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Tuberculosis (TB) is one of humanity's three major infectious diseases. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia due to impaired insulin secretion or impaired insulin function. It has been reported that DM is a primary risk factor for TB disease. Given the increasing public health threat to people's health, more and more studies have focused on diabetes complicated by TB. Hyperglycemia can affect the function of human immune cells, promote primary infections and reactivation of TB, and increase the susceptibility and severity of TB. However, the immunological mechanism behind it is still not clear. By reviewing the related articles on tuberculosis complicated with diabetes published in recent years, this paper expounds on the effect of hyperglycemia on innate immunity and adaptive immunity of patients with TB. This review provides new insights for elucidating the immunological mechanism of TB complicated with DM and lays the foundation for finding potential targets for preventing and treating TB combined with DM. [ABSTRACT FROM AUTHOR]

The investigation of pathological diseases largely relies on laboratory examinations. The ability to identify and characterise cells is an essential process for clinicians to reach an accurate diagnosis and inform appropriate treatments. There is currently a gap between the advancement of scientific knowledge on cellular and molecular pathways and the development of novel techniques capable of detecting subtle cellular changes associated with disease. Biospectroscopy is the use of spectroscopy techniques to investigate biological materials. Within a biological sample, important molecules such as lipids, carbohydrates, nucleic acids, and proteins are held together by chemical bonds; these bonds will vibrate following excitation with infrared light. By measuring the vibrational energy of each molecule present in a biological sample, a unique spectrum, known as the "molecular fingerprint" is generated. As disease-related changes in biological samples will be reflected in the molecular fingerprint, biospectroscopy is a well-placed candidate for the investigation of disease. Biospectroscopy has been gaining wider acceptance and application in the clinical setting over the past decade; however, it has yet to reach diagnostic laboratories and healthcare clinics as a routine platform for clinical assessment. Immunological disorders are complex, often demonstrating interaction across multiple molecular pathways which results in delayed diagnosis. Vibrational spectroscopy is being applied in many fields, and here we present a review of its use in cellular immunology. Potential benefits, including an enhanced definition of molecular processes and the use of spectroscopy in disease diagnosis, monitoring, and treatment response, are discussed. The translation of vibrational spectroscopic techniques into clinical practice offers rapid, noninvasive, and inexpensive methods to obtain information on the molecular composition of biological samples. The potential clinical benefits of biospectroscopy include providing a more prompt and accurate disease diagnosis, thus improving patient care and resulting in better health outcomes. [ABSTRACT FROM AUTHOR]

Cancer stem cells (CSCs) express pluripotent markers and share many features with normal pluripotent stem cells. It is possible that immunity induced by embryonic stem cells (ESCs) and induced pluripotent stem cells- (IPSCs-) based vaccines may selectively target CSCs. In our study, cells expressing the pluripotent marker CD133 in the murine ovarian cancer cell-line ID8 were isolated and identified as CSCs. We investigated the preventive efficacy of ESCs and IPSCs-based vaccines against the development of ovarian cancer in vivo and evaluated the humoral and cellular immunities targeting CSCs in vitro. Our study showed that preimmunization with both mouse-derived embryonic stem cells (mESCs) and mouse-induced pluripotent stem cells (mIPSCs) lysates, combined with an immunostimulatory adjuvant CpG, elicited strong humoral and cellular responses. These responses effectively suppressed the development of CSC-derived tumors. Immune sera collected from mESCs and mIPSCs-vaccinated mice contained antibodies that were capable of selectively targeting CSCs, resulting in the lysis of CSCs in the presence of complement. Cytotoxic T-lymphocytes generated from splenocytes of mESCs and mIPSCs-vaccinated hosts could secrete interferon- (IFN-) γ in response to CSCs and kill CSCs in vitro. These findings indicate that vaccines based on mESCs and mIPSCs can elicit effective antitumor immunities. These immunities are related to the conferring of humoral and cellular responses that directly target CSCs. [ABSTRACT FROM AUTHOR]

Indoleamine 2,3-dioxygenase 1 (IDO1), the L-tryptophan-degrading enzyme, plays a key role in the immunomodulatory effects on several types of immune cells. Originally known for its regulatory function during pregnancy and chronic inflammation in tumorigenesis, the activity of IDO1 seems to modify the inflammatory state of infectious diseases. The pathophysiologic activity of L-tryptophan metabolites, kynurenines, is well recognized. Therefore, an understanding of the regulation of IDO1 and the subsequent biochemical reactions is essential for the design of therapeutic strategies in certain immune diseases. In this paper, current knowledge about the role of IDO1 and its metabolites during various infectious diseases is presented. Particularly, the regulation of type I interferons (IFNs) production via IDO1 in virus infection is discussed. This paper offers insights into new therapeutic strategies in the modulation of viral infection and several immune-related disorders. [ABSTRACT FROM AUTHOR]

Collectins are characterized by a collagen-like sequence and a carbohydrate recognition domain and are members of the vertebrate C-type lectin superfamily. Recently, "novel collectins", different from "classical collectins" consisting of mannan-binding lectin (MBL) and surfactant proteins A and D (SP-A and SP-D), have been found by reverse genetics. These "novel collectins" consist of collectin liver 1 (CL-L1), collectin kidney 1 (CL-K1), and collectin placenta 1 (CL-P1) and are encoded by three separate genes. Experimental findings on human and animal collectins have shown that both novel collectins and classical collectins play an important role in innate immunity. Based on our recent results and those of others, in this paper, we summarize the new biological functions of these novel collectins in embryonic morphogenesis and development. [ABSTRACT FROM AUTHOR]

Treatment options for malignant mesothelioma are limited, and the results with conventional therapies have been rather disappointing to this date. Chemotherapy is the only evidence-based treatment for mesothelioma patients in good clinical condition, with an increase in median survival of only 2 months. Therefore, there is urgent need for a different approach to battle this malignancy. As chronic inflammation precedes mesothelioma, the immune system plays a key role in the initiation of this type of tumour. Also, many immunological cell types can be found within the tumour at different stages of the disease. However, mesothelioma cells can evade the surveillance capacity of the immune system. They build a protective tumour microenvironment to harness themselves against the immune system's attacks, in which they even abuse immune cells to act against the antitumour immune response. In our opinion, modulating the immune system simultaneously with the targeting of mesothelioma tumour cells might prove to be a superior treatment. However, this strategy is challenging since the tumour microenvironment possesses numerous forms of defence strategies. In this paper, we will discuss the interplay between immunological cells that can either inhibit or stimulate tumour growth and the challenges associated with immunotherapy. We will provide possible strategies and discuss opportunities to overcome these problems. [ABSTRACT FROM AUTHOR]

