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Copyright of Journal of Xinjiang University (Natural Science Edition) is the property of Xinjiang University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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 objective of this paper is to investigate a mathematical model describing the interactions between hepatitis B virus with DNA-containing capsids, liver cells (hepatocytes) and the adaptive immune response. This adaptive immunity will be represented by cytotoxic T-lymphocytes and antibody immune responses. The positivity and boundedness of solutions for non negative initial data are proved which is consistent with the biological studies. The local stability of the equilibria is established. In addition to this, the global stability of the disease-free equilibrium and the endemic equilibria is fulfilled by using appropriate Lyapunov functions. Finally, numerical simulations are performed to support our theoretical findings. [ABSTRACT FROM AUTHOR]

This paper develops a mathematical model to investigate the Human Immunodeficiency Virus (HIV) infection dynamics. The model includes two transmission modes (cell-to-cell and cell-free), two adaptive immune responses (cytotoxic T-lymphocyte (CTL) and antibody), a saturated CTL immune response, and latent HIV infection. The existence and local stability of equilibria are fully characterized by four reproduction numbers. Through sensitivity analyses, we assess the partial rank correlation coefficients of these reproduction numbers and identify that the infection rate via cell-to-cell transmission, the number of new viruses produced by each infected cell during its life cycle, the clearance rate of free virions, and immune parameters have the greatest impact on the reproduction numbers. Additionally, we compare the effects of immune stimulation and cell-to-cell spread on the model's dynamics. The findings highlight the significance of adaptive immune responses in increasing the population of uninfected cells and reducing the numbers of latent cells, infected cells, and viruses. Furthermore, cell-to-cell transmission is identified as a facilitator of HIV transmission. The analytical and numerical results presented in this study contribute to a better understanding of HIV dynamics and can potentially aid in improving HIV management strategies. [ABSTRACT FROM AUTHOR]

Whether prostate brachytherapy (BT) results in opportunistic biological changes that can improve clinical outcomes is not well studied. We sought to investigate the impact of prostate BT on the immune system. A scoping review was performed using PubMed/Scopus for papers published between 2011-2021. Search terms were "brachytherapy" AND "immune" AND "prostate". A total of 81 records were identified and 6 were selected for further review. 2 low-dose-rate BT papers (n=68) evaluated changes in the peripheral blood following I-125 monotherapy. Both showed significant increases in peripheral CD3+ and CD4+ T cells post-BT. One also demonstrated significant increases in Treg subsets up to 150 days post-BT. 4 high-dose-rate (HDR) studies (n=37) were identified, and all were done in combination with EBRT. The largest study (n=24) showed a single 10 Gy fraction of HDR converted 80% of "cold" tumors into an "intermediate" or "hot" state, based on a tumor inflammation signature when comparing a pre-BT biopsy to one prior to a second HDR fraction. Prostate BT can invoke an immune activating phenotype; however, changes in immunosuppressive cells are also seen. Additional data is needed to understand how to promote synergy between BT and the immune system. [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]

In this paper, the dynamical behaviors for a five-dimensional virus infection model with diffusion and two delays which describes the interactions of antibody, cytotoxic T-lymphocyte (CTL) immune responses and a general incidence function are investigated. The reproduction numbers for virus infection, antibody immune response, CTL immune response, CTL immune competition and antibody immune competition, respectively, are calculated. By using the Lyapunov functionals and linearization methods, the threshold conditions on the global stability of the equilibria for infection-free, immune-free, antibody response, CTL response and antibody and CTL responses, respectively, are established if the space is assumed as homogeneous. When the space is inhomogeneous, the effects of diffusion, intracellular delay and production delay are obtained by the numerical simulations. [ABSTRACT FROM AUTHOR]

This paper studies an (n+4)‐dimensional nonlinear virus dynamics model that characterizes the interactions of the viruses, susceptible host cells, n‐stages of infected cells, B cells and cytotoxic T lymphocyte (CTL) cells. Both viral and cellular infections have been incorporated into the model. The infected‐susceptible and virus‐susceptible infection rates as well as the generation and removal rates of all compartments are described by general nonlinear functions. Five threshold parameters are computed, which insure the existence of the equilibria of the model under consideration. A set of conditions on the general functions has been established, which is sufficient to investigate the global dynamics of the model. The global asymptotic stability of all equilibria is proven by utilizing Lyapunov function and LaSalle's invariance principle. The theoretical results are illustrated by numerical simulations of the model with specific forms of the general functions. [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]

