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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]

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]

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]

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]

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]

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]

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]

Abstract To date, numerable reviews are found in the literature prominent to the effect of caffeine on the immune system, with the latest review published in 2006. Database screening reveals around three thousand articles that have been published during the last decade. Interestingly, less than hundred articles involved humans and rodents as tested models, out of which 20% is of interest to this paper excluding studies done on the nervous and cardiac systems, and in pregnant and cancer cases. In this review, information pertaining to the experimental setup of various studies, namely, the tested model, the study type (in vivo or in vitro), and caffeine dose is covered to discern the behaviour of major cellular and molecular immune components in light of caffeine exposure. Although it is hard to extrapolate results done in rodents to humans and to relay conclusions from in vitro to in vivo studies, most of the collected data favor the suppressive effects of caffeine on the proliferation of stimulated lymphocytes. Macrophages and natural killer cells also exhibited a reduced activity in the presence of high caffeine doses compared to increased activity at low doses. Immunosuppression is also supported by reduced levels of major anti-inflammatory cytokines, IL-2, IL-6, TNF-α. Moreover, certain innate and adaptive immune receptors, such as TLR1, TLR2, TLR4, and MHC class I-related chain B (MICB) molecules, exhibited decreased expression levels. Thus, we support the use of caffeine to alleviate various inflammatory conditions and autoimmune diseases. [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]

The selective modulation of immunity is an emerging concept driven by the vast advances in our understanding of this crucial host defense system. Invertebrates have raised researchers’ interest as potential sources of new bioactive molecules owing to their antibacterial, anticancer and immunomodulatory activities. A LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates the transcript, Ci 8 short, with cis -regulatory elements in the 3′ UTR region that are essential for shaping innate immune responses. The derived amino acidic sequence in silico analysis showed specific binding to human Major Histocompatibility Complex (MHC) Class I and Class II alleles. The role of Ci 8 short peptide was investigated in a more evolved immune system using human Peripheral Blood Mononuclear Cells (PBMCs) as in vitro model. The biological activities of this molecule include the activation of 70 kDa TCR ζ chain Associated Protein kinase (ZAP-70) and T Cell Receptor (TCR) Vβ oligo clonal selection on CD4 + T lymphocytes as well as increased proliferation and IFN-γ secretion. Furthermore Ci 8 short affects CD4 + /CD25 high induced regulatory T cells (iTreg) subset selection which co-expressed the functional markers TGF-β1/Latency Associated Protein (LAP) and CD39/CD73. This paper describes a new molecule that modulates important responses of the human adaptive immune system. [ABSTRACT FROM AUTHOR]

This paper develops and analyzes a SARS-CoV-2 dynamics model with logistic growth of healthy epithelial cells, CTL immune and humoral (antibody) immune responses. The model is incorporated with four mixed (distributed/discrete) time delays, delay in the formation of latent infected epithelial cells, delay in the formation of active infected epithelial cells, delay in the activation of latent infected epithelial cells, and maturation delay of new SARS-CoV-2 particles. We establish that the model's solutions are non-negative and ultimately bounded. We deduce that the model has five steady states and their existence and stability are perfectly determined by four threshold parameters. We study the global stability of the model's steady states using Lyapunov method. The analytical results are enhanced by numerical simulations. The impact of intracellular time delays on the dynamical behavior of the SARS-CoV-2 is addressed. We noted that increasing the time delay period can suppress the viral replication and control the infection. This could be helpful to create new drugs that extend the delay time period. • A SARS-CoV-2 dynamics model with logistic growth of healthy epithelial cells is developed and rigorously analyzed. • Both CTL and antibody immune responses are incorporated. • The model is incorporated with four mixed (distributed/discrete) time delays. • Well-posedness of the model and existence of equilibria are established. • Global stability of the equilibria is established by means of Lyapunov functionals. • The analytical results are enhanced by numerical simulations. [ABSTRACT FROM AUTHOR]

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]

The inflammation theory of depression, proposed over 20 years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced ‘omics’ technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account. [ABSTRACT FROM AUTHOR]

