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Measles disease is caused by the measles virus (MV), which is a highly contagious viral infection that mainly affects children. Measles disease is one of the vaccine-preventable diseases, despite the availability of an effective vaccine, measles remains a significant public health concern globally. Understanding the immune responses to the MV is very important for the development of improved vaccines and therapeutic strategies. The aim of the current study is to summarize current knowledge on the innate and adaptive immune responses to measles infection, including the role of various immune system components; cells, cytokines, and antibodies. In addition to that, the paper discusses the immunological memory generated following measles infection or vaccination and its implications for long-term protection. [ABSTRACT FROM AUTHOR]

The application of mathematical biology and dynamical systems has proven to be an effective approach for studying viral infection models. To contribute to this research, our paper proposes a new CHIKV model that takes into account an adaptive immune response and distributed time delays, which accurately reflects the time lag between initial viral contacts and the production of new active CHIKV particles. By analyzing the model’s qualitative behavior, we establish a biological threshold number that can predict whether CHIKV will be cleared from or persist in the body. We demonstrate the global stability of both CHIKV-present and CHIKV-free steady states using the Lyapunov functional method and LaSalle’s invariance principle. In addition, we conduct numerical simulations to examine how time delays can affect the stability of the steady states. Through these simulations, we gain insights into how varying time delays can influence the persistence or clearance of CHIKV within the host. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, which is defined by its positive-sense single-stranded RNA (ssRNA) structure. It is in the order Nidovirales, suborder Coronaviridae, genus Betacoronavirus, and sub-genus Sarbecovirus (lineage B), together with two bat-derived strains with a 96% genomic homology with other bat coronaviruses (BatCoVand RaTG13). Thus far, two Alphacoronavirus strains, HCoV-229E and HCoV-NL63, along with five Betacoronaviruses, HCoV-HKU1, HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2, have been recognized as human coronaviruses (HCoVs). SARS-CoV-2 has resulted in more than six million deaths worldwide since late 2019. The appearance of this novel virus is defined by its high and variable transmission rate (RT) and coexisting asymptomatic and symptomatic propagation within and across animal populations, which has a longer-lasting impact. Most current therapeutic methods aim to reduce the severity of COVID-19 hospitalization and virus symptoms, preventing the infection from progressing from acute to chronic in vulnerable populations. Now, pharmacological interventions including vaccines and others exist, with research ongoing. The only ethical approach to developing herd immunity is to develop and provide vaccines and therapeutics that can potentially improve on the innate and adaptive system responses at the same time. Therefore, several vaccines have been developed to provide acquired immunity to SARS-CoV-2 induced COVID-19-disease. The initial evaluations of the COVID-19 vaccines began in around 2020, followed by clinical trials carried out during the pandemic with ongoing population adverse effect monitoring by respective regulatory agencies. Therefore, durability and immunity provided by current vaccines requires further characterization with more extensive available data, as is presented in this paper. When utilized globally, these vaccines may create an unidentified pattern of antibody responses or memory B and T cell responses that need to be further researched, some of which can now be compared within laboratory and population studies here. Several COVID-19 vaccine immunogens have been presented in clinical trials to assess their safety and efficacy, inducing cellular antibody production through cellular B and T cell interactions that protect against infection. This response is defined by virus-specific antibodies (anti-N or anti-S antibodies), with B and T cell characterization undergoing extensive research. In this article, we review four types of contemporary COVID-19 vaccines, comparing their antibody profiles and cellular aspects involved in coronavirus immunology across several population studies. [ABSTRACT FROM AUTHOR]

The objective of this paper is to investigate a mathematical model describing the infection of hepatitis B virus (HBV) in intrahepatic and extrahepatic tissues. Additionally, the model includes the effect of the cytotoxic T cell (CTL) immunity, which is described by a linear activation rate by infected cells. The positivity and boundedness of solutions for non-negative initial data are proven, which is consistent with the biological studies. The local stability of the equilibrium is established. In addition to this, the global stability of the disease-free equilibrium and the endemic equilibrium is fulfilled by using appropriate Lyapanov functions. Finally, numerical simulations are performed to support our theoretical findings. It has been revealed that the fractional-order derivatives have no influence on the stability but only on the speed of convergence toward the equilibria. [ABSTRACT FROM AUTHOR]

