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With the deepening of people's understanding of lung cancer, the research of lung cancer immunotherapy has gradually become the focus of attention. As we all know, the treatment of many diseases relies on the rich sources, complex and varied compositions and wide range of unique biological properties of natural products. Studies have shown that natural products can exert anticancer effects by inducing tumor cell death, inhibiting tumor cell proliferation, and enhancing tumor cell autophagy. More notably, natural products can adjust and strengthen the body's immune response, which includes enhancing the function of NK cells and promoting the differentiation and proliferation of T lymphocytes. In addition, these natural products may enhance their anticancer effects by affecting inhibitory factors in the immune system, hormone levels, enzymes involved in biotransformation, and modulating other factors in the tumor microenvironment. The importance of natural products in lung cancer immunotherapy should not be underestimated. However, the specific links and correlations between natural products and lung cancer immunity are not clear enough, and further studies are urgently needed to clarify the relationship between the two. In this paper, we will focus on the correlation between natural products and lung cancer immune responses, with a view to providing new research perspectives for immunotherapy of lung cancer. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Immunology. It discusses the role of adaptive immunity in atherosclerosis, a condition that contributes to acute cardiovascular events. The editorial highlights the importance of chronic inflammation in atherosclerosis and the potential for new intervention strategies. It also explores the use of new immunological techniques to study the role of the adaptive immune system in the development, progression, and regression of atherosclerosis. The document includes summaries of several research papers that investigate different aspects of adaptive immunity in atherosclerosis, including T cell and B cell responses. Overall, the editorial provides an overview of the latest findings in this field and serves as a valuable resource for researchers interested in studying adaptive immunity in atherosclerosis. [Extracted from the article]

In this paper, we study a model that enhances our understanding of cytokine-influenced HIV-1 infection. The impact of adaptive immune response (cytotoxic T lymphocytes (CTLs) and antibodies) and time delay on HIV-1 infection is included. The model takes into account two types of distributional delays, (i) the delay in the HIV-1 infection of CD4+T cells and (ii) the maturation delay of new virions. We first investigated the fundamental characteristics of the system, then found the system's equilibria. We derived five threshold parameters, ℜ i , i = 0, 1,..., 4, which completely determine the existence and stability of the equilibria. The Lyapunov method was used to prove the global asymptotic stability for all equilibria. We illustrate the theoretical results by performing numerical simulations. We also performed a sensitivity analysis on the basic reproduction number ℜ 0 and identified the most-sensitive parameters. We found that pyroptosis contributes to the number ℜ 0 , and then, neglecting it will make ℜ 0 underevaluated. Necrosulfonamide and highly active antiretroviral drug therapy (HAART) can be effective in preventing pyroptosis and at reducing viral replication. Further, it was also found that increasing time delays can effectively decrease ℜ 0 and, then, inhibit HIV-1 replication. Furthermore, it is shown that both CTLs and antibody immune responses have no effect on ℜ 0 , while this can result in less HIV-1 infection. [ABSTRACT FROM AUTHOR]

This paper deals with a non-linear delay mathematical model with adaptive immunity. The past literature has given insight to the disease progression but the effect of antigen-driven CD4 Tcell, delay, activation of CTL's response during the infection process have not been introduced and analysed in detail. Hence, this paper is an attempt to propose a mathematical model involving the above factors along with defining new thresholds Rq,Ri,R2,Ri, through which the local stability of the boundary and interior equilibrium points can be obtained. Further, the global stability analysis of interior equilibrium point through geometrical approach is also a new advanced method not discussed yet. Finally, the numerical simulation and sensitivity analysis based on all the parameters is performed to validate the results followed by global sensitivity analysis of thresholds AS - AU which are performed using Latin hypercube sampling scheme(LHS). [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic has demonstrated the need to create highly effective antivirals and vaccines against various RNA viruses, including SARS coronaviruses. This paper provides a short review of innovative strategies in the development of antivirals and vaccines against SARS coronaviruses, with a focus on antisense antivirals, oligonucleotide adjuvants in vaccines, and oligonucleotide vaccines. Well-developed viral genomic databases create new opportunities for the development of innovative vaccines and antivirals using a post-genomic platform. The most effective vaccines against SARS coronaviruses are those able to form highly effective memory cells for both humoral and cellular immunity. The most effective antivirals need to efficiently stop viral replication without side effects. Oligonucleotide antivirals and vaccines can resist the rapidly changing genomic sequences of SARS coronaviruses using conserved regions of their genomes to generate a long-term immune response. Oligonucleotides have been used as excellent adjuvants for decades, and increasing data show that oligonucleotides could serve as antisense antivirals and antigens in vaccine formulations, becoming a prospective tool for immune system tuning. [ABSTRACT FROM AUTHOR]

In this paper, we formulate a generalized hepatitis B virus (HBV) infection model with two modes of infection transmission and adaptive immunity and investigate its dynamical properties. Both the virus‐to‐cell and cell‐to‐cell infection transmissions are modeled by general functions which satisfy some biologically motivated assumptions. Furthermore, the model incorporates three distributed time delays for the production of active infected hepatocytes, mature capsids, and virions. The well‐posedness of the proposed model is established by showing the non‐negativity and boundedness of solutions. Five equilibria of the model are identified in terms of five threshold parameters R0,R1,R2,R3$$ {R}_0,{R}_1,{R}_2,{R}_3 $$, and R4$$ {R}_4 $$. Further, the global stability analysis of each equilibrium under certain conditions is carried out by employing suitable Lyapunov function and LaSalle's invariance principle. Finally, we present an example with numerical simulations to illustrate the applicability of our study. Nonetheless, the results obtained in this study are valid for a wide class of HBV infection models. [ABSTRACT FROM AUTHOR]

