白念珠菌、烟曲霉及新生隐球菌感染的宿主特异性免疫应答研究进展

白念珠菌、烟曲霉及新生隐球菌是3种机会致病真菌。这些真菌一旦感染人体,即与机体免疫系统相互作用,激活机体的天然免疫,继而产生特异性细胞免疫及体液免疫应答,其中特异性细胞和体液免疫应答对宿主抵御感染和防止菌体免疫逃逸发挥重要作用。概述近几年有关白念珠菌、烟曲霉及新生隐球菌感染的特异性免疫应答的研究现状,并分析3种真菌免疫的异同点,以期为开展此类研究提供有益借鉴。     

银屑病发病机制与Toll样受体

有越来越多的证据显示银屑病是免疫介导的炎症过程,包括天然免疫和获得性免疫效应机制促进这种慢性皮肤病理过程.Toll样受体是对抗微生物侵入的天然免疫中的关键受体.这些受体不仅表达于外周血细胞也表达于气道上皮细胞和皮肤这些宿主和病原体相互作用部位的免疫细胞,也可能是触发或加重银屑病的微生物感染发生的部位.由于Toll样受体在触发天然免疫和影响获得性免疫中起重要作用,调节Toll样受体的表达可能与银屑病等疾病的病理生理相关.     

人类乳头瘤病毒感染的免疫逃逸机制

尖锐湿疣是一种容易复发的性传播疾病。人类乳头瘤病毒感染的免疫逃逸机制在尖锐湿疣的发病机制中起重要作用。文中将从天然免疫 (炎症反应 ,细胞因子如干扰素、白介素 - 18等 )和获得性免疫 (病毒抗原的捕获及呈递 ,特异性T细胞免疫应答 )两个方面来综述人类乳头瘤病毒逃逸机体免疫防卫机制     

人类乳头瘤病毒感染的免疫逃逸机制

尖锐湿疣是一种容易复发的性传播疾病。人类乳头瘤病毒感染的免疫逃逸机制在尖锐湿疣的发展机制中起重要作用。文中将从天然免疫（炎症反应、细胞因子如干扰素、白介素－18等）和获得性免疫（病毒抗原的捕获及呈递，特异性T细胞免疫应答）两个方面来综述人类乳头瘤病毒逃逸机体免疫防卫机制。     

Dectin-1与真菌β-葡聚糖介导的天然免疫

β-葡聚糖是真菌胞壁的主要多糖成分。天然免疫系统识别这一成分后触发髓系细胞的免疫应答反应,杀伤和清除入侵微生物。该文主要介绍天然免疫细胞的模式识别受体dectin-1与β-葡聚糖的特性以及它们通过何种信号传导途径激活天然免疫系统。对β-葡聚糖和dectin-1的研究必将为研制抗真菌免疫制剂和抗真菌药物靶点提供崭新的思路。     

获得性免疫与真菌感染的相关性

近年来,机会性真菌感染发病率呈逐年升高的趋势。机体的免疫系统在防御和清除入侵的病原真菌中发挥重要作用,其中获得性免疫是免疫系统的重要组成,越来越多的学者致力于研究真菌感染与获得性免疫的相关性。本文从获得性免疫在机体抵御真菌感染中的作用、遗传性免疫缺陷与真菌感染的易感性以及真菌感染的免疫治疗等方面对获得性免疫与真菌感染的相关性进行评述,以期从机体免疫应答和免疫防御方面找到突破口,为真菌感染的诊治找到新靶点。     

细胞外囊泡在真菌与宿主相互作用中的研究进展

真菌感染一直是严重的全球健康问题,随着发病率的逐年增加和耐药菌株的不断出现,对其致病机制和耐药机制的研究亟待深入。但人们对真菌如何在感染过程中与宿主相互作用,甚至对宿主进行操纵知之甚少。近年来,细胞外囊泡的功能研究成为热点。囊泡内运输的物质除保证其生存必需,可通过激活/抑制宿主细胞免疫应答,或其他作用于宿主细胞影响其内部微环境的方式改变感染进程和结果。该文对真菌细胞外囊泡的分类、形成、功能及其与宿主间相互作用加以综述,以期了解真菌如何利用细胞外囊泡改变宿主的免疫和非免疫反应,从而提高对真菌细胞间通讯的理解,有助于解析真菌与宿主之间相互交流的复杂性,从而针对性开发出对抗真菌感染的治疗策略。     

Toll样受体在抗系统性真菌感染中的作用

近年发现的Toll样受体是细胞表面的天然受体蛋白,能识别许多微生物结构和机体的内源性成分,传导炎症信号,介导多种生物学效应。Toll样受体能识别真菌成分,在抗系统性真菌感染的天然免疫中发挥重要作用,同时,它也是天然免疫与获得性免疫的连接点。通过对Toll样受体的研究,可深入探讨机体抗系统性真菌感染的机制,为临床治疗提供新思路。     

