Probiotics and down-regulation of the allergic response

The first clinical trials with probiotics, especially in the treatment of atopic eczema, have yielded encouraging results. Experimental studies have found that probiotics exert strain-specific effects in the intestinal lumen and on epithelial cells and immune cells with anti-allergic potential. These effects include enhancement in antigen degradation and gut barrier function and induction of regulatory and proinflammatory immune responses, the latter of which occurs more likely beyond the intestinal epithelium. Future studies should address more accurately how these and other possible mechanisms operate in the complex gastrointestinal macroenvironment in vivo and how these mechanisms are related to the clinical effects in a dose-dependent manner.     

胆固醇代谢与免疫反应

胆固醇及多种胆固醇代谢物是细胞膜和细胞器膜的最重要的组成成分,在调控细胞膜的流动性和通透性、脂筏的形成、信号传导等方面发挥着重要作用。最近的研究表明,胆固醇中间代谢产物及其衍生物参与调控免疫细胞的增殖、 分化、迁移、效应功能或者耗竭功能、免疫监视或者免疫逃逸等多种功能,靶向胆固醇代谢能够干预感染、炎症和肿瘤等多种疾病进程。本文主要介绍感染、肿瘤或炎症反应过程中,胆固醇代谢酶和代谢物参与调节免疫细胞生理或病理功能的研究进展。     

microRNAs and the immune response

microRNA (miRNA)-mediated RNA interference has been identified as a novel mechanism that regulates protein expression at the translational level. Recent publications have provided compelling evidence that a range of miRNAs are involved in the regulation of immunity, including the development and differentiation of B and T cells, proliferation of monocytes and neutrophils, antibody switching and the release of inflammatory mediators. In this review, we examine what is presently known of the function and mechanism of action of these miRNAs in the regulation of the innate and acquired immune response.     

NOD 蛋白与免疫应答

NOD 蛋白包括NOD1 和NOD2,两者识别细菌肽聚糖的片段,诱导促炎和抗菌反应。在本篇综述中,我们介绍 近年来NOD 蛋白的研究进展,包括激活的方式,信号途径的调节,在细胞中的定位以及在免疫防御过程中发挥的作用。洞悉 NOD 蛋白诱导的信号通路有助于了解相关疾病的致病机理,为疾病的治疗提供新的视角。     

Matrix metalloproteinases and the immune response

The timely breakdown of the extracellular matrix (ECM) is essential in many physiological and biological processes. The matrix-degradation process involves tissue remodeling and immune/inflammatory reactions that occur in the stroma. Thus, the proteolytic and destructive potential of the matrix metalloproteinase (MMP) family is a major concern in several pathological conditions involving ECM degradation. This review details the structures and functions of MMPs and presents an overview of the interaction of MMPs with components of the immune system.     

Nitric oxide and the immune response

During the past two decades, nitric oxide (NO) has been recognized as one of the most versatile players in the immune system. It is involved in the pathogenesis and control of infectious diseases, tumors, autoimmune processes and chronic degenerative diseases. Because of its variety of reaction partners (DNA, proteins, low-molecular weight thiols, prosthetic groups, reactive oxygen intermediates), its widespread production (by three different NO synthases (NOS) and the fact that its activity is strongly influenced by its concentration, NO continues to surprise and perplex immunologists. Today, there is no simple, uniform picture of the function of NO in the immune system. Protective and toxic effects of NO are frequently seen in parallel. Its striking inter- and intracellular signaling capacity makes it extremely difficult to predict the effect of NOS inhibitors and NO donors, which still hampers therapeutic applications.     

Tim基因家族与T辅助细胞免疫反应

Th参与的免疫应答在许多疾病的发生发展中起重要作用,随着研究的深入,其新的调控机制不断被发现,Tim基因家族是新近发现的Th免疫应答中的重要调控因子,它们参与了许多Th免疫反应相关疾病的发病,了解Tim与Th免疫反应关系很有必要.     

NF-kappaB and the innate immune response

In the innate immune reaction, microbial pathogens activate phylogenetically conserved cellular signal transduction pathways that regulate the ubiquitous nuclear factor-kappaB (NFkappaB). NF-kappaB has pleiotropic functions in immunity; however, it is also critical for development and cellular survival. Many aspects of how the different pathways utilize a common kinase complex that ultimately activates NF-kappaB have been clarified by gene inactivation and biochemical analysis.     