This paper studies the global dynamics of a general diffusive hepatitis B virus (HBV) infection model. The model includes both enveloped viruses and DNA containing capsids. Two immune responses are recruited to attack the virus and infected hepatocytes. These are the cytotoxic T-lymphocytes (CTL) which kill the infected liver cells, and B cells which send antibodies to attack the virus. The non-negativity and boundedness of the solutions are discussed. The existence of spatially homogeneous equilibrium points is examined. The global stability of all possible equilibrium points is proved by choosing suitable Lyapunov functionals. Some numerical simulations are performed to enhance the theoretical results and present the behavior of solutions in space and time. [ABSTRACT FROM AUTHOR]

Introduction: To comprehensively identify and provide an overview of in vivo or clinical studies of nucleic acids (NA)-based vaccines against TB we included human or animal studies of NA vaccines for the prevention or treatment of TB and excluded in vitro or in silico research, studies of microorganisms other than M. tuberculosis, reviews, letters, and low-yield reports. Methods: We searched PubMed, Scopus, Embase, selected Web of Science and ProQuest databases, Google Scholar, eLIBRARY.RU, PROSPERO, OSF Registries, Cochrane CENTRAL, EU Clinical Trials Register, clinicaltrials.gov, and others through WHO International Clinical Trials Registry Platform Search Portal, AVMA and CABI databases, bioRxiv, medRxiv, and others through OSF Preprint Archive Search. We searched the same sources and Google for vaccine names (GX-70) and scanned reviews for references. Data on antigenic composition, delivery systems, adjuvants, and vaccine efficacy were charted and summarized descriptively. Results: A total of 18,157 records were identified, of which 968 were assessed for eligibility. No clinical studies were identified. 365 reports of 345 animal studies were included in the review. 342 (99.1%) studies involved DNA vaccines, and the remaining three focused on mRNA vaccines. 285 (82.6%) studies used single-antigen vaccines, while 48 (13.9%) used multiple antigens or combinations with adjuvants. Only 12 (3.5%) studies involved multiepitope vaccines. The most frequently used antigens were immunodominant secretory antigens (Ag85A, Ag85B, ESAT6), heat shock proteins, and cell wall proteins. Most studies delivered naked plasmid DNA intramuscularly without additional adjuvants. Only 4 of 17 studies comparing NA vaccines to BCG after M. tuberculosis challenge demonstrated superior protection in terms of bacterial load reduction. Some vaccine variants showed better efficacy compared to BCG. [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential nutrient that has gained attention for its impact on the human immune system. The purpose of this review is to explore Se's immunomodulatory properties and to make up-to-date information available so novel therapeutic applications may emerge. People acquire Se through dietary ingestion, supplementation, or nanoparticle applications. These forms of Se can beneficially modulate the immune system by enhancing antioxidant activity, optimizing the innate immune response, improving the adaptive immune response, and promoting healthy gut microbiota. Because of these many actions, Se supplementation can help prevent and treat pathogenic diseases, autoimmune diseases, and cancers. This review will discuss Se as a key micronutrient with versatile applications that supports disease management due to its beneficial immunomodulatory effects. Further research is warranted to determine safe dosing guidelines to avoid toxicity and refine the application of Se in medical treatments. [ABSTRACT FROM AUTHOR]

In this paper we propose and analyze a pathogen dynamics model with antibody and Cytotoxic T Lymphocyte (CTL) immune responses. We incorporate latently infected cells and three distributed time delays into the model. We show that the solutions of the proposed model are nonnegative and ultimately bounded. We derive four threshold parameters which fully determine the existence and stability of the five steady states of the model. Using Lyapunov functionals, we established the global stability of the steady states of the model. The theoretical results are confirmed by numerical simulations. [ABSTRACT FROM AUTHOR]

Recognizing the "essential" factors that contribute to a clinical outcome is critical for designing appropriate therapies and prioritizing limited medical resources. Demonstrating a high correlation between a factor and an outcome does not necessarily imply an essential role of the factor to the outcome. Human protective adaptive immune responses to pathogens vary among (and perhaps within) pathogenic strains, human individual hosts, and in response to other factors. Which of these has an "essential" role? We offer three statistical approaches that predict the presence of newly contributing factor(s) and then quantify the influence of host, pathogen, and the new factors on immune responses. We illustrate these approaches using previous data from the protective adaptive immune response (cellular and humoral) by human hosts to various strains of the same pathogenic bacterial species. Taylor's law predicts the existence of other factors potentially contributing to the human protective adaptive immune response in addition to inter-individual host and intra-bacterial species inter-strain variability. A mixed linear model measures the relative contribution of the known variables, individual human hosts and bacterial strains, and estimates the summed contributions of the newly predicted but unknown factors to the combined adaptive immune response. A principal component analysis predicts the presence of sub-variables (currently not defined) within bacterial strains and individuals that may contribute to the combined immune response. These observations have statistical, biological, clinical, and therapeutic implications. [ABSTRACT FROM AUTHOR]

