Core fucosylation and its roles in gastrointestinal glycoimmunology

Glycosylation is a common post-translational modification in eukaryotic cells.It is involved in the production of many biologically active glycoproteins and the regulation of protein structure and function.Core fucosylation plays a vital role in the immune response.Most immune system molecules are core fucosylated glycoproteins such as complements,cluster differentiation antigens,immunoglobulins,cytokines,major histocompatibility complex molecules,adhesion molecules,and immune molecule synthesis-related transcription factors.These core fucosylated glycoproteins play important roles in antigen recognition and clearance,cell adhesion,lymphocyte activation,apoptosis,signal transduction,and endocytosis.Core fucosylation is dominated by fucosyltransferase 8(Fut8),which catalyzes the addition ofα-1,6-fucose to the innermost GlcNAc residue of N-glycans.Fut8 is involved in humoral,cellular,and mucosal immunity.Tumor immunology is associated with aberrant core fucosylation.Here,we summarize the roles and potential modulatory mechanisms of Fut8 in various immune processes of the gastrointestinal system.

Exercise immunology:Future directions

Several decades of research in the area of exercise immunology have shown that the immune system is highly responsive to acute and chronic exercise training.Moderate exercise bouts enhance immunosurveillance and when repeated over time mediate multiple health benefits.Most of the studies prior to 2010 relied on a few targeted outcomes related to immune function.During the past decade,technologic advances have created opportunities for a multi-omics and systems biology approach to exercise immunology.This article provides an overview of metabolomics,lipidomics,and proteomics as they pertain to exercise immunology,with a focus on immunometabolism.This review also summarizes how the composition and diversity of the gut microbiota can be influenced by exercise,with applications to human health and immunity.Exercise-induced improvements in immune function may play a critical role in countering immunosenescence and the development of chronic diseases,and emerging omics technologies will more clearly define the underlying mechanisms.This review summarizes what is currently known regarding a multi-omics approach to exercise immunology and provides future directions for investigators.

A Multi-Agent Immunology Model for Security Computer

This paper presents a computer immunology model for computer security, whose main components are defined as idea of Multi Agent. It introduces the natural immune system on the principle, discusses the idea and characteristics of Multi Agent. It gives a system model, and describes the structure and function of each agent. Also, the communication method between agents is described.

Immunology of tuberculosis

Various T cells and macrophages as well as cytokines are involved in the immunopathogenesis of tuberculosis(TB). A better understanding of immunology of TB can not only lead to the discovery of new immunodiagnostic tools, accelerate and facilitate the assessment of new therapeutic methods, but also find new treatment regimens. In this highlight topic we cover the latest developments in the role of T cells, macrophages, Natural killer(NK) cells, invariant NK T(iN KT) cells and γδ T cells with TB infection. Histologically, TB displays exudative inflammation, proliferative inflammation and productive inflammation depending on the time course. T cells first recognize antigen within the mycobacterially-infected lung, and then activate, differentiate, but the first T cell activation occurs in the draining lymph nodes of the lung. When protective T cells reach sufficient numbers, they can stop bacterial growth. Except for T cells, neutrophils also participate actively in defense against early-phase TB. NK cells are innate lymphocytes which are a first line of defense against mycobacterial infection. Human NK cells use the NKp46, NCRs and NKG2 D receptors to lyse Mycobacterium TB-infected monocytes and alveolar macrophages. NK cells produce not only interferon-γ, but also interleukin(IL)-22, which is induced by IL-15 and DAP-10. iN KT cells show different phenotypes and functions. Many iN KT cells are CD4+,few iN KT cells are CD8+, while an additional fraction of iN KT cells are negative for both CD4 and CD8. γδ T cells represent an early innate defense in antimycobacterial immunity. Studies done in humans and animal models have demonstrated complex patterns of γδ T cell immune responses during chronic TB. Human alveolar macrophages and monocytes can serve as antigen presentation cells for γδ T cells. Furthermore, the predominance of Vγ9Vδ2 T cells in TB has been confirmed.

Liver immunology and herbal treatment

Beyond the metabolic functions, the liver recently has been defined as an organ of immune system(IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review.

Progresses in Integrated Traditional Chinese and Western Medical Research on Reproductive Immunology

Reproductive immunology is a crossed subject of reproductive biology and immunobiology. Great progresses have been achieved in the subject along with the deep development in life science. Modern reproductive immunology includes immunological regulation of fertility, materno-fetal immuno-regu-lation, and neuro-reproductive endocrino-immune network. With the integrated traditional Chinese and western medicine (ICWM) applied to reproductive immunology it has been greatly enriched in research contents and depth. The present review is to introduce the recent progresses in research of integrated medicine on reproductive immunology.

