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Immune Dysfunction and Antiretroviral Therapy Challenges in Children and Adolescents Living with Human Immunodeficiency Virus 感染人类免疫缺陷病毒的儿童和青少年的免疫功能障碍和抗逆转录病毒治疗挑战
Pub Date : 2020-04-27 DOI: 10.5772/intechopen.91667
Mirvat Said, Adam W. Bartlett
Human immunodeficiency virus (HIV) infection results in progressive decline in immune function ultimately leading to acquired immunodeficiency syndrome (AIDS) characterised by increased susceptibility to opportunistic infections and malignancies. In addition, it causes immune dysfunction, which manifests as a persistent inflammatory state due to dysregulation of cytokine production. Antiretroviral therapy (ART) not only improves immune function but also mitigates systemic immune activation associated with disease progression. Early initiation of ART in children living with HIV has led to a growing cohort surviving into adolescence and beyond. As such, they will experience lifelong exposure to an array of physiologic processes associated with systemic infection, immune dysfunction and antiretroviral medications. This leaves them not only susceptible to a range of morbidities associated with chronic inflammation, immune dysregulation, and drug toxicity but also vulnerable to treatment fatigue leading to issues with treatment adherence and engagement in care. Children experience additional barriers to maintaining suppressive ART due to limited paediatric-friendly formulations that are palatable and contribute to regimen complexity. Tolerability and durability of long-term ART are integral in optimising outcomes for children and adolescents living with HIV and maximising viability of future ART regimens throughout adulthood.
人类免疫缺陷病毒(艾滋病毒)感染导致免疫功能逐渐下降,最终导致获得性免疫缺陷综合征(艾滋病),其特征是对机会性感染和恶性肿瘤的易感性增加。此外,它引起免疫功能障碍,表现为由于细胞因子产生失调而持续的炎症状态。抗逆转录病毒治疗(ART)不仅可以改善免疫功能,还可以减轻与疾病进展相关的全身免疫激活。感染艾滋病毒的儿童早期开始接受抗逆转录病毒治疗,导致越来越多的儿童存活到青春期及以后。因此,他们将终生暴露于与全身感染、免疫功能障碍和抗逆转录病毒药物相关的一系列生理过程中。这使得他们不仅容易受到与慢性炎症、免疫失调和药物毒性相关的一系列疾病的影响,而且还容易受到治疗疲劳的影响,从而导致治疗依从性和参与护理的问题。儿童在维持抑制性抗逆转录病毒治疗方面遇到了额外的障碍,因为儿科友好的配方有限,这些配方可口且有助于治疗方案的复杂性。长期抗逆转录病毒治疗的耐受性和持久性对于优化感染艾滋病毒的儿童和青少年的预后以及最大限度地提高整个成年期抗逆转录病毒治疗方案的可行性至关重要。
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引用次数: 3
Role of Interferon in Cancer Metabolism 干扰素在肿瘤代谢中的作用
Pub Date : 2020-04-22 DOI: 10.5772/intechopen.92020
Vaishali Chandel, Dhruv Kumar
Interferons (IFNs), a pleotropic cytokine that has long been regarded as an important effector molecule, are increasingly recognized due to their role in cancer and in antitumor immune response regulation. Interferons broadly alter cellular functions in response to viral and other infections. Dysregulation of interferon has been implicated in cancer, autoimmune disorders, and pathogenesis of chronic viral infections. However, the association between interferons and cancer cell metabolism is poorly understood. Emerging evidence suggests the importance of lipid, energy, and amino acid metabolic pathway in regulating interferon response against cancer. Additionally, viruses exploit and modulate the host cell and induce the major metabolic reprogramming causing cancer. In response, interferons upregulate the transcription of large number of interferon stimulating gene (ISG) whose products play a major role in the innate and adaptive immune response against viral infection. Immense research is being done on understanding the role of IFNs in cancer metabolism. Therefore, systematic evaluation of these associations between interferons and cancer metabolism may have important implications for the development of anticancer therapeutics targeting IFN, minimizing toxicity, and limiting off-target effects.
