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.

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.

Crypto-Giardia antigen rapid test versus conventional modified Ziehl-Neelsen acid fast staining method for diagnosis of cryptosporidiosis

Objectove:To evaluate the validity of Crypto-Giardia antigen rapid test(CA-RT) in comparison with the conventional mollified Ziehl-Neelsen acid fast(MZN-AF) staining method for the diagnosis of cryptosporidiosis.Methods:Fifteen preserved stool samples from previously confirmed infections were used as positive controls and 40 stool samples from healthy people were used as negative control.A total of 85 stool samples were collected from suspected patients with cryptosporidiosis over 6 months during the period from January till June.2011.The stud) was conducted in the department of parasitology,central laboratory.Alnoor Specialist Hospital, Makkah.Saudi Arabia.All samples were subjected to CA-RT and conventional MZN-AF staining method.Validation parameters including sensitivity(SN).specificity(SP),accuracy index (AI).positive predictive value(PPV).and negative predictive value(NPV) were evaluated for both tests.Results:Out of 15[lositive controls,CA-RT detected 13(86.7%) while MZN-AF detected 11(73.3%) positive cases.However.CA-RT detected no positive case in 40 normal controls but MZN-AF detected 2(5%) as positive cases.Based on the results,the SN.SP.AI.PPV and NPV were high in CA-RT than MZN-AF staining method,ie..86.7%vs.73.3%.100%vs.95%.96.4%vs.89.1%. 100%vs.84.6%and 95.2%vs.90.5%.respectively.Out of a total of 85 suspected specimens.CART detected 7(8.2%) but MZN-AF detected 6(7.1%) cases as positive.Conclusions:CA-RT immunoassay is more valid and reliable than MZN-AF staining method.

Cryptosporidiosis-an overview

Apicomplexan protozoan parasites of the genus Cryptosporidium infect the gastrointestinal tract and lungs of a wide variety of animals, including humans. The majority of human infections are due to either Cryptosporidium hominis （C. hominis） and/or Cryptosporidium parvum （C. parvum）. The parasite has a complex life cycle that includes both asexual and sexual stages. While there are invasive free living stages, proliferation and differentiation take place within a unique parasitrophorous vacuole under the host cell brush border but outside the host cell cytoplasm. Infection is spread by environmentally resistant spores that primarily contaminate drinking water and occasionally food sources, which may cause significant outbreaks of diarrhea that generally lasts less than 2 w in immunocompetent individuals. In immunodeficient or immunosuppressed individuals, diarrhea may be copious and can result in significant morbidity and mortality, particularly in AIDS patients. Although diagnosis is relatively simple, effective drug treatment, particulary for infections in immunodeficient patients, has not been uniformly successful. This overview summarizes the species known to infect humans, aspects of the parasite life cycle, sources of infection, the pathophysiology of cryptosporidiosis, the immune response to infection, diagnosis, treatment and some aspects of cryptosporidiosis in China.

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.

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.

Disseminated cryptosporidiosis:Case report and literature review

Cryptosporidiosis,better known as an intestinal disease may disseminate to infect other sites including the respiratory tract. Little information however is available on respiratory cryptosporidiosis that may largely be due to lower frequency of respiratory cryptosporidiosis. Respiratory cryptosporidiosis has been majorly reported in immunocompromised individuals and children. Here we report a case of respiratory and intestinal cryptosporidiosis in a fifteen months old child with CD8+ deficiency. The patient in spite of treatment with Nitazoxanide and Azithromycin followed by Intravenous immunoglobulin and Bovine colostrum had a fatal outcome. The Cryptosporidium spp. isolate was subjected to molecular characterization. The Cryptosporidium spp. was identified both in stool specimen and Endotracheal aspirate(ETA). The blood sample was negative for Cryptosporidium spp. The Cryptosporidium spp. isolate from stool as well as ETA was identified as Cryptosporidium hominis(C. hominis) using Multiplex Allele Specific Polymerase Chain Reaction assay and was subtyped as Ia A23G1R1 subtype using gp60 gene polymerase chain reaction assay followed by sequencing.

