Search

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]

Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis , proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro : P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. When the T cellular response was evaluated, two peptides: P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 +/CD45RO+ T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN−) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis. [ABSTRACT FROM AUTHOR]

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

Created with BioRender.com [Display omitted] Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems. [ABSTRACT FROM AUTHOR]

Malaria is a life-threatening disease caused by infection with Plasmodium parasites. The goal of developing an effective malaria vaccine is yet to be reached despite decades of massive research efforts. CD4+ helper T cells, CD8+ cytotoxic T cells, and γδ T cells are associated with immune responses to both liver-stage and blood-stage Plasmodium infection. The immune responses of T cell-lineages to Plasmodium infection are associated with both protection and immunopathology. Studies with mouse model of malaria contribute to our understanding of host immune response. In this paper, we focus primarily on mouse malaria model with blood-stage Plasmodium berghei infection and review our knowledge of T cell immune responses against Plasmodium infection. Moreover, we also discuss findings of experimental human studies. Uncovering the precise mechanisms of T cell-mediated immunity to Plasmodium infection can be accomplished through further investigations using mouse models of malaria with rodent Plasmodium parasites. Those findings would be invaluable to advance the efforts for development of an effective malaria vaccine. [ABSTRACT FROM AUTHOR]

Endometriosis is a benign, chronic inflammatory disease that presents alterations in immune response that can be detected in eutopic endometrium, peritoneal fluid and peripheral blood of affected women. Regulatory T (T Reg ) cells are a subpopulation of T lymphocytes specialized in immune regulation that seem to participate in the development of endometriosis, by suppressing the immune response and favoring the establishment of lesions. Our aim was to review the scientific literature that evaluates T Reg cell phenotypes in the context of endometriosis. PRISMA statement for systematic reviews was applied, using “regulatory T cells” and “endometriosis” as keywords in the following databases: PubMed, Cochrane, EMBASE and Lilacs. The initial search and abstract review yielded 41 papers relating to the subject. At the end, 12 studies, published between 2009 and 2016, were included. Most studies that analyzed T Reg cells did not characterize these cells with current Bona Fide markers. In peritoneal fluid and endometriotic lesions, there was a higher concentration of T Reg cell phenotype and/or T Reg cell expression markers in patients with endometriosis when compared with controls. However, there is still not a consensus about T Reg cells concentration in eutopic endometrium and peripheral blood between the revised studies. Taken together, this data collection suggests that endometriosis is related to T Reg cells alterations, although further studies are necessary to reach more precise conclusions, especially regarding the percentage of these cells in eutopic endometrium and peripheral blood. This systematic review attempted to provide instructive and up-to-date collection of data that may help better design future studies. [ABSTRACT FROM AUTHOR]

Emerging evidence reveals the controversial role of B cells in antitumor immunity, but the underlying mechanisms have to be explored. Three latest articles published in the issue 521 of Nature in 2015 reconfirmed the puzzling topic and put forward some explanations of how B cells regulate antitumor T-cell responses both positively and negatively. This paper attempts to demonstrate that different B-cell subpopulations have distinct immunological properties and that they are involved in either antitumor responses or immunosuppression. Recent studies supporting the positive and negative roles of B cells in tumor development were summarized comprehensively. Several specific B-cell subpopulations, such as IgG(+), IgA(+), IL-10(+), and regulatory B cells, were described in detail. The mechanisms underlying the controversial B-cell effects were mainly attributed to different B-cell subpopulations, different B-cell-derived cytokines, direct B cell-T cell interaction, different cancer categories, and different malignant stages, and the immunological interaction between B cells and T cells is mediated by dendritic cells. Promising B-cell-based antitumor strategies were proposed and novel B-cell regulators were summarized to present interesting therapeutic targets. Future investigations are needed to make sure that B-cell-based pharmacological strategies benefit cancer immunotherapy substantially. [ABSTRACT FROM AUTHOR]

In this paper, we consider the combined effects of cytotoxic T lymphocyte (CTL) responses on the competition dynamics of two Simian immunodeficiency virus (SIV) strains model. One of strains concerns a relatively slowly replicating and mildly cytopathic virus in the early infection (SIVMneCL8), the other is faster replicating and more cytopathic virus at later stages of the infection (SIVMne170). It is shown that the global dynamics of the ordinary differential equations can be determined by several threshold parameters, and we prove the global stability of the equilibria by rigorous mathematical analysis. To account for a series of infection mechanism leading to viral production, we incorporate time delays in the infection term. Using the methods of constructing suitable Lyapunov functionals and LaSalle’s invariance principle, we obtain the sufficient conditions for the global attractiveness of infection-free equilibrium with both virus strains going extinct, single-infection equilibrium with one of two virus strains out-competing the other one and the two strains coexisting infection equilibrium. We establish that the intracellular delays can destabilize the single-infection equilibrium leading to Hopf bifurcation and periodic oscillations. We show that introduction of immune responses is responsible for the coexistence of two virus strains and the intracellular delays may alter the two-strain competition results. Numerical simulations are presented to illustrate the theoretical conclusions. [ABSTRACT FROM AUTHOR]