干扰素(IFNs)是一种多效性细胞因子,长期以来一直被认为是一种重要的效应分子,由于其在癌症和抗肿瘤免疫反应调节中的作用而越来越受到重视。干扰素广泛地改变细胞功能以应对病毒和其他感染。干扰素的失调与癌症、自身免疫性疾病和慢性病毒感染的发病机制有关。然而,干扰素与癌细胞代谢之间的关系尚不清楚。越来越多的证据表明,脂质、能量和氨基酸代谢途径在调节干扰素抗癌反应中的重要性。此外,病毒利用和调节宿主细胞并诱导导致癌症的主要代谢重编程。作为回应,干扰素上调大量干扰素刺激基因(ISG)的转录,其产物在对抗病毒感染的先天和适应性免疫反应中发挥重要作用。人们正在进行大量的研究来了解ifn在癌症代谢中的作用。因此,系统评估干扰素与癌症代谢之间的关联,可能对开发靶向IFN的抗癌疗法、减少毒性和限制脱靶效应具有重要意义。
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引用次数: 2
Plasticity in Interferon Responses Modulates T-Cell Immunity in Parasitic Infections: Periphery to Thymus 在寄生虫感染中干扰素反应的可塑性调节t细胞免疫:胸腺外周
Pub Date : 2020-04-22 DOI: 10.5772/intechopen.92191
Lovlesh Thakur, N. Akhtar, Aklank Jain, Hridayesh Parkash, Manju Jain
Parasitic infections are the major threat prevalent in tropical and subtropical regions throughout the world. Different parasitic infections take a huge toll on mortality and morbidity at global level. Different parasites invade the host system, multiply inside host cells of their choice and sabotage defense mechanisms to overpower the host. T-cell immunity is majorly affected in different parasitic diseases such that the peripheral T-cell immune response is altered along with lesser explored thymic changes. Direct and/or indirect effect of parasitic infection leads to alterations in T-cell development, differentiation and activation resulting in deregulated T-cell immune mechanisms. Cytokines of interferon family play a significant role in determining the disease outcome and severity. Therefore, in this chapter, we here provide a detailed overview of the functional role played by IFNs during parasitic diseases in terms of their influence on peripheral T-cell activation and tolerance along with lesser explored impact on developing T cells in the thymus with altered microenvironmental niches.
寄生虫感染是世界各地热带和亚热带地区普遍存在的主要威胁。不同的寄生虫感染在全球范围内造成了巨大的死亡率和发病率。不同的寄生虫侵入宿主系统,在它们选择的宿主细胞内繁殖,破坏防御机制以压倒宿主。t细胞免疫主要在不同的寄生虫病中受到影响,因此外周t细胞免疫反应随着较少探索的胸腺变化而改变。寄生虫感染的直接和/或间接影响导致t细胞发育、分化和激活的改变,从而导致t细胞免疫机制的失调。干扰素家族细胞因子在决定疾病结局和严重程度中起重要作用。因此,在本章中,我们详细概述了ifn在寄生虫病中对外周T细胞活化和耐受性的影响,以及对胸腺微环境生态位改变对T细胞发育的影响。
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引用次数: 0
Immune Dysfunction during Enteric Protozoal Infection: The Current Trends 肠道原虫感染期间的免疫功能障碍:当前趋势
Pub Date : 2020-04-15 DOI: 10.5772/intechopen.91698
Renu Kumari Yadav, S. Malhotra, N. Duggal
Enteric protozoa usually cause severe morbidity and mortality in humans. Protozoal infections contribute to the high burden of infectious diseases. Despite recent advances in the epidemiology, diagnostic tool, molecular biology, and treatment of protozoan illnesses, gaps in knowledge still exist; hence, protozoal infections require further research. We are describing here some important enteric protozoal infections along with the immune dysfunction produced by them. Genus- 1. Entamoeba; 2. Giardia; 3. Cryptosporidium; 4. Cyclospora; 5. Cystoisospora; 6. Dientamoeba; 7. Blastocystis; 8. Balantidium.
肠道原生动物通常在人类中引起严重的发病率和死亡率。原生动物感染造成了传染病的高负担。尽管最近在流行病学、诊断工具、分子生物学和原生动物疾病治疗方面取得了进展,但知识差距仍然存在;因此,原生动物感染需要进一步研究。我们在这里描述了一些重要的肠道原虫感染及其产生的免疫功能障碍。属- 1。痢疾;2. 贾第虫属;3.隐孢子虫;4. 环孢子虫;5. Cystoisospora;6。双核内变形虫属;7. 酵母菌属;8. 肠袋虫属。
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引用次数: 1
Congenital and Acquired Interferonopathies: Differentiated Approaches to Interferon Therapy 先天性和获得性干扰素病变:干扰素治疗的不同方法
Pub Date : 2020-03-20 DOI: 10.5772/intechopen.91723
Nesterova Irina, S. Kovaleva, V. Malinovskaya, G. Chudilova, T. Rusinova
This chapter reviews various interferon (IFN) system disturbances—interferonopathies. The authors describe clinical specifics of type I interferonopathy associated with overexpression of IFNα—which is a rare Mendelian genetic disease. Certain autoimmune diseases (systemic lupus erythematosus (SLE), vasculitis, immune dysregulation syndrome, etc.) are also characterized by overproduction of IFNα. Furthermore the most common interferonopathies are described—deficiencies of IFN, congenital or acquired IFNα/IFNβ and IFNγ deficiencies in children and adults. Deficiency of IFNα/IFNβ associated with severe recurrent viral infections and deficiency of IFNγ cause mycobacterial infection. Interferon-corrective therapy methods are described. The target therapy of type I interferonopathies (biologics) binds IFNα and normalizes the high level of IFNα. From the other side, patients with congenital IFNα deficiencies are needed in replacement IFN therapy. In case of acquired IFNα deficiency, the differentiated interferon-corrective therapy is performed. In both replacement and interferon-corrective therapies, recombinant human IFNα2b in complex with antioxidants (Viferon®) can be used, because their application is safe and has good clinical efficiency and no side effects.