The adaptive immune response induced by SARS-CoV-2 plays a key role in the antiviral process and can protect the body from the threat of infection for a certain period of time. However, owing to the limitations of clinical studies, the antiviral mechanisms, protective thresholds, and persistence of the immune memory of adaptive immune responses remain unclear. This review summarizes existing research models for SARS-CoV-2 and elaborates on the advantages of animal models in simulating the clinical symptoms of COVID-19 in humans. In addition, we systematically summarize the research progress on the SARS-CoV-2 adaptive immune response and the remaining key issues, as well as the application and prospects of animal models in this field. This paper provides direction for in-depth analysis of the anti-SARS-CoV-2 mechanism of the adaptive immune response and lays the foundation for the development and application of vaccines and drugs. [ABSTRACT FROM AUTHOR]

Cancer is a main life-threatening disease worldwide. Due to the adverse effects of conventional chemotherapies and radiotherapies, immunotherapy has emerged as a potent strategy to treat cancer. In cancer immunotherapy, cancer immune surveillance plays a crucial role in the cancer process, which contains various effector cells from innate and adaptive immunity. This review summarized the functions of innate and adaptive immune cells in cancer immunosurveillance and their main reported targets. Moreover, the potential targets about the modulatory effects of cancer immunosurveillance were predicted using network-based target analysis, with total predicted pathways not only reporting previously reported pathways, but also putative signaling pathways pending for investigation. In addition, the potential use of herbal medicines and their phytochemicals in the modulation of cancer immunosurveillance were also discussed. Taken together, this review paper aims to provide scientific insight into further drug development, particularly herbs, phytochemicals, and TCM formulae, in the modulatory effects of cancer immunosurveillance. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with hyperactive innate and adaptive immune systems that cause dermatological, cardiovascular, renal, and neuropsychiatric problems in patients. SLE's multifactorial nature and complex pathogenesis present significant challenges in its clinical classification. In addition, unpredictable treatment responses in patients emphasize the need for highly specific and sensitive SLE biomarkers that can assist in understanding the exact pathogenesis and, thereby, lead to the identification of novel therapeutic targets. Recent studies on microRNA (miRNA), a non-coding region involved in the regulation of gene expression, indicate its importance in the development of the immune system and thus in the pathogenesis of various autoimmune disorders such as SLE. miRNAs are fascinating biomarker prospects for SLE categorization and disease monitoring owing to their small size and high stability. In this paper, we have discussed the involvement of a wide range of miRNAs in the regulation of SLE inflammation and how their modulation can be a potential therapeutic approach. [ABSTRACT FROM AUTHOR]

In this paper, we employ the nonstandard finite difference method to discretize a nonlinear initial boundary value problem that describes the global dynamics of hepatitis B virus infection with adaptive immunity. The model considered incorporates intracellular HBV DNA-containing capsids, a general incidence function and two categories of infected hepatocytes: exposed infected hepatocytes and productively infected hepatocytes. Adaptive immunity cells are recruited to attack all infected hepatocytes and free virus particles. The dynamics of fundamental properties of both discrete and continuous models are thoroughly studied, and it is shown that the discrete system is dynamically consistent with the continuous model. These properties include existence, nonnegativity and boundedness of solutions as well as the global stability of spatially homogeneous equilibria. We carry out some numerical simulations to support the theoretical findings and illustrate the behaviour of the solution in space and time. [ABSTRACT FROM AUTHOR]

Distribution static compensator (DSTATCOM) is a shunt compensation device that is generally used to solve power quality problems in distribution systems. In an all-electric ship power system, power quality issues arise due to high-energy demand loads such as pulse loads. This paper presents the application of a DSTATCOM to improve the power quality in a ship power system during and after pulse loads. The control strategy of the DSTATCOM plays an important role in maintaining the voltage at the point of common coupling. A novel adaptive control strategy for the DSTATCOM based on artificial immune system (AIS) is presented in this paper. The optimal parameters of the controller are first obtained by using the particle swarm optimization algorithm. This provides a sort of innate immunity (robustness) to common system disturbances. For unknown and random system disturbances, the controller parameters are modified online, thus providing adaptive immunity to the control system. The performance of the DSTATCOM and the AIS-based adaptive control strategy is first investigated in MATLAB-/Simulink-based simulation platform. It is verified through a real-time ship power system implementation on a real-time digital simulator and the control algorithm on a digital signal processor. [ABSTRACT FROM AUTHOR]

Between 1969 and 1983 the lab of Kevin Lafferty in Canberra developed the concept of the T‐cell "costimulator," an essential second signal for activation. A great deal of the work appeared in this journal before it was known as Immunology & Cell Biology (ICB). As part of the 100‐year anniversary of the journal, I offer a personal reflection on Kevin's legacy and impact. [ABSTRACT FROM AUTHOR]

Background: In December of 2019, coronavirus disease 2019 (Covid-19) was reported in Wuhan, China, and has now rapidly swept around the world. Much research has been carried out since the outbreak, but few studies have focused on the dysfunction of the adaptive immunity. Methods: In this retrospective and multi-center study, 373 patients with laboratory-confirmed COVID-19 from Shanghai Public Health Clinical Center and Affiliated Hospital of Putian University were recruited. Demographic, clinical, radiological features, and laboratory data were recorded and analyzed at admission and at discharge. Results of immunological tests were followed up until the patients were discharged. Results: Of the 373 patients with COVID-19 pneumonia, 322 were in the non-severe group and 51 were in the severe group. Number of T cells, CD4+ and CD8+ T cells, and total lymphocytes declined remarkably upon admission and elevated when the patients were discharged. At admission, counts of total lymphocytes, T cells, CD4+ and CD8+ T cells, and levels of C3 and C4 in the severe group were lower than those in the non-severe group, whereas the neutrophil to lymphocyte ratio (NLR) was higher in the severe group. Counts of T cells, CD4+ and CD8+ T cells, and total lymphocytes were negatively correlated with lactate dehydrogenase and C-reactive protein. Conclusion: COVID-19 might target adaptive immunity and cause a decrease in lymphocytes, especially T cells and subsets. Physicians should pay close attention to the adaptive immunity of patients upon admission. Monitoring NLR, T lymphocytes, and subsets would help physicians with the proper diagnosis and treatment of COVID-19. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