Old game, new players: Linking classical theories to new trends in transplant immunology

The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.

Systems Immunology Enabled Immune Engineering

The immune checkpoint blockade has revolutionized cancer treatment.However,not all cancer types are susceptible to this therapy.Even in melanoma,one of the best scenario,about half of the patients do not respond to immune checkpoint blockade.Since CD8+T cell is the main driving force behind cancer elimination,then having a complete and competent T cell repertoire to cover all possible cancer antigens expressed by cancer cells should be a determining factor to the success of this therapy.Conversely,if there are'holes'in patients’T cell repertoire and/or'weak spots'manifested as functional dysregulation or exhaustion on T cells specific to a set of cancer antigens that dominantly expressed by cancer cells,cancer immune escape is inevitable.However,these two types of cancer immune escape might need different treatment strategies:the first group with'holes'in the T cell repertoire,whether the'holes'are taking on a form of missing T cells to cover these cancer antigens or missing high-affinity TCRs that are known to be more sensitive to antigen stimulation,would be benefited from TCR re-directed adoptive cell transfer(ACT)therapy;the other group with T cell repertoire'weak spots'would be benefited from immune checkpoint blockade alone or in combination with additional stimulatory factors such as cytokines and peptide vaccine.In the past decade,we have developed several tools to profile the T cell repertoire from T cell receptor diversity to T cell receptor affinity to high-throughput linking antigen specificity to single T cell receptor sequences in large scale.In this talk,I will first introduce these tools and then give examples on how we use them to answer some of the fundamental questions in systems immunology with a focus on cancer immunology,which in turn help us design new therapeutics immune engineering.

尹玉新教授课题组在Nature Immunology发表研究成果

北京大学系统生物医学研究所尹玉新教授课题组最新研究发现了自身免疫系统调控开关——双重特异性磷酸酶2（dual-specificity phosphatase 2,DUSP2/PAC1）,它可以调控自身免疫反应,影响自身免疫疾病的发生发展,其相关研究论文＂The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates TH17 differentiation＂于2015年10月19日在线发表于Nature Immunology，北京大学基础医学院吕丹博士和2009级基础医学八年制博士研究生刘亮为该论文的共同第一作者。该项研究得到国家重点基础研究发展计划（973计划）、国家自然科学基金和北京大学一清华大学生命科学联合中心的支持。

A Novel Evolutionary Feedforward Neural Network with Artificial Immunology

A hybrid algorithm to design the multi layer feedforward neural network was proposed. Evolutionary programming is used to design the network that makes the training process tending to global optima. Artificial immunology combined with simulated annealing algorithm is used to specify the initial weight vectors, therefore improves the probabiligy of training algorithm to converge to global optima. The applications of the neural network in the modulation style recognition of analog modulated rader signals demonstrate the good performance of the network.

Welcome to the World Journal of Immunology

We are pleased to announce the launch of the World Journal of Immunology （WJI） as a new member of the family of the World series of journals. The pace of discovery in the field of immunology has accelerated signifcantly in recent years due to important discover-ies and the implementation of new technologies and methodologies that have become readily accessible to many investigators. WJI is an open-access, peer-reviewed journal, whose preparatory work was initiated on November 30, 2010 and will be offcially published on December 27, 2011. The WJI Editorial Board con-sists of 99 experts in experimental medicine from 23 countries. By taking into account the widespread use of the internet and the necessity that scientifc journals should reach out to wider audiences through the provi-sion of barrier-free information, WJI aims to provide rapid publication through an established system that is targeted at dissemination to the scientific community via online open-access.

Role of the clinical immunology laboratory in disease monitoring

Immunological investigations provide useful informa-tion to guide diagnosis of several disorders. Many such tests are also commonly repeated at intervals, in an effort to facilitate disease monitoring. In general how-ever, immunology test results are often slow to alter. Furthermore, audit activity has indicated that repeated testing accounts for a substantial workload in many immunology services, which may waste resources and compromise the effcient completion of necessary tests. Consequently, the need and appropriate mini-mum interval between repeated testing requires critical evaluation. In this review, the clinical utility of repeat-ed performance of several common immunology inves-tigations has been evaluated, based upon published evidence. In some cases （ e.g. , paraprotein quantifca-tion, or measurement of anti-glomerular basement membrane antibodies）, repeated testing provides vital clinical information and can be justifed on a frequent and individualized basis. However, many other investi-gations provided by immunology services provide less valuable information when used to aid disease moni-toring rather than diagnosis. It is hoped that the data summarized here will facilitate a more evidence-based approach to repeated testing. Such information may also assist with the local implementation of demand management strategies based upon setting of mini-mum retesting intervals for these investigations.

