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Certain innovative technologies applied to medical product development require novel evaluation approaches and/or regulations. Horizon scanning for such technologies will help regulators prepare, allowing earlier access to the product for patients and an improved benefit/risk ratio. This study investigates whether citation network analysis and text mining of scientific papers could be a tool for horizon scanning in the field of immunology, which has developed over a long period, and attempts to grasp the latest research trends. As the result of the analysis, the academic landscape of the immunology field was identified by classifying 90,450 papers (obtained from PubMED) containing the keyword "immune* and t lymph*" into 38 clusters. The clustering was indicative of the research landscape of the immunology field. To confirm this, immune checkpoint inhibitors were used as a retrospective test topic of therapeutics with new mechanisms of action. Retrospective clustering around immune checkpoint inhibitors was found, supporting this approach. The analysis of the research trends over the last 3 to 5 years in this field revealed several candidate topics, including ARID1A gene mutation, CD300e, and tissue resident memory T cells, which shows notable progress and should be monitored for future possible product development. Our results have demonstrated the possibility that citation network analysis and text mining of scientific papers can be a useful objective tool for horizon scanning of life science fields such as immunology. [ABSTRACT FROM AUTHOR]

Leukaemia is diagnosed conventionally by observing the peripheral blood and bone marrow smear using a microscope and with the help of advanced laboratory tests. Image processing-based methods, which are simple, fast, and cheap, can be used to detect and classify leukemic cells by processing and analysing images of microscopic smear. The proposed study aims to classify Acute Lymphoblastic Leukaemia (ALL) by Deep Learning (DL) based techniques. The study used Deep Convolutional Neural Networks (DNN s) to classify ALL according to WHO classification scheme without using any image segmentation and feature extraction that involves intense computations. Images from an online image bank of American Society of Haematology (ASH) were used for the classification. A classification accuracy of 94.12% is achieved by the study in isolating the B-cell and T-cell ALL images using a pretrained CNN AlexNet as well as LeukNet , a custom-made deep learning network designed by the proposed work. The study also compared the classification performances using three different training algorithms. The paper detailed the use of DNNs to classify ALL, without using any image segmentation and feature extraction techniques. Classification of ALL into subtypes according to the WHO classification scheme using image processing techniques is not available in literature to the best of the knowledge of the authors. The present study considered the classification of ALL only, and detection of other types of leukemic images can be attempted in future research. • Deep Learning based classification of ALL. • Classification of ALL based on WHO scheme. • ALL is classified into B – cell lymphoblasts and T – cell lymphoblasts. • Use of Convolutional Neural Networks (CNN) for leukaemia classification. • Leukaemia classification without image segmentation and feature extraction. [ABSTRACT FROM AUTHOR]

Copyright of Revista Brasileira de Medicina do Esporte is the property of Redprint Editora Ltda. 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.)

Metastasis is the leading cause of death in cancer patients. Eliciting anti-tumor immune responses against lung metastasis is hindered by the immunosuppressive microenvironment. This study explored a biomimetic nanoformulation, comprising a nanovaccine (OP) that delivers tumor antigens and adjuvants spatially and temporally in a virus-like manner, and a pulmonary surfactant-biomimetic liposome with an immunomodulator, JQ1 (PS-JQ1). The findings of this study showed that intratracheal administration of OP+PS-JQ1 activated lung immune cells without concomitant excess inflammation, enhanced tumor antigen cross-presentation, generated a significantly high antigen-specific CD8+ T cell response, and reshaped the immunocellular composition in B16 melanoma tumor-bearing lung. OP+PS-JQ1 nanoformulation exhibited a striking immunotherapeutic efficacy, induced local and systemic tumor suppression, improved survival of mice, initiated immune memory that prevents recurrence of secondary tumors. This stable and nontoxic nanoformulation provides a simple, flexible, and robust strategy for augmenting anti-tumor immunity for metastatic cancer. Egg glue proteins are produced by female insects, which can make the eggs firmly attached to the oviposition sites, not affected by wind and rain. However, genes encoding insect egg glue proteins have not yet been reported, and the molecular mechanism underpinning their adhesion is still unknown. Our study makes a significant contribution to the literature as it identifies the sequence, structure, adhesive property, and mechanism of silkworm egg glue protein. Furthermore, it outlines key insights into the structure-function relationships associated with egg glue proteins. We believe that this paper will be of interest to the readership of your journal as it identifies the first complete sequence of insect egg glue proteins, thereby highlighting their potentials future applications in both the biomedical and technical fields. [Display omitted] [ABSTRACT FROM AUTHOR]