Immune response to Mycobacterium tuberculosis, the causal agent of tuberculosis, is critical for protection. For many decades, consistent to classical biochemistry, most studies regarding immunity to the tubercle bacilli focused mainly on protein structures. But the atypical, highly impermeable and waxy coat of mycobacteria captured the interest of structural biologists very early, allowing the description of amazing molecules, such as previously unknown carbohydrates or fatty acids of astonishing lengths. From their discovery, cell wall components were identified as important structural pillars, but also as molecular motifs able to alter the human immune response. Recently, as new developments have emerged, classical conceptions of mycobacterial immune modulators have been giving place to unexpected discoveries that, at the turn of the last century, completely changed our perception of immunity vis-`a-vis fat compounds. In this paper, current knowledge about chemical and ultrastructural features of mycobacterial cell-wall is overviewed, with an emphasis on the relationships between cell-wall nonpeptide molecules and immune response. Remarks regarding the potential of these molecules for the development of new tools against tuberculosis are finally discussed. [ABSTRACT FROM AUTHOR]

In the last twenty years, the general view of the plasma membrane has changed from a homogeneous arrangement of lipids to a mosaic of microdomains. It is currently thought that islands of highly ordered saturated lipids and cholesterol, which are laterally mobile, exist in the plane of the plasma membrane. Lipid rafts are thought to provide a means to explain the spatial segregation of certain signalling pathways emanating from the cell surface. They seem to provide the necessary microenvironment in order for certain specialised signalling events to take place, such as the innate immune recognition. The innate immune system seems to employ germ-lined encoded receptors, called pattern recognition receptors (PRRs), in order to detect pathogens. One family of such receptors are the Toll-like receptors (TLRs), which are the central "sensing" apparatus of the innate immune system. In recent years, it has become apparent that TLRs are recruited into membrane microdomains in response to ligands. These nanoscale assemblies of sphingolipid, cholesterol, and TLRs stabilize and coalesce, forming signalling platforms, which transduce signals that lead to innate immune activation. In the current paper, we will investigate all past and current literature concerning recruitment of extracellular and intracellular TLRs into lipid rafts and how this membrane organization modulates innate immune responses. [ABSTRACT FROM AUTHOR]

APOBEC proteins appeared in the cellular battle against HIV-1 as part of intrinsic cellular immunity. The antiretroviral activity of some of these proteins is overtaken by the action of HIV-1 Viral Infectivity Factor (Vif) protein. Since the discovery of APOBEC3G (A3G) as an antiviral factor, many advances have been made to understand its mechanism of action in the cell and how Vif acts in order to counteract its activity. The mainstream concept is that Vif overcomes the innate antiviral activity of A3G by direct protein binding and promoting its degradation via the cellular ubiquitin/proteasomal pathway. Vif may also inhibit A3G through mechanisms independent of proteasomal degradation. Binding of Vif to A3G is essential for its degradation since disruption of this interaction is predicted to stimulate intracellular antiviral immunity. In this paper we will discuss the different binding partners between both proteins as one of the major challenges for the development of new antiviral drugs. [ABSTRACT FROM AUTHOR]

Cytokine-induced killer (CIK) cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations. [ABSTRACT FROM AUTHOR]

Neutrophils have a dual affect on epithelial pIgR/SC, the critical receptor for transcellular routing ofmucosal IgA, but mechanisms of pIgR/SC upregulation remain elusive. Requirements of cytokine, redox, and signalling pathways for pIgR/SC production were assessed in human bronchial epithelial (Calu-3) cells cocultured with increasing numbers of blood neutrophils. Increased SC production was observed after incubation for 48 hrs with intermediate neutrophil numbers (1.25 to 2.5 × 106), was favoured by the elastase inhibitor SLPI, and correlated with increased TGF-β production. Exogenous TGF-β stimulated SC production with a maximal effect at 48 hrs and both TGF-β- and neutrophil-driven SC upregulation were dependent on redox balance and p38 MAP-kinase activation. This paper shows that activated neutrophils could upregulate epithelial pIgR/SC production through TGF-β-mediated activation of a redox-sensitive and p38 MAPK-dependent pathway. An imbalance between the two neutrophildriven opposite mechanisms (SC upregulation and SC degradation) could lead to downregulation of pIgR/SC, as observed in severe COPD. [ABSTRACT FROM AUTHOR]

The dysfunction of pancreatic β-cell and the reduction in β-cell mass are the decisive events in the progression of type 2 diabetes. There is increasing evidence that cytokines play important roles in the procedure of β-cell failure. Cytokines, such as IL-1β, IFN-γ, TNF-α, leptin, resistin, adiponectin, and visfatin, have been shown to diversely regulate pancreatic β-cell function. Recently, isletderived cytokine PANcreatic DERived factor (PANDER or FAM3B) has also been demonstrated to be a regulator of islet β-cell function. The change in cytokine profile in islet and plasma is associated with pancreatic β-cell dysfunction and apoptosis. In this paper, we summarize and discuss the recent studies on the effects of certain important cytokines on pancreatic β-cell function. The imbalance in deleterious and protective cytokines plays pivotal roles in the development and progression of pancreatic β-cell dysfunction under insulin-resistant conditions. [ABSTRACT FROM AUTHOR]

