Induction of immune tolerance with heart-thymus composite allotransplantation in rats

Objective To study on the role of thymus transplantation for heart allograft in rats. Methods Vascularized heart-thymus combined transplantation was performed with microsurgical technique. Graft survival, histopathology, level of IL-2, IL-4 and its mRNA expression in serum and cardiac grafts were investigated. Results Heart-thymus combined transplantation achieved effect in the prolongation of cardiac graft survival with short-term administration of cyclosporine. Conclusions Vascularized thymus transplantation induced immune tolerance in thymectomized rats.     

基于免疫算法的Hopfield神经网络多用户检测器

提出的基于免疫算法的Hopfield神经网络多用户检测器，将扰乱的Hopfield神经网络多用户检测器的输出作为免疫算法的初始种群，利用了免疫算法的全局收敛的特点，从而克服了Hopfield易收敛到局部能量最小点的缺点。理论分析和仿真结果表明：该检测器具有良好的抗多址干扰和抗远近效应的能力。     

一种基于网络安全风险评估的入侵检测方法

针对传统的入侵检测系统存在报警数量大、误报率高等缺陷,提出了一种基于网络安全风险评估的入侵检测方法,该方法基于入侵检测结果,引入抗体浓度随入侵强度动态变化这一人工免疫理论的最新研究成果进行网络安全风险的计算,然后根据当前网络面临的实时安全风险动态设置报警策略。实验结果表明,该方法能够实时、定量地计算主机和网络所面临的风险,并极大地降低报警数量和误报率。     

入侵检测主流技术及发展动态

入侵检测技术是网络安全的主要技术和网络研究的热点,入侵检测方法包括基于数据挖掘、粗糙集、模式识别、支持向量机和人工免疫等主要技术,详细分析了各种检测方法在入侵检测应用中的优缺点。通过回顾研究人员近期的研究成果,提出了该技术的主要发展方向,为进一步研究提供参考。     

Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE

Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14⁺⁺CD16⁺ monocytes, CD56⁺ CD16^dim natural killer cells, marginal zone-like IgD⁺CD27⁺ B cells, and on CD4⁺ and CD8⁺ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.     

基于危险理论的人工免疫原理与应用*

侧重以危险理论的基本机制为线索,对危险理论的研究现状加以系统论述.首先以危险理论的免疫模型入手,归纳提炼出仿真机理并建立起隐喻算法;介绍其中具有代表性领域中的应用情况;最后对基于危险理论的人工免疫研究的下一步工作进行展望.     

Transcriptomic Profiles of CD47 in Breast Tumors Predict Outcome and Are Associated with Immune Activation

Targeting the innate immune system has attracted attention with the development of anti- CD47 antibodies. Anti-CD47 antibodies block the inhibition of the phagocytic activity of macrophages caused by the up-regulation of CD47 on tumor cells. In this study, public genomic data was used to identify genes highly expressed in breast tumors with elevated CD47 expression and analyzed the association between the presence of tumor immune infiltrates and the expression of the selected genes. We found that 142 genes positively correlated with CD47, of which 83 predicted favorable and 32 detrimental relapse-free survival (RFS). From those associated with favorable RFS, we selected the genes with immunologic biological functions and defined a CD47-immune signature composed of PTPRC, HLA-E, TGFBR2, PTGER4, ETS1, and OPTN. In the basal-like and HER2+ breast cancer subtypes, the expression of the CD47-immune signature predicted favorable outcome, correlated with the presence of tumor immune infiltrates, and with gene expression signatures of T cell activation. Moreover, CD47 up-regulated genes associated with favorable survival correlated with pro-tumoral macrophages. In summary, we described a CD47-immune gene signature composed of 6 genes associated with favorable prognosis, T cell activation, and pro-tumoral macrophages in breast cancer tumors expressing high levels of CD47.     

Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

Lipid Droplet Motility Increases Following Viral Immune Stimulation

Lipid droplets (LDs) have traditionally been thought of as solely lipid storage compartments for cells; however, in the last decade, they have emerged as critical organelles in health and disease. LDs are highly dynamic within cells, and their movement is critical in organelle–organelle interactions. Their dynamics are known to change during cellular stress or nutrient deprivation; however, their movement during pathogen infections, especially at very early timepoints, is under-researched. This study aimed to track LD dynamics in vitro, in an astrocytic model of infection. Cells were either stimulated with a dsRNA viral mimic, poly I:C, or infected with the RNA virus, Zika virus. Individual LDs within infected cells were analysed to determine displacement and speed, and average LD characteristics for multiple individual cells calculated. Both LD displacement and mean speed were significantly enhanced in stimulated cells over a time course of infection with an increase seen as early as 2 h post-infection. With the emerging role for LDs during innate host responses, understanding their dynamics is critical to elucidate how these organelles influence the outcome of viral infection.