免疫细胞可塑性与免疫病理机制研究进展

免疫细胞是由造血干细胞发育分化而来,是免疫应答的主要执行者。在不同应激或免疫病理状态下,免疫细胞具有较强的可塑性潜能,能够转分化形成不同类型的免疫细胞亚群。转分化的免疫细胞执行特定的免疫功能,从而调控疾病的演进过程。近年来研究发现,终末分化的免疫细胞亚群之间能够互相转换,实现类型和功能的转变,即转分化。目前发现T细胞、固有淋巴样细胞、巨噬细胞和嗜中性粒细胞等均存在细胞类型转分化的现象,细胞的转分化调控着疾病的发生发展进程。免疫细胞的可塑性与感染、肿瘤和自身免疫性疾病等都有密切联系。因此,揭示免疫细胞的可塑性调控机制将为深入理解免疫相关疾病的发生发展进程提供重要的理论依据,并为疾病的干预提供新策略。本文拟将对免疫细胞可塑性的主要细胞类型、免疫细胞可塑性调节机制以及免疫细胞可塑性与疾病等作一综述。     

The impact of concurrent HIV and type II diabetes on immune maturation,immune regulation and immune activation

Chronic immune activation and inflammation are constant findings in people living with HIV (PLWH) and contribute to the risk of non‐AIDS‐related morbidities, including cardiovascular diseases (CVD). Type 2 diabetes (T2D) is also characterized by immune activation and inflammation. We aimed to investigate the impact of concurrent HIV infection and T2D on T‐cell subsets. The study included PLWH with T2D (HIV+T2D+, N = 25) and without T2D (HIV+T2D?, N = 25) and HIV‐negative controls with T2D (HIV?T2D+, N = 22) and without T2D (HIV?T2D?, N = 28). All PLWH in the study were receiving combination antiretroviral therapy. We examined T‐cell homeostasis by determining T‐cell subsets (immune maturation, immune regulation and immune activation) using flow cytometry. HIV+T2D? had lower proportion of Tc17 cells and higher proportion of apoptotic cells than HIV?T2D?. When comparing HIV+T2D+ and HIV+T2D? a lower proportion of CD4+ recent thymic emigrants (RTE) was found (p = 0.028). Furthermore, HIV+T2D+ had a higher proportion of non‐suppressive CD4+ Tregs compared to HIV+T2D? (p = 0.010). In conclusion, even in the setting of treated HIV infection, distinct immunological alterations are found. In PLWH with concomitant T2D, most alterations in T‐cell subsets were related to HIV and only few differences were found between PLWH with and without diabetes.     

Role of natural and immune IgM antibodies in immune responses

IgM antibodies constitute the major component of the natural antibodies and is also the first class of antibodies produced during a primary antibody response. The IgM-type antibodies differ from other classes of antibodies in that they are predominantly produced by B1 cells, in the absence of apparent stimulation by specific antigens. In addition, IgM antibodies are mostly encoded by germline V gene segments and have low affinities but broad specificites to both foreign and self structures. New developments regarding the function of both immune IgM antibodies and natural IgM antibodies will be examined here.     

The proteasome and its inhibitors in immune regulation and immune disorders

The ubiquitin-proteasome pathway is a well-characterized mechanism deputed to the degradation of intracellular proteins. Proteasomal degradation intervenes in the regulation of numerous cellular functions including signal transduction, apoptosis, cell cycle, and antigen presentation. In vitro and in vivo studies have shown that both normal and malignant cells of the immune system are exquisitely affected by inhibition of proteasome activity. This property is currently exploited in the treatment of multiple myeloma and mantle cell lymphoma, two B-cell malignancies that respond to treatment with the proteasome inhibitor bortezomib. Pharmacological inhibitors of the proteasome also affect function and survival of B and T lymphocytes and of dendritic cells and were shown to reduce autoimmune and inflammatory manifestations in several models of immune-mediated disorders. The present review offers an overview of the mechanisms implicated in the immunomodulatory effects of proteasome inhibitors and discusses prospective future applications for these small molecules in immune and inflammatory diseases.     

Secreted immune metabolites that mediate immune cell communication and function

Metabolites are emerging as essential factors for the immune system that are involved in both metabolic circuits and signaling cascades. Accumulated evidence suggests that altered metabolic programs initiated by the activation and maturation of immune cell types are accompanied by the delivery of various metabolites into the local environment. We propose that, in addition to protein/peptide ligands, secreted immune metabolites (SIMets) are essential components of immune communication networks that fine-tune immune responses under homeostatic and pathological conditions. We summarize recent advances in our understanding of SIMets and discuss the potential mechanisms by which some metabolites engage in immunological responses through receptor-, transporter-, and post-translational-mediated regulation. These insights may contribute to understanding physiology and developing effective therapeutics for inflammatory and immune-mediated diseases.     