IFN‐γ plays a critical role in the immune response to bacterial infections. It is established that IFN‐γ is mainly produced by NK/ILC1 cells and T cells, and most of papers have rejected the biologic reality of alternative sources for more than 20 years. Here, we are proposing to revisit this dogma and discuss the role of macrophage‐derived IFN‐γ in bacterial infections. Our hypothesis is based on a panel of publications and is recently revived by our results on placenta, a chimeric organ in which the immune response is tailored to protect the fetus from mother's immune response. The culture of purified placental macrophages is associated with a production of IFN‐γ that may contribute to fetal protection from bacterial infections before eliciting a Th1‐like immune response potentially pathogenic for pregnancy. Hence, macrophage IFN‐γ may be a novel actor of early crosstalk between innate and adaptive immunity in the context of host defense against bacterial infections. [ABSTRACT FROM AUTHOR]

The clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated proteins (Cas) are immune systems in prokaryotes present in most Bacteria and Archaea. They provide adaptive immunity against foreign elements such as bacteriophages/viruses, plasmids and transposons. During immunization a small sequence of foreign DNA, a so-called spacer is integrated into the CRISPR locus in the host cell. Spacers are then transcribed into small RNA guides that direct cleavage of foreign DNA by Cas nucleases. Immunization through spacer acquisition is transferred vertically to the progeny. It is possible that this genetic immune system of bacteria participates in modulating the microbiome of 'chronic' periodontitis, in which Porphyromonas gingivalis has been identified as a keystone pathogen causing microbial dysbiosis. An in-depth review of our current knowledge on the CRISPR-Cas systems in P. gingivalis is given in this paper with the attempt to understand how this anaerobic bacterium may protect itself in the periodontal pocket where bacteriophages are abundant and even out-number bacteria. [ABSTRACT FROM AUTHOR]

The adaptive immune response has recently emerged as an important factor in a wide variety of cardiovascular disorders including atherosclerosis, hypertension, cardiac remodeling, and heart failure; however, its role is not fully understood. Since an assortment of innate responsive cells, e.g., neutrophils and monocytes/macrophages, coordinate with adaptive immunity, e.g., T cells, dendritic cells, and B cells, the temporal response and descriptions pertinent to the cellular phenotype and inflammation processes, in general, need additional investigation, clarification, and consensus particularly in cardiovascular disease. This Perspectives article reviews the contributions of 15 articles (including 7 reviews) published in the American Journal of Physiology-Heart and Circulatory Physiology in response to the Call for Papers: Adaptive Immunity in Cardiovascular Disease. Here, we summarize the crucial reported findings at the cardiac, vascular, immune, and molecular levels and discuss the translational feasibility and benefits of future prospective research into the adaptive immune response. Readers are encouraged to evaluate the data and learn from this collection of novel studies. [ABSTRACT FROM AUTHOR]

Aging is generally regarded as an irreversible process, and its intricate relationship with the immune system has garnered significant attention due to its profound implications for the health and well-being of the aging population. As people age, a multitude of alterations occur within the immune system, affecting both innate and adaptive immunity. In the realm of innate immunity, aging brings about changes in the number and function of various immune cells, including neutrophils, monocytes, and macrophages. Additionally, certain immune pathways, like the cGAS-STING, become activated. These alterations can potentially result in telomere damage, the disruption of cytokine signaling, and impaired recognition of pathogens. The adaptive immune system, too, undergoes a myriad of changes as age advances. These include shifts in the number, frequency, subtype, and function of T cells and B cells. Furthermore, the human gut microbiota undergoes dynamic changes as a part of the aging process. Notably, the interplay between immune changes and gut microbiota highlights the gut's role in modulating immune responses and maintaining immune homeostasis. The gut microbiota of centenarians exhibits characteristics akin to those found in young individuals, setting it apart from the microbiota observed in typical elderly individuals. This review delves into the current understanding of how aging impacts the immune system and suggests potential strategies for reversing aging through interventions in immune factors. [ABSTRACT FROM AUTHOR]

Postpartum breast cancer (PPBC) is a unique subset of breast cancer, accounting for nearly half of the women diagnosed during their postpartum years. Mammary gland involution is widely regarded as being a key orchestrator in the initiation and progression of PPBC due to its unique wound-healing inflammatory signature. Here, we provide dialogue suggestive that lactation may also facilitate neoplastic development as a result of sterile inflammation. Immune cells are involved in all stages of postnatal mammary development. It has been proposed that the functions of these immune cells are partially directed by mammary epithelial cells (MECs) and the cytokines they produce. This suggests that a more niche area of exploration aimed at assessing activation of innate immune pathways within MECs could provide insight into immune cell contributions to the developing mammary gland. Immune cell contribution to pubertal development and mammary gland involution has been extensively studied; however, investigations into pregnancy and lactation remain limited. During pregnancy, the mammary gland undergoes dramatic expansion to prepare for lactation. As a result, MECs are susceptible to replicative stress. During lactation, mitochondria are pushed to capacity to fulfill the high energetic demands of producing milk. This replicative and metabolic stress, if unresolved, can elicit activation of innate immune pathways within differentiating MECs. In this review, we broadly discuss postnatal mammary development and current knowledge of immune cell contribution to each developmental stage, while also emphasizing a more unique area of study that will be beneficial in the discovery of novel therapeutic biomarkers of PPBC. [ABSTRACT FROM AUTHOR]