Toll样受体在抗系统性真菌感染中的作用

近年发现的Toll样受体是细胞表面的天然受体蛋白，能识别许多微生物结构和机体的内源性成分，传导炎症信号，介导多种生物学效应。Toll样受体能识别真菌成分，在抗系统性真菌感染的天然免疫中发挥重要作用，同时，它也是天然免疫与获得性免疫的连接点。通过对Toll样受体的研究，可深入探讨机体抗系统性真菌感染的机制，为临床治疗提供新思路。     

Toll样受体与皮肤抗感染免疫

天然免疫分子Toll样受体是一个广泛存在于昆虫、脊椎动物和植物中序列高度保守而古老的家族。它们在天然免疫中可发挥重要的抗感染免疫功能,并与免疫耐受、特异性抗感染免疫,以及一些疾病具有相关性。研究Toll样受体在皮肤组织中识别和抵御常见的几种细菌、病毒及真菌过程中的机制,通过对Toll样受体及其整个系统的认识将为防治各种皮肤感染性疾病开辟广阔前景。     

Chemokines: key players in innate and adaptive immunity

Healthy individuals initiate an immediate immune response to microbes by using a set of germline-encoded receptors that recognize common molecular patterns found on the surface of pathogens that are distinct from self-antigens. This innate immune response is the first line of defense against microorganisms in vertebrates, and constitutes the only immune response in plants and invertebrates. The innate immune system includes cellular components, as well as a host of soluble products (antimicrobial peptides, complement fragments, cytokines, and chemokines). The adaptive immune response, which provides long-lasting protection, takes days to develop and requires somatic mutations leading to the development of antigen-specific T cell receptors (cell-mediated immunity) and immunoglobulins (humoral immunity). Members of the chemokine superfamily are crucially involved in both innate and adaptive responses. We review the biological actions of the chemokine superfamily, focusing on several functions that are relevant for both immune responses, such as cell recruitment, microbicidal activity, cell activation, polarization of CD4+ T cells, and effects on structural cells. In particular, we will illustrate the central role that chemokines play in host defense, best demonstrated by the tremendous number of chemokine and chemokine receptor homologs found in microbial genomes, which deflect the immune response of the host.     

天然免疫相关细胞因子在人类真菌感染中的作用

研究表明,白细胞介素?1β、4、6、10、12、17、23,肿瘤坏死因子α和干扰素γ等天然免疫相关细胞因子在人类真菌感染过程中具有重要作用.它们在介导天然免疫反应的同时又可以通过诱导Th0细胞的分化类型而调节适应性免疫反应,对真菌感染的转归产生了巨大的影响.依照"病原真菌?天然免疫细胞?细胞因子?靶细胞?生物学效应"这一条真菌感染的天然免疫反应主线,逐个梳理主要天然免疫相关细胞因子在人类真菌感染过程中的细胞来源、基本功能及其相互间作用,列举并分析各种原因造成其功能异常时所导致的真菌感染性疾病,可为人类真菌感染性疾病寻找更多的治疗靶点.     

Toll样受体与病毒感染性皮肤病研究进展

Toll样受体是机体主要的固有免疫受体分子,可识别病原微生物高度保守的PAMP,激活特异性信号转导途径,连接机体固有免疫与获得性免疫,在机体抗感染过程中发挥着极为重要的作用。本文对Toll样受体在病毒感染性皮肤病中的作用及相关抗病毒药物和疫苗的研制进展进行了综述。     

Recalcitrant trichophytic granuloma associated with NK-cell deficiency in a SLE patient treated with corticosteroid