Programmed cell death receptor 1 (PD-1) is a membrance-spanning protein mostly expressed in the T cell, and combines with programmed cell death ligand 1 (PD-L1) in the targeting cell. When binding to the ligand on tumor cells, PD-1 as an immunosuppressive molecule, can inhibit the immune function of T cells, thus tumor immune escape. For example, depletion of peripheral effector T cell and accelerate the transformation of effector T cells into regulator T cells. To solve this problem, PD-1 antibody is used to bind to PD-1 on T cells to inhibit the interaction between PD-1 on the T cells and PD-L1 on the tumor cells so that it can restore the function of T cells to kill tumor cell. PD-1 antibodies, such as Nivolumab and Pembrolizumb, are approved as a first-line treatment for advanced non-small cell lung cell cancer. However, due to the interaction of tumor cells, T cells and cytokines, some patients developed drug resistance which reduces the efficacy of immunotherapy. Hence, how to overcome resistance has become a urgent problem. Cereblon (CRBN), a substrate receptor of the DDB1-cullin-RING E3 ubiquitin ligase complex and the only known molecular receptor of immunoregulatory drugs, has been found to reverse PD-1 antibody resistance by binding to CRBN regulatory agents (CMS), exert T cell immune function by regulating proliferation, activation and metabolism of T cell. In this paper, the mechanism of down-regulation of T cells leading to resistance of PD-1 antibody in lung cancer, the mechanism of CRBN regulating T cells, and research progress of CRBN regulator in the treatment of lung cancer were reviewed. [ABSTRACT FROM AUTHOR]

Copyright of Revista Odonto Ciencia is the property of EDIPUCRS - Editora Universitaria da PUCRS 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.)

In the present paper, a HIV - 1 infection of CD 4 + T-cells with the impact of drug treatment model of arbitrary order have been examined with the aid of Legendre wavelet operational matrix method. The technique employed to convert differential equations of arbitrary order into the linear or nonlinear algebraic equations, which are easy to handle by mathematical software. The comparison among the discussed methods with RK4, homotopy perturbation scheme, homotopy analysis approach, Laplace adomian-decomposition technique and Adam-Bashforth predictor-corrector scheme divulge that the present technique is authentic and valid for other engineering problems. It is noticed that the suggested scheme are more efficient and effective. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Computer Science & Technology (JCS&T) is the property of Journal of Computer Science & Technology 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.)

hronic obstructive pulmonary disease (COPD) and lung cancer are global high incidence and high mortality diseases, which seriously increase the socio-economic burden. Smoke exposure, genetic susceptibility and chronic inflammation are common susceptible factors. At present, abnormal inflammatory immune response plays an important role in the occurrence and development of the two diseases. In the process of immune response, tumor microenvironment (TME) is gradually produced, which is beneficial to angiogenesis and immunosuppression, and finally leads to immune escape of tumor cells, leading to tumor formation. In this paper, the present situation of COPD complicated with lung cancer and the relationship between abnormal immune response, especially Treg/Th17, and its occurrence and development are briefly reviewed. [ABSTRACT FROM AUTHOR]

With the in-depth study of tumor immunity, immunotherapy represented by immune checkpoint inhibitors has made a great breakthrough in solid tumors. Small cell lung cancer (SCLC) accounts for about 15%-20% of all lung cancers, with high malignancy, early metastasis and lack of effective treatment strategy. The appearance of immune checkpoint inhibitors brings new hope for SCLC. Several clinical trials have demonstrated the persistent efficacy and clinical activity of the programmed death receptor/ligand 1 (PD-1/L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the treatment of SCLC. However, its efficacy and safety are not very accurate, and the markers that can effectively predict the efficacy of immunotherapy have not been concluded. In this paper, for further changing the treatment strategy of SCLC clinical practice and providing theoretical basis of research, we reviewed the progress of immune checkpoint inhibitors, related markers in the treatment of SCLC by exploring the value, problems and challenges of immunotherapy in SCLC. [ABSTRACT FROM AUTHOR]