Background: Small non-coding RNA molecules (miRs) are involved in immune cell maturation and function and might influence immunopathological processes of systemic lupus erythematosus (SLE) pathogenesis. Methods and Results: This paper presents the results of a literature search for publications dealing with the relationship between miRs and pathological factors related to SLE such as genetic background, immune dysregulation and gender-associated differences participating in SLE development. In SLE, distinct miRs are differentially expressed in SLE cells of innate and adaptive immunity. The miR-146a and miR-155 genes, among others, interfere with intracellular signalling pathways downstream of toll-like receptors 7 and 9 (TLR- 7, TLR-9) and influences interferon (IFN)-type I synthesis in plasmacytoid dendritic cells. In T and B cells, miR-126, miR-21, miR-146a, miR-155, miR-1246 and others might influence gene expression by epigenetic modifications, support abnormal cytosine release, differentiation of cell subsets, B cell hyperactivity and autoantibody production. Besides, estrogen might up- and downregulate immunologically active miRs, which are potential mediators of hormonal influences in SLE development. Moreover, SLE genetic basis included some polymorphisms of the miR-146a gene, which varies across populations. Conclusion: Distinct miRs are differentially expressed in both SLE mice models and human patients and promote autoimmune features of immune processes. MiRs are important molecules modulating susceptibility to SLE as well as its onset, clinical diversity and progression.

The field of immunometabolism is burgeoning, with hundreds of papers published on the topic each year. Our understanding of the contribution of immune cells to metabolic regulation has expanded from a simple idea of innate immune cells, such as macrophages, altering adipose tissue function in obesity, to an awareness of the complex role of adaptive immunity in many different organ systems. Recent findings have clearly demonstrated the presence of adaptive lymphocytes, such as T and B cells, in adipose tissue. Furthermore, these data demonstrated T-cell accumulation and limited T-cell receptor repertoire diversity in obese adipose tissue, indicating that an antigen-specific immune response may occur within this tissue. In a recently published paper, we reported that a mouse model of weight cycling resulted in increased T-cell accumulation in adipose tissue. In the current commentary, we discuss the possibility that this increase in adipose tissue T-cell number could represent a local secondary immune response to self-antigens exposed in adipose tissue during obesity. If further experimentation indicates that this hypothesis is true, these data will fortify the concept that obesity is a complex immune-mediated disease and would emphasize the importance of designing therapies to maintain weight loss. [ABSTRACT FROM AUTHOR]

Retrospective as well as prospective clinical studies indicate that episodes of high fever as a typical reaction to an acute infection during the entire human life span are inversely related to cancer incidence. Laboratory data aimed at discovering why fever incidents appear beneficial in lowering the risk of cancer remain rudimentary at best. Several hypotheses have been presented thus far, and recent debates have pointed to the effect of fever on innate and adaptive immune functions. In this paper we focus on a particular mode of adaptive immune functioning that involves a type of T cells carrying a receptor composed of gamma/delta chain heterodimer (γδ T-cell receptor; γδ TCR). We present an argument for a key role of infectious fever in the recruitment and enhancement of immune antitumor competence of γδ T cells during the life span of a human being. The unique physiology of γδ T lymphocytes indicating a possible cellular link between innate and adaptive immunity—including modes of antigen recognition as well their presence in tissues prone to infections, metabolic stress, and neoplastic development—makes them a target for exploration in the context of fever and cancer risk, and for future cancer immunotherapy. [ABSTRACT FROM AUTHOR]

B cells and the antibodies they produce are critical in host defense against pathogens and contribute to various immune-mediated diseases. B cells responding to activating signals in vitro release extracellular vesicles (EV) that carry surface antibodies, yet B cell production of EVs that express antibodies and their function in vivo is incompletely understood. Using transgenic mice expressing the Cre recombinase in B cells switching to IgG1 to induce expression of fusion proteins between emerald green fluorescent protein (emGFP) and the EV tetraspanin CD63 as a model, we identify emGFP expression in B cells responding to foreign antigen in vivo and characterize the emGFP+ EVs they release. Our data suggests that emGFP+ germinal center B cells undergoing immunoglobulin class switching to express IgG and their progeny memory B cells and plasma cells, also emGFP+, are sources of circulating antigen-specific IgG+ EVs. Furthermore, using a mouse model of influenza virus infection, we find that IgG+ EVs specific for the influenza hemagglutinin antigen protect against virus infection. In addition, crossing the B cell Cre driver EV reporter mice onto the Nba2 lupus-prone strain revealed increased circulating emGFP+ EVs that expressed surface IgG against nuclear antigens linked to autoimmunity. These data identify EVs loaded with antibodies as a novel route for antibody secretion in B cells that contribute to adaptive immune responses, with important implications for different functions of IgG+ EVs in infection and autoimmunity. [ABSTRACT FROM AUTHOR]

Through immune memory, infections have a lasting effect on the host. While memory cells enable accelerated and enhanced responses upon rechallenge with the same pathogen, their impact on susceptibility to unrelated diseases is unclear. We identify a subset of memory T helper 1 (Th1) cells termed innate acting memory T (TIA) cells that originate from a viral infection and produce IFN-γ with innate kinetics upon heterologous challenge in vivo. Activation of memory TIA cells is induced in response to IL-12 in combination with IL-18 or IL-33 but is TCR independent. Rapid IFN-γ production by memory TIA cells is protective in subsequent heterologous challenge with the bacterial pathogen Legionella pneumophila. In contrast, antigen-independent reactivation of CD4+ memory TIA cells accelerates disease onset in an autoimmune model of multiple sclerosis. Our findings demonstrate that memory Th1 cells can acquire additional TCR-independent functionality to mount rapid, innate-like responses that modulate susceptibility to heterologous challenges. [ABSTRACT FROM AUTHOR]