In a post-growth multicellular organism, the phenomenon in which a small number of rare cells can be the starting point for inducing a dramatic change in the entire system is considered a "biological singularity." The immune response and cancer can be regarded as singularity phenomena in mammals, but their nature is fundamentally different. The immune response is considered a "programmed" singularity, whereas cancer is an "unprogrammed" singularity. These two systems perpetually engage in a cycle of attack and defense within the organism. The outcome is depending on the wining system, which determines whether the individual experiences a state resembling light or darkness. However, the overall mechanism of the competition remains unclear and is expected to be elucidated with future innovations in bioimaging technologies. Immune checkpoint blockade therapy is a means by which the two singularity balances can be artificially manipulated; therefore, mechanistic insight is necessary for cancer treatment strategies. Altogether, these findings provide a different perspective crucial for understanding the behavior of dynamic cell populations in multicellular organisms. [ABSTRACT FROM AUTHOR]

Aims: Agonistic antibodies against neurohumoral receptors can induce cardio‐noxious effects by altering the baseline receptor activity. To estimate the prevalence of autoantibodies directed against the beta‐1 receptor (b1‐AAB) in patients admitted to the hospital for acute heart failure (HF) at (i) baseline and (ii) after 6 months of follow‐up (F6) and (iii) after another 12 months of follow‐up (i.e. 18 months after index hospitalization), to estimate their prognostic impact on clinical outcome (death or first hospitalization for HF). Methods and results: In 47 patients, b1‐AAB were serially determined in serum samples collected at index hospitalization and at 6 months of follow‐up (F6) with a flow cytometry‐based assay: median age 71 years (quartiles 60, 80), 23 (49%) women, 24 (51%) HF with preserved ejection fraction. Beta1‐AAB were detected in three subjects at index hospitalization (6%), and in eight subjects at F6 (17%). There were no differences apparent between patients with and without b1‐AAB at F6 with regard to age, sex, type, duration, or main cause of HF. During the 12 month period following F6 (i.e. up to month 18), eight events occurred. Event‐free survival was associated with prevalence of b1‐AAB at F6. Compared with patients without b1‐AAB at F6, age‐adjusted Cox regression indicated a higher event risk in patients harbouring b1‐AAB, with a hazard ratio of 8.96 (95% confidence interval 1.81–44.50, P = 0.007). Conclusions: Our results suggest a possible adverse prognostic relevance of b1‐AAB in patients with acute HF, but this observation needs to be confirmed in larger patient collectives. [ABSTRACT FROM AUTHOR]

T cells represent a crucial component of the adaptive immune system and mediate anti-tumoral immunity as well as protection against infections, including respiratory viruses such as SARS-CoV-2. Next-generation sequencing of the Tcell receptors (TCRs) can be used to profile the T-cell repertoire. We developed a customized pipeline for Network Analysis of Immune Repertoire (NAIR) with advanced statistical methods to characterize and investigate changes in the landscape of TCR sequences. We first performed network analysis on the TCR sequence data based on sequence similarity. We then quantified the repertoire network by network properties and correlated it with clinical outcomes of interest. In addition, we identified (1) disease-specific/associated clusters and (2) shared clusters across samples based on our customized search algorithms and assessed their relationship with clinical outcomes such as recovery from COVID-19 infection. Furthermore, to identify disease-specific TCRs, we introduced a new metric that incorporates the clonal generation probability and the clonal abundance by using the Bayes factor to filter out the false positives. TCR-seq data from COVID-19 subjects and healthy donors were used to illustrate that the proposed approach to analyzing the network architecture of the immune repertoire can reveal potential disease-specific TCRs responsible for the immune response to infection. [ABSTRACT FROM AUTHOR]