Antiallergic drugs and the immune response

Since the pharmacological treatment of allergic diseases is used in patients with alteration of the immune response due to atopy and possible concomitant infections, we have investigated the possible effects of such drugs as cromolyn, theophylline, ketotifen, oxatomide, astemizole, fenoterol, pirenzepine, and rosaprostol on the in vitro immune response, in order to obtain experimental data and, as a consequence, clinical conclusions. In a series of investigations by our group and other authors the following immunological parameters have been considered: T cell activation induced by different pathways (i.e. autologous stimulation, PHA, anti-CD3, -CD2 and -CD28 monoclonal antibodies), and lymphokine production (i.e. IL-1, IL-2 and gamma-IFN). For a more detailed experimental model the experiments have been performed both in bulk culture and by using T cell clones derived from the peripheral blood. The results show cromolyn to have an enhancing effect, theophylline and ketotifen a suppressing effect, whereas the remainder show no effect on the immune response. These data are considered and discussed from the aspect of their possible clinical relevance and also in light of the in vivo data previously reported.     

Humoral innate immune response and disease

The humoral innate immune response consists of multiple components, including the naturally occurring antibodies (NAb), pentraxins and the complement and contact cascades. As soluble, plasma components, these innate proteins provide key elements in the prevention and control of disease. However, pathogens and cells with altered self proteins utilize multiple humoral components to evade destruction and promote pathology. Many studies have examined the relationship between humoral immunity and autoimmune disorders. This review focuses on the interactions between the humoral components and their role in promoting the pathogenesis of bacterial and viral infections and chronic diseases such as atherosclerosis and cancer. Understanding the beneficial and detrimental aspects of the individual components and the interactions between proteins which regulate the innate and adaptive response will provide therapeutic targets for subsequent studies.     

The nephritogenic immune response

Recent work has improved our understanding of a number of aspects of the nephritogenic immune response. Progress has been made in the understanding of the development of idiotypic networks, and in understanding the structural nature of the targets of self-reactive T cells and the paracrine mediators that are released as part of the local inflammatory response.     

Probiotics, prebiotics, and synbiotics: impact on the gut immune system and allergic reactions

Probiotics and prebiotics, alone or together (synbiotics), can influence the intestinal microbiota and modulate the immune response. They may therefore be tools that can prevent or alleviate certain pathologies involving the gut immune system, such as allergies for which no treatment is yet available. This review focuses first on the definitions of probiotics, prebiotics, and synbiotics and key cells in the gut immune system. It then discusses their effects on mucosal immune stimulation. Experimental findings suggest that different probiotic species have similar effects on innate immunity by improving the mechanisms of pathogen destruction. On the contrary, their impacts seem to be variable on the adaptive immune system. Prebiotics can also exert an influence on the gut immune system via the stimulation of the autochthonous bacteria metabolism. Finally, this review focuses on the effects of food supplements on allergy. Different studies performed in humans or rodents have supported a potential role for selected probiotics and prebiotics in reducing some allergic parameters. Probiotic effects on allergy treatment are unclear, especially in human studies. However, they are potentially effective at short-term for prevention when they are administered in perinatal conditions. A clinical study performed with an infant cohort revealed a beneficial effect of prebiotics in preventing allergic manifestations at long-term. Further studies are nonetheless essential to confirm these findings. Food supplements offer potential tools for the prevention or treatment of allergy, but insufficient evidence is available at present to recommend their use in clinical practice.     

Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation

Background Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. Objective Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy‐prone infants. Methods In a randomized double‐blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C‐reactive protein (CRP), total IgA and IgE, food‐specific IgA, IgG, and IgE, IL‐2, IL‐4, IL‐6, IL‐10, TNF‐α, and IFN‐γ. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. Results Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL‐10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17–0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16–0.87), P=0.023] at age 2 years, when adjusted with probiotic use. Conclusion The association of CRP with a decreased risk of eczema at 2 years of age in allergy‐prone children supports the view that chronic, low‐grade inflammation protects from eczema. Probiotic‐induced low‐grade inflammation was characterized by elevation of IgE, IgA, and IL‐10, the changes typically observed in helminth infection‐associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.