Anaplasma Marginale, a rickettsial gram-negative bacterium, is responsible for causing bovine anaplasmosis which has widely spread among the different parts of the world causing death among cattle. It is mainly spread through the transmission of infected ticks. The manifestation of infected ticks could be controlled to a limited extent. However, subsequently, it is very much necessary for the cattle to develop strong immunity against A. marginale. It could be possible if a subunit vaccine is created against the rickettsial bacteria and introduced into the blood of the cattle for trials. In this paper, we have conducted a study to develop a multi-epitope subunit vaccine against A.marginale by using reverse vaccinology process. Five highly immunogenic outer membrane proteins of A. marginale were selected such as MSP1a, MSP2, Vir B10, OMP1 and OMP11. These proteins bind to the MHC class I molecules of the epithelial cells of mammals and MHC class II molecules of the antigen-presenting cells such as B-cells. The MHC class I molecules present antigens to the cytotoxic t-lymphocytes whereas the MHC class II molecules present antigens to the helper t-lymphocytes thus, initiating a strong immune response among the bovine species. We constructed three vaccine sequences from which two vaccine constructs V2 and V3, were found to be stable with high solubility and negative allergenicity. We also performed molecular docking of the two refined vaccine constructs with Rp-105 (30% resemblance in sequence to TLR4) and TLR-9. The vaccines interacted with the receptors with high binding energy. The best-designed vaccine construct was then reverse transcribed and adapted for the host E.coli K12 strain. The reverse transcribed sequence was later inserted into the pET28a (+) vector for the cloning and expression of the vaccine. The study could be a better initiative for in vitro and in vivo practice in developing an effective vaccine against A. marginale. • The five Outer surface proteins- MSP1a, MSP2, Vir B10, OMP1, and OMP11 were the most antigenic. • The proposed epitopes displayed high antigenic scores, high conservancy and non allergenicity. • Both the modeled vaccine V2 and V3 interacted with the bovine receptors rp-105 (TLR4) and TLR9 with high binding energy. • The designed construct, V3 was adapted for E. coli (K12) for cloning and expression. • Sequence of vaccine constructs showed no similarity with human proteins. [ABSTRACT FROM AUTHOR]

Copyright of Avian Diseases is the property of American Association of Avian Pathologists, Inc. 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.)

New therapies for systemic lupus erythematosus are rare. This is because of the complexity of the disease and its varied presentations. There are many variables and a variety of measurement scales that must be satisfied before a new agent is approved for use in humans. Attempts are ongoing to develop biological treatments for the disease using three approaches: B cell modulation, T cell regulation and cytokine inhibition. This paper reviews the current state of these three critical areas. [ABSTRACT FROM AUTHOR]

This paper presents the METINUS Plus (METhod of Immunohistochemical NUclei Segmentation Plus) method that has been developed for localization and quantification of the regulatory T cells’ nuclei. The proposed methodology performs color separation followed by the extraction and validation of objects. Objects categorized as clusters, based on the area and shape, are divided with locally applied watershed supported by color deconvolution. Objects are validated based on RGB, Lab color space, and color deconvolution data. The chosen validation criteria allow quantification and differentiation between the subpopulations of regulatory T cells and breast cancer cells, which express FOXP3. The evaluation is based on the quantity and quality of nuclei segmentation in comparison with the results of the manual counting, done by four pathologists on a set of 20 images. The results were analyzed in comparison with human evaluation using Kendall's tau-b correlation coefficient and the Wilcoxon signed-rank test. The main achievement of this study is a possibility to find criteria that allow differentiation between two types of immunopositive cells’ nuclei: regulatory T cells with homogeneous stained nuclei and all cells with FOXP3 expression; in both tumor and axillary node biopsies. A major advantage of computer image processing is the reproducibility of achieved results, thus minimizing human intervention, and providing traceable clinical information. [ABSTRACT FROM AUTHOR]