The spread of the respiratory viral infections is currently being widely investigated, and the influence of the immune response on the spread of these infections is of particular interest. In this work, the set of hierarchical models for the spread of infection with respect to the immune response is formulated and analysed. The models are based on the one-dimensional reaction-diffusion equations, and they are investigated both numerically and analytically. For these models, the speed of the wave propagation and the total viral load are evaluated, and their dependencies on the parameters characterizing the intensity of the innate and adaptive immune response are defined. These results show that more intense immune response leads to the small infectivity and severity of the decrease. Different parts of the immune response influence the infectivity and severity of the disease in different ways. These dependencies can help in planning of the treatment strategy. [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) causes a devastating viral hemorrhagic disease in domestic pigs and Eurasian wild boars, posing a foremost threat to the swine industry and pig farming. The development of an effective vaccine is urgently needed, but has been hampered by the lack of an in-depth, mechanistic understanding of the host immune response to ASFV infection and the induction of protective immunity. In this study, we report that immunization of pigs with Semliki Forest Virus (SFV) replicon-based vaccine candidates expressing ASFV p30, p54, and CD2v, as well as their ubiquitin-fused derivatives, elicits T cell differentiation and expansion, promoting specific T cell and humoral immunity. Due to significant variations in the individual non-inbred pigs in response to the vaccination, a personalized analysis was conducted. Using integrated analysis of differentially expressed genes (DEGs), Venn, KEGG and WGCNA, Toll-like receptor, C-type lectin receptor, IL17 receptor, NOD-like receptor and nucleic acid sensor-mediated signaling pathways were demonstrated to be positively correlated to the antigen-stimulated antibody production and inversely correlated to the IFN-γ secreting cell counts in peripheral blood mononuclear cells (PBMCs). An up-regulation of CIQA, CIQB, CIQC, C4BPA, SOSC3, S100A8 and S100A9, and down-regulation of CTLA4, CXCL2, CXCL8, FOS, RGS1, EGR1 and SNAI1 are general in the innate immune response post-the second boost. This study reveals that pattern recognition receptors TLR4, DHX58/DDX58 and ZBP1, and chemokines CXCL2, CXCL8 and CXCL10 may play important roles in regulating this vaccination-stimulated adaptive immune response. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the most specialized and proficient antigen-presenting cells. They bridge innate and adaptive immunity and display a powerful capacity to prime antigen-specific T cells. The interaction of DCs with the receptor-binding domain of the spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pivotal step to induce effective immunity against the S protein-based vaccination protocols, as well as the SARS-CoV-2 virus. Herein, we describe the cellular and molecular events triggered by virus-like particles (VLPs) containing the receptor-binding motif from the SARS-CoV-2 spike protein in human monocyte-derived dendritic cells, or, as controls, in the presence of the Toll-like receptors (TLR)3 and TLR7/8 agonists, comprehending the events of dendritic cell maturation and their crosstalk with T cells. The results demonstrated that VLPs boosted the expression of major histocompatibility complex molecules and co-stimulatory receptors of DCs, indicating their maturation. Furthermore, DCs' interaction with VLPs promoted the activation of the NF-kB pathway, a very important intracellular signalling pathway responsible for triggering the expression and secretion of proinflammatory cytokines. Additionally, co-culture of DCs with T cells triggered CD4+ (mainly CD4+Tbet+) and CD8+ T cell proliferation. Our results suggested that VLPs increase cellular immunity, involving DC maturation and T cell polarization towards a type 1 T cells profile. By providing deeper insight into the mechanisms of activation and regulation of the immune system by DCs, these findings will enable the design of effective vaccines against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