Abstract: NK cells are a major group of immune cells responsible for the phenomenon of natural, innate cytotoxicity. One of the better studied receptors of human NK cells are killer cell immunoglobulin-like receptors (KIR) responsible for checking the presence of MHC class I molecules, which serve as their ligands. Although previously treated as specific for NK cells, nowadays these receptors are known to also occur on T cells. Genetics of KIR molecules is very complicated, what create a great variability of haplotypes in various populations world-wide. In addition, some KIR are known to recognize HLA-C (epitopes C1 or C2), HLA-B (Bw4) or HLA-A (A3 and/or A11) molecules. Therefore, this makes a huge diversity of reactions among individuals, depending on the presence or absence of given KIR and their ligands, hence differential susceptibility to several diseases, including various dermatoses. This paper underlines the important role of both KIR genotypes and HLA class I genes with reference to the various skin diseases. [Copyright &y& Elsevier]

Abstract: This paper describes an immune-inspired system based on an alternate theory about the self–nonself distinction theory, which defines the negative selection process as a mechanism of a fuzzy system based on the affinity between antigen and T-cells. This theory may provide a decision making tool which improves the generation of detectors or even define new data monitoring in order to detect an extreme variation of the system behavior, which means anomalies occurrences. Through these algorithms, tests are performed to detect faults of a DC motor. Upon detection of faults, a participatory clustering algorithm is used to classify these faults and tested to obtain the best set of parameters to achieve the most accurate clustering for these tests in the application being discussed in the article. [Copyright &y& Elsevier]

Abstract: In this paper, we study a delayed six-dimensional human immunodeficiency virus (HIV) model with Cytotoxic T Lymphocytes (CTLs) immune response. Our model describes the interaction of HIV with two target cells: CD4+ T cells and macrophages. We derive that the global asymptotic attractivity of the model is completely determined by the basic reproduction number and the immune reproduction number for the viral infection. By constructing Lyapunov functionals, we have shown that the infection-free equilibrium , the immune-free equilibrium and the chronic-infection equilibrium are globally asymptotically attractive when and , respectively. [Copyright &y& Elsevier]

Abstract: Influenza is one of the most common infectious diseases afflicting humans, particularly the elderly. The murine model has been widely employed for investigation of immunity to influenza virus infection. In this paper, we review the recent advances in understanding the diminished CD8 T cell immune response to influenza virus infection in aged mice. Possible mechanisms of impaired CD8 T cell responses with aging are addressed, including: (1) the role of dendritic cells (DCs); (2) the effect of age-associated changes in the T cell repertoire; and (3) the interactions with CD4 T cells, including T regulatory (Treg) cells and CD4 T helper cells. The aged murine model of the CD8 T cell response to influenza virus is helping to elucidate the mechanisms of immunosenescence which can lead to therapeutic improvements in the primary CD8 T cell response to new infections, as well as the development of new strategies for immunization to prevent influenza in the elderly. [Copyright &y& Elsevier]

Two recent papers published in Immunity and Cell Host & Microbe underline the great importance of B cells and of antibodies (Abs) in orchestrating crucial T helper cell type 2 (Th2) protective immune responses to gastrointestinal nematodes. The findings in animal models now raise major questions as to how B cells and Abs carry out these functions in humans. Here we discuss recent technological advances in humanizing animal models at the level of both Abs and their Fc-receptors, that might provide some answers. [Copyright &y& Elsevier]

Abstract: Invading pathogens are controlled by the innate and adaptive arms of the immune system. Adaptive immunity, mediated by B and T lymphocytes, recognises pathogens via high affinity receptors. However, the establishment of a primary adaptive immune response is not rapid enough to eradicate invading microorganisms as it involves cell proliferation, gene activation and protein synthesis. More rapid defence mechanisms are provided by innate immunity, which recognises invading pathogens by germ-line-encoded pattern recognition receptors. Recent evidence shows that this recognition can mainly be attributed to the family of TOLL-like receptors (TLR). Binding of pathogen-associated molecular patterns to TLR induces the production of reactive oxygen and nitrogen intermediates, pro-inflammatory cytokines, and up-regulates expression of co-stimulatory molecules, subsequently initiating the adaptive immunity. In this paper, we will discuss the current knowledge with regards to the TLR, and in particular the bovine family of TLR. In addition, we will show the expression of TLR mRNA in bovine antigen-presenting cell subsets, summarise the discovery and the critical roles of TLR2 in host defence against Mycobacteria, and provide evidence for a mycobacteria species-specific response of bovine macrophages. [Copyright &y& Elsevier]