Inflammatory processes are known to be involved at least in the early phase of complex regional pain syndrome type 1 (CRPS1). Blister fluid obtained from the involved extremities displayed increased amounts of proinflammatory cytokines IL-6 and TNFα compared with the noninvolved extremities. The aim of this paper is to investigate the involvement of mediators by measurement of several other cytokines using new detection techniques that enable multiple cytokine measurement in small samples. The use of a multiplex-25 bead array cytokine assay and Luminex technology enabled simultaneous measurement of representative (1) proinflammatory cytokines such as GM-CSF, IL-1β, IL-1RA, IL-6, IL-8, and TNF-α; (2) Th1/Th2 distinguishing cytokines IFN-γ, IL-2, IL-2R, IL-4, IL-5, and IL-10; (3) nonspecific acting cytokines IFN-α, IL-7, IL-12p40/p70, IL-13, IL-15, and IL-17; and (4) chemokines eotaxin, IP-10, MCP-1, MIP-1α, MIP-1β, MIG, and RANTES. Although minimal detection levels are significantly higher in the bead array system than those in common ELISA assays, in blister fluid, IL-1RA, IL-6, IL-8, TNF-α, IL-12p40/p70, MCP-1, and MIP-1β were detectable and increased in CRPS1 affected extremities. Levels of IL-6 and TNF-α simultaneously measured by ELISA (Sanquin Compact kit) and by multiplex-25 bead array assay (Biosource) were highly correlated (r = 0.85,P < .001 for IL-6 and r = 0.88, P < .001 for TNF-α). Furthermore, IP-10 and eotaxin were detectable but diminished in CRPS1, whereas detectable amounts of IL-10 were similar in involved and noninvolved extremities. Multiplex bead array assays are useful systems to establish the involvement of cytokines in inflammatory processes by measurements in blister fluids of CRPS1. Ten representative cytokines were detectable. However, detection levels and amounts measured are at least 3 times higher in the multiplex-25 array assay than in the ELISA assays used simultaneously for the measurement of cytokines. [ABSTRACT FROM AUTHOR]

Background. The relationship between H. pylori infection and gastric cancer (GC) has been widely studied, and H. pylori is considered as the main factor. Utilizing bioinformatics analysis, this study examined gene signatures related to progressing H. pylori-associated GC. Materials and Methods. The dataset GSE13195 was chosen to search for abnormally expressed genes in H. pylori-associated GC and normal tissues. The TCGA-STAD database was chosen to verify the expression of key genes in GC and normal tissues. Results. In GSE13195, a total of 332 differential expression genes (DEGs) were screened. The results of weighted gene co-expression network analysis showed that the light cyan, plum2, black, and magenta4 modules were associated with stages (T3, T2, and T4), while the orangered4, salmon2, pink, and navajowhite2 modules were correlated with lymph node metastasis (N3, N2, and N0). Based on the results of DEGs and hub genes, a total of 7 key genes (ADAM28, FCER1G, MRPL14, SOSTDC1, TYROBP, C1QC, and C3) were screened out. These gene mRNA levels were able to distinguish between normal and H. pylori-associated GC tissue using receiver operating characteristic curves. After transcriptional level verification and survival analysis, ADAM28 and C1QC were excluded. An immune infiltration study revealed that key genes were involved in regulating the infiltration levels of cells associated with innate immune response, antigen presentation process, humoral immune response, or Tcell-mediated immune response. In addition, drugs targeting FCER1G and TYROBP have been approved and are under investigation. Conclusion. Our study identified five key genes involved in H. pylori-associated GC tumorigenesis. Patients with higher levels of C3 expression had a poorer prognosis than those with lower levels. In addition, these key genes may serve as biomarkers and therapeutic targets for H. pylori-associated GC diagnosis, targeted therapy, and immunotherapy in the future. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including human herpesviruses, herpes vaccine development, and mucosal immunity.

Objective. Sepsis, showing high mortality, is a lethal dysfunction of organs caused by an infection-induced disorder in the host response. It has complicated pathogenesis, which has not yet been elucidated completely. Recently, the principal factors causing pathogenesis and even death in sepsis patients are imbalance in inflammatory response and immunosuppression occurring when the host is challenged by infection. Previous studies found that Lycium barbarum polysaccharide (LBP) worked well in enhancing immunity. This study aims at exploring the efficacy of pretreatment with LPB in regulating splenic immunity during the pathogenesis of sepsis induced by cecum ligation perforation (CLP) in rats. Methods. This research established the cecum ligation perforation rat model. Using immunohistochemistry and flow cytometry, the effects of Lycium barbarum polysaccharide in various doses in influencing splenic immunity and prognosis of sepsis induced by cecum ligation perforation in rats were examined. Results. This study showed that LBP lowered the 72-hour mortality of sepsis rats induced by CLP, relieved systemic inflammation, improved the ratio of T-cell subgroups positive in CD3+, CD4+, or CD8+ and expression of HLA-DR protein, and repaired damage to splenic tissue, implying its efficacy in enhancing the immunity of sepsis rats induced by CLP. Conclusions. LBP may ameliorate clinical symptoms of rats with cecum ligation perforation, improve cellular immunity in the spleen, and treat sepsis so as to provide a theoretical basis for the pathogenesis and development of sepsis as well as its diagnosis and treatment, and offer scientific proof for the development and utilization of LBP applied to critical diseases. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the extracts of Curcuma mangga Valeton & Zijp rhizomes and Picria fel-terrae Lour. leaves could modulate cellular- and humoral-mediated immunity in macrophages and animal models. In the present study, the immunomodulatory effects of combined ethanol extracts of C. mangga rhizomes and P. fel-terrae leaves were investigated on cellular- and humoral-mediated immunity in Wistar rats and mice. The phytochemical constituents of the ethanol extracts of C. mangga and P. fel-terrae, and combined extracts were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Mice were orally administered with combined extracts of C. mangga and P. fel-terrae (1 : 1) at doses of 25, 50, and 100 mg/kg·bw for 7 days, and the carbon clearance method was used to investigate their phagocytosis activity. Wistar rats were treated orally with the combined extracts 72 h prior to sensitization with Staphylococcus aureus and continued for 14 days. The effect of extracts on delayed-type hypersensitivity (DTH) response was determined by the paw edema method, while the effects on antibody (IgG and IgM) and interleukin-2 (IL-2) production were analyzed using enzyme-linked immunosorbent assay (ELISA). Picfeltarraenin VI and ferruginol were the major components in the extracts of P. fel-terrae and C. mangga, respectively. The combined extracts at 1 : 1 ratio demonstrated a dose-dependent stimulation of both cellular- and humoral-mediated immunity in both animal models. The combined extracts displayed the strongest stimulation on DTH response and phagocytosis activity at 100 mg/kg·bw, which were comparable with those of the positive control, levamisole. IgG and IgM production and IL-2 release were also stimulated after treatment with extracts. The combined extracts of C. mangga and P. fel-terrae possess strong stimulatory activities on cellular- and humoral-mediated immunity and may be developed as a potential nutraceutical for the modulation of immune responses. [ABSTRACT FROM AUTHOR]