Our ability to fight pathogens relies on major histocompatibility complex class I (MHC-I) molecules presenting diverse antigens on the surface of diseased cells. The transporter associated with antigen processing (TAP) transports nearly the entire repertoire of antigenic peptides into the endoplasmic reticulum for MHC-I loading. How TAP transports peptides specific for MHC-I is unclear. In this study, we used cryo-EM to determine a series of structures of human TAP, both in the absence and presence of peptides with various sequences and lengths. The structures revealed that peptides of eight or nine residues in length bind in a similarly extended conformation, despite having little sequence overlap. We also identified two peptide-anchoring pockets on either side of the transmembrane cavity, each engaging one end of a peptide with primarily main chain atoms. Occupation of both pockets results in a global conformational change in TAP, bringing the two halves of the transporter closer together to prime it for isomerization and ATP hydrolysis. Shorter peptides are able to bind to each pocket separately but are not long enough to bridge the cavity to bind to both simultaneously. Mutations that disrupt hydrogen bonds with the N and C termini of peptides almost abolish MHC-I surface expression. Our findings reveal that TAP functions as a molecular caliper that selects peptides according to length rather than sequence, providing antigen diversity for MHC-I presentation. [ABSTRACT FROM AUTHOR]

Introduction: Antibodies against the SARS-CoV-2 spike protein are a critical immune determinant for protection against the virus. While virus neutralization is a key function of spike-specific antibodies, antibodies also mediate Fcdependent activities that can play a role in protection or pathogenesis. Methods: This study characterized serum antibody responses elicited after two doses of heterologous adenovirus-vectored (Ad26/Ad5) vaccines. Results: Vaccine-induced antibody binding titers and Fc-mediated functions decreased over six months, while neutralization titers remained stable. Comparison of antibody isotypes elicited after Ad26/Ad5 vs. LNP-mRNA vaccination and after infection showed that anti-spike IgG1 were dominant and produced to high levels in all groups. The Ad26/Ad5 vaccines also induced IgG4 but not IgG2 and IgG3, whereas the LNP-mRNA vaccines elicited a full Ig spectrum (IgM, IgG1-4, IgA1-2). Convalescent COVID-19 patients had mainly IgM and IgA1 alongside IgG1. Despite these differences, the neutralization potencies against early variants were similar. However, both vaccine groups had antibodies with greater Fc potencies of binding complement and Fcg receptors than the COVID-19 group. The Ad26/Ad5 group also displayed a greater potency of RBD-specific antibody-mediated cellular phagocytosis. Discussion: Antibodies with distinctive quality were induced by different vaccines and infection. The data imply the utility of different vaccine platforms to elicit antibody responses with fine-tuned Fc activities. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Immunology. It discusses the importance of prognostic and predictive factors in autoimmune connective tissue disorders. These disorders are complex and can have variable disease courses, making it difficult to predict outcomes and determine the most effective treatments. The editorial highlights the need for biomarkers that can help predict disease severity and long-term survival. The document also mentions several research articles that were published on this topic, covering various aspects of autoimmune connective tissue disorders and their prognostic factors. [Extracted from the article]

Background: Comparative genomic and/or transcriptomic analyses involving elasmobranchs remain limited, with genome level comparisons of the elasmobranch immune system to that of higher vertebrates, non-existent. This paper reports a comparative RNA-seq analysis of heart tissue from seven species, including four elasmobranchs and three teleosts, focusing on immunity, but concomitantly seeking to identify genetic similarities shared by the two lamnid sharks and the single billfish in our study, which could be linked to convergent evolution of regional endothermy. Results: Across seven species, we identified an average of 10,877 Swiss-Prot annotated genes from an average of 32,474 open reading frames within each species' heart transcriptome. About half of these genes were shared between all species while the remainder included functional differences between our groups of interest (elasmobranch vs. teleost and endotherms vs. ectotherms) as revealed by Gene Ontology (GO) and selection analyses. A repeatedly represented functional category, in both the uniquely expressed elasmobranch genes (total of 259) and the elasmobranch GO enrichment results, involved antibody-mediated immunity, either in the recruitment of immune cells (Fc receptors) or in antigen presentation, including such terms as "antigen processing and presentation of exogenous peptide antigen via MHC class II", and such genes as MHC class II, HLA-DPB1. Molecular adaptation analyses identified three genes in elasmobranchs with a history of positive selection, including legumain (LGMN), a gene with roles in both innate and adaptive immunity including producing antigens for presentation by MHC class II. Comparisons between the endothermic and ectothermic species revealed an enrichment of GO terms associated with cardiac muscle contraction in endotherms, with 19 genes expressed solely in endotherms, several of which have significant roles in lipid and fat metabolism. Conclusions: This collective comparative evidence provides the first multi-taxa transcriptomic-based perspective on differences between elasmobranchs and teleosts, and suggests various unique features associated with the adaptive immune system of elasmobranchs, pointing in particular to the potential importance of MHC Class II. This in turn suggests that expanded comparative work involving additional tissues, as well as genome sequencing of multiple elasmobranch species would be productive in elucidating the regulatory and genome architectural hallmarks of elasmobranchs. [ABSTRACT FROM AUTHOR]

