful regular MRI surveillance for further assessment. Potential active interventions to trigger an abscopal effect are currently not known. Further research of this beneficial effect for our patients should be supported.
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  • 文章类型: Journal Article
    免疫检查点是在免疫应答期间调节T细胞受体(TCR)对抗原的识别的信号通路。这些检查点在抑制过度免疫应答和维持针对病毒或微生物感染的免疫稳态中起关键作用。有几种FDA批准的免疫检查点抑制剂(ICIs),包括ipilimumab,pembrolizumab,和Avelumab.这些ICIs靶向细胞毒性T淋巴细胞相关蛋白4(CTLA-4),程序性细胞死亡蛋白1(PD-1),和程序性死亡配体1(PD-L1)。此外,正在进行的努力集中在开发具有新兴潜力的新ICI。与常规治疗相比,ICI具有减少副作用和持久反应的优点。人们对将不同的ICIs与化疗相结合的潜力越来越感兴趣,放射治疗,或靶向治疗。本文全面回顾了分类,作用机制,应用程序,以及ICIs在各种癌症中的组合策略,并讨论了它们目前的局限性。我们的目标是为将来开发针对免疫检查点的更有效的抗癌药物做出贡献。
    An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an immune response. These checkpoints play a pivotal role in suppressing excessive immune responses and maintaining immune homeostasis against viral or microbial infections. There are several FDA-approved immune checkpoint inhibitors (ICIs), including ipilimumab, pembrolizumab, and avelumab. These ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PD-L1). Furthermore, ongoing efforts are focused on developing new ICIs with emerging potential. In comparison to conventional treatments, ICIs offer the advantages of reduced side effects and durable responses. There is growing interest in the potential of combining different ICIs with chemotherapy, radiation therapy, or targeted therapies. This article comprehensively reviews the classification, mechanism of action, application, and combination strategies of ICIs in various cancers and discusses their current limitations. Our objective is to contribute to the future development of more effective anticancer drugs targeting immune checkpoints.
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  • 文章类型: Journal Article
    湿疹(特应性皮炎,AD)是一种由多种因素引起的以皮肤屏障功能障碍为特征的皮肤病,包括遗传学,免疫系统异常,和环境触发因素。润肤剂和局部药物如皮质类固醇和神经钙蛋白抑制剂的应用形成了这种挑战性病症的治疗的主要支柱。这篇综述旨在总结基于植物化学的局部应用治疗AD和正在使用的不同载体的最新进展。在这次审查中,讨论了几种植物提取物和生物活性植物化学化合物治疗AD的临床疗效。通过改善特应性皮炎评分(SCORAD)指数,表皮厚度减少,减少经皮水分流失,减轻受AD影响的个体以及AD小鼠模型的瘙痒和干燥。在AD小鼠模型中进行的组织病理学研究和血清分析显示关键炎症因子的减少,包括胸腺基质淋巴细胞生成素(TSLP),血清免疫球蛋白E(IgE),白细胞介素(IL)。此外,观察到丝聚蛋白(FLG)基因的上调,调节构成角质层的蛋白质,表皮的最外层。载体在局部药物应用中起着至关重要的作用,影响剂量输送,保留,和生物利用度。本讨论深入探讨了各种纳米载体的功效,包括脂质体,乙醇体,纳米乳液,胶束,纳米晶体,固体-脂质纳米粒,和聚合物纳米颗粒。因此,潜在的长期副作用,如萎缩,喷发,淋巴瘤疼痛,以及与当前局部治疗相关的过敏反应,包括润肤剂,外用皮质类固醇,局部钙调磷酸酶抑制剂,还有crisaborole,可以通过使用基于植物化学的天然局部治疗来缓解。
    Eczema (atopic dermatitis, AD) is a skin disease characterized by skin barrier dysfunction due to various factors, including genetics, immune system abnormalities, and environmental triggers. Application of emollients and topical drugs such as corticosteroids and calcineurin inhibitors form the mainstay of treatments for this challenging condition. This review aims to summarize the recent advances made in phytochemical-based topical applications to treat AD and the different carriers that are being used. In this review, the clinical efficacy of several plant extracts and bioactive phytochemical compounds in treating AD are discussed. The anti-atopic effects of the herbs are evident through improvements in the Scoring Atopic Dermatitis (SCORAD) index, reduced epidermal thickness, decreased transepidermal water loss, and alleviated itching and dryness in individuals affected by AD as well as in AD mouse models. Histopathological studies and serum analyses conducted in AD mouse models demonstrated a reduction in key inflammatory factors, including thymic stromal lymphopoietin (TSLP), serum immunoglobulin E (IgE), and interleukins (IL). Additionally, there was an observed upregulation of the filaggrin (FLG) gene, which regulates the proteins constituting the stratum corneum, the outermost layer of the epidermis. Carriers play a crucial role in topical drug applications, influencing dose delivery, retention, and bioavailability. This discussion delves into the efficacy of various nanocarriers, including liposomes, ethosomes, nanoemulsions, micelles, nanocrystals, solid-lipid nanoparticles, and polymeric nanoparticles. Consequently, the potential long-term side effects such as atrophy, eruptions, lymphoma, pain, and allergic reactions that are associated with current topical treatments, including emollients, topical corticosteroids, topical calcineurin inhibitors, and crisaborole, can potentially be mitigated through the use of phytochemical-based natural topical treatments.