Bioactive peptides are naturally found in various foods and were shown to have various distinct physiological as well as medicinal benefits. In this study shrimp peptide hydrolysate (SPH) was prepared to investigate its immunomodulatory effect against cyclophosphamide (CTX) induced immunosuppressed mice. The SPH effect was also analyzed on murine macrophage (RAW264.7 cells). The findings show that SPH stimulates macrophages to form multiple pseudopodia, has no cytotoxic effect, and increases phagocytic activity in RAW264.7 cells. Furthermore, the immunosuppressed in‐vivo model illustrates the improvement in various aspects, that is body weight, escalation in immune organ index, and ameliorates histopathological transformation of thymus along with the spleen. SPH enhances cell‐mediated immunity by facilitating splenocyte proliferation and inhibit excessive apoptosis. Moreover, the significant outcome had been observed with the upregulation of cytokines interferon‐gamma (IFN‐ϒ), interleukin‐2 (IL‐2) level and simultaneously downregulate certain genes include interleukin‐4 (IL‐4) and interleukin‐10 (IL‐10). Additionally, SPH expedites cellular immunity by enhancing the regulation of immunoglobulin A (IgA) and immunoglobulin M (IgM). However, these findings support the hypothesis that SPH is an effective immunomodulatory agent capable of preventing immune system hypofunction. It is necessary to investigate the detailed mechanism to rule out any unforeseen effects of SPH in future research. Practical applications: Chemotherapy medications, despite their dominating detrimental effects of damaging immunological organs such as the spleen and thymus, extend the treatment process as well as the destruction of the self‐immune system. This study found that SPH is an effective immunomodulatory agent capable of avoiding immune organ hypofunction and improving cell mediate immunity by enhancing macrophage activation, phagocytosis, spleenocyte proliferation, suppressing apoptosis, and elevating cytokines and antibodies. As a result, SPH can be utilized as a nutritional and functional dietary supplement to boost immunological modulation in combination with chemotherapy medications in order to lessen their adverse effects. [ABSTRACT FROM AUTHOR]

Identification of epitopes which invokes strong humoral responses is an essential issue in the field of immunology. Various computational methods that have been developed based on the antigen structures and the mimotopes these years narrow the search for experimental validation. These methods can be divided into two categories: antigen structure-based methods and mimotope-based methods. Though new methods of the two kinds have been proposed in these years, they cannot maintain a high degree of satisfaction in various circumstances. In this paper, we proposed a new conformational B-cell epitope prediction method based on antigen preprocessing and mimotopes analysis. The method classifies the antigen surface residues into “epitopes” and “nonepitopes” by six epitope propensity scales, removing the “nonepitopes” and using the preprocessed antigen for epitope prediction based on mimotope sequences. The proposed method gives out the mean F score of 0.42 on the testing dataset. When compared with other publicly available servers by using the testing dataset, the new method yields better performance. The results demonstrate the proposed method is competent for the conformational B-cell epitope prediction. [ABSTRACT FROM AUTHOR]

The phosphatidylinositol 3-kinase signaling pathway plays a central role in regulating the host inflammatory response. The net effect can either be pro- or anti-inflammatory depending on the systemand cellular context studied. This paper focuses on phosphatidylinositol 3-kinase signaling in innate and adaptive immune cells of the intestinal mucosa. The role of phosphatidylinositol 3- kinase signaling in mouse models of inflammatory bowel disease is also discussed. With the development of new isoform specific inhibitors, we are beginning to understand the specific role of this complex pathway, in particular the role of the ɣ isoform in intestinal inflammation. Continued research on this complex pathway will enhance our understanding of its role and provide rationale for the design of new approaches to intervention in chronic inflammatory conditions such as inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Cutaneous homeostasis and defenses are maintained by permanent cross-talk among particular epidermal keratinocytes and immune cells residing or recruited in the skin, through the production of cytokines. If required, a coordinated inflammatory response is triggered, relayed by specific cytokines. Due to numerous reasons, troubles in the resolution of this phenomenon could generate a cytokine-mediated vicious circle, promoting skin chronic inflammation, the most common being atopic dermatitis and psoriasis. In this paper, we discuss the biological effects of cytokine on keratinocytes, more particularly on specific or shared cytokines involved in atopic dermatitis or psoriasis. We report and discuss monolayer or 3D in vitro models of keratinocytes stimulated by specific sets of cytokines to mimic atopic dermatitis or psoriasis. IL-22, TNFa, IL-4, and IL-13 combination is able to mimic an "atopic dermatitis like" state. In psoriasis lesions, over expression of IL-17 is observed whereas IL-4 and IL-13 were not detected; the replacement of IL-4 and IL-13 by IL-17 from this mix is able to mimic in vitro a "psoriasis like" status on keratinocytes. We conclude that specific cytokine environment deregulation plays a central role on skin morphology and innate immunity, moving towards specific pathologies and opening the way to new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Innate immune system is the first line of defence against invading pathogens that is critical for the overall survival of the host. Human liver is characterised by a dual blood supply, with 80% of blood entering through the portal vein carrying nutrients and bacterial endotoxin from the gastrointestinal tract. The liver is thus constantly exposed to antigenic loads. Therefore, pathogenic microorganism must be efficiently eliminated whilst harmless antigens derived from the gastrointestinal tract need to be tolerized in the liver. In order to achieve this, the liver innate immune system is equipped with multiple cellular components; monocytes, macrophages, granulocytes, natural killer cells, and dendritic cells which coordinate to exert tolerogenic environment at the same time detect, respond, and eliminate invading pathogens, infected or transformed self to mount immunity. This paper will discuss the innate immune cells that take part in human liver inflammation, and their roles in both resolution of inflammation and tissue repair. [ABSTRACT FROM AUTHOR]

