The innate immune system and its role in allergic disorders

BACKGROUND: There has been an increasing prevalence of allergic diseases in the Western world over the last decades. The hygiene hypothesis has been proposed as a possible explanation for this epidemical trend in allergy. A key role in this theory is assigned to the reduced microbial stimulation of the Toll-like receptors (TLRs) in early life, which could lead to a weaker Th1 response and a stronger Th2 response to allergens. The individual immunological response is determined by the interplay between the dose and timing of exposure to endotoxins, other environmental factors and genetic predisposition. In the development and progression of allergic disorders, the innate immune system plays an important role. OBJECTIVE: In this review, we discuss the paradoxical effects that may appear when the innate immune components are triggered. We review the influence of changes in the gene sequence and TLR expression in relation to the overall pattern of commensals and pathogens. We explored the possibility of alternative stimulations of the immune system by CpG oligodeoxynucleotides and probiotics as therapeutic devices against this endemic disease in Western society. METHODS: Selection of papers was based on the importance of their contribution to the understanding of innate immunity and its implications. RESULTS AND CONCLUSION: The innate immune system plays an important role in both the protection against and the enhancement of allergic disorders, but the mechanisms are still unclear. Nevertheless, gene polymorphisms and triggers of the innate immune system provide therapeutic targets for protection against and treatment of allergic disorders.     

GITR及其在免疫调节中的作用

糖皮质激素诱导的TNFR家族相关受体（GITR），也被称为TNFRSF18、AITR（人类）。静止T细胞低水平表达GITR，而CD4^＋CD25^＋调节性T细胞则呈高水平表达。GITR与其配体（GITRL）结合后会增强T细胞激活、增殖、分泌细胞因子、MAPKs和NF-κB激活效应、抑制CD4^＋CD25^＋Treg细胞的功能，从而加强效应性T细胞的活性，有利于增强抗肿瘤免疫和抗病毒免疫。随着生物学环境的变化，GITR激活Siva或者TRAF，起着促进或诱导凋亡的作用。     

多巴胺及其受体免疫调节作用的研究进展

多巴胺(DA)是重要的儿茶酚胺类神经递质,与多巴胺受体(DR)组成多巴胺能神经系统。免疫细胞可合成、储存和运输DA,并通过自分泌/旁分泌方式,调节免疫细胞的静息、活化和凋亡。DRs几乎存在所有免疫细胞上,DA或DRs激动剂激活DR能影响免疫细胞分化和细胞因子释放,实现DA及DRs对免疫细胞异常的免疫系统疾病的调节。     

Ubiquitin makes its mark on immune regulation

Ubiquitination, the covalent attachment of ubiquitin molecules to proteins, is emerging as a widely utilized mechanism for rapidly regulating cell signaling. Recent studies indicate that ubiquitination plays potent roles in regulating a variety of signals in both innate and adaptive immune cells. Here, we will review recent studies of ubiquitin ligases, ubiquitin chain linkages, and ubiquitin binding proteins that highlight the diversity and specificity of ubiquitin dependent functions in immune cells. We will also review studies that shed light on how ubiquitination signals are integrated in cell-type-specific fashion to regulate the immune system in?vivo.     

Role of complement in immune regulation and its exploitation by virus

Complement is activated during the early phase of viral infection and promotes destruction of virus particles as well as the initiation of inflammatory responses. Recently, complement and complement receptors have been reported to play an important role in the regulation of innate as well as adaptive immune responses during infection. The regulation of host immune responses by complement involves modulation of dendritic cell activity in addition to direct effects on T-cell function. Intriguingly, many viruses encode homologs of complement regulatory molecules or proteins that interact with complement receptors on antigen-presenting cells and lymphocytes. The evolution of viral mechanisms to alter complement function may augment pathogen persistence and limit immune-mediated tissue destruction. These observations suggest that complement may play an important role in both innate and adaptive immune responses to infection as well as virus-mediated modulation of host immunity.     

锰在免疫调节中的功能及其应用

锰是一种人体必需的微量元素,在发育、生殖、代谢、神经功能和抗氧化等方面发挥着重要的作用。近年来, 锰在机体免疫中的重要作用逐步被认识和重视。锰作为一种损伤相关分子模式,具有强劲的免疫激活能力。锰离子诱导细胞产生大量的包括Ⅰ型干扰素在内的细胞因子,调控机体的天然免疫和适应性免疫反应,在免疫佐剂和肿瘤免疫治疗方面展现出巨大的潜力。本文首先总结了锰在机体内的稳态调节及其在机体免疫中的作用,之后对锰及其衍生物在免疫佐剂和肿瘤免疫治疗方面的一系列应用进行了详细的讨论,并对其未来的发展进行了展望。     

Thrombosis and immune disorders

The purpose of this review has been to draw the attention of clinicians towards the possibility that some of the patients they are treating for thrombosis may have an underlying immune disturbance. This could involve functional abnormalities of the complement system (as in acquired angioneurotic oedema or in paroxysmal nocturnal haemoglobinuria), or cell-mediated immunological damage to the vessel wall (as in Behcet's syndrome or Buerger's disease), or the presence of circulating antibodies (the lupus anticoagulant or antibodies to heparin). While obviously our knowledge on most aspects is still very incomplete, the awareness of the association of thrombosis with certain immune disorders should encourage further detailed studies of mechanisms and enhance our understanding of the role of blood constituents and the vessel wall in thrombogenesis.     

The regulation of the immune system

Fundamental questions about the processes of immune recognition are now being asked with the powerful techniques of molecular biology and biochemistry. The extent to which these disciplines have converged with cellular immunology was particularly striking at a recent meeting on the regulation of the immune response.     

The new face of anaphylatoxins in immune regulation

Anaphylatoxins are a group of small peptides (i.e. C3a, C4a and C5a) generated by complement activation and play important roles in innate immunity through the initiation and regulation of inflammatory responses. More recent studies have revealed that, in addition to their traditional roles in inflammation, anaphylatoxins also significantly influence the adaptive immune response. It does so through a number of mechanisms and by targeting various cells. One important mechanism is that anaphylatoxins (C3a, C5a) act on their receptors expressed on innate immune cells such as dendritic cells. This modulates cell activation and their functions in initiating and regulating T cell responses and thus influencing T cell immunity. This review provides an overview of anaphylatoxins in adaptive immune regulation focusing on their roles in modulating dendritic cell and macrophage functions and the importance of local production of complement in this regulation.     

Tolerance and immune regulation

Understanding of both the phenomenon of immunological tolerance and the mechanisms by which it is achieved is rapidly advancing, as was evident from a recent meeting. This report summarizes key developments in both T- and B-cell biology.