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.

Effect of Egyptian propolis on cryptosporidiosis in immunosuppressed rats with special emphasis on oocysts shedding,leukogram,protein profile and ileum histopathology

Objective:To investigate the activity of Egyptian propolis extracts(ethanol and water)on cryptosporidiosis in experimentally infected dexamethasone-immunosuppressed rats.Methods:A total of 180 male rats(190-220)g BWt were randomly divided into 9 equal groups(G1-G9).Groups of rats were kept as(G1):normal control,(G2-G9):immunosuppressed with dexamethasone and(G3-G9):infected with Cryptosporidium oocysts.Rats from(G4to G9)were given orally ethanol and water extract of propolis(at a dose of 50 mg/kg BWt)and nitazoxanide(standard anti-cryptosporidial drug at a dose of 100 mg/kg BWt)to infected rats with different regimes.Faecal pellets were collected from all groups to monitor oocysts shedding from the 2nd to the 15th day post infection.At the end of the experiment,blood was collected from all groups for determination of leukogram and serum proteins.Ileum specimens were also examined histopathologically.Results:The highest reduction of oocysts shedding in faecal samples was 88%in rats prophylactically treated with propolis ethanol extract at the 4th dpi,and in rats prophylactically treated with water extract of propolis,was91%at the 6th dpi.There was a marked increase in neutrophils count and α_2-andβ-globulins levels in infected rats treated with both extracts,while a significant decrease was detected in lymphocytes compared to the infected non treated group.β-globulin level markedly increased in the rats administered nitazoxanide.Histopathological changes were observed in the ileum of rats infected with Cryptosporidium.Conclusions:Egyptian propolis extracts have an activity on cryptosporidiosis in rats.Moreover,propolis modulated the immunity in dexamethasone-immunosuppressed rats.

Hepatic portal venous gas due to cryptosporidiosis in a patient with acquired immunodefi ciency syndrome

Although the presence of hepatic portal venous gas (HPVG) on computed tomography (CT) is typically an ominous finding, HPVG may sometimes be less catastrophic. The clinical significance of HPVG is variable, and it depends primarily on the underlying pathol ogy. We report a case of a patient with acquired immunodeficiency syndrome (AIDS) who was found to have HPVG on CT as a presumed result of gastrointestinal cryp tosporidiosis, an association that, to our knowledge, has not been reported. This case illustrates another cause of HPVG that should be considered in patients with AIDS.

