Synthesis of glycopeptides from type II collagen-incorporating galactosylated hydroxylysine mimetics and their use in studying the fine specificity of arthritogenic T cells

Five analogues of the bovine type II collagen (bCII) immunodominant glycopeptide [beta-D-Gal-(5R)-5-Hyl264]CII(256-270) (1) carrying diverse modifications at the critical hydroxylysine (Hyl) 264 side chain were designed and synthesised, to explore the fine specificity of bCII-reactive T cells involved in the initiation and/or regulation of collagen-induced arthritis (CIA), a mouse model for rheumatoid arthritis (RA). Beta-D-galactosyl-(5R)-5-hydroxy-L-lysine (19) and corresponding mimetics (22-25), conveniently protected for solid-phase synthesis, were all obtained by a divergent route involving enantiopure 5-hydroxylated 6-oxo-1,2-piperidinedicarboxylates as the key intermediates. All three bCII-specific T hybridomas used, as well as a recurrent pathogenic CD4+ T-cell clone isolated from bCII-immunised DBA/1 mice, recognised the galactosylated form 1 of the immunodominant bCII (256-270) epitope. These cells were extremely sensitive to changes at the epsilon-amino group of Hyl264, but differed in their pattern of recognition of analogues with a Hyl264 side chain modified at C-5 (i.e. inversion of stereochemistry, methylation). These data further document the importance of collagen post-translational modifications in autoimmunity and in the CIA model in particular, and provide a new insight into the molecular interaction between glycopeptide 1 and the TCR of pathogenic T cells.     

Towards a quantitative understanding of the within-host dynamics of influenza A infections

Although the influenza A virus has been extensively studied, a quantitative understanding of the infection dynamics is still lacking. To make progress in this direction, we designed several mathematical models and compared them with data from influenza A infections of mice. We find that the immune response (IR) plays an important part in the infection dynamics. Both an innate and an adaptive IR are required to provide adequate explanation of the data. In contrast, regrowth of epithelial cells did not seem to be an important mechanism on the time scale of the infection. We also find that different model variants for both innate and adaptive responses fit the data well, indicating the need for additional data to allow further model discrimination.     

进程异常检测中淋巴细胞的逻辑语义模型

论文针时反向选择算法无法有效地捕捉某些复杂问题空间的语义信息的缺点,以逻辑程序设计领域中的稳定模型为理论基础,提出一个淋巴细胞的逻辑语义模型。该模型采用逻辑程序表示淋巴细胞和抗原,通过计算它们的稳定模型来进行异常检测。最后,以进程异常检测为背景,设计了一个系统框架。该框架充分考虑了进程系统调用短序列的语义信息。能有效地提高异常检测的准确率。     

免疫原理在入侵检测技术中的应用研究

文章介绍了生物免疫的免疫原理及入侵检测系统的原理,论述了免疫原理在入侵检测技术中的应用,着重讨论了阴性选择模型与危险理论及有关算法在入侵检测系统中的应用最后在分析入侵捡测方法存在问题的基础上,探讨了基于免疫原理的入侵检测系统的研究方向。     

Adipokines as Immune Cell Modulators in Multiple Sclerosis

Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease of the central nervous system (CNS), is a major clinical and societal problem, which has a tremendous impact on the life of patients and their proxies. Current immunomodulatory and anti-inflammatory therapies prove to be relatively effective; however, they fail to concomitantly stop ongoing neurological deterioration and do not reverse acquired disability. The proportion to which genetic and environmental factors contribute to the etiology of MS is still incompletely understood; however, a recent association between MS etiology and obesity was shown, with obesity greatly increasing the risk of developing MS. An altered balance of adipokines, which are white adipose tissue (WAT) hormones, plays an important role in the low-grade chronic inflammation during obesity by their pervasive modification of local and systemic inflammation. Vice versa, inflammatory factors secreted by immune cells affect adipokine function. To explore the role of adipokines in MS pathology, we will here review the reciprocal effects of adipokines and immune cells and summarize alterations in adipokine levels in MS patient cohorts. Finally, we will discuss proof-of-concept studies demonstrating the therapeutic potential of adipokines to target both neuroinflammation and neurodegeneration processes in MS.     

