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Time of day affects how well the immune system responds to viral or bacterial infections. While it is well known that the immune system is regulated by the circadian clock, the dynamic origin of time-of-day-dependent immunity remains unclear. In this paper, we studied the circadian control of immune response upon infection of influenza A virus through mathematical modeling. Dynamic simulation analyses revealed that the time-of-day-dependent immunity was rooted in the relative phase between the circadian clock and the pulse of viral infection. The relative phase, which depends on the time the infection occurs, plays a crucial role in the immune response. It can drive the immune system to one of two distinct bistable states, a high inflammatory state with a higher mortality rate or a safe state characterized by low inflammation. The mechanism we found here also explained why the same species infected by different viruses has different time-of-day-dependent immunities. Further, the time-of-day-dependent immunity was found to be abolished when the immune system was regulated by an impaired circadian clock with decreased oscillation amplitude or without oscillations. [ABSTRACT FROM AUTHOR]

In this paper, we study a delayed HIV infection model with nonmonotonic immune response and perform stability and bifurcation analysis. Our results show that the delayed HIV infection system with nonmonotonic immune response has bistability and stable periodic solution appear. We find that both the uninfected and immune-free equilibria are globally asymptotically stable under certain conditions which are not affected by time delay. However, the time delay makes one immune equilibrium always unstable for τ ≥ 0 and also makes another immune equilibrium appear stability switches; meanwhile, the system will exhibit local Hopf bifurcation, global Hopf bifurcation, and saddle-node-Hopf bifurcation. Numerical simulations are carried out to verify our results. [ABSTRACT FROM AUTHOR]

DNA oncoviruses represent an intriguing subject due to their involvement in oncogenesis. These viruses have evolved mechanisms to manipulate the host immune response, facilitating their persistence and actively contributing to carcinogenic processes. This paper describes the complex interactions between DNA oncoviruses and the innate immune system, with a particular emphasis on the cGAS-STING pathway. Exploring these interactions highlights that DNA oncoviruses strategically target and subvert this pathway, exploiting its vulnerabilities for their own survival and proliferation within the host. Understanding these interactions lays the foundation for identifying potential therapeutic interventions. Herein, we sought to contribute to the ongoing efforts in advancing our understanding of the innate immune system in oncoviral pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Sexual dimorphism is observed in the occurrence, course, and severity of human disease. The difference in immune response between males and females can in part be attributed to sexual genotype. However, immunological differences can also be explained by endocrine–immune interactions. Specifically, androgens possess the ability of directly modulating the development and function of immune cells. Although androgens generally contribute to immunosuppressive effects, this is not necessarily always the case. Aim: The aim of the review is to uncover the role of androgens in shaping the innate immune response. Material & Methods: Authors included papers in this review which discussed the impact of androgens on specific innate immune cells. Results: Androgens modulate the innate immune response through various mechanisms. However, there is conflicting evidence in the literature regarding the interplay betwen androgens and the innate immune system. Discussion: Conflicting evidence presented in this review could in part be explained by the limitations present in interpreting results. Conclusion: This review is of great importance for our understanding of occurence and mechanism of human inflammatory disease. [ABSTRACT FROM AUTHOR]

Aptamers are artificial oligonucleotides with excellent molecule-targeting ability. Compared with monoclonal antibodies, aptamers have the advantages of low cost, no batch effect, and negligible immunogenicity, making them promising candidates for cancer immunotherapy. To date, a series of aptamer agonists/antagonists have been discovered and directly used to activate immune response, such as immune checkpoint blockade, immune costimulation, and cytokine regulation. By incorporating both tumor- and immune cell-targeting aptamers, multivalent bispecific aptamers were designed to pursue high tumor affinity and enhanced immune efficacy. More importantly, benefiting from feasible chemical modification and programmability, aptamers can be engineered with diverse nanomaterials (e.g., liposomes, hydrogels) and even living immune cells (e.g., NK cells, T cells). These aptamer-based assemblies exhibit powerful capabilities in targeted cargo delivery, regulation of cell–cell interactions, tumor immunogenicity activation, tumor microenvironment remodeling, etc., holding huge potential in boosting immunotherapeutic efficacy. In this review, we focus on the recent advances in aptamer-based immune drug systems (AptIDCs) and highlight their advantages in cancer immunotherapy. The current challenges and future prospects of this field are also pointed out in this paper. [ABSTRACT FROM AUTHOR]