Brucellosis is a globally zoonotic bacterial disease of humans and various animals including goats, sheep, and cattle. Brucella melitensis M5-90, a live attenuated vaccine strain, has been widely used to prevent brucellosis in goats and sheep. However, the molecular mechanisms governing protective immunity response in non-professional phagocytes infected with B. melitensis M5-90 have not been fully investigated, especially in goats. In our research, goat fibroblasts were used as in vitro models to determine these mechanisms by transcriptome analysis. After incubating with B. melitensis M5-90 3 h, the infected goat fibroblasts were collected at 0 h, 4 h, 24 h, 48 h and 72 h for RNA-seq. The results indicated that there were totally 11,819 differentially expressed genes (DEGs) and 777 differentially expressed (DE) miRNAs found in experiment groups compared with the control groups (|log2 (Foldchange)|=1, FDR<0.05). GO and KEGG enrichment analyses revealed that down-regulated genes were involved in the riboflavin metabolism and positive regulation of IL-8 secretion pathway. The up-regulated genes were mainly involved in adaptive immunity, including TNF signaling pathway, MAPK signaling pathway and JAK/STAT pathway. Additionally, cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity and toll-like receptor signaling pathway, which associated with innate immunity pathways, were also induced. Based on the Pearson correlation coefficients and prediction results of TargetScan and miRanda, the miRNA-mRNA networks of NFKB1, IFNAR2 and IL10RB were constructed and verified in goat fibroblasts by qPCR, which demonstrated that goat fibroblasts displayed immunomodulatory properties. Our findings provide a deeper insight into the host miRNA-driven B. melitensis defense mechanism and reveal the transcriptome changes involved in the innate and adaptive immune response of the goats to B. melitensis infection. [ABSTRACT FROM AUTHOR]

Background: Protective immunity against intestinal helminths requires induction of robust type-2 immunity orchestrated by various cellular and soluble effectors which promote goblet cell hyperplasia, mucus production, epithelial proliferation, and smooth muscle contractions to expel worms and reestablish immune homeostasis. Conversely, defects in type-2 immunity result in ineffective helminth clearance, persistent infection, and inflammation. Macrophages are highly plastic cells that acquire an alternatively activated state during helminth infection, but they were previously shown to be dispensable for resistance to Trichuris muris infection. Methods: We use the in vivo mouse model A20myel-KO, characterized by the deletion of the potent anti-inflammatory factor A20 (TNFAIP3) specifically in the myeloid cells, the excessive type-1 cytokine production, and the development of spontaneous arthritis. We infect A20myel-KO mice with the gastrointestinal helminth Trichuris muris and we analyzed the innate and adaptive responses. We performed RNA sequencing on sorted myeloid cells to investigate the role of A20 on macrophage polarization and type-2 immunity. Moreover, we assess in A20myel-KO mice the pharmacological inhibition of type-1 cytokine pathways on helminth clearance and the infection with Salmonella typhimurium. Results: We show that proper macrophage polarization is essential for helminth clearance, and we identify A20 as an essential myeloid factor for the induction of type-2 immune responses against Trichuris muris. A20myel-KO mice are characterized by persistent Trichuris muris infection and intestinal inflammation. Myeloid A20 deficiency induces strong classical macrophage polarization which impedes anti-helminth type-2 immune activation; however, it promotes detrimental Th1/Th17 responses. Antibody-mediated neutralization of the type-1 cytokines IFN-γ, IL-18, and IL-12 prevents myeloid-orchestrated Th1 polarization and re-establishes type-2-mediated protective immunity against T. muris in A20myel-KO mice. In contrast, the strong Th1-biased immunity in A20myel-KO mice offers protection against Salmonella typhimurium infection. Conclusions: We hereby identify A20 as a critical myeloid factor for correct macrophage polarization and appropriate adaptive mucosal immunity in response to helminth and enteric bacterial infection. [ABSTRACT FROM AUTHOR]

The optimal immune response eliminates invading pathogens, restoring immune equilibrium without inflicting undue harm to the host. However, when a cascade of immunological reactions is triggered, the immune response can sometimes go into overdrive, potentially leading to harmful long-term effects or even death. The immune system is triggered mostly by infections, allergens, or medical interventions such as vaccination. This review examines how these immune triggers differ and why certain infections may dysregulate immune homeostasis, leading to inflammatory or allergic pathology and exacerbation of pre-existing conditions. However, many vaccines generate an optimal immune response and protect against the consequences of pathogen-induced immunological aggressiveness, and from a small number of unrelated pathogens and autoimmune diseases. Here, we propose an "immuno-wave" model describing a vaccine-induced "Goldilocks immunity", which leaves fine imprints of both pro-inflammatory and anti-inflammatory milieus, derived from both the innate and the adaptive arms of the immune system, in the body. The resulting balanced, 'quiet alert' state of the immune system may provide a jump-start in the defense against pathogens and any associated pathological inflammatory or allergic responses, allowing vaccines to go above and beyond their call of duty. In closing, we recommend formally investigating and reaping many of the secondary benefits of vaccines with appropriate clinical studies. [ABSTRACT FROM AUTHOR]

Currently, vaccine development against different respiratory diseases is at its peak. It is of utmost importance to find suitajble adjuvants that can increase the potency of the vaccine candidates. This study aimed to determine the systemic and splenic immune mechanisms in mice models induced by anionic and cationic lipid adjuvants in the presence of the vaccine-candidate influenza antigen hemagglutinin (HA). In the presence of the HA antigen, the cationic adjuvant (N3) increased conventional dendritic cell 1 (cDC1) abundance with enhanced MHCI and CD80-CD86 costimulatory marker expression, and significantly higher CD8T and Th17 populations with enhanced interferon-gamma (IFNγ) expression in CD8T and CD4T populations. Conversely, the anionic adjuvant (L3) increased the cDC2 population percentage with significantly higher MHCII and DEC205 expression, along with an increase in the CD4T and regulatory T cell populations. The L3-treated group also exhibited higher percentages of activated B and plasma cell populations with significantly higher antigen-specific IgG and IgA titer and virus neutralization potential. While the anionic adjuvant induced significantly higher humoral responses than the cationic adjuvant, the latter influenced a significantly higher Th1/Th17 response. For customized vaccine development, it is beneficial to have alternative adjuvants that can generate differential immune responses with the same vaccine candidate antigen. This study will aid the selection of adjuvants based on their charges to improve specific immune response arms in the future development of vaccine formulation. [ABSTRACT FROM AUTHOR]