Epidemiological survey of cryptosporidiosis in Anhui Province China

AIM: To provide scientific evidence for prevention and controlling of cryptosporidiosis, the infection of Cryptosporidium parvum and its epidemiological characteristics were studied in some areas of Anhui Province.METHODS: The oocyst of Cryptosporidium parvum in 5421fresh stool samples from eleven areas of Anhui Provincewas tested by auramine-phenol stain and improved anti-acidstain respectively. The specific antibody of IgG, IgM and Tsubsets of 41 patients with positive Cryptosporidium parvumin stools were detected by ELISA and biotin-streptavidin(BSA) respectively.RESULTS: The total infective rate of Cryptosporidiumparvum was 1.33 % (74/5421). Among them, the positiverates of oocyst in the areas of Huaibei (1. 82 % ) and Fuyang( 1. 80 % ) were higher. The positive rates of oocyst in stoolsof infants, pupils, middle school students, collegestudents, adults, patients with diarrhea, and those withimmunodeficiency were 3.15 % (28/889), 0.82 % (9/1098), 0.82 %(9/1092), 0.83 %(8/969), 0.85 % (9/1095), 2.88 %(8/27g) and 8.33 %(3/36) % respectively. The positive rates ofoocyst in infants and the patients with diarrhea andimmunodeficiency were significantly higher than those incontrols ( P ＜ 0.01 ). The positive rate of oocyst in maleswas similar to that in females ( P＞ 0.05). The positive rateof oocyst in urban areas ( 1. 13 %) was significantly lowerthan those in rural areas ( 1. 72 %, P ＜ 0.01 ). The positiverates of specific IgG, IgM and IgG + IgM in sera of thepatients with positive oocyst in stool were 63.4 % ( 26/41 ),17.1% (7/41), 19.5 % (8/41) respectively. The numberfractions of T subsets of CD3 + , CD4 + , CD8 + and CD4 +/CD8 + of the patients were 0.66 ± 0.07, 0.44 ± 0.06, 0.28 ± 0.04 and 1. 58 ± 0.32 respectively. The difference between thepatients and the controls was significant ( P ＜ 0. 05). Themain manifestations of the patients were subclinicalinfection, in forms of slight abdominal pain, mild diarrhea,and loose stool.CONCLUSION: There are two infection peaks in infection ofCryptosporidium parvum and its infection can he foundmore often in infants, patients with diarrhea orimmunodeficiency, and in rural areas. Subclinical infectionis the main manifestation and might he easily misdiagnosed.When the therapeutic effectiveness is low for diarrhea, theinfection of Cryptosporidium parvum should he considered,conceming their age and immune function.

Prevalence of cryptosporidiosis in animals in Iran: A systematic review and meta-analysis

Objective:To review the prevalence of cryptosporidiosis among animal population of Iran.Methods:Data were systematically gathered from 1 January 2000 to 1 January 2020 in the Islamic Republic of Iran from the following electronic databases:Pub Med,Springer,Google Scholar,Science Direct,Scopus,Web of Science,Magiran,and Scientific Information Database(SID).According to the preferred reporting items for systematic reviews and meta-analyses(PRISMA)and inclusion criteria,88 eligible studies were obtained.Results:The pooled prevalence of cryptosporidiosis using random and fixed effects model according to heterogeneity among animals was as follows:rodents 18.8%(95%CI 12.6%-25.0%),camels 17.1%(95%CI 8.6%-25.7%),cattle 16.8%(95%CI 13.4%-20.1%),goats 14.1%(95%CI 5.2%-23.0%),horses 12.2%(95%CI 8.3%-16.2%),birds 10.5%(95%CI 7.6%-13.4%),sheep 9.9%(95%CI 2.4%-4.9%),cats 8.8%(95%CI 4.8%-12.8%)and dogs 3.7%(95%CI 7.0%-12.8%).Conclusions:Cryptosporidiosis has been reported and present in a wide range of animals in Iran over the years and has a high prevalence in most of these species.

Current status and challenges in drug discovery against the globally important zoonotic cryptosporidiosis

The zoonotic cryptosporidiosis is globally distributed,one of the major diarrheal diseases in humans and animals.Cryptosporidium oocysts are also one of the major environmental concerns,making it a pathogen that fits well into the One Health concept.Despite its importance,fully effective drugs are not yet available.Anti-cryptosporidial drug discovery has historically faced many unusual challenges attributed to unique parasite biology and technical burdens.While significant progresses have been made recently,anti-cryptosporidial drug discovery still faces a major obstacle:identification of systemic drugs that can be absorbed by patients experiencing watery diarrhea and effectively pass through electron-dense(ED)band at the parasite-host cell interface to act on the epicellular parasite.There may be a need to develop an in vitro assay to effectively screen hits/leads for their capability to cross ED band.In the meantime,non-systemic drugs with strong mucoadhesive properties for extended gastrointestinal exposure may represent another direction in developing anti-cryptosporidial therapeutics.For developing both systemic and non-systemic drugs,a non-ruminant animal model exhibiting diarrheal symptoms suitable for routine evaluation of drug absorption and anti-cryptosporidial efficacy may be very helpful.

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.

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.