In this work, we develop mathematical models of the immune response to respiratory viral infection, taking into account some particular properties of the SARS-CoV infections, cytokine storm and vaccination. Each model consists of a system of ordinary differential equations that describe the interactions of the virus, epithelial cells, immune cells, cytokines, and antibodies. Conventional analysis of the existence and stability of stationary points is completed by numerical simulations in order to study the dynamics of solutions. The behavior of the solutions is characterized by large peaks of virus concentration specific to acute respiratory viral infections. At the first stage, we study the innate immune response based on the protective properties of interferon secreted by virus-infected cells. Viral infection down-regulates interferon production. This competition can lead to the bistability of the system with different regimes of infection progression with high or low intensity. After that, we introduce the adaptive immune response with antigen-specific T- and B-lymphocytes. The resulting model shows how the incubation period and the maximal viral load depend on the initial viral load and the parameters of the immune response. In particular, an increase in the initial viral load leads to a shorter incubation period and higher maximal viral load. The model shows that a deficient production of antibodies leads to an increase in the incubation period and even higher maximum viral loads. In order to study the emergence and dynamics of cytokine storm, we consider proinflammatory cytokines produced by cells of the innate immune response. Depending on the parameters of the model, the system can remain in the normal inflammatory state specific for viral infections or, due to positive feedback between inflammation and immune cells, pass to cytokine storm characterized by the excessive production of proinflammatory cytokines. Finally, we study the production of antibodies due to vaccination. We determine the dose–response dependence and the optimal interval of vaccine dose. Assumptions of the model and obtained results correspond to the experimental and clinical data. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine chronic inflammatory enteropathy (CIE) is a chronic disease affecting the small or large intestine and, in some cases, the stomach of dogs. This gastrointestinal disorder is common and is characterized by recurrent vomiting, diarrhea, and weight loss in affected dogs. The pathogenesis of IBD is not completely understood. Similar to human IBD, potential disease factors include genetics, environmental exposures, and dysregulation of the microbiota and the immune response. Some important components of the innate and adaptive immune response involved in CIE pathogenesis have been described. However, the immunopathogenesis of the disease has not been fully elucidated. In this review, we summarized the literature associated with the different cell types and molecules involved in the immunopathogenesis of CIE, with the aim of advancing the search for biomarkers with possible diagnostic, prognostic, or therapeutic utility. Canine chronic inflammatory enteropathy (CIE) is one of the most common chronic gastrointestinal diseases affecting dogs worldwide. Genetic and environmental factors, as well as intestinal microbiota and dysregulated host immune responses, participate in this multifactorial disease. Despite advances explaining the immunological and molecular mechanisms involved in CIE development, the exact pathogenesis is still unknown. This review compiles the latest reports and advances that describe the main molecular and cellular mechanisms of both the innate and adaptive immune responses involved in canine CIE pathogenesis. Future studies should focus research on the characterization of the immunopathogenesis of canine CIE in order to advance the establishment of biomarkers and molecular targets of diagnostic, prognostic, or therapeutic utility. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of cancer is very often accompanied by systemic immune alterations which can be further aggravated by major anti-cancer therapies. However, there is very little known about how long these alterations persist in patients successfully cured of cancer. The aim of our work was to investigate how cancer and radiotherapy as major anti-cancer treatment modalities impact the immune system long after the successful treatment of a tumor. We investigated prostate cancer patients treated with a special form of radiotherapy (low-dose rate brachytherapy) often used for the treatment of prostate cancer and followed a wide range of immune parameters at regular intervals up to 3 years after the start of the treatment. Our results showed that some immune alterations did not recover after the treatment of the disease, on the contrary, they persisted, and in some cases got even worse. Further studies are needed to explain the causes and the potential long-term consequences of these alterations. Background: The development of cancer and anti-tumor therapies can lead to systemic immune alterations but little is known about how long immune dysfunction persists in cancer survivors. Methods: We followed changes in the cellular immune parameters of prostate cancer patients with good prognostic criteria treated with low dose rate brachytherapy before and up to 3 years after the initiation of therapy. Results: Patients before therapy had a reduced CD4+ T cell pool and increased regulatory T cell fraction and these alterations persisted or got amplified during the 36-month follow-up. A significant decrease in the total NK cell number and a redistribution of the circulating NK cells in favor of a less functional anergic subpopulation was seen in patients before therapy but tumor regression led to the regeneration of the NK cell pool and functional integrity. The fraction of lymphoid DCs was increased in patients both before therapy and throughout the whole follow-up. Increased PDGF-AA, BB, CCL5 and CXCL5 levels were measured in patients before treatment but protein levels rapidly normalized. Conclusions: while NK cell dysfunction recovered, long-term, residual alterations persisted in the adaptive and partly in the innate immune system. [ABSTRACT FROM AUTHOR]