Introduction. Cyphostemma adenocaule (Steud. ex A. Rich) Descoings ex wild & Drummond (Vitaceae) has been used in traditional medicine for the management of various immunological and hematological disorders in different areas of Ethiopia and the rest of the world. In Ethiopia, the plant is used for the management of enlarged spleen, rabies virus, helminthic infection, snake bite, and various types of tumors. Objective. To evaluate the effect of hydroethanolic root extract and solvent fractions of Cyphostemma adenocaule on cell-mediated immunity (delayed-type hypersensitivity), organ index (spleen and liver), and blood cell count in Swiss albino mice. Materials and Methods. Acute oral toxicity test was conducted using nulliparous and nonpregnant Swiss albino mice following OECD 425 limit test method. Delayed-type hypersensitivity model was used to evaluate the effect on cell-mediated immunity. The experimental animals were divided into twelve groups which were sensitized and challenged with sheep red blood cells on day 0 and day 7, respectively. Levamisole 50 mg/kg was used as stimulant control, whereas cyclophosphamide 30 mg/kg was used as suppressant control. Hydroethanolic root extract (100 mg/kg, 200 mg/kg, and 400 mg/kg), aqueous fraction (100 mg/kg, 200 mg/kg, and 400 mg/kg), and n-butanol fraction (100 mg/kg, 200 mg/kg, and 400 mg/kg) were administered for seven days. The paw volume was measured using a digital plethysmometer before challenge and 24 hours after challenge. Blood was collected, and organs (spleen and liver) were isolated from each challenged mouse to determine blood cell count and organ index, respectively. Results. No mortality and noticeable behavioral changes were observed among all mice receiving hydroethanolic root extract and solvent fractions at a dose of 2000 mg/kg. Hydroethanolic root extract and solvent fractions of Cyphostemma adenocaule showed enhancement of delayed-type hypersensitivity, organ index, and blood cell count. Hydroethanolic root extract at a dose of 400 mg/kg showed the highest and statistically significant stimulation of delayed-type hypersensitivity (0.123 ± 0.010) and blood cell count compared to the vehicle. Conclusion. Hydroethanolic root extract and solvent fractions of Cyphostemma adenocaule showed a stimulatory effect on cell-mediated immunity and hematopoiesis. [ABSTRACT FROM AUTHOR]

Background. COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened every civilian as a global pandemic. The immune system poses the critical interactive chain between the human body and the virus. Here, we make efforts to examine whether comorbidity with type 2 diabetes (T2D) affects the immunological response in COVID-19 patients. Methods. We conducted a retrospective pilot study investigating immunological characteristics of confirmed cases of COVID-19 with or without comorbid T2D. Two subcohorts of sex- and age-matched participants were eligible for data analysis, of which 33 participants were with T2D and the remaining 37 were nondiabetic (NDM). Cellular immunity was assessed by flow cytometric determination of surface markers including CD3, CD4, CD8, CD19, CD16, and CD56 in peripheral blood. Levels of C reactive protein, immunoglobulin (IgG, IgM, IgA, and IgE), and complements (C3, C4) were detected by rate nephelometry immunoassay. And Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were detected by Cytometric Bead Array. Results. Neutrophil counts were found to be significantly higher in the T2D group than in the NDM group and had a significant relevance with clinical severity. Lymphocyte frequencies showed no significant differences in the two groups. However, the proportions and absolute counts of T, Tc, Th, and NK cells decreased in both groups to different degrees. An abnormal increase in neutrophil count and a decrease in lymphocyte subpopulations may represent risk factors of COVID-19 severity. The level of IgG, IgM, IgA, C3, and C4 showed no significant difference between the two groups, while the IgE levels were higher in the T2D group than in the NDM group (p < 0.05). Th1 cytokines including IFN-γ, TNF-α, and IL-6, as well as CRP, appeared significantly higher in the T2D group. Conclusions. The COVID-19 patients comorbid with T2D demonstrated distinguishable immunological parameters, which represented clinical relevancies with the predisposed disease severity in T2D. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-γ, TNF-α, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with soluble Leishmania antigen, we observed an early, robust, and incremental increase of IFN-γ, TNF-α, and IP-10 levels in all patients during treatment. Moreover, based on the IFN-γ levels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two main Leishmania species. The levels of IFN-γ, IP-10, or TNF-α also seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN-γ and IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases. [ABSTRACT FROM AUTHOR]

The epidemiological situation in Tajikistan Republic deteriorated in the 1990s, when an influx of refugees from Afghanistan resulted in mass importation of Plasmodium vivax and Plasmodium falciparum malaria to Khatlon region. The National Programme of Malaria Control was successful and malaria transmission was interrupted in 2009. Background. The aim of this study was to investigate the mechanisms of immunological response in Tajik children with tropical Plasmodium falciparum malaria. Materials and Methods. We examined 124 patients with P. falciparum malaria at the age of 6 months up to 14 years that were hospitalized in Clinical Infectious Diseases Hospital in Dushanbe city and in Regional hospital of Khatlon region in the period 2000-2007. In most cases, they were school-age children (56%). The peak incidence was recorded in July-October. Verification of the diagnosis was based on clinical, epidemiological data, and the results of blood microscopy. In all patients, along with the standard, clinical, and laboratory tests, a number of indicators of the immune status were performed that include the T-immunity, the content of serum immunoglobulins of three main classes, the level of circulating immune complexes (CIC), C3 complement, and the concentration of key serum cytokines that have been studied in the dynamics of infectious process. Finding. The study of cellular and humoral immunity in patients with Plasmodium falciparum malaria is an obvious additional criterion in assessing the severity of infection. The imbalance of cytokine profile is an important pathogenic factor in the development of severe and recurrent forms of the disease, since the formation of a defective immune response to parasitic antigens contributes to adverse outcomes. Conclusions. Plasmodium falciparum malaria was characterized by depression of cellular and humoral immunity, the degree of which depended on the severity of the pathological process. [ABSTRACT FROM AUTHOR]

Follicular helper T cells (Tfh cells) are closely related to the occurrence and development of antibody-mediated rejection (AMR) after renal transplantation. Exosomes play a key role in the rejection after organ transplantation. However, whether Tfh-derived exosomes are involved in AMR has not been reported. We collected peripheral blood from 42 kidney transplant patients and found no significant differences in CD4+CXCR5+ and CD4+CXCR5+CXCR3+CCR6-exosomes between AMR and non-AMR groups, whereas the proportion of CD4+CXCR5+CXCR3-exosomes was significantly higher in AMR group than that in non-AMR group; CTLA-4 expression of CD4+CXCR5+exosomes was significantly lower in AMR group than that in non-AMR group. HLA-G expression was not significantly different between two groups. We further separated CD4+CXCR5+cells from patients by magnetic beads. Coculture experiments showed that Tfh cell-derived exosomes in AMR patients significantly promoted B cell proliferation and differentiation, compared with non-AMR group, the percentage of B cells and plasma cells increased by 87.52% and 110.2%, respectively. In conclusion, our study found that Tfh cell-derived exosomes could promote the proliferation and differentiation of B cells and they may play an important role in the development of AMR after renal transplantation. [ABSTRACT FROM AUTHOR]