Background: Vaccination against COVID-19 is highly effective in preventing severe disease and hospitalization, but primary COVID mRNA vaccination schedules often differed from those recommended by the manufacturers due to supply chain issues. We investigated the impact of delaying the second dose on antibody responses to COVID mRNA-vaccines in a prospective cohort of health-care workers in Quebec. Methods: We recruited participants from the McGill University Health Centre who provided serum or participant-collected dried blood samples (DBS) at 28- days, 3 months, and 6 months post-second dose and at 28-days after a third dose. IgG antibodies to SARS-CoV2 spike (S), the receptor-binding domain (RBD), nucleocapsid (N) and neutralizing antibodies to the ancestral strain were assessed by enzyme-linked immunosorbent assay (ELISA). We examined associations between long (≤89 days) versus short (<89 days) between-dose intervals and antibody response through multivariable mixed-effects models adjusted for age, sex, prior covid infection status, time since vaccine dose, and assay batch. Findings: The cohort included 328 participants who received up to three vaccine doses (>80% Pfizer-BioNTech). Weighted averages of the serum (n=744) and DBS (n=216) cohort results from the multivariable models showed that IgG anti-S was 31% higher (95% CI: 12% to 53%) and IgG anti-RBD was 37% higher (95% CI: 14% to 65%) in the long vs. short interval participants, across all time points. Interpretation: Our study indicates that extending the covid primary series between-dose interval beyond 89 days (approximately 3 months) provides stronger antibody responses than intervals less than 89 days. Our demonstration of a more robust antibody response with a longer between dose interval is reassuring as logistical and supply challenges are navigated in low-resource settings. [ABSTRACT FROM AUTHOR]

Babesia microti (B. microti) is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by B. microti infection can range from asymptomatic to fatal. Risk factors for severe disease include general immune suppression, advanced age (>50) and lack of a spleen. However, severe disease can occur in the absence of any known risk factors. The degree to which tick-transmitted B. microti infection confers protection from subsequent exposure is largely unexplored. This is an important question as both the prevalence and geographic range of tick-transmitted B. microti infection continues to increase and individuals in endemic regions may have multiple exposures over their lifetime. In the current study we used a mouse model to evaluate the degree to which primary infection with B. microti protected against secondary challenge with the same parasite strain. We show that CD4 T cells, and to a lesser extent B cells, contribute to protection. However, mice exhibited significant protection from secondary parasite challenge even in the absence of either CD4 T cells or B cells. The protection mediated by CD4 T cells did not depend on their production of IFN-γ as mice with a targeted gene deletion for the IFN-γ receptor remained fully protected against secondary challenge. Other factors including inducible nitric oxide synthase (iNOS) and the adaptor protein MyD88, important for toll-like receptors, IL-18 and IL-1 signaling, were not important for protection against primary or secondary challenge with B. microti. Thus, our study shows that resolution of primary infection with B. microti results in robust protection against secondary challenge with parasites, at least in the short term. Further studies are needed to evaluate the length of protection and the degree to which protection is impacted by parasite heterogeneity. Although we show an important role for CD4 T cells in protection against secondary challenge, our results suggest that no single aspect of the immune system is solely responsible for adequate protection against secondary challenge with B. microti. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection can trigger cytokine storm in some patients, which characterized by an excessive production of cytokines and chemical mediators. This hyperactive immune response may cause significant tissue damage and multiple organ failure (MOF). The severity of COVID-19 correlates with the intensity of cytokine storm, involving elements such as IFN, NF-κB, IL-6, HMGB1, etc. It is imperative to rapidly engage adaptive immunity to effectively control the disease progression. CD4+ T cells facilitate an immune response by improving B cells in the production of neutralizing antibodies and activating CD8+ T cells, which are instrumental in eradicating virus-infected cells. Meanwhile, antibodies from B cells can neutralize virus, obstructing further infection of host cells. In individuals who have recovered from the disease, virus-specific antibodies and memory T cells were observed, which could confer a level of protection, reducing the likelihood of re-infection or attenuating severity. This paper discussed the roles of macrophages, IFN, IL-6 and HMGB1 in cytokine release syndrome (CRS), the intricacies of adaptive immunity, and the persistence of immune memory, all of which are critical for the prevention and therapeutic strategies against COVID-19.

First described by Paul Ehrlich in 1879, who noted its characteristic staining by acidophilic dyes, for many years, the eosinophil was considered to be an end-effector cell associated with helminth infections and a cause of tissue damage. Over the past 30 years, research has helped to elucidate the complexity of the eosinophil's function and establish its role in host defense and immunity. Eosinophils express an array of ligand receptors which play a role in cell growth, adhesion, chemotaxis, degranulation, and cell-to-cell interactions. They play a role in activation of complement via both classical and alternative pathways. Eosinophils synthesize, store and secrete cytokines, chemokines, and growth factors. They can process antigen, stimulate T cells, and promote humoral responses by interacting with B cells. Eosinophils can function as antigen presenting cells and can regulate processes associated with both T1 and T2 immunity. Although long known to play a role in defense against helminth organisms, the interactions of eosinophils with these parasites are now recognized to be much more complex. In addition, their interaction with other pathogens continues to be investigated. In this paper, we review the eosinophil's unique biology and structure, including its characteristic granules and the effects of its proteins, our developing understanding of its role in innate and adaptive immunity and importance in immunomodulation, and the part it plays in defense against parasitic, viral, fungal and bacterial infections. Rather than our worst enemy, the eosinophil may, in fact, be one of the most essential components in host defense and immunity. [ABSTRACT FROM AUTHOR]