This paper investigates an adaptive immunity HIV infection model with three types of distributed time delays. The model describes the interaction between healthy CD4+T cells, silent infected cells, active infected cells, free HIV particles, Cytotoxic T lymphocytes (CTLs) and antibodies. The healthy CD4+T cells can be infected when they contacted by free HIV particles or silent infected cells or active infected cells. The incidence rates of the healthy CD4+T cells with free HIV particles, silent infected cells, and active infected cells are given by general functions. Moreover, the production/proliferation and removal/death rates of the virus and cells are represented by general functions. The model is an improvement of the existing HIV infection models which have neglected the infection due to the incidence between the silent infected cells and healthy CD4+T cells. We show that the model is well posed and it has five equilibria and their existence are governed by five threshold parameters. Under a set of conditions on the general functions and the threshold parameters, we have proven the global asymptotic stability of all equilibria by using Lyapunov method. We have illustrated the theoretical results via numerical simulations. We have studied the effect of cell-to-cell (CTC) transmission and time delays on the dynamical behavior of the system. We have shown that the inclusion of time delay can significantly increase the concentration of the healthy CD4+ T cells and reduce the concentrations of the infected cells and free HIV particles. While the inclusion of CTC transmission decreases the concentration of the healthy CD4+ T cells and increases the concentrations of the infected cells and free HIV particles.

This paper studies an (n + 4)-dimensional nonlinear viral infection model that characterizes the interactions of the viruses, susceptible host cells, n-stages of infected cells, CTL cells and B cells. Both viral and cellular infections have been incorporated into the model. The well-posedness of the model is justified. The model admits five equilibria which are determined by five threshold parameters. The global stability of each equilibrium is proven by utilizing Lyapunov function and LaSalle's invariance principle. The theoretical results are illustrated by numerical simulations.

Abstract This paper studies the global dynamics of a general diffusive hepatitis B virus (HBV) infection model. The model includes both enveloped viruses and DNA containing capsids. Two immune responses are recruited to attack the virus and infected hepatocytes. These are the cytotoxic T-lymphocytes (CTL) which kill the infected liver cells, and B cells which send antibodies to attack the virus. The non-negativity and boundedness of the solutions are discussed. The existence of spatially homogeneous equilibrium points is examined. The global stability of all possible equilibrium points is proved by choosing suitable Lyapunov functionals. Some numerical simulations are performed to enhance the theoretical results and present the behavior of solutions in space and time.

Aims: It has been hypothesized that cardiac decompensation accompanying acute heart failure (AHF) episodes generates a pro‐inflammatory environment boosting an adaptive immune response against myocardial antigens, thus contributing to progression of heart failure (HF) and poor prognosis. We assessed the prevalence of anti‐myocardial autoantibodies (AMyA) as biomarkers reflecting adaptive immune responses in patients admitted to the hospital for AHF, followed the change in AMyA titres for 6 months after discharge, and evaluated their prognostic utility. Methods and results: AMyA were determined in n = 47 patients, median age 71 (quartiles 60; 80) years, 23 (49%) female, and 24 (51%) with HF with preserved ejection fraction, from blood collected at baseline (time point of hospitalization) and at 6 month follow‐up (visit F6). Patients were followed for 18 months (visit F18). The prevalence of AMyA increased from baseline (n = 21, 45%) to F6 (n = 36, 77%; P < 0.001). At F6, the prevalence of AMyA was higher in patients with HF with preserved ejection fraction (n = 21, 88%) compared with patients with reduced ejection fraction (n = 14, 61%; P = 0.036). During the subsequent 12 months after F6, that is up to F18, patients with newly developed AMyA at F6 had a higher risk for the combined endpoint of death or rehospitalization for HF (hazard ratio 4.79, 95% confidence interval 1.13–20.21; P = 0.033) compared with patients with persistent or without AMyA at F6. Conclusions: Our results support the hypothesis that AHF may induce patterns of adaptive immune responses. More studies in larger populations and well‐defined patient subgroups are needed to further clarify the role of the adaptive immune system in HF progression. [ABSTRACT FROM AUTHOR]

The objective of this paper is to investigate a mathematical model describing the infection of hepatitis B virus (HBV) in intrahepatic and extrahepatic tissues. Additionally, the model includes the effect of the cytotoxic T cell (CTL) immunity, which is described by a linear activation rate by infected cells. The positivity and boundedness of solutions for non-negative initial data are proven, which is consistent with the biological studies. The local stability of the equilibrium is established. In addition to this, the global stability of the disease-free equilibrium and the endemic equilibrium is fulfilled by using appropriate Lyapanov functions. Finally, numerical simulations are performed to support our theoretical findings. It has been revealed that the fractional-order derivatives have no influence on the stability but only on the speed of convergence toward the equilibria.