Acknowledgments to reviewers of World Journal of Immunology

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Immunology. The editors and authors of the articles submitted to the journal are grateful to the following reviewers for evaluating the articles （including those published in this issue and those rejected for this issue） during the last editing time period.

Frontiers in Molecular Immunology

Immunology is a discipline to investigate the structure and function of the immune molecules or immune pathway and the causes of immunity to disease, which cover the study of all aspects of the immune system. The earliest concept of acquired immunology was originated from the inoculation of smallpox occurs inWan Quan’s (1499- 1582) Douzhenxinfa,[1] and was further developed by Edward Jenner with the discovery of smallpox vaccine in 1796.[2] Immunology made a great advance towards the end of the 19th century, with the isolation of infectious bacteria by Robert Koch[3] and the demonstration of antibody activity against diphtheria and tetanus toxins by Emil von Behring and Kitasato Shibasaburo.

Acknowledgments to reviewers of World Journal of Immunology

Many reviewers have contributed their expertise and time to the peer review, a critical process to ensure the quality of World Journal of Immunology. The editors and authors of the articles submitted to the journal are grateful to the following reviewers for evaluating the articles （including those published in this issue and those rejected for this issue） during the last editing time period.

International Conference on Immunology 2007

Shanghai,China July 12-15,2007 The conference will provide a forum to bring together immunologists and scientists from around the world in related fields to review the latest progress and development,to exchange their experience,progress

The sea bass Dicentrarchus labrax as a marine model species in immunology:Insights from basic and applied research

This review summarizes the current knowledge on immune defence activities of the European sea bass Dicentrarchus labrax by reporting the consistent amount of work done on this economically-important species.A draft genome sequence is available for this species,together with whole transcriptomes from lymphoid and non-lymphoid tissues.Available full-length coding sequences of many immunoregulatory and immune-related genes allow for targeted quantitative PCR analysis,nowadays needed for-omics data verification,ex vivo and in vitro.The first anti-T cells monoclonal antibody teleost-wise was obtained in sea bass,followed by several monoclonal and polyclonal markers of lymphocyte populations,namely T cells(pan-T,CD3ε,TcRγ,CD45),and B cells(IgM,IgT,IgD).The combined use of molecular and biochemical tools enabled investigations on innate and acquired immune responses of sea bass in unstimulated/stimulated fish,along the development and under variable environmental conditions and food regimes.An overview of sea bass viral and bacterial pathogens and available vaccines against these microorganisms is also provided.The knowledge accumulated in the past 25 years validates the European sea bass as a reference marine model in the field of fish immunology.

The implication of pyroptosis in cancer immunology:Current advances and prospects

Pyroptosis is a regulated cell death pathway involved in numerous human diseases,especially malignant tumors.Recent studies have identified multiple pyroptosis-associated signaling molecules,like caspases,gasdermin family and inflammasomes.In addition,increasing in vitro and in vivo studies have shown the significant linkage between pyroptosis and immune regulation of cancers.Pyroptosis-associated biomarkers regulate the infiltration of tumor immune cells,such as CD4^(+) and CD8^(+) T cells,thus strengthening the sensitivity to therapeutic strategies.In this review,we explained the relationship between pyroptosis and cancer immunology and focused on the significance of pyroptosis in immune regulation.We also proposed the future application of pyroptosis-associated biomarkers in basic research and clinical practices to address malignant behaviors.Exploration of the underlying mechanisms and biological functions of pyroptosis is critical for immune response and cancer immunotherapy.

New era of cancer immunology driven by big data

Cancer immunology has witnessed remarkable development over the past century.In the early 20^(th) century,William Coley embarked on pioneering efforts to activate the immune system against cancer using heat-killed Streptococcus pyogenes and Serratia marcescens^([1]).These attempts yielded varying clinical outcomes,some of which were notably successful,providing early evidence of the immune system’s potential in combating cancer.Moving into the mid-20th century,Dr.Lewis Thomas and Dr.Macfarlane Burnet introduced the concept“immune surveillance”^([2]).This theory proposed that the immune systemconstantlymonitors the body,identifying and eliminating emerging cancer cells to prevent them from developing into full-fledged tumors.This concept laid the foundation for future research in cancer immunology.Simultaneously,the concept of immune evasion emerged,emphasizing how cancer cells can elude immune detection and destruction,enabling them to proliferate and spread within the body.Thus,understanding and overcoming these mechanisms of immune escape became a pivotal focus of cancer immunotherapy.