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  • 文章类型: Journal Article
    尽管细菌感染减少,成功率提高,在种植牙科中广泛使用全身性抗生素预防是有争议的.这种使用导致了日益增长的抗菌素耐药性问题,同时造成巨大的健康和经济负担。引起植入物感染的基本机制可以通过新的预防和治疗方法来靶向,这也可以导致全身性抗生素暴露及其相关副作用的减少。本文旨在总结基于抗致病机制和免疫平衡机制的先进生物材料应用于植入物组件的策略。它强调修饰牙种植体表面和调节早期免疫反应是有前途的策略,这可以进一步预防或减缓植入物周围感染的发展,随后的失败。
    Despite reductions in bacterial infection and enhanced success rate, the widespread use of systemic antibiotic prophylaxis in implant dentistry is controversial. This use has contributed to the growing problem of antimicrobial resistance, along with creating significant health and economic burdens. The basic mechanisms that cause implant infection can be targeted by new prevention and treatment methods which can also lead to the reduction of systemic antibiotic exposure and its associated adverse effects. This review aims to summarize advanced biomaterial strategies applied to implant components based on anti-pathogenic mechanisms and immune balance mechanisms. It emphasizes that modifying the dental implant surface and regulating the early immune response are promising strategies, which may further prevent or slow the development of peri-implant infection, and subsequent failure.
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  • 文章类型: Journal Article
    由于免疫系统失调,脓毒症构成了重大的全球健康挑战。这篇叙述性综述探讨了抗生素与免疫系统之间的复杂关系,旨在阐明所涉及的机制及其临床影响。从临床前研究来看,抗生素表现出各种免疫调节作用,包括调节促炎细胞因子的产生,与Toll样受体相互作用,P38/Pmk-1通路的调制,抑制基质金属蛋白酶,阻断一氧化氮合酶,和调节caspase诱导的细胞凋亡。此外,抗生素诱导的微生物组改变与全身免疫的变化有关,影响细胞和体液反应。脓毒症患者的抗生素辅助使用,尤其是大环内酯类,由于它们的免疫调节作用而引起了人们的关注。然而,比较不同类型的大环内酯类药物的数据有限。更有力的证据来自对社区获得性肺炎的研究,特别是在严重的高炎症反应的情况下。虽然关于脓毒性休克的研究显示了关于死亡率和免疫反应调节的混合结果,大环内酯类药物在急性呼吸窘迫综合征中的发现也相互矛盾.总之,迫切需要根据患者的免疫状况调整抗生素治疗,以优化脓毒症治疗的结局。
    Sepsis poses a significant global health challenge due to immune system dysregulation. This narrative review explores the complex relationship between antibiotics and the immune system, aiming to clarify the involved mechanisms and their clinical impacts. From pre-clinical studies, antibiotics exhibit various immunomodulatory effects, including the regulation of pro-inflammatory cytokine production, interaction with Toll-Like Receptors, modulation of the P38/Pmk-1 Pathway, inhibition of Matrix Metalloproteinases, blockade of nitric oxide synthase, and regulation of caspase-induced apoptosis. Additionally, antibiotic-induced alterations to the microbiome are associated with changes in systemic immunity, affecting cellular and humoral responses. The adjunctive use of antibiotics in sepsis patients, particularly macrolides, has attracted attention due to their immune-regulatory effects. However, there are limited data comparing different types of macrolides. More robust evidence comes from studies on community-acquired pneumonia, especially in severe cases with a hyper-inflammatory response. While studies on septic shock have shown mixed results regarding mortality rates and immune response modulation, conflicting findings are also observed with macrolides in acute respiratory distress syndrome. In conclusion, there is a pressing need to tailor antibiotic therapy based on the patient\'s immune profile to optimize outcomes in sepsis management.