Trypanosoma brucei parasites successfully evade the host immune system by periodically switching the dense coat of variant surface glycoprotein (VSG) at the cell surface. Each parasite expresses VSGs in a monoallelic fashion that is tightly regulated. The consequences of exposing multiple VSGs during an infection, in terms of antibody response and disease severity, remain unknown. In this study, we overexpressed a high-mobility group box protein, TDP1, which was sufficient to open the chromatin of silent VSG expression sites, to disrupt VSG monoallelic expression, and to generate viable and healthy parasites with a mixed VSG coat. Mice infected with these parasites mounted a multi-VSG antibody response, which rapidly reduced parasitemia. Consequently, we observed prolonged survival in which nearly 90% of the mice survived a 30-d period of infection with undetectable parasitemia. Immunodeficient RAG2 knock-out mice were unable to control infection with TDP1-overexpressing parasites, showing that the adaptive immune response is critical to reducing disease severity. This study shows that simultaneous exposure of multiple VSGs is highly detrimental to the parasite, even at the very early stages of infection, suggesting that drugs that disrupt VSG monoallelic expression could be used to treat trypanosomiasis. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells inhibit tumor development in mouse models and their presence in tumors correlates with patient survival. However, tumor-associated NK cells become dysfunctional; thus, stimulation of NK cells in cancer is emerging as an attractive immunotherapeutic strategy. In a mouse model of lung adenocarcinoma, NK cells localized to tumor stroma with immature phenotypes and low functional capacity. To test their responsiveness within established disease,we engineered a system for inducible expression of activating ligands in tumors. After stimulation, NK cells localized inside tumors, with increased cytokine production capacity. Strikingly, T cells were also recruited to tumors in an NK cell-dependent manner, and exhibited higher functionality. In neoantigen-expressing tumors, NK cell stimulation enhanced the number and function of tumor-specific T cells and, in long-term settings, reduced tumor growth. Thus, even in established disease NK cells can be activated to contribute to antitumor immunity, supporting their potential as an important target in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Ehrlichia chaffeensis is an obligate intracellular bacterium belonging to the order, Rickettsiales and is a frequent cause of severe and fatal tick-borne infection in people in North America. The reservoir host for E. chaffeensis is the white-tailed deer, while humans and dogs are regarded as common incidental hosts. In dogs, we and others have shown that E. chaffeensis establishes a chronic infection that persists for several weeks to months, while promoting the development of Th1 and Th17 cellular responses and pathogen-specific humoral immunity. We demonstrate here that vaccination with a live, attenuated clone of E. chaffeensis bearing a targeted mutation in the Ech_0230 gene neither promotes the development of long-lived cellular or humoral immunity, nor confers protection against secondary wild-type E. chaffeensis challenge. In dogs, a population of mature CD4+CD8+ double-positive (DP) T cells exists in the periphery that shares similarities with the DP T cell populations that have been described in humans and swine. Little is known about the function of these cells, particularly in the context of infectious diseases. Here, we demonstrate that canine DP T cells expand significantly in response to E. chaffeensis infection. Using in vitro antigen recall assays, we further demonstrate that canine DP T cells undergo clonal expansion, produce IFNγ and IL-17, and upregulate expression of granzyme B and granulysin. Together, our results demonstrate that DP T cells accumulate in the host during E. chaffeensis infection, and suggest that alternative lymphocyte populations may participate in the immune response to tick-borne infections in the incidental host. [ABSTRACT FROM AUTHOR]