• Oral submucous fibrosis (OSMF) is a fibrotic disease associated with myofibroblasts driven fibrosis. • Fibroblast activating factor (FAP) is expressed on such activated myofibroblasts. • Adoptive transfer of T cells that express a chimeric antigen receptor against FAP is proposed as a targeted immunotherapy for OSMF. • This therapy will reduce the fibrosis and down-regulate the myofibroblasts associated with malignant transformation events. Despite several advancements in understanding the pathogenesis of oral submucous fibrosis (OSMF), there is no definitive therapy for the complete remission of the disease process. This is attributed to the fact that any chronic fibrotic disease targeting myofibroblasts, the primary cells responsible for fibrosis is challenging. The betel quid-associated chemicals, predominantly, arecoline and arecaidine, advance the activation of resident fibroblasts to myofibroblasts in OSMF, resulting in uncontrolled and excessive production of collagen. The myofibroblasts, which are associated with the malignant transformation express fibroblast-activating protein (FAP) on their surface that could be selectively targeted for the treatment of OSMF. In the present paper, we propose that the adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein (FAP CAR T cell therapy) results in a significant reduction in fibrosis and restoration of function in OSMF. The detailed procedural aspects of this therapy along with experimental designs are also discussed. Since myofibroblasts are involved in the malignant transformation of OSMF, the selective elimination of these cells will reduce the cancer development and ultimately the cancer burden. [ABSTRACT FROM AUTHOR]

This paper discusses potential avenues to abate the last bulwark to the HIV-1 eradication i.e. viral reservoirs in the body, consisting mainly of viral DNA hidden, in latent form, into long-lived memory CD4 + T-cells, resulting unaffected by either drugs or immune system. Activation of the innate immune system is necessary for the induction of adaptive immune responses against invading pathogens. In part, this is achieved by recognition of molecules associated with infection by a plethora of pattern recognition receptors comprising Toll-like receptors (TLRs) which are express on numerous cells of immune system such as, dendritic cells and B cells, and are activated by some TLR ligands. TLR-9, localized in endosomal compartment, specifically recognizes unmethylated oligonucleotide sequences containing CpG motifs which are particularly abundant in microbial genome, including HIV-1 DNA. Naïve B cells are activated following antigen binding to the B cell receptor (BCR). The complex antigen/BCR, internalises and synergises with TLR leading to hyper activation of B cells and antibodies production. Cross-link of the BCR with TLR9, followed by upregulation of TLR-9, in response to self DNA-containing antigens, on DNA-specific B lymphocytes lead to the development of DNA-specific autoantibodies. This occur in systemic autoimmune disorders, such as, systemic lupus erythematosus (SLE). Although such DNA-specific B lymphocytes, are usually present in B cell repertoire at low frequency, they normally do not produce autoantibodies, they can be activated by antigen BCR ligation, with plasmacytoid dendritic cells (pDCs) providing helper signals. The hypothesis here derives by insight that stimulation of BCR, by exogenously added HIV-1 DNA, on potentially reactive HIV-1 DNA-specific B cells, from HIV-1 and/or HIV-1/SLE patients, co-cultured with autologous viral DNA-stimulated pDCs, could lead to desirable in vitro production of antibodies direct against HIV-1 DNA by involving BCR/TLR9 pathway. These antibodies, suitably delivered into infected or uninfected CD4 + T-cells, by a carrier, such as, peptide transduction domain of Tat, could selectively recognize viral nucleic acid, rich in CpG motifs, respect to host DNA, both in productively than latently infected T cells. Because HIV-1 DNA into latently infected cells is heavily methylated and deacetylated, co-treatment with a small molecule inhibitor of DNA methylation, such as 5-aza-2′-deoxycytidine (aza-Cdr), and histone deacetylase inhibitors (HDACi), they would favor higher accessibility by antibodies to viral DNA, which is harbored into human chromosomes. The in vitro production of anti-HIV-1 DNA antibodies and their in vivo reintroduction, could find future application as interesting strategy to pave the way to an eventual cure to decrease and/or eliminate viral reservoirs from the body, and providing possible therapeutic applications not only for HIV-1/AIDS, but also for other infectious diseases. [ABSTRACT FROM AUTHOR]