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  • 文章类型: Journal Article
    处理雪貂免疫系统解剖结构的基本信息,介绍了雪貂白细胞与体外多克隆和单克隆抗体的交叉反应性以及对有丝分裂原和各种感染的免疫反应。与其他物种相比,雪貂外周血中的白细胞数量较低,到目前为止,在雪貂中仅鉴定出一种IgG亚类。淋巴细胞占健康成年雪貂外周血中所有白细胞的12-67%。淋巴细胞亚群与其他哺乳动物相似,包括T淋巴细胞和B淋巴细胞。T淋巴细胞分化成辅助(Th)淋巴细胞和细胞毒性(Tc)淋巴细胞。目前,雪貂粒细胞(CD11),B淋巴细胞(CD79α),T淋巴细胞(CD3),T淋巴细胞(CD3,CD4),Tc淋巴细胞(CD3,CD8),使用许多多克隆以及单克隆抗体检测CD30、CD45亚群。在淋巴细胞转化试验中,外周血单核细胞对刀豆蛋白A(ConA)的有丝分裂原反应,植物血凝素(PHA),和商陆有丝分裂原(PWM)分别在第2、2和3天最大。在犬瘟热感染期间,在雪貂中观察到严重的淋巴细胞减少。在第5天观察到淋巴细胞转化活性的显着降低,并在第8-11天达到最大降低,在用犬瘟热病毒接种实验室雪貂后第23-30天完全恢复。雪貂还被用于与幽门螺杆菌感染中免疫系统功能相关的研究,克罗恩病和支气管哮喘。
    The basic information dealing with the anatomy of the ferret\'s immune system, cross-reactivity of the ferret leukocytes with polyclonal and monoclonal antibodies in vitro and immune response to the mitogens and various infections are presented. The leukocyte numbers in the peripheral blood in the ferrets are lower compared to other species and only one subclass of IgG has been identified in ferrets so far. Lymphocytes make up 12-67% of all the leukocytes in the peripheral blood of the healthy adult ferrets. Lymphocyte subpopulations are similar to other mammals and include T- and B-lymphocytes. T-lymphocytes differentiate into helper (Th) lymphocytes and cytotoxic (Tc) lymphocytes. Currently, ferret granulocytes (CD11), B-lymphocytes (CD79α), T-lymphocytes (CD3), Th-lymphocytes (CD3, CD4), Tc-lymphocytes (CD3, CD8), and CD30, CD45 subpopulations are detected with the use of a number of polyclonal as well as with monoclonal antibodies. In a lymphocyte transformation assay, the mitogen response of the peripheral blood mononuclear cells to concanavalin A (ConA), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM) is the greatest at day 2, 2 and 3, respectively. Serious lymphopenia is observed in ferrets during a distemper infection. A significant decrease in the lymphocyte transformation activity is observed on day 5 and reaches a maximal decrease on days 8-11, with full recovery on days 23-30 after the inoculation of laboratory ferrets with the distemper virus. Ferrets have also been used in studies related to the function of the immune system in Helicobacter pylori infections, Crohn\'s disease and bronchial asthma.
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  • 文章类型: Journal Article
    身体活动和锻炼的好处,尤其是那些被归类为中度至剧烈活动(MVPA)的活动,在预防健康成年人的非传染性疾病和心理健康问题方面已经建立了良好的基础。然而,身体活动和运动与急性呼吸道感染(ARI)的预防和管理之间的关系,一种全球高负担疾病,一直没有定论。关于运动与针对ARI病原体的免疫反应之间的关系,科学出版物之间存在辩论和分歧。这篇叙事综述旨在探索充分解释运动之间相关性的理论,免疫反应,和ARI。差异的潜在根本原因来自与“打开窗口”假设相关的研究。这些研究有几个局限性,在研究设计中迫切需要未来的改进来解决这些问题,数据收集,运动干预,主题招聘,感染和炎症的生物标志物,营养和代谢状态,以及解决混杂变量的问题。总之,数据支持运动的临床优势对改善免疫反应有调节作用,这反过来又有可能保护人类免受ARI的侵害。然而,必须谨慎采用与其负面影响有关的假设。
    The benefits of physical activity and exercise, especially those classified as moderate-to-vigorous activity (MVPA), have been well-established in preventing non-communicable diseases and mental health problems in healthy adults. However, the relationship between physical activity and exercise and the prevention and management of acute respiratory infection (ARI), a global high-burden disease, has been inconclusive. There have been debates and disagreements among scientific publications regarding the relationship between exercise and immune response against the causative agents of ARI. This narrative review aims to explore the theory that sufficiently explains the correlation between exercise, immune response, and ARI. The potential root causes of discrepancies come from research associated with the \"open window\" hypothesis. The studies have several limitations, and future improvements to address them are urgently needed in the study design, data collection, exercise intervention, subject recruitment, biomarkers for infection and inflammation, nutritional and metabolism status, and in addressing confounding variables. In conclusion, data support the clinical advantages of exercise have a regulatory contribution toward improving the immune response, which in turn potentially protects humans fromARI. However, the hypothesis related to its negative effect must be adopted cautiously.