Immunotherapy is crucial in fighting cancer and achieving successful remission. Many novel strategies have recently developed, but there are still some obstacles to overcome before we can effectively attack the cancer cells and decimate the cancer environment by inducing a cascade of immune responses. To successfully demonstrate antitumor activity, immune cells must be delivered to cancer cells and exposed to the immune system. Such cutting-edge technology necessitates meticulously designed delivery methods with no loss or superior homing onto cancer environments, as well as high therapeutic efficacy and fewer adverse events. In this paper, we discuss recent advances in cancer immunotherapy delivery techniques, as well as their future prospects. [ABSTRACT FROM AUTHOR]

Inflammaging is one of the evolutionarily conserved mechanisms underlying aging and is defined as the long-term consequence of the chronic stimulation of the innate immune system. As macrophages are intimately involved in initiating and regulating the inflammatory process, their dysregulation plays major roles in inflammaging. The paracrine factors, and in particular extracellular vesicles (EVs), released by mesenchymal stromal cells (MSCs) retain immunoregulatory effects on innate and adaptive immune responses. In this paper, we demonstrate that EVs derived from MSCs preconditioned with hypoxia inflammatory cytokines exerted an anti-inflammatory role in the context of inflammaging. In this study, macrophages isolated from aged mice presented elevated pro-inflammatory factor levels already in basal conditions compared to the young counterpart, and this pre-activation status increased when cells were challenged with IFN-γ. EVs were able to attenuate the age-associated inflammation, inducing a decrease in the expression of TNF-α, iNOS, and the NADase CD38. Moreover, we demonstrate that EVs counteracted the mitochondrial dysfunction that affected the macrophages, reducing lipid peroxidation and hindering the age-associated impairment of mitochondrial complex I activity, oxygen consumption, and ATP synthesis. These results indicate that preconditioned MSC-derived EVs might be exploited as new anti-aging therapies in a variety of age-related diseases. [ABSTRACT FROM AUTHOR]

In host-parasite coevolution, the parasite is selected to increase its infectivity while host is selected to resist the parasite infection. It is widely held that parasite-mediated sexual selection can further amplify the selective pressure on the host to overcome parasite infection. In this paper we focus on certain types of parasites, those that can impair the activity of the host immune function to prevent signs of sickness. We show that the effect of sexual selection can actually reduce the selective pressure on the host immune response to adapt to the parasite infection. We design a simple mathematical model for a population of sexually reproducing organism in which individuals are choosy, preferring traits that are correlated negatively with immune system activity. We introduce to this population a parasite that can suppress activation of the host's immune response. Our results show that even though the host immune system is likely to ultimately evolve and adapt to the parasite infection, when sexual selection is part of this process, it can slow down this evolution on the host and give the parasite more time to get established. [ABSTRACT FROM AUTHOR]

Summary: The immune system plays a critical role in protecting the host against infection but is subject to numerous levels of control that are necessary to prevent pathological, tissue-damaging responses. Inappropriate inflammatory immune responses to self-antigens, innocuous commensal microorganisms, or environmental antigens can lead to chronic, debilitating, and degenerative diseases. Regulatory T cells have an essential, non-redundant, and dominant function in preventing pathological immune responses, as shown by the development of systemic fatal autoimmunity in humans and animals with a genetic deficiency in regulatory T cells. In addition to controlling immune responses, there is a growing understanding that regulatory T cells also contribute directly to tissue homeostasis by promoting tissue regeneration and repair. For these reasons, the prospect of enhancing regulatory T-cell numbers and/or function in patients represents an appealing therapeutic opportunity with potential applications in many diseases, including some where the pathological role of the immune system has only recently been recognized. Approaches to enhance regulatory T cells are now starting to be explored in clinical studies in humans. This review series brings together papers highlighting the Treg-enhancing approaches that are most advanced clinically and examples of therapeutic opportunities based on our growing understanding of regulatory T-cell functions. [ABSTRACT FROM AUTHOR]

The anthraquinones (AQs) and derivatives are widely distributed in nature, including plants, fungi, and insects, with effects of anti-inflammation and anti-oxidation, antibacterial and antiviral, anti-osteoporosis, anti-tumor, etc. Inflammation, including acute and chronic, is a comprehensive response to foreign pathogens under a variety of physiological and pathological processes. AQs could attenuate symptoms and tissue damages through anti-inflammatory or immuno-modulatory effects. The review aims to provide a scientific summary of AQs on immune responses under different pathological conditions, such as digestive diseases, respiratory diseases, central nervous system diseases, etc. It is hoped that the present paper will provide ideas for future studies of the immuno-regulatory effect of AQs and the therapeutic potential for drug development and clinical use of AQs and derivatives. [ABSTRACT FROM AUTHOR]