Abstract: Distributed and on-demand vaccine production could be game-changing for infectious disease treatment in the developing world by providing new therapeutic opportunities and breaking the refrigeration “cold chain”. Here, we show that a fusion protein between a calcium phosphate binding domain and the model antigen ovalbumin can mineralize a biocompatible adjuvant in a single step. The resulting 50nm calcium phosphate core-immunogen shell particles are comparable to soluble protein in inducing ovalbumin-specific antibody response and class switch recombination in mice. However, single dose vaccination with nanoparticles leads to higher expansion of ovalbumin-specific CD8+ T cells upon challenge with an influenza virus bearing the ovalbumin-derived SIINFEKL peptide, and these cells produce high levels of IFN-γ. Furthermore, mice exhibit a robust antigen-specific CD8+ T cell recall response when challenged with virus 8months post-immunization. These results underscore the promise of immunogen-controlled adjuvant mineralization for just-in-time manufacturing of effective T cell vaccines. From the Clinical Editor: This paper reports that a fusion protein between a calcium phosphate binding domain and the model antigen ovalbumin can mineralize into a biocompatible adjuvant in a single step, enabling distributed and on-demand vaccine production and eliminating the need for refrigeration of vaccines. The findings highlight the possibility of immunogen-controlled adjuvant mineralization for just-in-time manufacturing of effective T cell vaccines. [Copyright &y& Elsevier]

Power consumption is becoming a pressing issue in SRAM cell design. Recent research shows that SRAM power contributes a key part of the whole chip power consumption. In this paper, we present a new 6T-SRAM cell structure for nano-scale technology with stability of low power application by using separate write and read operation. Simulation results with standard 65nm CMOS technology show the correct operation, the speed is closed to the traditional 6T cell, power consumption reduces about 22.45 % during write 0. In particular, this structure maintains its data with leakage current and positive feedback in idle mode which can greatly improve the power consumption of the nano-scale SRAM. [ABSTRACT FROM AUTHOR]

Abstract: Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) have long been regarded as primarily T helper cell type 1-mediated diseases. However, recent evidence suggests that TH17 cells, a mostly unexplored subset of T helper cells, may be even more pathogenic than TH1 cells. In the EAE model, this cell type is crucial for the recruitment of leukocytes into the CNS and for triggering parenchymal inflammation. In humans, TH17 cells are found in acutely active and on the borders of chronically active lesions. Overall, CD4+ T cells only recognize antigens presented on MHC class II complexes, and these are seldom found in the CNS. MHC class I, in contrast, can be induced on neurons and myelin. This also makes CD8+ T cells promising candidates as effector cell types. Indeed, CD8+ T cells outnumber CD4+ T cells in the lesions of MS patients, and can induce axonal pathology. New data on B cells have likewise stimulated unconventional paths of reasoning about the disease. B cells can contribute to the pathogenesis by secreting autoantibodies and presenting antigens to T cells. By the formation of ectopic B cell aggregates in the CNS, B cell differentiation and response can take place remote from the periphery, thus autonomously fueling pathology. In addition, cells of the innate immune system including macrophages, dendritic cells and mast cells are present in the inflamed CNS. On the one hand, these cells can recognize pathogen-associated molecular patterns via Toll-like receptors (TLRs), generating proinflammatory signals that trigger adaptive immune responses. On the other hand, these cells support the autoimmune process by the secretion of effector molecules such as nitric oxide (NO). Apart from a solely pathogenic autoimmune role, regulatory T cells, NK cells and NKT cells can suppress autoreactive cells. In this paper, we review data on how a complex network of immune mechanisms is involved in the pathogenesis of MS and EAE. We also critically reevaluate the traditional CD4/TH1 paradigm. [Copyright &y& Elsevier]

Copyright of Pediatric Endocrinology, Diabetes & Metabolism is the property of Termedia Publishing House 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.)