Aim: In our study we explored a possible relationship between PTX3 and CD. Background: Gluten sensitivity is known as a hallmark of celiac disease (CD). The diagnosis of CD requires demonstration of a typical enteropathy, and positive serology supports the diagnosis. The CD immune response involves the adaptive, as well as the innate immunity and is characterized by the presence of anti-gliadin (AGA) and anti-transglutaminase 2 antibodies (tTGA), lymphocytic infiltration in the intestinal epithelial membrane and expression of multiple cytokines. The long pentraxin 3 (PTX3), an acute-phase inflammatory molecule, plays an important role in innate immunity. Methods: 108 CD patients were divided according to Marsh Histological grade following Marsh criteria classification in three groups: Group 1: Marsh 0, patients with a known history of CD under gluten free diet, complete remission; Group 2: Marsh1 and Marsh 2; Group 3: Marsh 3. Healthy age-matched controls without a known history of CD or gastrointestinal symptoms (n=30) served as controls. PTX3 serum levels were measured by sandwich ELISA on an automated platform. Results: PTX3 serum levels were significantly elevated in group 3 and group 2 compared with HC (mean 3.31± 1.27 ng/mL and 3.97 ± 0.54 ng/mL versus 1.06 ± 0.59 ng/mL; P < 0.005), with group 1 (0.76±0.31 ng/mL). No statistically significant differences were found between group 1 and HC group. We found a strong linear correlation between PTX3 serum levels and AGA levels in group 2 (r=0.78, P <0.0001), and group 3 (r =0.63, P < 0.005) but no correlations were detected between PTX3 serum levels and tTGA levels (group 2, r= 0.04; group 3, r=0.24). Serological data revealed that PTX3 correlated with major gastrointestinal damage patients. Conclusion: PTX3 is a component of the humoral arm of the innate immune system. Our data showed that PTX3 serum levels were high in active disease patients with pathological levels of AGA. We also demonstrated that patients with normal AGA IgA levels had PTX3 serum levels compared to healthy control. We hypothesized that PTX3 is able to modulate the innate response to gliadin in CD and it could regulate the adaptive immune response. [ABSTRACT FROM AUTHOR]

Background: Recently moderate-virulence classical swine fever virus (CSFV) strains have been proven capable of generating postnatal persistent infection (PI), defined by the maintenance of viremia and the inability to generate CSFV-specific immune responses in animals. These animals also showed a type I interferon blockade in the absence of clinical signs. In this study, we assessed the infection generated in 7-week-old CSFV PI wild boars after infection with the African swine fever virus (ASFV). The wild boars were divided in two groups and were infected with ASFV. Group A comprised boars who were CSFV PI in a subclinical form and Group B comprised pestivirus-free wild boars. Some relevant parameters related to CSFV replication and the immune response of CSFV PI animals were studied. Additionally, serum soluble factors such as IFN-α, TNF-α, IL-6, IL-10, IFN-γ and sCD163 were analysed before and after ASFV infection to assess their role in disease progression. Results: After ASFV infection, only the CSFV PI wild boars showed progressive acute haemorrhagic disease; however, the survival rates following ASFV infection was similar in both experimental groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered over the study; likewise, the ASFV DNA load detected after infection was similar between groups. Interestingly, systemic type I FN-α and IL-10 levels in sera were almost undetectable in CSFV PI animals, yet detectable in Group B, while detectable levels of IFN-γ were found in both groups. Finally, the flow cytometry analysis showed an increase in myelomonocytic cells (CD172a+) and a decrease in CD4+ T cells in the PBMCs from CSFV PI animals after ASFV infection. Conclusions: Our results showed that the immune response plays a role in the progression of disease in CSFV subclinically infected wild boars after ASFV infection, and the immune response comprised the systemic type I interferon blockade. ASFV does not produce any interference with CSFV replication, or vice versa. ASFV infection could be a trigger factor for the disease progression in CSFV PI animals, as their survival after ASFV was similar to that of the pestivirus-free ASFV-infected group. This fact suggests a high resistance in CSFV PI animals even against a virus like ASFV; this may mean that there are relevant implications for CSF control in endemic countries. The diagnosis of ASFV and CSFV co-infection in endemic countries cannot be ruled out and need to be studied in greater depth. [ABSTRACT FROM AUTHOR]

There is a growing appreciation that cellular metabolism is important in determining the course of lymphocyte responses. Additionally, changes in metabolic processes have been linked to dysfunctional lymphocyte functions in a number of different diseases. While most early studies of metabolic regulation of lymphocyte function focused on T lymphocytes, an understanding of how metabolic pathways impact upon natural killer (NK) cell responses is now starting to emerge. In this review article, we will discuss how cellular metabolism influences lymphocyte function with a particular focus upon NK cells. [ABSTRACT FROM AUTHOR]

It has become clear that the biological and clinical behaviour of malignant lymphoma is not only determined by the properties of the tumour cells themselves but are also largely by the interaction of the tumour cells with their nonmalignant microenvironment. The composition and functional status of the tumour microenvironment is highly variable between different classes of malignant lymphoma and may provide both growth-supportive and growth suppressive signals via components of the adaptive and innate immune response. In this review, the functional interactions and clinical consequences of these insights are discussed in indolent and aggressive B-cell lymphomas and in classical Hodgkin’s lymphoma. [ABSTRACT FROM AUTHOR]