In this paper, we study intra-host viral adaptation by antigenic cooperation - a mechanism of immune escape that serves as an alternative to the standard mechanism of escape by continuous genomic diversification and allows to explain a number of experimental observations associated with the establishment of chronic infections by highly mutable viruses. Within this mechanism, the topology of a cross-immunoreactivity network forces intra-host viral variants to specialize for complementary roles and adapt to the host's immune response as a quasi-social ecosystem. Here we study dynamical changes in immune adaptation caused by evolutionary and epidemiological events. First, we show that the emergence of a viral variant with altered antigenic features may result in a rapid re-arrangement of the viral ecosystem and a change in the roles played by existing viral variants. In particular, it may push the population under immune escape by genomic diversification towards the stable state of adaptation by antigenic cooperation. Next, we study the effect of a viral transmission between two chronically infected hosts, which results in the merging of two intra-host viral populations in the state of stable immune-adapted equilibrium. In this case, we also describe how the newly formed viral population adapts to the host's environment by changing the functions of its members. The results are obtained analytically for minimal cross-immunoreactivity networks and numerically for larger populations. • Antigenic cooperation is a mechanism of immune escape which provides an alternative to immune escape by continuous genomic diversification. • Intra-host viral variants create a network of cross-immunoreactivity, with each variant performing a different role to escape the host immune system. • Emergence of a new viral variant with altered antigenic features may result in a rapid rearrangement of the viral ecosystem and a change in the roles played by existing viral variants. • Emergence of a new viral variant with altered antigenic features may push the viral population into a stable state of immune escape by antigenic cooperation. • Viral transmission between two infected hosts results in the merging of two intra-host viral populations and results in changes in the functions of its members to adapt to the new host environment. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy has the goal of enhancing a patient's intrinsic immune processes in order to mount a successful immune response against tumor cells. Cancer cells actively employ tactics to evade, delay, alter, or attenuate the anti-tumor immune response. Immune checkpoint inhibitors (ICIs) modulate endogenous regulatory immune mechanisms to enhance immune system activation, and have become the mainstay of therapy in many cancer types. This activation occurs broadly and as a result, activation is supraphysiologic and relatively non-specific, which can lead to immune-related adverse events (irAEs), the frequency of which depends on the patient, the cancer type, and the specific ICI antibody. Careful assessment of patients for irAEs through history taking, physical exam, and routine laboratory assessments are key to identifying irAEs at early stages, when they can potentially be managed more easily and before progressing to higher grades or more serious effects. Generally, most patients with low grade irAEs are eligible for re-challenge with ICIs, and the use of corticosteroids to address an irAE is not associated with poorer patient outcomes. This paper reviews immune checkpoint inhibitors (ICIs) including their mechanisms of action, usage, associated irAEs, and their management. [ABSTRACT FROM AUTHOR]

In this paper, a new mathematical model is formulated that describes the interaction between uninfected cells, infected cells, viruses, intracellular viral RNA, Cytotoxic T-lymphocytes (CTLs), and antibodies. Hence, the model contains certain biological relations that are thought to be key factors driving this interaction which allow us to obtain precise logical conclusions. Therefore, it improves our perception, that would otherwise not be possible, to comprehend the pathogenesis, to interpret clinical data, to control treatment, and to suggest new relations. This model can be used to study viral dynamics in patients for a wide range of infectious diseases like HIV, HPV, HBV, HCV, and Covid-19. Though, analysis of a new multiscale HCV model incorporating the immune system response is considered in detail, the analysis and results can be applied for all other viruses. The model utilizes a transformed multiscale model in the form of ordinary differential equations (ODE) and incorporates into it the interaction of the immune system. The role of CTLs and the role of antibody responses are investigated. The positivity of the solutions is proven, the basic reproduction number is obtained, and the equilibrium points are specified. The stability at the equilibrium points is analyzed based on the Lyapunov invariance principle. By using appropriate Lyapunov functions, the uninfected equilibrium point is proven to be globally asymptotically stable when the reproduction number is less than one and unstable otherwise. Global stability of the infected equilibrium points is considered, and it has been found that each equilibrium point has a specific domain of stability. Stability regions could be overlapped and a bistable equilibria could be found, which means the coexistence of two stable equilibrium points. Hence, the solution converges to one of them depending on the initial conditions. [ABSTRACT FROM AUTHOR]