Summary: There are many documented associations of the HLA B27-related diseases – the seronegative arthropathies (SNAs) and acute anterior uveitis (AAU). However, to date no single pathogenic mechanism has been proposed which can account for more than a few of these associations. The hypothesis presented in this paper is that individual inflammatory episodes in the SNAs and HLA B27 AAU are initiated locally within the inflamed site, in response to tiny quantities of innately recognised molecules – pathogen associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs). However, clinically significant responses to such small amounts of PAMPs/DAMPs only occur in those individuals who possess pre-existing tissue-specific autoreactive effector memory T-cells, which once recruited into the tissue where their autoantigen resides, can mediate inflammatory damage. The mechanism put forward here could explain much of the research evidence and distinguishing clinical features of the HLA B27-associated diseases. These include: the well documented involvement of micro-organisms and tissue damage in these diseases; the more frequent involvement of certain organs compared with others; the often local and asymmetrical presentation of the SNAs/AAU, which contrasts with other autoimmune diseases that effect many sites in a more diffuse/symmetrical pattern; the fact that these diseases which are thought to be mediated by T-cells, are nonetheless refractory to treatment with T-cell activation blockers. Finally, if correct, the mechanism would define a 5th type of clinical hypersensitivity reaction, one manifested by an excessive reaction to small pro-inflammatory signals, in individuals who possess tissue-specific autoreactive effector memory T-cells. [Copyright &y& Elsevier]

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia 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.)

Copyright of Pediatric Endocrinology, Diabetes & Metabolism is the property of Termedia Publishing House 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.)

Background: Periodontitis is an infection with an episodic pattern of tissue-support destruction. During the generation of a primary CD4+ T helper 1 (Th1) response, interferon-gamma (IFN-γ) acts as a positive regulator by selectively inducing Th1 differentiation through increased transcription of T-bet. The aims of this work were to determine IFN-γ levels in samples of gingival crevicular fluid (GCF) and to determine IFN-γ and transcription factor T-bet expression in gingival tissue from patients undergoing the progression of chronic periodontitis. Methods: One hundred six patients with moderate or advanced chronic periodontitis were selected. Periodontitis was characterized by at least six sites with probing depth ≥5 mm, clinical attachment loss ≥3 mm, and radiographic bone loss. Periodontitis progression was determined by the tolerance method. GCF was collected using a paper strip, and enzyme-linked immunosorbent assay was performed to determine the total amount of IFN-γ. Gingival biopsies were obtained from patients for real-time reverse transcription-polymerase chain reaction to determine IFN-γ and T-bet expression. Statistical analysis was performed using statistical software. Data were expressed as subject means ± SD. The χ² and Student t tests were used. Results: The total amount and concentration of cytokine IFN-γ were significantly higher in active sites than in inactive sites (99.90 versus 68.90 pg; P= 0.03; 106.62 pg/mg versus 75.64 pg/mg, P= 0.04, respectively). Active sites showed a significantly lower Δ cycle threshold (Ct) of IFN-γ than inactive sites (P= 0.04), whereas the expression of transcription factor T-bet was increased 1.42-fold in active sites compared to inactive sites. Conclusion: The total amount and concentration of cytokine IFN-γ in GCF samples and transcription factor T-bet expression were increased in progressive periodontal lesions in patients with chronic periodontitis. [ABSTRACT FROM AUTHOR]

Summary: This paper presents a hypothetical model of role for iron in the development of venous leg ulcers and multiple sclerosis. Elevated concentrations of iron were found in the skin affected by venous hypertension and also in the areas of brain with multiple sclerosis lesions. Individuals with hemochromatosis gene (HFE) mutations: C282Y and H63D, which result in a less efficient transport of iron by macrophages, are characterized by an increased risk for venous leg ulcer and multiple sclerosis. Multiple sclerosis is a T cell-mediated disease, and T cells probably participate in the development of venous ulcers. This deleterious role of ferric ions could be related to the regulation of T cell proliferation and apoptosis. Under normal conditions excessive accumulation of T cells cannot take place, because nitric oxide and interferon-gamma drive these cells toward apoptosis. However, in tissues with a high concentration of iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INF-γR2 chain of the interferon-gamma receptor, the downregulation of inducible nitric oxide synthase expression in macrophages and the inactivation of the active site of caspases. Yet, it should be emphasized that this hypothesis does not claim for the increased concentration of iron as a direct causal factor for the development of venous ulcerations or multiple sclerosis, but rather, iron is a factor that modulates and exaggerates the autoimmune process. Iron chelators, administered systemically or locally, should potentially exhibit therapeutic and prophylactic activity against venous leg ulcers and multiple sclerosis. [Copyright &y& Elsevier]