The inflammatory response to chronic injury affects tissue regeneration and has become an important factor influencing the prognosis of patients. In previous stem cell treatments, it was revealed that stem cells not only have the ability for direct differentiation or regeneration in chronic tissue damage but also have a regulatory effect on the immune microenvironment. Stem cells can regulate the immune microenvironment during tissue repair and provide a good "soil" for tissue regeneration. In the current study, the regulation of immune cells by mesenchymal stem cells (MSCs) in the local tissue microenvironment and the tissue damage repair mechanisms are revealed. The application of the concepts of "seed" and "soil" has opened up new research avenues for regenerative medicine. Tissue engineering (TE) technology has been used in multiple tissues and organs using its biomimetic and cellular cell abilities, and scaffolds are now seen as an important part of building seed cell microenvironments. The effect of tissue engineering techniques on stem cell immune regulation is related to the shape and structure of the scaffold, the preinflammatory microenvironment constructed by the implanted scaffold, and the material selection of the scaffold. In the application of scaffold, stem cell technology has important applications in cartilage, bone, heart, and liver and other research fields. In this review, we separately explore the mechanism of MSCs in different tissue and organs through immunoregulation for tissue regeneration and MSC combined with 3D scaffolds to promote MSC immunoregulation to repair damaged tissues. [ABSTRACT FROM AUTHOR]

PYR-41 and thalidomide have therapeutic effects on inflammation-associated diseases with side effects such as tumorigenesis. Cross-presentation allows dendritic cells (DC) to present endogenous antigen and induce protective immunity against microbe infection and tumors. But, up to now, the effects of PYR-41 and thalidomide on cross-presentation are still uncertain. In this study, we investigated the effect and mechanism of PYR-41 and thalidomide on DC cross-presentation by observing Myddosome formation, endosomal recruitment of p97 and Sec61, NF-κB activation, and cross-priming ability. We demonstrated that the inhibition of endosomal recruitment of p97 and Sec61, together with attenuated NF-κB activation and Myddosome formation, contributes to PYR-41- and thalidomide-impaired cross-presentation and thereby reverses cross-activation of T cells. These observations suggest that NF-κB signaling and p97 and Sec61 molecules are candidates for dealing with the side effects of PYR-41 and thalidomide. [ABSTRACT FROM AUTHOR]

The mechanism of pain reduction involves bidirectional processes of pain blocking (nociception) and reductions in the levels of proinflammatory cytokines in the blood. Does transcutaneous electrical nerve stimulation (TENS) reduce blood levels of proinflammatory cytokines? For this systematic review, we searched in six databases to identify randomized controlled trials with the criteria: humans older than 18 years (adults), use of TENS in the experimental group, and having at least one pre- and postintervention blood level of at least one proinflammatory cytokine. The risk of bias and the level of evidence were assessed. Five studies were included involving 240 participants. The heterogeneity of the studies was high (I2: 85%); therefore, we used a random-effects meta-analysis. It was observed through the meta-analysis synthesis measures that there were statistically significant differences following the use of TENS to reduce the general group of cytokines. When grouped by chronic disease, by postoperative settings, or by individual studies in the case of IL-6, it was observed that the significant reduction of cytokines related to the use of TENS was maintained. The use of TENS reduced the blood levels of proinflammatory cytokines (we observed a protective factor of TENS in relation to inflammation). The protocol of the systematic review was registered in PROSPERO, CRD42017060379. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD), a long-lasting cognitive decline after surgery, is currently a major clinical problem with no clear pathophysiological mechanism or effective therapy. Accumulating evidence suggests that neuroinflammation plays a critical role in POCD. After surgery, alarmins are leaked from the injury sites and proinflammatory cytokines are increased in the peripheral circulation. Neurons in the hippocampus, which is responsible for learning and memory, can be damaged by cytokines transmitted to the brain parenchyma. Microglia, bone marrow-derived macrophages, mast cells, and T cells in the central nervous system (CNS) can be activated to secrete more cytokines, further aggravating neuroinflammation after surgery. Conversely, blocking the inflammation network between these immune cells and related cytokines alleviates POCD in experimental animals. Thus, a deeper understanding of the roles of immune cells and the crosstalk between them in POCD may uncover promising therapeutic targets for POCD treatment and prevention. Here, we reviewed several major immune cells and discussed their functional roles in POCD. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC) immunotherapy has been effective for prevention of type 1 diabetes (T1D) in NOD mice but fails to protect if initiated after active autoimmunity. As autoreactivity expands inter- and intramolecularly during disease progression, we investigated whether DCs unpulsed or pulsed with β cell antigenic dominant determinants (DD), subdominant determinants (SD), and ignored determinants (ID) could prevent T1D in mice with advanced insulitis. We found that diabetes was significantly delayed by DC therapy. Of interest, DCs pulsed with SD or ID appeared to provide better protection. T lymphocytes from DC-treated mice acquired spontaneous proliferating capability during in vitro culture, which could be largely eliminated by IL-2 neutralizing antibodies. This trend maintained even 29 weeks after discontinuing DC therapy and appeared antigen-independent. Furthermore, CD4+Foxp3+ T regulatory cells (Tregs) from DC-treated mice proliferated more actively in vitro compared to the controls, and Tregs from DC-treated mice showed significantly enhanced immunosuppressive activities in contrast to those from the controls. Our study demonstrates that DC therapy leads to long-lasting immunomodulatory effects in an antigen-dependent and antigen-independent manner and provides evidence for peptide-based intervention during a clinically relevant window to guide DC-based immunotherapy for autoimmune diabetes. [ABSTRACT FROM AUTHOR]

Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials. However, as these humoral immune barriers to cross-species transplantation are overcome with advanced transgenics, cellular immunity to these novel xenografts remains an outstanding issue. Therefore, understanding and optimizing immunomodulation will be paramount for successful clinical xenotransplantation. Costimulation blockade agents have been introduced in xenotransplantation research in 2000 with anti-CD154mAb. Most recently, prolonged survival has been achieved in solid organ (kidney xenograft survival > 400 days with anti-CD154mAb, heart xenograft survival > 900 days, and liver xenograft survival 29 days with anti-CD40mAb) and islet xenotransplantation (>600 days with anti-CD154mAb) with the use of these potent experimental agents. As the development of novel genetic modifications and costimulation blocking agents converges, we review their impact thus far on preclinical xenotransplantation and the potential for future application. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) continues to confound transplant surgeons and physicians. There are no effective methods to predict the patients at risk for recurrence so far although many studies have sought meaningful biomarkers. The ImmuKnow (IMK) assay is an immune cell function assay that detects cell-mediated immunity in an immunosuppressed population, mainly measuring peripheral blood CD4(+) adenosine triphosphate (ATP) release. The aim of this study was to assess the relationship between cellular immune function measured by the ImmuKnow assay and HCC recurrence post-OLT.Methods: A total of 76 HCC cases underwent Donation after Cardiac Death (DCD) liver transplant, which confirmed hepatocellular carcinoma by histology postoperatively. The ImmuKnow assay was prospectively performed in these cases at a range of 6-36 months post-OLT. Every test was repeated 1 week later, obtaining the average value for every patient. In addition, every case had liver imaging findings at approximately the exam time.Results: Fifteen cases with liver imaging findings showed HCC recurrence (19.7%) post-OLT, and the average ImmuKnow assay in these patients was 190 ± 48 ng/ml, which was less (p < 0.05) than in patients without HCC recurrence, whose average ATP level was 313 ± 90 ng/ml. ATP levels post-OLT were found to be significantly associated with the risk of tumour recurrence. The ratio of T reg cells and the levels of TGFβ and IL-10 were higher in recurrence patients than in recurrence-free patients.Conclusion: Greater suppression of cellular immunity, as measured by the ImmuKnow assay, was associated with progression of HCC recurrence post-OLT. ImmuKnow assay was helpful in determining the risk of early recurrence of HCC postliver transplant. A pathway consisting of T reg cells, TGFβ and IL-10 might be the HCC recurrence-predominant pathway. [ABSTRACT FROM AUTHOR]

The infection of both captive and free-ranging wildlife species with pathogenic mycobacteria (including Mycobacterium tuberculosis) poses a zoonotic risk and continues to cause challenges for the livestock industry, zoos and governments around the world. Central to the management and control of tuberculosis is timely and accurate diagnosis. In many cases, bacterial culture is insufficiently sensitive and confirmation of TB post-mortem is neither feasible nor desirable. In this context, there is still considerable research interest in, and need for, immunological methods for diagnosis. Reviews on this topic were published in 2005 and 2009, but since then veterinarians and other researchers have continued to evaluate immunodiagnostic approaches to TB. These include serological tests such as lateral-flow devices, and enzyme-linked immunosorbent assay ( ELISA) and those based on evaluation of cell-mediated immunity, such as the tuberculin skin test and interferon-gamma release assay ( IGRA). Since 2009, the range of publications on this topic has been extended to a number of new species, including South American camelids, black rhinoceros, lions and non-human primates. Therefore, it seemed appropriate to review the literature in the 3 years since 2009 and provide an overview of progress. [ABSTRACT FROM AUTHOR]

Cell adhesion is of utmost importance in normal development and cellular functions. ICAM-5 (intercellular adhesion molecule-5, telencephalin, TLN) is a member of the ICAM family of adhesion proteins. As a novel cell adhesion molecule, ICAM-5 shares many structural similarities with the other members of IgSF, especially the ICAM subgroup; however, ICAM-5 has several unique properties compared to the other ICAMs.With its nine extracellular Ig domains, ICAM-5 is the largestmember of ICAM subgroup identified so far. Therefore, it is much more complex than the other ICAMs. The expression of ICAM-5 is confined to the telencephalic neurons of the central nervous system whereas all the other ICAM members are expressed mostly by cells in the immune and blood systems. The developmental appearance of ICAM-5 parallels the time of dendritic elongation and branching, and synapse formation in the telencephalon. As a somatodendrite-specific adhesion molecule, ICAM-5 not only participates in immune-nervous system interactions, it could also participate in neuronal activity, Dendrites' targeting signals, and cognition. It would not be surprising if future investigations reveal more binding partners and other related functions of ICAM-5. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a multisystemic disease of unknown etiology characterized by chronic relapsing oral-genital ulcers and uveitis. Multiple systemic associations including articular, gastrointestinal, cardiopulmonary, neurologic, and vascular involvement are also observed in BD. Although the etiopathogenesis of the disease remains unknown, increased neutrophil functions such as chemotaxis, phagocytosis, and excessive production of reactive oxygen species (ROS), including superoxide anion, which may be responsible for oxidative tissue damage seen in BD, and also immunological alterations, T lymphocyte abnormalities in both subpopulation and function have been considered to be correlated with the etiopathogenesis of BD. There is some clinical evidence suggesting that emotional stress and hormonal alterations can influence the course and disease activity of BD. [ABSTRACT FROM AUTHOR]

Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis.Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2)macrophages.M1macrophages express a series of proinflammatory cytokines, chemokines, and effectormolecules, such as IL-12, IL-23, TNF-α, iNOS and MHCI/II. In contrast, M2 macrophages express a wide array of anti-inflammatory molecules, such as IL-10, TGF-β, and arginase1. In most tumors, the infiltrated macrophages are considered to be of the M2 phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, tumor-associated macrophages secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression. Recently, it was also found that tumor-associated macrophages interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. So mediating macrophage to resist tumors is considered to be potential therapy. [ABSTRACT FROM AUTHOR]

Amniotic fluid embolism (AFE) is one of the leading causes of maternal mortality and morbidity in developed countries. Current thinking about pathophysiology has shifted away from embolism toward a maternal immune response to the fetus. Two immunologic mechanisms have been studied to date. Anaphylaxis appears to be doubtful while the available evidence supports a role for complement activation. With the mechanism remaining to be elucidated, AFE remains a clinical diagnosis. It is diagnosed based on one or more of four key signs/symptoms: cardiovascular collapse, respiratory distress, coagulopathy, and/or coma/seizures. The only laboratory test that reliably supports the diagnosis is the finding of fetal material in the maternal pulmonary circulation at autopsy. Perhaps the most compelling mystery surrounding AFE is not why one in 20,000 parturients are afflicted, but rather how the vast majority of women can tolerate the foreign antigenic presence of their fetus both within their uterus and circulation? [ABSTRACT FROM AUTHOR]

The best hope of controlling the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) pandemic is the development of an effective vaccine. However, in spite of several clinical trials, starting as early as 1920s, no vaccine has been proven sufficiently safe and efficient to warrant commercial development. In recent years, great strides in cellular and molecular immunology have stimulated creative efforts in controlling herpes infection and disease. However, before moving towards new vaccine strategy, it is necessary to answer two fundamental questions: (i) why past herpes vaccines have failed? (ii) Why the majority of HSV seropositive individuals (i.e., asymptomatic individuals) are naturally "protected" exhibiting few or no recurrent clinical disease, while other HSV seropositive individuals (i.e., symptomatic individuals) have frequent ocular, orofacial, and/or genital herpes clinical episodes? We recently discovered several discrete sets of HSV-1 symptomatic and asymptomatic epitopes recognized by CD4+ and CD8+ T cells from seropositive symptomatic versus asymptomatic individuals. These asymptomatic epitopes will provide a solid foundation for the development of novel herpes epitope-based vaccine strategy. Here we provide a brief overview of past clinical vaccine trials, outline current progress towards developing a new generation "asymptomatic" clinical herpes vaccines, and discuss future mucosal "asymptomatic" prime-boost vaccines that could optimize local protective immunity. [ABSTRACT FROM AUTHOR]