本章回顾了各种干扰素(IFN)系统紊乱-干扰素病。作者描述了与ifn α -过表达相关的I型干扰素病的临床特点,这是一种罕见的孟德尔遗传疾病。某些自身免疫性疾病(系统性红斑狼疮(SLE)、血管炎、免疫失调综合征等)也以IFNα的过量产生为特征。此外,最常见的干扰素病变是IFN缺乏,儿童和成人先天性或获得性IFNα/IFNβ和IFNγ缺乏。IFNα/IFNβ缺乏与严重复发性病毒感染相关,IFNγ缺乏引起分枝杆菌感染。描述了干扰素矫正治疗方法。I型干扰素病变(生物制剂)的靶向治疗结合IFNα并使高水平的IFNα正常化。另一方面,先天性干扰素α缺乏的患者需要干扰素替代治疗。在获得性干扰素α缺乏的情况下,进行分化干扰素矫正治疗。在替代疗法和干扰素矫正疗法中,重组人IFNα2b联合抗氧化剂(Viferon®)均可使用,因为其应用安全,临床疗效好,无副作用。
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引用次数: 1
Multiplex Technology for Biomarker Immunoassays 生物标志物免疫测定的多重技术
Pub Date : 2020-03-17 DOI: 10.5772/intechopen.91730
H. Ahsan, R. Ahmad
The simultaneous measurement of different substances from a single sample is an emerging area for achieving efficient and high-throughput detection in several applications. Although immunoanalytical techniques are established and advantageous over alternative screening analytical platforms, one of the challenges for immunoassays is multiplexing. While ELISA is still commonly used to characterise a single analyte, laboratories and organisations are moving towards multiplex immunoassays. The validation of novel biomarkers and their amalgamation into multiplex immunoassays confers the prospects of simultaneous measurement of multiple analytes in a single sample, thereby minimising cost, time and sample. Therefore, the technological advancement in clinical sciences is helpful in the identification of analytes or biomarkers in test samples. However, the analytical bioanalysers are expensive and capable of detecting only a small amount or type of analytes. The simultaneous measurement of different substances from a single sample called multiplexing has become increasingly important for the quantification of pathological or toxicological samples. Although multiplex assays have many advantages over conventional assays, there are also problems that may cause apprehension among clinicians and researchers. Hence, many challenges still remain for these multiplexing systems which are at early stages of development.
从单个样品中同时测量不同物质是在几种应用中实现高效和高通量检测的新兴领域。尽管免疫分析技术已经建立,并且优于其他筛选分析平台,但免疫分析的挑战之一是多路复用。虽然ELISA仍然通常用于表征单一分析物,但实验室和组织正朝着多重免疫测定的方向发展。新型生物标志物的验证及其合并到多重免疫测定中,为在单个样品中同时测量多种分析物提供了前景,从而最大限度地降低了成本、时间和样品。因此,临床科学的技术进步有助于检测样品中的分析物或生物标志物的鉴定。然而,分析生物分析仪价格昂贵,只能检测少量或类型的分析物。从单个样品中同时测量不同物质(称为多路复用)对于病理或毒理学样品的定量已变得越来越重要。虽然多重检测比传统检测有许多优点,但也存在一些可能引起临床医生和研究人员担忧的问题。因此,这些多路复用系统仍处于发展的早期阶段,面临着许多挑战。
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引用次数: 7
Innate Immune Defense in the Male Reproductive System and Male Fertility 男性生殖系统的先天免疫防御与男性生育能力
Pub Date : 2019-09-25 DOI: 10.5772/INTECHOPEN.89346
Fei Wang, Ran Chen, Daishu Han
To protect the male germ cells from adverse immune reaction, the male reproductive system adopts special immune environment such as immunoprivileged status. The male genital organs can be infected by various microorganisms via hematogenous dissemination and ascending genitourinary tracts. To overcome the immunoprivileged status, the male genital organs also adopt their own innate defense against microbial infection. The tissue-specific cells in the male reproductive system are well equipped with innate immune machineries, including pattern recognition receptors (PRRs) and their negatively regulatory system. PRR-initiated immune responses must be tightly regulated by the negative regulatory system for the maintenance of immune homeostasis. The immune homeostasis can be disrupted by unrestrictive innate immune response, which may lead to inflammatory conditions in the male genital tracts, an important etiological factor contributing to male infertility. This chapter describes the current understanding of the innate immune responses in the male reproductive system and their effects on male fertility.
为了保护男性生殖细胞免受不良免疫反应的影响,男性生殖系统采用特殊的免疫环境,如免疫特权状态。男性生殖器官可被各种微生物通过血液传播和上升的泌尿生殖道感染。为了克服免疫特权地位,男性生殖器官也采用自己的先天防御微生物感染。男性生殖系统中的组织特异性细胞具有先天免疫机制,包括模式识别受体(PRRs)及其负调控系统。prr引发的免疫反应必须受到负调控系统的严格调控,以维持免疫稳态。不受限制的先天免疫反应可破坏免疫稳态,从而导致男性生殖道炎症,这是导致男性不育的重要病因。本章描述了目前对男性生殖系统先天免疫反应及其对男性生育能力的影响的理解。
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引用次数: 7
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Innate Immunity in Health and Disease
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