Summary: In this paper, it is hypothesized that in chronic wounds the process of homing of bone marrow-derived precursors of keratinocytes is disturbed, and that the interaction between cutaneous T-cell attracting chemokine (CTACK/CCL27) and soluble P-selectin glycoprotein ligand-1 (PSGL-1) can be the cause of this impairment. Several studies have revealed that bone marrow-derived cells (BMDC) trans-differentiate into various cellular lineages, and probably they participate also in healing of wounded skin. Recent studies have demonstrated that BMDC can engraft into the epidermis, and probably they do not engraft into epidermis as keratinocyte stem cells, but rather as transient amplifying cells. So, bone marrow-derived keratinocytes build provisional epidermal layer, and later they are replaced by keratinocytes migrating from surrounding skin. Probably after injury BMDC are recruited by pro-inflammatory cytokines, like granulocyte-macrophage colony stimulating factor. Further homing to the skin is mediated by CTACK/CCL27. This chemokine is exclusively secreted by keratinocytes. In chronic wounds the recruitment of BMDC seems to be impaired. Inhibition of CTACK/CCL27 by as yet not determined factor could be the cause of delayed healing. PSGL-1 appears to be a good candidate for such inhibiting factor. PSGL-1 is expressed by several populations of leukocytes, and can be released from surface of activated neutrophils. It was demonstrated that soluble PSGL-1 binds CTACK/CCL27, and inhibits chemotaxis mediated by this chemokine. Because there are many activated neutrophils in the wound, it should be expected that wound exudate contains large amount of soluble PSGL-1. Thus, CTACK/CCL27 in the wound would be inhibited, and homing of bone marrow-derived precursors of keratinocytes would be disturbed. If this interaction were found to be the main cause of wound chronicity, above-mentioned molecules could be the potential targets for pharmaceutical agents. [Copyright &y& Elsevier]

A defining characteristic of persistent viral infections is the loss and functional inactivation of antiviral effector T cells, which prevents viral clearance. Interleukin-10 (IL-10) suppresses cellular immune responses by modulating the function oft cells and antigen-presenting cells. In this paper, we report that IL-10 production is drastically increased in mice persistently infected with lymphocytic choriomeningitis virus. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in rapid resolution of the persistent infection. IL-10 secretion was diminished and interferon γ production by antiviral CD8+ T cells was enhanced. In persistently infected mice, CD8α+ dendritic cell (DC) numbers declined early after infection, whereas CD8α- DC numbers were not affected. CD8α- DCs supported IL-10 production and subsequent dampening of antiviral T cell responses Therapeutic IL-10R blockade broke the cycle of IL-10-mediated immune suppression, preventing IL-10 priming by CD8α- DCs and enhancing antiviral responses and thereby resolving infection without causing immunopathology. [ABSTRACT FROM AUTHOR]

T cells recognize protein antigens as short peptides processed and displayed by antigen-presenting cells. However, the mechanism of peptide selection is incompletely understood, and, consequently, the differences in the immunogenicity of protein antigens remain largely unpredictable and difficult to manipulate. In this paper we show that the susceptibility of protein antigens to lysosomal proteolysis plays an important role in determining immunogenicity in vivo. We compared the immunogenicity of proteins with the same sequence (same T cell epitopes) and structure (same B cell epitopes) but with different susceptibilities to lysosomal proteolysis. After immunizing mice with each of the proteins adsorbed onto aluminum hydroxide as adjuvant, we measured serum IgG responses as a physiological measure of the antigen's ability to be presented on major histocompatibility complex class II molecules and to prime CD4+ T cells in vivo. For two unrelated model antigens (RNase and horseradish peroxidase), we found that only the less digestible forms were immunogenie, inducing far more efficient T cell priming and antibody responses. These findings suggest that stability to lysosomal proteolysis may be an important factor in determining immunogenicity, with potential implications for vaccine design. [ABSTRACT FROM AUTHOR]

CD4+ T cells are classically thought to orchestrate adaptive immune responses. But recent studies demonstrate that they can also kill infected cells directly. A new paper shows that highly efficient processing of Epstein Barr virus (EBV) glycoproteins for presentation on MHC class II makes virus-transformed B cells susceptible to lysis by CD4+ T cells. Thus, antiviral vaccines should aim to stimulate both helper and cytolytic CO4+ T cells. [ABSTRACT FROM AUTHOR]