Since the identification of APOBEC3G (A3G) as a potent restriction factor of HIV-1, a tremendous amount of effort has led to a broadened understanding of both A3G and the APOBEC3 (A3) family to which it belongs. In spite of the fine-tuned viral counterattack to A3 activity, in the form of the HIV-1 Vif protein, enthusiasm for leveraging the Vif : A3G axis as a point of clinical intervention remains high. In an impressive explosion of information over the last decade, additional A3 family members have been identified as antiviral proteins, mechanistic details of the restrictive capacity of these proteins have been elucidated, structure-function studies have revealed important molecular details of the Vif : A3G interaction, and clinical cohorts have been scrutinized for correlations between A3 expression and function and viral pathogenesis. In the last year, novel and unexpected findings regarding the role of A3G in immunity have refocused efforts on exploring the potential of harnessing the natural power of this immune defense. These most recent reports allude to functions of the A3 proteins that extend beyond their well-characterized designation as restriction factors. The emerging story implicates the A3 family as not only defense proteins, but also as participants in the broader innate immune response. [ABSTRACT FROM AUTHOR]

dsRNA can be detected by pattern recognition receptors, for example, TLR3,MDA-5, NLRP3 to induce proinflammatory cytokines responsible for innate/adaptive immunity. Recognized by endosomal TLR3 in myeloid DCs (mDCs), dsRNA can activate mDCs into mature antigen presenting cells (mAPCs) which in turn present antigen epitopes with MHC-I molecules to naïve T cells. Coadministration of protein and synthetic dsRNA analogues can elicit an antigen-specific Th1-polarized immune response which stimulates the CD8+ CTL response and possibly dampen Th17 response. Synthetic dsRNA analogues have been tested as vaccine adjuvant against viral infections in animal models. However, a dsRNA receptor, TLR3 can be expressed in tumor cells while other members of TLR family, for example, TLR4 and TLR2 have been shown to promote tumor progression, metastasis, and chemoresistance. Thus, the promising potential of dsRNA analogues as a tumor therapeutic vaccine adjuvant should be evaluated cautiously. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF)-α is not just a proinflammatory cytokine. It has also been proposed to be an immunoregulatory molecule that can alter the balance of T regulatory cells. Anti-TNF-α therapies have been provided clinical benefit to many patients and introduced for treating moderate to severe rheumatoid arthritis, Crohn's disease, and other chronic inflammatory disorders. However, their use also is accompanied by new or aggravated forms of autoimmunity, such as formation of autoantibodies, including antinuclear antibodies (ANAs), antidouble-stranded DNA (dsDNA) antibodies, and anticardiolipin antibodies (ACL). Systemic lupus erythematosus (SLE) is a disease with autoimmune disturbance and inflammatory damage. The role of TNF-α in human SLE is controversial. Here we review the role of TNF-α in the pathophysiological processes of SLE and the likely effects of blocking TNF-a in treatment of SLE. [ABSTRACT FROM AUTHOR]

Graft-versus-Host Disease (GvHD) is the most serious complication of allogeneic stem cell transplantation (SCT) and results from an activation of donor lymphocytes by recipient antigen-presenting cells (APCs). For a long time, it has been postulated that the intestinal microflora and endotoxin exert a crucial step in this APC activation, as there is early and severe gastrointestinal damage induced by pretransplant conditioning. With the detailed description of pathogen-associated molecular patterns and pathogen recognition receptors single nucleotide polymorphisms of TLRs and especially NOD2 have been identified as potential risk factors of GvHD and transplant related complications thus further supporting the crucial role of innate immunity in SCT, related complications. Gastrointestinal decontamination and neutralization of endotoxin have been used to interfere with this early axis of activation with some success but more specific approaches of modulation of innate immunity are needed for further improvement of clinical outcome. [ABSTRACT FROM AUTHOR]

Patients with head and neck squamous cell carcinoma (HNSCC) are at considerable risk for death, with 5-year relative survival rates of approximately 60%. The profound multifaceted deficiencies in cell-mediated immunity that persist in most patients after treatment may be related to the high rates of treatment failure and second primary malignancies. Radiotherapy and chemoradiotherapy commonly have severe acute and long-term side effects on immune responses. The development of immunotherapies reflects growing awareness that certain immune system deficiencies specific to HNSCC and some other cancers may contribute to the poor long-termoutcomes. Systemic cell-mediated immunotherapy is intended to activate the entire immune system and mount a systemic and/or locoregional antitumor response. The delivery of cytokines, either by single cytokines, for example, interleukin-2, interleukin-12, interferon-?, interferon-a, or by a biologic mix of multiple cytokines, such as IRX-2, may result in tumor rejection and durable immune responses. Targeted immunotherapy makes use of monoclonal antibodies or vaccines. All immunotherapies for HNSCC except cetuximab remain investigational, but a number of agents whose efficacy and tolerability are promising have entered phase 2 or phase 3 development. [ABSTRACT FROM AUTHOR]

The effects of capsular polysaccharides, galactoxylomannan (GalXM) and glucuronoxylomannan (GXM), from acapsular (GXM negative) and encapsulate strains of Cryptococcus neoformans were investigated in RAW 264.7 and peritoneal macrophages. Here, we demonstrate that GalXM and GXM induced different cytokines profiles in RAW 264.7 macrophages. GalXM induced production of TNF-α, NO and iNOS expression, while GXM predominantly induced TGF-β secretion. Both GalXM and GXM induced early morphological changes identified as autophagy and late macrophages apoptosis mediated by Fas/FasL interaction, a previously unidentified mechanism of virulence. GalXM was more potent than GXM at induction of Fas/FasL expression and apoptosis on macrophages in vitro and in vivo. These findings uncover a mechanism by which capsular polysaccharides from C. neoformans might compromise host immune responses. [ABSTRACT FROM AUTHOR]