Although deep trichophytic infection often occurs in immunocompromised patients, the immune deficiency in such patients has not been clarified. A 28-year-old man who suffered from recalcitrant trichophytic granuloma and tinea universalis during treatment for SLE with corticosteroid is described here to define the immunological abnormalities. In addition to routine immunological tests, we evaluated the patient's innate and specific immune functions to dermatophytes, including T cell, natural killer (NK) cell and neutrophil functions and activation of the complement cascade. We measured the minimum inhibitory concentration (MIC) of itraconazole for the isolated fungus and its concentrations in the patient's serum and pus. Trichophyton (T.) rubrum was constantly isolated from the exudates of the patient's skin lesions, although the concentrations of itraconazole in his serum (198 ng/ml) and lesions (210 ng/ml) were sufficient to inhibit the growth of the isolated fungus in vitro. Specific cell-mediated immune responses, determined by T cell stimulation and IFN-gamma production, were evoked following stimulation with trichophytic antigens. The patient's innate immunity, assessed by activation of the complement cascade and neutrophil-mediated phagocytosis, was not impaired. The number of circulating NK cells was markedly decreased (0.2% of the peripheral blood mononuclear cells), and was associated with low NK cell activity against K-562 cells even though lymphopenia had improved. The deficiency of innate immunity mediated by NK cells might be responsible for a part of the persistence of trichophytic granuloma in our case. Dermatophytes usually affect the horny layer of the skin and do not invade the living layers because the host immune system uses various mechanisms to eliminate the fungi. Both specific T cell-mediated immunity and nonspecific immunological mechanisms provide host defense against fungal infections. An adaptive immune response is usually preceded by innate immune responses mediated by neutrophils, NK cells, and circulating proteins such as complement components and anti-microbial peptides. However, in patients with localized or systemic immunological defects, granulomatous cutaneous infection of dermatophytes mostly caused by trichophytic fungi may occur [1]. Trichophytic granuloma includes Majocchi's granuloma [2] and disseminated trichophytic granuloma [3]. Recently, we experienced a patient with trichophytic granuloma and tinea universalis caused by Trichophyton (T.) rubrum infection during treatment with corticosteroid for systemic lupus erythematosus (SLE). We describe the clinical details of this patient, focusing on his immunological defects which led to the persistence of the fungal infection.     

Control of cutaneous antimicrobial peptides by vitamin D3

Constant exposure to a wide variety of microbial pathogens represents a major challenge for our skin. Antimicrobial peptides (AMPs) are mediators of cutaneous innate immunity and protect primarily against microbial infections. Cathelicidins were among the first AMPs identified in human skin and recent evidence suggests that they exert a dual role in innate immune defense: At first, due to their antimicrobial activity they kill pathogens directly. In addition, these peptides initiate a potent host response to infection resulting in cytokine release, inflammation and a cellular response. Disturbed cathelicidin expression and function was observed in several common inflammatory skin diseases, such as psoriasis where cathelicidin peptide converts inert self-DNA and self-RNA into an autoimmune stimulus. In atopic dermatitis decreased levels of cathelicidin facilitating microbial superinfections have been discussed. Furthermore, abnormally processed cathelicidin peptides induce inflammation and a vascular response in rosacea. Until recently, the molecular mechanisms underlying cathelicidin regulation were unknown. Recently, the vitamin D3 pathway was identified as the major regulator of cathelicidin expression. Consequently, vitamin D3 entered the spotlight as an immune modulator with impact on both innate and adaptive immunity. Therapies targeting vitamin D3 signaling may provide new approaches for infectious and inflammatory skin diseases by affecting both innate and adaptive immune functions.     

固有免疫应答在系统性硬皮病发病机制中的研究进展

系统性硬皮病（systemic sclerosis, SSc）是以皮肤及各内脏器官慢性纤维化为特征的自身免疫病。SSc发病中,固有免疫应答在激活免疫系统和纤维化过程中均发挥重要作用。固有免疫系统一方面通过抗原提呈作用,建立与适应性免疫应答的桥梁;另一方面通过分泌和调节关键的细胞因子促进炎症反应和组织纤维化过程。本文针对固有免疫系统中关键的单核/巨噬细胞、肥大细胞、中性粒细胞和树突状细胞等细胞成分,以及近年来重点关注的Toll样受体及其配体和IL-4、IL-6、TGF-β等细胞因子进行综述,旨在阐明固有免疫应答在SSc发病中的作用,以助于本病的临床评估及靶向分子治疗。     

白念珠菌细胞壁在其感染免疫中的作用

白念珠菌的细胞壁结构非常复杂，其主要成分为葡聚糖、甘露聚糖、几丁质、细胞壁蛋白和脂质等。白念珠菌的细胞壁蛋白参与白念珠菌的黏附和侵入。白念珠菌细胞壁的葡聚糖、甘露糖等可以通过吞噬细胞和树突状细胞表面相应的受体如Toll样受体、Dectin-1等诱导机体的固有免疫和获得性免疫，还可以通过诱导白介素-10和调节性T细胞逃逸机体的免疫应答。     

梅毒免疫和梅毒螺旋体的研究进展

梅毒螺旋体有着独特的基因和蛋白结构,对其基因分型有利于梅毒分子流行病学的研究.梅毒螺旋体缺乏脂多糖与外膜蛋白,但可表达多种脂蛋白,这些脂蛋白同梅毒螺旋体的组织黏附及播散有关,同时可诱导机体发生免疫应答.机体对于梅毒螺旋体的免疫应答过程十分复杂,固有免疫、体液免疫及细胞免疫均在梅毒螺旋体的感染过程中参与了应答过程.Th1型细胞免疫在梅毒的发生发展过程中起重要作用,梅毒患者在局部及系统免疫方面都存在细胞免疫的异常.