Abstract: The T-cell antigen-activated signaling pathway is a highly regulated intracellular biochemical system that is crucial for initiating an appropriate adaptive immune response. To improve the understanding of the complex regulatory mechanisms controlling the early events in T-cell signaling, a detailed mathematical model was developed that utilizes ordinary differential equations to describe chemical reactions of the signaling pathway. The model parameter values were constrained by experimental data on the activation of a specific signaling intermediate and indicated an initial rapid cascade of phosphorylation events followed by a comparatively slow signal downregulation. Nonlinear analysis of the model suggested that thresholding and bistability occur as a result of the embedded positive and negative feedback loops within the model. These nonlinear system properties may enhance the T-cell receptor specificity and provide sub-threshold noise filtering with switch-like behavior to ensure proper cell response. Additional analysis using a reduced second-order model led to further understanding of the observed system behavior. Moreover, the interactions between the positive and negative feedback loops enabled the model to exhibit, among a variety of other feasible dynamics, a sustained oscillation that corresponds to a stable limit cycle in the two-dimensional phase plane. Quantitative analysis in this paper has helped identify potential regulatory mechanisms in the early T-cell signaling events. This integrated approach provides a framework to quantify and discover the ensemble of interconnected T-cell antigen-activated signaling pathways from limited experimental data. [Copyright &y& Elsevier]

Protection of influenza virus infection is mainly mediated by neutralizing immunoglobulins that bind to the virus strain-specific haemagglutinin. The IgG antibody is known to contribute mostly to virus neutralization. Age-related decline in immune responsiveness is characterized by a decrease in antibody production and a reduced ability of T lymphocytes. Our primary objective is to enhance IgG antibody production in aged mice. In this paper, we demonstrate that Mao–Bushi–Saishin-To (MBST, Ma-Huang-Fu-Zi-Xin-Tang) activates IgG antibody production and the T cell helper activity concerning IgG antibody production in aged mice. These results indicate that the use of MBST has important benefits to protect against influenza virus infection in elderly people. [Copyright &y& Elsevier]

T-cells provide antigen specific focus to the adaptive immune response. However, the receptors that initiate functional responses are not in themselves specific, as they can recognise many different ligands. In this paper, we propose that the immune system deals with TCR degeneracy by an adaptive process that effects both T-cell activation and T-cell function, and exploits TCR degeneracy to limit pathogenic autoimmune disease. [Copyright &y& Elsevier]

This paper discusses some consequences of the discovery that antigen receptors are degenerate: Immune specificity, in contrast to the tenets of the clonal selection paradigm, must be generated by the immune response down-stream of initial antigen recognition; and specificity is a property of a collective of cells and not of single clones. [Copyright &y& Elsevier]

A major challenge for immunologists has been the development of vaccines designed to emphasize cellular immune responses. One particularly promising approach is the prime–boost strategy, which has been shown to generate high levels of T-cell memory in animal models. Recently, several papers have highlighted the power of prime–boost strategies in eliciting protective cellular immunity to a variety of pathogens and have demonstrated efficacy in humans. Coupled with recent advances in our understanding of the mechanisms underlying the generation, maintenance and recall of T-cell memory, the field is poised to make tremendous progress. This Review discusses the impact of these recent developments on the future of prime–boost vaccine strategies. [Copyright &y& Elsevier]

Immunobiologics provide the hope for safe and effective long-term management of psoriasis, a life-disabling condition. The use of targeted immunotherapies as pathogenic probes has led to scientific discoveries that help uncover new information on the pathogenesis of psoriasis and on the control of cutaneous immunity. The research described in this paper employs targeted immunotherapies as pathogenic probes of T1-mediated immune disorders, using psoriasis as the primary disease model. This approach has wide applicability to other immune-mediated inflammatory isorders. [ABSTRACT FROM AUTHOR]

Immunology in recent years has taken a somewhat surprising turn, expressed by a renewed interest in innate immunity. Especially intriguing is the regulatory role exerted by the innate components on the adaptive response, with Toll receptors and complement components being the most investigated. This function has been firmly established for complement protein CR2 (CD21) as part of the BCR co-receptor CD19/CD21/CD81. New findings are now providing a broader picture of complement and its tuning of the immune response; for example, complement proteins have been implicated in the control of T-cell-mediated responses. We will review some of these data here and summarize new discoveries in areas of research on more traditional topics within the complement literature, such as complement and renal diseases, and the therapeutic use of C1-Inhibitor. We cover papers selected from studies presented at the XIX International Complement Workshop, held in Palermo in September 2002, and published within the past six months. [Copyright &y& Elsevier]

