Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

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.

Immunological disturbance effect of exogenous histamine towards key immune cells

Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.

Integrative bioinformatics and in vitro exploration of EVI2A expression:unraveling its immunological and prognostic implications in kidney renal clear cell carcinoma

EVI2A has emerged as a significant biomarker in various diseases;however,its biological role and mechanism in kidney renal clear cell carcinoma(KIRC)remains unexplored.We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments.Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves.The gene’s immune relevance was explored through analyses of the tumor microenvironment(TME),Tumor Immune Single-cell Hub(TISCH),immune checkpoints,and immunotherapy sensitivity.Our results indicate that EVI2A expression is upregulated in KIRC,showing correlations with tumor grade and T/N/M stage.EVI2A demonstrates high diagnostic accuracy(AUC=0.906)and predicts poor overall and progression-free survival in KIRC patients.Furthermore,EVI2A expression exhibits significant associations with immunity,including TME scores and specific immune cell types such as Tfh cells,CD4 memory T cells,and CD8+T cells.Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors.In vitro assays confirmed the impact of EVI2A on KIRC behavior,with its knockdown resulting in reduced cell proliferation and migration.In conclusion,our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC.These findings hold significant implications for further research and potential clinical applications.

Obstructive sleep apnea-hypopnea syndrome immunological relationship

Obstructive sleep apnea-hypopnea syndrome(OSAHS)is a complex disorder cha-racterized by symptoms resulting from intermittent hypoxia and hypopnea,with research indicating a crucial role of immune system dysregulation and genetic variations in its pathogenesis.A recent Zhao et al study utilizes Mendelian ran-domization analysis to explore the causal relationship between immune cell characteristics and OSAHS.The study identifies specific lymphocyte subsets as-sociated with OSAHS,providing valuable insights into the disease's pathophy-siology and potential targets for therapeutic intervention.The findings underscore the significance of genetic and immunological factors in sleep disorders,offering a fresh perspective on OSAHS's complexities.Compared to existing literature,Zhao et al's study stands out for its focus on genetic markers and specific immune responses associated with OSAHS,expanding upon previous research primarily centered on systemic inflammation.In conclusion,the study represents a signi-ficant advancement in the field,shedding light on the causal role of immune cells in OSAHS and paving the way for future research and targeted treatments.

Rapamycin ameliorates experimental autoimmune uveoretinitis by inhibiting Th1/Th2/Th17 cells and upregulating CD4+CD25+ Foxp3 regulatory T cells

· AIM: To determine the effects of rapamycin on experimental autoimmune uveoretinitis(EAU) and investigate of role of rapamycin on T cell subsets in the disease.·METHODS: EAU was induced in rats using peptides1169 to 1191 of the interphotoreceptor binding protein(IRBP). Rapamycin(0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4 +CD25 + regulatory T cells(Tregs)from rat spleen were detected by flow cytometry.·RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro.Rapamycin also significantly increased TGF-β1production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore,rapamycin decreased the ratio of Th17 cells/CD4 +T cells and upregulated Tregs in EAU, as detected by flow cytometry.·CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU.Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

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.

Metabolic profile analysis of free amino acids in experimental autoimmune uveoretinitis rat plasma

AIM: To determine the differences of amino acid(AA) levels in experimental autoimmune uveoretinitis(EAU). METHODS: AA analysis of the plasma samples in EAU rats induced by interphotoreceptor retinoid-binding protein emulsion were performed with high performance liquid chromatography(HPLC) and phenylisothiocyanate(PITC) pre-column derivation methods were performed. Using partial least squares discriminant analysis(PLS-DA), the potential biomarkers were identified in EAU rat plasma, and the metabolic pathways related to EAU were further analyzed. RESULTS: The method results showed that linear(r≥0.9957), intra-day reproducible [relative standard deviation(RSD)=0.04%-1.33%], inter-day reproducible(RSD=0.06%-2.07%), repeatability(RSD=0.03%-0.89%), stability(RSD=0.05%-2.48%) and recovery(RSD=1.98%-4.39%), with detection limits of 0.853-11.4 ng/mL. The metabolic profile in EAU rats was different from that in the control groups five AAs concentrations were increased and nine AAs were reduced. Moreover, five metabolic pathways were related to the development of EAU. CONCLUSION: The developed method is a simple, rapid and convenient for determination of AAs in EAU rat plasma, and these findings will provide a comprehensiveinsight on the metabolic profiling of the pathological changes in EAU.

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.

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.

Osteopontin is a biomarker for early autoimmune uveoretinitis

Osteopontin(OPN)is an extracellular matrix protein with a diverse range of functions,including roles in cell adhesion,migration,and immunomodulation,which are associated with the modulation of neuroinflammation in the central nervous system.The present study was performed to evaluate the involvement of OPN in the eyes of an experimental autoimmune uveoretinitis(EAU)model.The EAU model was developed by immunization of Lewis rats with interphotoreceptor retinoid-binding protein.The results showed the OPN level was remarkably upregulated in the eye of EAU rats on day 9 post-immunization.The level of CD44,a ligand of OPN,was increased in the ciliary body of EAU rats.Furthermore,OPN was also detected in the ciliary body and activated microglia/macrophages in the EAU retina.The results suggest that OPN was significantly upregulated in the eyes of EAU rats,and that it may be useful as an early biomarker of ocular autoimmune diseases.All animal experiments were approved by the Institutional Animal Care and Use Committee of Jeju National University(approval No.2020-0012)on March 11,2020.

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.

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.

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.

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.