The advent of high throughput sequencing has permitted to investigate the genome and the transcriptome of novel non-model species with unprecedented depth. This technological advance provided a better understanding of the evolution of adaptive immune genes in gnathostomes, revealing several unexpected features in different fish species which are of particular interest. In the present paper, we review the current understanding of the adaptive immune system of the coelacanth, the elephant shark and the Atlantic cod. The study of coelacanth, the only living extant of the long thought to be extinct Sarcopterygian lineage, is fundamental to bring new insights on the evolution of the immune system in higher vertebrates. Surprisingly, coelacanths are the only known jawed vertebrates to lack IgM, whereas two IgD/W loci are present. Cartilaginous fish are of great interest due to their basal position in the vertebrate tree of life; the genome of the elephant shark revealed the lack of several important immune genes related to T cell functions, which suggest the existence of a primordial set of T H 1-like cells. Finally, the Atlantic cod lacks a functional major histocompatibility II complex, but balances this evolutionary loss with the expansion of specific gene families, including MHC I, Toll-like receptors and antimicrobial peptides. Overall, these data point out that several fish species present an unconventional adaptive immune system, but the loss of important immune genes is balanced by adaptive evolutionary strategies which still guarantee the establishment of an efficient immune response against the pathogens they have to fight during their life. [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]

Growing evidence indicates that overactivation and prolongation of the inflammatory response after acute myocardial infarction (AMI) result in worse left ventricular remodelling, dysfunction and progression to heart failure. This post-AMI inflammatory response is characterised by the critical involvement of cells from both the innate and adaptive immune systems. In this review paper, we aim to summarise and discuss the emergence of immune cells in the bloodstream and myocardium after AMI in men and mice. Subset composition, phenotypes, and kinetics of immune cells are considered. In addition, the relation with post-MI cardiac remodelling, function and outcome is reported. Increased knowledge of immune components, the mechanisms and interactions by which these cells contribute to myocardial damage and repair following AMI may help to close the gaps that limit improvement of treatments of those who survive the acute infarction. [ABSTRACT FROM AUTHOR]

Vitiligo is an autoimmune disease of the skin that is characterized by patchy depigmentation (i.e., white spots) and results from the loss of melanocytes, which are pigment-producing cells. The pathogenesis of human vitiligo consists of an interaction between intrinsic melanocyte defects, environmental factors, and autoimmune mechanisms that target these cells for destruction. Human clinical and translational studies have outlined pathways that are important in human disease; however, combining human correlative studies with mechanistic studies in representative preclinical animal models is a powerful approach to study disease pathogenesis and develop new treatments. Because of the complex pathogenesis of vitiligo, it is unlikely that any one single animal model will adequately reflect all factors implicated in the initiation, progression, and maintenance of the disease. Therefore, vitiligo is best modeled by multiple systems—each with its strengths and weaknesses—that allow insight into specific components of vitiligo pathogenesis. In this paper, we describe some of the available animal models that have been developed to study vitiligo. [ABSTRACT FROM AUTHOR]

Amphioxus, one of the most closely related invertebrates to vertebrates, is an important animal model for studying the origin and evolution of vertebrate immunity, especially the transition from innate immunity to adaptive immunity. The current research progresses of amphioxus in the field of immune organs, immune cells, complement system, cytokines, nuclear factor kappa B, immune-related lectins and enzymes are summarized, and some issues that remain to be understood or are in need of further clarification are highlighted. We hope to provide references for more in-depth study of the amphioxus immune system and lay a solid foundation for the construction of three-dimensional immune network in amphioxus from ontogeny to phylogeny. • Amphioxus is an important model for studying the origin and evolution of vertebrate immunity. • This paper summarizes advances in immunological research of amphioxus. • This review highlights some issues that need to be understood or further clarified. [ABSTRACT FROM AUTHOR]

Usefulness of Pidotimod and its role as immunostimulant, has been discussed, we know, for several decades. Nevertheless, there is still much to know. Understanding its mechanisms and its potential usefulness in airway infections and its prevention, asthma both Th2 and non Th2 type, bronchiectasis, as adjuvant in vaccination and in allergen immunotherapy still remains to clearly unveil. The aim of this paper was to provide a useful updated review of the role of the main available immunostimulants, giving particular focus on Pidotimod use and its potentials utility in respiratory diseases. Pidotimod showed its usefulness in reducing need for antibiotics in airway infections, increasing the level of immunoglobulins (IgA, IgM, IgG) and T-lymphocyte subsets (CD3+, CD4+) endowed with immunomodulatory activity that affect both innate and adaptive immune responses. Higher expression of TLR2 and of HLA-DR molecules, induction of dendritic cell maturation and release of pro-inflammatory molecules, stimulation of T lymphocyte proliferation and differentiation toward a Th1 phenotype, as well as an increase of the phagocytosis have been demonstrated to be associated with Pidotimod in in vitro studies. All these activities are potentially useful for several respiratory conditions such as asthma, COPD, and recurrent respiratory tract infections. [ABSTRACT FROM AUTHOR]