State-of-the-art immune genetic and immune biological aspects of rheumatoid arthritis

One of the actual problems of clinical rheumatology was and remains the necessity of the earliest diagnostics of rheumatoid arthritis (RA) with the aim of adequate therapy for prevention of development of destructive changes, function ability loss and complication leading to reduction in patient's life quality, invalidization and lethal outcome. The predictors of the course of disease in its early stages, knowledge of its development mechanisms, are the base for optimal therapeutic influence on specific targets with the existing drugs and for development new ones. State-of-the-art data in genetic and immunological RA markers, whose detection in RA early stages helps to make RA diagnosis and to predict the disease course are represented. Immunological markers-antibodies to cyclic citrullinized peptide (aCCP) and rheumatoid factor (RF) have high specificity and sensitivity to RA diagnostics. Some alleles of the HLA-DRB1 locus coding shared epitope (SE) play the role of immune genetic factor predisposing to RA development and giving additional information for RA diagnostics in case of negative values of aCCP and RF.     

Atherogenesis and immune inflammation

Modern concepts on the role of inflammation in atherogenesis are reviewed. The evidence indicating that changes in cellular composition of the vascular wall are associated with the expression of mediators of inflammation and lead to the development of the protective-compensatory reaction under conditions of autoantigen production is presented. The hypotheses on the pathogenesis of atherosclerosis are discussed that associated the causes and conditions for emergence of leukocytes in the arterial intima against the background of apoprotein B-containing lipoprotein deposition. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 4–8, July, 1996     

HLA-G与免疫耐受

HLA-G是一种非经典人类主要组织相容性复合物Ⅰ类分子,与器官移植、生殖及肿瘤等多种免疫反应有关,是引起免疫耐受的一种因子.     

Lithium and immune function

Lithium has potent antiviral and immunostimulating properties which are probably consequences of its actions on prostaglandin synthesis. Although lithium has considerable potential in the prophylaxis of some viral illnesses and other manifestations of defective immune function, it is, paradoxically, capable of activating autoimmune mechanisms in predisposed patients.     

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.     

Leptin as immune mediator: Interaction between neuroendocrine and immune system

Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates.     

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.     

Telomeres and immune competency

Telomeres are essential for the integrity of chromosomes and for cellular replication. Attrition of telomeres occurs during DNA replication owing to the inability of conventional DNA polymerase to replicate chromosomal termini and the insufficient compensation for telomere loss by telomerase, an enzyme that synthesizes telomeric DNA. A number of genetic defects have been described in humans and in animal models that cause accelerated telomere attrition, in turn leading to severe phenotypes of hematopoietic and other proliferating cells. Telomere length, most frequently measured as an average value in heterogeneous peripheral blood leukocyte populations in humans, has been associated with a wide range of health conditions and diseases of immune and non-immune cells. Here, I review recent studies of telomere length dynamics with particular relevance to immune function.     

Sleep and immune function

Sleep and the circadian system exert a strong regulatory influence on immune functions. Investigations of the normal sleep–wake cycle showed that immune parameters like numbers of undifferentiated na?ve T cells and the production of pro-inflammatory cytokines exhibit peaks during early nocturnal sleep whereas circulating numbers of immune cells with immediate effector functions, like cytotoxic natural killer cells, as well as anti-inflammatory cytokine activity peak during daytime wakefulness. Although it is difficult to entirely dissect the influence of sleep from that of the circadian rhythm, comparisons of the effects of nocturnal sleep with those of 24-h periods of wakefulness suggest that sleep facilitates the extravasation of T cells and their possible redistribution to lymph nodes. Moreover, such studies revealed a selectively enhancing influence of sleep on cytokines promoting the interaction between antigen presenting cells and T helper cells, like interleukin-12. Sleep on the night after experimental vaccinations against hepatitis A produced a strong and persistent increase in the number of antigen-specific Th cells and antibody titres. Together these findings indicate a specific role of sleep in the formation of immunological memory. This role appears to be associated in particular with the stage of slow wave sleep and the accompanying pro-inflammatory endocrine milieu that is hallmarked by high growth hormone and prolactin levels and low cortisol and catecholamine concentrations.