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在慢性乙型肝炎病毒感染和健康供体的个体之间,人类白细 [复制链接]

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发表于 2016-12-26 18:06 |只看该作者 |倒序浏览 |打印
J Viral Hepat. 2016 Dec 23. doi: 10.1111/jvh.12667. [Epub ahead of print]
Antibody-dependent and -independent uptake of HBsAg across human leukocyte subsets is similar between individuals with chronic hepatitis B Virus infection and healthy donors.Tharinger H1, Rebbapragada I1, Samuel D2, Novikov N2, Nguyen M3, Jordan R4, Frey CR1, Pflanz S1.
Author information
  • 1Department of Immunology, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA.
  • 2Biology Core Support , Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA.
  • 3Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Palo Alto, CA, 94304, USA.
  • 4Discovery Virology, Gilead Sciences, Inc., 333 Lakeside Dr., Foster City, CA, 94404, USA.


AbstractMaintaining detectable levels of antibodies to hepatitis B surface antigen (HBsAg) in serum, i.e. HBsAg sero-conversion, is the key clinical endpoint indicative of recovery from infection with hepatitis B virus (HBV). HBV-infected hepatocytes secrete HBsAg sub-viral particles in vast excess over HBV virions. Therefore, detectable hepatitis B surface antibody (anti-HBs) titers imply complete elimination of HBV virions as well as HBsAg particles. Although intrahepatic phagocytes, e.g. Kupffer cells, are thought to mediate clearance of HBsAg via antibody (Ab)-dependent and -independent mechanisms, the relative contributions of circulating phagocytic cell types to HBsAg elimination are poorly characterized. Understanding the role of various immune cell subsets in the clearance of HBsAg is important because Ab-dependent or -independent phagocytic HBsAg uptake may modulate presentation of HBsAg-derived epitopes to antigen-specific T cells and hence plays a critical role in adaptive immunity against HBV. This study aims to characterize phagocytic leukocyte subsets capable of internalizing HBsAg immune complexes (HBsAg:IC) or un-complexed HBsAg particles in whole blood directly ex vivo. The data shows that uptake of HBsAg:IC occurs most prominently in monocytes, B cells, dendritic cells, and in neutrophils. In contrast, B cells, and to a lesser degree also monocytes, seem to be effective phagocytes for un-complexed HBsAg. Importantly, a similar pattern of phagocytic HBsAg uptake was observed in blood from chronic hepatitis B (CHB) patients compared to healthy controls, suggesting that phagocytosis-related cellular functions are not altered in the context of CHB. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.



KEYWORDS: CHB; HBV; Phagocytes; immune complexes

PMID:28012213DOI:10.1111/jvh.12667

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发表于 2016-12-26 18:06 |只看该作者
J病毒Hepat。 2016 12月23日。doi:10.1111 / jvh.12667。 [打印前的电子版]
在慢性乙型肝炎病毒感染和健康供体的个体之间,人类白细胞亚群中HBsAg的抗体依赖性和非依赖性摄取是相似的。
Tharinger H1,Rebbapragada I1,Samuel D2,Novikov N2,Nguyen M3,Jordan R4,Frey CR1,Pflanz S1。
作者信息

    1Department of Immunology,Inc.,333 Lakeside Dr.,Foster City,CA,94404,USA。
    2Biology Core Support,Inc.,333 Lakeside Dr.,Foster City,CA,94404,USA。
    3Division of Gastroenterology and Hepatology,Stanford University Medical Center,750Welch Road,Palo Alto,CA,94304,USA。
    4Discovery Virology,Gilead Sciences,Inc.,333 Lakeside Dr.,Foster City,CA,94404,USA。

抽象

在血清中保持可检测水平的抗乙型肝炎表面抗原(HBsAg),即HBsAg血清转化,是指示从乙型肝炎病毒(HBV)感染恢复的关键的临床终点。 HBV感染的肝细胞分泌HBsAg亚病毒颗粒,超过HBV病毒颗粒。因此,可检测的乙型肝炎表面抗体(抗HBs)滴度意味着完全消除HBV病毒体以及HBsAg颗粒。虽然肝内吞噬细胞, Kupffer细胞被认为通过抗体(Ab) - 依赖和非依赖性机制介导HBsAg清除,循环吞噬细胞类型对HBsAg消除的相对贡献很差的特征。理解各种免疫细胞亚群在清除HBsAg中的作用是重要的,因为Ab依赖性或非依赖性吞噬HBsAg摄取可以调节HBsAg衍生的表位向抗原特异性T细胞的呈递,因此在对HBV的适应性免疫中起关键作用。这项研究旨在表征吞噬白细胞亚群能够内部化HBsAg免疫复合物(HBsAg:IC)或未复杂的HBsAg粒子在全血直接离体。数据显示HBsAg:IC的摄取在单核细胞,B细胞,树突细胞和嗜中性粒细胞中最显着地发生。相反,B细胞,以及较小程度上也是单核细胞,似乎是未复合的HBsAg的有效吞噬细胞。重要的是,与健康对照相比,在来自慢性乙型肝炎(CHB)患者的血液中观察到吞噬性HBsAg摄取的类似模式,表明吞噬作用相关的细胞功能在CHB的背景下不改变。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词:

CHB;乙型肝炎;吞噬细胞;免疫复合物

PMID:
    28012213
DOI:
    10.1111 / jvh.12667
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