It has recently become clear that many bacterial and archaeal species possess adaptive immune systems. These are typified by multiple copies of DNA sequences known as clustered regularly interspaced short palindromic repeats (CRISPRs). These CRISPR repeats are the sites at which short spacers containing sequences of previously encountered foreign DNA are integrated, and the spacers serve as the molecular memory of previous invaders. In vivo work has demonstrated that two CRISPR-associated proteins - Cas1 and Cas2 - are required for spacer integration, but the mechanism by which this is accomplished remained unclear. Here we review a recent paper describing the in vitro reconstitution of CRISPR spacer integration using purified Cas1 and Cas2 and place the results in context of similar DNA transposition reactions and the crystal structure of the Cas1/Cas2 complex. [ABSTRACT FROM AUTHOR]

The larval waste, exoskeleton shedding, and leftover feed components of the black soldier fly and its larvae make up the by-product known as frass. In this study, we subjected channel catfish (Ictalurus punctatus) to a 10-week feeding trial to assess how different dietary amounts of frass inclusion would affect both systemic and mucosal tissue gene expression, especially in regard to growth and immunerelated genes. Fish were divided in quadruplicate aquaria, and five experimental diets comprising 0, 50, 100, 200, and 300 g of frass per kilogram of feed were fed twice daily. At the end of the trial, liver, head kidney, gill, and intestine samples were collected for gene expression analyses. First, liver and intestine samples from fish fed with a no frass inclusion diet (control), low-frass (50 g/kg) inclusion diet, or a high-frass (300 g/kg) inclusion diet were subjected to Illumina RNA sequencing to determine global differential gene expression among diet groups. Differentially expressed genes (DEGs) included the upregulation of growth-related genes such as glucose-6-phosphatase and myostatin, as well as innate immune receptors and effector molecules such as toll-like receptor 5, apolipoprotein A1, C-type lectin, and lysozyme. Based on the initial screenings of low/high frass using RNA sequencing, a more thorough evaluation of immune gene expression of all tissues sampled, and all levels of frass inclusion, was further conducted. Using targeted quantitative PCR panels for both innate and adaptive immune genes from channel catfish, differential expression of genes was identified, which included innate receptors (TLR1, TLR5, TLR9, and TLR20A), proinflammatory cytokines (IL-1ß type a, IL-1ß type b, IL-17, IFN-1, and TNFa), chemokines (CFC3 and CFD), and hepcidin in both systemic (liver and head kidney) and mucosal (gill and intestine) tissues. Overall, frass from black soldier fly larvae inclusion in formulated diets was found to alter global gene expression and activate innate and adaptive immunity in channel catfish, which has the potential to support disease resistance in this species in addition to demonstrated growth benefits. [ABSTRACT FROM AUTHOR]

Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-). Similarly to adults, a significant reduction of cross-reactive neutralizing capacity against delta and omicron VOC was observed 6 months after SARS-CoV-2 infection. While SAR-CoV-2 neutralizing capacity was comparable among children and C + V- against all VOC, children demonstrated as expected an inferior humoral response when compared to C + V+. Nevertheless, children generated SARS-CoV-2 reactive T cells with broad cross-recognition potential. When compared to V + C+, children presented even comparable frequencies of WT-reactive CD4 + and CD8 + T cells with high avidity and functionality. Taking into consideration the limitations of study - unknown disease onset for 53% of the asymptomatic pediatric subjects, serological detection of SARS-CoV-2 infection-, our results suggest that following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained SARS-CoV-2 cellular response cross-reactive to VOC. Key statement: Following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained robust SARS-CoV-2 cellular response cross-reactive to VOC, comparable to vaccinated convalescent adults with respect to magnitude and functionality. [ABSTRACT FROM AUTHOR]

Otitis media is the most common infection second only to viral upper respiratory infection in the outpatient setting. Tympanostomy tube insertion (TTI) is the most common ambulatory surgical procedure in the USA. While many risk factors for otitis media have been identified, atopic conditions have been underrecognized as risk factors for recurrent and persistent otitis media. Given that asthma and other atopic conditions are the most common chronic conditions during childhood, it is worth examining the association between atopic conditions and risk of otitis media, which can provide insight into how atopic conditions influence the risk of microbial infections. This paper focuses its discussion on otitis media; however, it is important that the association between atopic conditions and risk of otitis media be interpreted in the context of the association of atopic conditions with increased risks of various microbial infections. [ABSTRACT FROM AUTHOR]

The worldwide spread of a novel influenza A (H1N1) virus in 2009 showed that influenza remains a significant health threat, even for individuals in the prime of life. This paper focuses on the unusually high young adult mortality observed during the Spanish flu pandemic of 1918. Using historical records from Canada and the U.S., we report a peak of mortality at the exact age of 28 during the pandemic and argue that this increased mortality resulted from an early life exposure to influenza during the previous Russian flu pandemic of 1889–90. We posit that in specific instances, development of immunological memory to an influenza virus strain in early life may lead to a dysregulated immune response to antigenically novel strains encountered in later life, thereby increasing the risk of death. Exposure during critical periods of development could also create holes in the T cell repertoire and impair fetal maturation in general, thereby increasing mortality from infectious diseases later in life. Knowledge of the age-pattern of susceptibility to mortality from influenza could improve crisis management during future influenza pandemics. [ABSTRACT FROM AUTHOR]

This article, published in Frontiers in Immunology, discusses the role of adipose tissue and resident immune cells in infections. Adipose tissue can influence immune responses to infection by regulating the expression of certain molecules. Immune cells within adipose tissue can also impact the overall metabolism of the body. The article also explores the idea that adipose tissue may serve as a safe haven for parasites, allowing them to establish chronic infections. The authors emphasize the need for further research to better understand the interactions between parasites and adipose tissue, which could lead to new therapeutic approaches. [Extracted from the article]