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  • 文章类型: Journal Article
    像利什曼病这样的传染病,疟疾,艾滋病毒,结核病,麻风病和丝虫病对公共卫生系统造成了巨大负担。其中,利什曼病属于I类疾病,因为它是由WHO(世界卫生组织)基于多样性和复杂性而选择的。成本高,利什曼原虫传统药物的耐药性和毒性效应需要识别和开发治疗替代方案。由于自然感染会引发强大的免疫力,一致的努力正在继续开发一种成功的疫苗。已经对使用特定利什曼原虫抗原表位配制的疫苗如Leish-F1、F2和F3进行了临床试验。目前的策略利用来自寄生虫或其昆虫媒介的唾液腺提取物的单个或组合抗原,具有或不具有增强功效的佐剂制剂。有前途的动物数据支持多种候选疫苗(Lmcen-/-,LmexCen-/-),其中一些已经在或正在进行临床试验。利什曼原虫疫苗开发的关键挑战是将研究知识转化为负担得起的和可获得的控制工具,为那些易感感染的人改善结果。这篇综述集中在利什曼原虫疫苗的最新发现,并强调疫苗开发和实施面临的困难。
    Infectious diseases like leishmaniasis, malaria, HIV, tuberculosis, leprosy and filariasis are responsible for an immense burden on public health systems. Among these, leishmaniasis is under the category I diseases as it is selected by WHO (World Health Organization) on the ground of diversity and complexity. High cost, resistance and toxic effects of Leishmania traditional drugs entail identification and development of therapeutic alternative. Since the natural infection elicits robust immunity, consistence efforts are going on to develop a successful vaccine. Clinical trials have been conducted on vaccines like Leish-F1, F2, and F3 formulated using specific Leishmania antigen epitopes. Current strategies utilize individual or combined antigens from the parasite or its insect vector\'s salivary gland extract, with or without adjuvant formulation for enhanced efficacy. Promising animal data supports multiple vaccine candidates (Lmcen-/-, LmexCen-/-), with some already in or heading for clinical trials. The crucial challenge in Leishmania vaccine development is to translate the research knowledge into affordable and accessible control tools that refines the outcome for those who are susceptible to infection. This review focuses on recent findings in Leishmania vaccines and highlights difficulties facing vaccine development and implementation.
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  • 文章类型: Journal Article
    牛的子宫疾病会损害繁殖性能和盈利能力,并增加抗生素的使用和抗菌素耐药性。因此,益生菌提供了一种有希望的替代疗法。这篇综述提出了有关益生菌在管理子宫疾病和奶牛生育能力方面的功效的概念性发现。含有乳酸菌的益生菌。和双歧杆菌属。已知单独或复合配方可以提高生育力。这些制剂的策略性阴道内给药可能会增强子宫免疫力。特别是在产后期间。虽然目前关于子宫健康益处的发现令人鼓舞,仍然缺少大量知识,包括缺乏大规模田间试验的经验信息。这篇综述强调了益生菌循证指南的必要性,例如配方的基因组选择,有针对性的交付,或与其他干预措施的潜在协同作用。未来的研究应该解决这些差距,以最大限度地发挥益生菌在管理子宫疾病和增强奶牛生殖健康方面的潜力。
    Uterine disease in cattle impairs reproductive performance and profitability and increases antibiotic use and antimicrobial resistance. Thus, probiotics offer a promising alternative therapy. This review presents conceptual findings on the efficacy of probiotics in managing uterine diseases and fertility in cows. Probiotics containing Lactobacillus spp. and Bifidobacterium spp. individually or as composite formulations are known to improve fertility. Strategic intravaginal administration of these formulations would likely enhance uterine immunity, particularly during the postpartum period. While current findings on the benefits to uterine health are encouraging, there is still significant knowledge missing, including a lack of empirical information from large-scale field trials. This review underscores the need for evidence-based guidelines for probiotics, such as genomic selection of formulations, targeted delivery, or potential synergy with other interventions. Future research should address these gaps to maximize the potential of probiotics in managing uterine diseases and enhancing the reproductive health of dairy cattle.
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