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]

Purpose of Review: To review the role of the immune cells and their interaction with cells found in gingiva, periodontal ligament, and bone that leads to net bone loss in periodontitis or bone remodeling in orthodontic tooth movement. Recent Findings: Periodontal disease is one of the most common oral diseases causing inflammation in the soft and hard tissues of the periodontium and is initiated by bacteria that induce a host response. Although the innate and adaptive immune response function cooperatively to prevent bacterial dissemination, they also play a major role in gingival inflammation and destruction of the connective tissue, periodontal ligament, and alveolar bone characteristic of periodontitis. The inflammatory response is triggered by bacteria or their products that bind to pattern recognition receptors that induce transcription factor activity to stimulate cytokine and chemokine expression. Epithelial, fibroblast/stromal, and resident leukocytes play a key role in initiating the host response and contribute to periodontal disease. Single-cell RNA-seq (scRNA-seq) experiments have added new insight into the roles of various cell types in the response to bacterial challenge. This response is modified by systemic conditions such as diabetes and smoking. In contrast to periodontitis, orthodontic tooth movement (OTM) is a sterile inflammatory response induced by mechanical force. Orthodontic force application stimulates acute inflammatory responses in the periodontal ligament and alveolar bone stimulated by cytokines and chemokines that produce bone resorption on the compression side. On the tension side, orthodontic forces induce the production of osteogenic factors, stimulating new bone formation. A number of different cell types, cytokines, and signaling/pathways are involved in this complex process. Summary: Inflammatory and mechanical force-induced bone remodeling involves bone resorption and bone formation. The interaction of leukocytes with host stromal cells and osteoblastic cells plays a key role in both initiating the inflammatory events as well as inducing a cellular cascade that results in remodeling in orthodontic tooth movement or in tissue destruction in periodontitis. [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]

Background: The overall survival of melanoma patients remains poor despite advancements in surgical treatment and targeted therapies. Therefore, there is a need to develop new therapeutic strategies for melanoma. 2-methoxyestradiol (2-ME) is a major metabolite of estrogen that has been shown to have anti-tumor effects against many malignancies. However, the effects and mechanisms of action of 2-ME against melanoma remain unclear. Materials and methods: Melanoma cells (B16) were treated with 2-ME in vitro. Cell proliferation was detected by CCK8 and clone formation, transwell was carried out to measure the migration of B16 cells with or without 2-ME. Flow cytometry was performed to measure the apoptosis and cell cycle. C57BL/6 mice were used for tumor-bearing of B16 cells, tumor volumes were measured once a day, and sacrificed after it was over 2000 mm3, then immunofluorescence was implemented to examine the marker of CD3, CD8 and PD-L1. Results: In our study, we found that 2-ME significantly affected the proliferation, migration, apoptosis, and cell cycle of melanoma in vitro. Our results also showed that 2-ME had strong anti-tumor effects against melanoma in vivo and increased the infiltration of tumor-specific cytotoxic lymphocytes CD8+ T cells in the tumor microenvironment. Besides, PD-L1 expression in tumor cells was significantly higher in the 2-ME-treated group than in the control group, indicating that 2-ME could exhibit stronger anti-tumor effects against melanoma if combined with PD-1 blockade therapy. Conclusion: 2-ME suppresses melanoma in vivo and in vitro and is a promising synergistic enhancer of PD-1 blockade immunotherapy. [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]

We propose and study a new mathematical model of the human immunodeficiency virus (HIV). The main novelty is to consider that the antibody growth depends not only on the virus and on the antibodies concentration but also on the uninfected cells concentration. The model consists of five nonlinear differential equations describing the evolution of the uninfected cells, the infected ones, the free viruses, and the adaptive immunity. The adaptive immune response is represented by the cytotoxic T-lymphocytes (CTL) cells and the antibodies with the growth function supposed to be trilinear. The model includes two kinds of treatments. The objective of the first one is to reduce the number of infected cells, while the aim of the second is to block free viruses. Firstly, the positivity and the boundedness of solutions are established. After that, the local stability of the disease free steady state and the infection steady states are characterized. Next, an optimal control problem is posed and investigated. Finally, numerical simulations are performed in order to show the behavior of solutions and the effectiveness of the two incorporated treatments via an efficient optimal control strategy. [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise des Laboratoires is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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.