This paper briefly reviews what human γδ T lymphocytes are and what they can do in anticancer and anti-infectious immunity. Both phosphoantigens, a new class of immunostimulatory leads, and some anticancer aminobisphosphonates selectively activate these lymphocytes. So, new molecules under development and endowed with diverse additional bioactivities are promising new leads for the design of highly innovative anticancer immunotherapies. [Copyright &y& Elsevier]

Background: Neopterin, a marker of cellular immune activation, is produced by human macrophages after induction by interferon gamma that is secreted by T lymphocytes. Neopterin concentrations in diverse body fluids have been reported to increase in parallel with bacteria in the clinical course of infections. Therefore, determination of neopterin in body fluids was thought to be useful for predicting the prognosis and diagnosis of aggressive forms of periodontal disease, in which the cell-mediated immune response plays an important role in immunopathogenesis. The aim of the present study was to observe the role of neopterin in the pathogenesis of aggressive periodontitis (AgP). Methods: Thirteen individuals who were systemically and periodontally healthy and 16 systemically healthy individuals diagnosed with AgP were recruited for this study. Mixed saliva and urine samples were collected from each subject. Gingival crevicular fluid (GCF) samples were obtained from 6 teeth with ≥5 mm probing depth (PD). After evaluation of GCF amount from paper strips, enzyme-linked immunosorbent assay (ELISA) was employed to determine the amount of neopterin in urine, saliva, and GCF. Results: The amount of neopterin in urine and saliva measured 235.77 ± 405.31 µmol neopterin/mol creatinine and 9.85 ± 7.66 nmol/l, respectively, for the AgP group and 225.45 ± 100.72 µmol neopterin/mol creatinine and 5.25 ± 5.76 nmol/l, respectively, for controls. The present data demonstrate that, while salivary neopterin levels were found to be significantly different between periodontitis and control subjects, there were non-significant differences in urine neopterin levels. The amount and concentration of neopterin in GCF measured was 18 ± 12.75 nmol/l and 3.67 ± 2.40 nmol/ml for the AgP group and 2.51 ± 1.72 nmol/l and 3.88 ± 4.50 nmol/ml for the control group. When total amounts of neopterin are taken into consideration, a significant difference between AgP and controls is shown; however, no significant difference in net concentration of neopterin was found between both groups. Conclusions: This study is the first report to evaluate the involvement of neopterin in AgP and this might be considered of value in understanding periodontal disease mechanisms. [ABSTRACT FROM AUTHOR]

In this paper the authors propose an immune network which considers B cell interactions based on the immune response network of an organism. The authors modeled a network based on an immune mechanism which uses B cell interactions for an immune response network with interactions between B cells and T cells in an organism. They then created an immune network. Finally, the authors describe the validity of pattern recognition using their immune network by performing simulations on the proposed network. © 2001 Scripta Technica, Syst Comp Jpn, 32(10): 31–41, 2001 [ABSTRACT FROM AUTHOR]

Abstract: Cancer recurrence is one of the most important causes of cancer-related deaths. In present, it has been revealed that there exist some factors especially opioids being able to affect the recovery of cancer patients in a long period. As the most commonly used potent analgesics in practice, morphine appears to be of crucial importance in the regulation of neoplastic tissues by modulating immune responses and promoting angiogenesis. Indeed, regulatory T cells have been shown to inhibit the response of the immune system to tumor and thereby to worsen prognoses. Some reliable evidences indicate that morphine acts directly on regulatory T cells through VEGFR 2 and opioid receptors present in, both of which play a vital role in the cancer recurrence. In addition, morphine might have a noticeable effect on regulatory T cells by regulating the function of some other immune cells or cytokines, TGF-β and IL-2 for instance. Thus, this paper speculates that morphine could induce cancer recurrence by disturbing the behavior of the regulatory T cells and provides a logical reasoning. [Copyright &y& Elsevier]

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Quantitative and qualitative aspects of commensal bacteria determine the active and quiescent status of host immunity. In a recent Science paper, identify Clostridium clusters IV and XIVa as indigenous commensal bacteria that induce regulatory T cells for the creation and maintenance of immunological homeostasis. [Copyright &y& Elsevier]