食品微生物快速检测技术研究进展

随着食品工业的迅速发展,建立食品微生物快速检测方法,对食品生产、运输、销售过程中质量的监控具有十分重要的意义.综述了目前较为先进的微生物快速检测技术的原理和应用,主要有免疫学技术、代谢学技术和分子生物学技术.     

Molecular Mechanisms Underlying the Association between Endometriosis and Ectopic Pregnancy

Endometriosis is a common inflammatory disease characterized by the presence of endometrial cells outside the uterine cavity. It is estimated that it affects 10% of women of reproductive age. Its pathogenesis covers a wide range of abnormalities, including adhesion, proliferation, and cell signaling disturbances. It is associated with a significant deterioration in quality of life as a result of chronic pelvic pain and may also lead to infertility. One of the most serious complications of endometriosis is an ectopic pregnancy (EP). Currently, the exact mechanism explaining this phenomenon is unknown; therefore, there are no effective methods of prevention. It is assumed that the pathogenesis of EP is influenced by abnormalities in the contraction of the fallopian tube muscles, the mobility of the cilia, and in the fallopian microenvironment. Endometriosis can disrupt function on all three levels and thus contribute to the implantation of the embryo beyond the physiological site. This review takes into account aspects of the molecular mechanisms involved in the pathophysiology of endometriosis and EP, with particular emphasis on the similarities between them.     

基于免疫的入侵检测模型中空洞的分析及对策

根据人工免疫的原理、体系结构,建立了一种新的基于免疫原理的分布式网络入侵检测系统模型。该模型中存在着检测子集合无法检测到的非我--"空洞"。"空洞"会导致模型性能的下降,漏报率的增高。在详细分析了"空洞"产生的原因以及"空洞"的相关特性后,给出了减少 "空洞"的对策,并用模拟试验的方式验证了不同形状的检测子可以有效弥补"空洞",从而使系统的漏报率下降。     

免疫防火墙模型的构造

为了改变传统防火墙静态的缺点,在计算机免疫学原理的指导下,通过借鉴自然免疫系统特征,提出了免疫防火墙模型。该模型是两层结构,第1层采用传统的防火墙技术,第2层是基于免疫原理的免疫层。免疫层采用规则树编码的识别器,通过在self、nonself集上进行学习和识别训练,获得self、nonself的主要特征,产生动态规则,即免疫层的免疫(淋巴)细胞,以自适应的方式阻拦非法数据,并利用演化计算对识别器进行演化。该防火墙模型具有一定的自适应性和动态性。     

Synthesis and evaluation of an alpha-C-galactosylceramide analogue that induces Th1-biased responses in human natural killer T cells

An alpha-galactosylceramide (alphaGalCer, 1) and its isosteric C-glycoside analogue (2) were found to possess promising immunostimulatory activity because of their ability to activate natural killer T (NKT) cells. We report the synthesis of compound 3, a truncated nonisosteric C-alphaGalCer analogue, that like 2 is not enzymatically labile at the glycosidic linkage, but has the anomeric carbon directly bonded to the C1 of the phytoceramide backbone. We compared the biological activity of the three ligands using an in vitro system with human dendritic cells as the antigen-presenting cells and human NKT cells as the responding cells. Although 3 was a less potent agonist for NKT cells than 1 and 2, it induced cytokine production with the highest IFN-gamma:IL-4 and IFN-gamma:IL-13 ratios. Therefore, our data suggest that the new mimetic of alphaGalCer might preferentially promote Th1-immune responses and serve as a potent adjuvant in the immunotherapy of cancer and infectious diseases.