Immunological memory can be regarded as the key aspect of adaptive immunity, i.e. a specific response to first contact with an antigen, which in mammals is determined by the properties of T, B and NK cells. Re-exposure to the same antigen results in a more rapid response of the activated specific cells, which have a unique property that is the immunological memory acquired upon first contact with the antigen. Such a state of immune activity is also to be understood as related to "altered behavior of the immune system" due to genetic alterations, presumably maintained independently of the antigen. It also indicates a possible alternative mechanism of maintaining the immune state at a low level of the immune response, "directed" by an antigen or dependent on an antigen, associated with repeated exposure to the same antigen from time to time, as well as the concept of innate immune memory, associated with epigenetic reprogramming of myeloid cells, i.e. macrophages and NK cells. Studies on Teleostei have provided evidence for the presence of immunological memory determined by T and B cells and a secondary response stronger than the primary response. Research has also demonstrated that in these animals macrophages and NK-like cells (similar to mammalian NK cells) are able to respond when re-exposed to the same antigen. Regardless of previous reports on immunological memory in teleost fish, many reactions and mechanisms related to this ability require further investigation. The very nature of immunological memory and the activity of cells involved in this process, in particular macrophages and NK-like cells, need to be explained. This paper presents problems associated with adaptive and innate immune memory in teleost fish and characteristics of cells associated with this ability. • The presence of adaptive and innate immune memory has been confirmed in fish. • Adaptive immune memory in fish develops with the participation of T and B lymphocytes. • Innate immune memory is related to the properties of macrophages and NK-like cells. • There is a need to further verify the biological basis of this property. [ABSTRACT FROM AUTHOR]

Currently, most classification algorithms may suffer from serious misclassification when faced with unbalanced or new data, for lacking feedback and update capability. Many existing classification methods learn from the continuous learning mechanism in the biological immune system to realize the learning of new data. However, these methods in classifying new data, because of the lack of feedback, lead to a search for a long time, even may deviate from the correct results. Humans can make the immune response proceed to a certain extent as they wish through a variety of intervention techniques. Motivated by this, this paper proposes a continual learning classification method with human-in-the-loop (H-CLCM) based on the artificial immune system. H-CLCM adjusts parameters online corresponding to misidentified data by integrating human experience during the testing phase. This enables it not only to converge to an accurate prediction model at minimal cost but also to have the capability to learn new classes of data without retraining the classifier. Experiments on 10 benchmark datasets demonstrate the performances and advantages of the proposed method. The experimental results show that H-CLCM has superior classification performance than the other approaches under the same data. • H-CLCM uses human intervention to improve its performance in real time. • H-CLCM adjusts cell parameters of error detection or increase the number of cells. • H-CLCM improves performance in identifying new types of data. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a chronic inflammatory disease caused by disorders of lipid metabolism. Abnormal deposition of low-density lipoproteins in the arterial wall stimulates the activation of immune cells, including the adhesion and infiltration of monocytes, the proliferation and differentiation of macrophages and lymphocytes, and the activation of their functions. The complex interplay between immune cells coordinates the balance between pro- and anti-inflammation and plays a key role in the progression of AS. Therefore, targeting immune cell activity may lead to the development of more selective drugs with fewer side effects to treat AS without compromising host defense mechanisms. At present, an increasing number of studies have found that the active ingredients of traditional Chinese medicine (TCM) can regulate the function of immune cells in multiple ways to against AS, showing great potential for the treatment of AS and promising clinical applications. In this paper, we review the mechanisms of immune cell action in AS lesions and the potential targets and/or pathways for immune cell regulation by the active ingredients of TCM to promote the understanding of the immune system interactions of AS and provide a relevant basis for the use of active ingredients of TCM as natural adjuvants for AS immunotherapy. [Display omitted] ● The immune system plays an important role in the progression of atherosclerosis. ● The active ingredients of TCM regulate the state and function of immune cells. ● The active ingredients of TCM can against atherosclerosis through immune pathways. ● TCMs are promising immunotherapy adjuvants for anti-atherosclerosis. [ABSTRACT FROM AUTHOR]