A physiologically structured population model of T cell populations at the end of an immune response is proposed and analysed. The proposed model describes a T cell population with a structured death rate mediated by cytokine receptor surface expression. This provides a structuring that determines the ability of a T cell to compete for survival cytokines. Homogeneous differentiation into memory combined with heterogeneous survival abilities leads to a system of nonlinear first-order integro differential equations. The mathematical model is studied analytically by a perturbation approach which agrees well with numerical integrations. We find that the structured death rate leads to selection of T cells expressing high cytokine receptor levels. Selection in this model is independent of the initial T cell distribution which allows us to define a universal selection curve, a property lost under receptor downregulation (i.e. loss of cytokine receptors from the surface). Furthermore, we examine the effects of a population dependent memory differentiation rate and of cytokine receptor downregulation on selection. A population dependent memory differentiation rate increases selection significantly while putting an upper bound on the number of T cells differentiating into memory. Under receptor downregulation a dramatic change of the memory T cell distribution is induced. We find that there exists a critical ratio of the receptor downregulation rate to the average T cell death rate for which selection becomes maximal. Our analysis reveals that this maximum property is the result of an interplay between single cell dynamics and population dynamics. We propose that the selection studied in this paper plays an important role in the selection of optimal T cells for the memory pool. [Copyright &y& Elsevier]

CD8+ memory T cells are critical for immunity against intracellular pathogens. Epidemiological evidence demonstrates that bystander infection can impact immune responses to co-infection or vaccination. A recent paper in Immunity demonstrates that persistent bystander inflammation can negatively impact CD8+ T cell effector to memory transition and protection from subsequent infection. [ABSTRACT FROM AUTHOR]

Abstract: In the past decade it has been established that regulatory T cells (Tregs) control all immune responses. As the induction and effector mechanisms used by Tregs are being unraveled, it is emerging that a reciprocal population of CD4+ T lymphocytes exists in the immune system that produces inflammatory cytokine IL-17, and coined "Th17 cells". Th17 cells have been implicated in the pathogenesis of many forms of human disease. The development, function, mechanism of action, and homeostasis of Tregs and Th17 cells, and the reciprocal control between Tregs and Th17 cells were presented at the Second International Conference on Regulatory T Cells and Th17 Cells and Clinical Application in Human Diseases in Shanghai on 17–20 July 2010 (China Tregs/Th17 2010). In this Special Issue of International Immunopharmacology, several paper submitted to the conference will highlight the biology of Tregs and Th17 cells, and their clinical application in human disease. [Copyright &y& Elsevier]

Abstract: Regulatory T cells (Tregs) are subsets of T cells that are specifically dedicated to controlling immune responses. It has been established that Tregs play a key role in regulating autoimmune disease, allergy, cancer, infectious disease, and in the induction of transplantation tolerance. The latest progress in the development, function, mechanism of action, and homeostasis of regulatory T cells, and their translation to the clinic were presented at the International Conference on Regulatory T Cells and Clinical Application in Human Diseases in Beijing on 25–27 October 2008 (China Tregs 2008). In this Special Issue of International Immunopharmacology, several papers submitted to the China Tregs 2008 will highlight some of the recent advances in the biology of regulatory T cells and current strategies to translate regulatory T cells into the clinic. [Copyright &y& Elsevier]

Multiple sclerosis (MS) is the most common demyelinating disease which mainly impacts the integrity of central nervous system (CNS). MS etiology is not clearly known but genetic, environmental factors and immune system are the most frequently explored risk factors. Adaptive immune responses have a critical role in MS pathogenesis in which auto-reactive T-cells and autoantibodies are main orchestrators. Immune responses are modulated by inhibitory molecules which regulates adaptive system activation and hemostasis interface. These molecules suppress immune responses through inhibition of cytokine secretion and T cell proliferation and subsequently reducing the inflammation and respective damage. Therefore the critical role of inhibitory molecules in regulating the healthy and safe immune responses make them very attractive target for immunotherapy. In this review paper, the role of inhibitory molecules expressed on the various immune cell types in MS pathogenesis and experimental autoimmune encephalomyelitis (EAE) animal model will be summarized. • VISTA is one of the goals in the therapeutic target for MS treatment. • CTLA-4 polymorphisms do not correlate with MS susceptibility. • Modulating Lag-3 can affect the autoimmune disease as well as MS. • TIM3–galectin-9 pathway associated with auto-reactive T cells. • Modulation of PD1 and PD-L1 pathways holds promise in MS therapeutic potential. [ABSTRACT FROM AUTHOR]

Immune suppression by Treg cells must be overcome to mount robust and effective anti-pathogen immune responses. A new paper in Immunity from Medzhitov and colleagues shows that IL-1-dependent activation of MyD88 promotes the development of Th1 cells by rendering them impervious to Treg cell-mediated inhibition. [ABSTRACT FROM AUTHOR]