粘膜免疫相关载体和佐剂研究进展

粘膜免疫系统是机体抵抗艾滋病病毒入侵的第1道免疫屏障,诱导粘膜免疫应答对艾滋病的预防和治疗及疫苗的研制具有重要的意义。对粘膜免疫系统的有效刺激需要合适的粘膜免疫相关载体和佐剂。许多学者在不耐热肠毒素、霍乱毒素、脂质体、细菌载体、聚乙烯亚胺等相关载体和佐剂方面做了众多有益的研究。     

女性生殖道黏膜免疫进展

黏膜免疫是抵御细菌、病毒等病原体侵入机体的第一道防线。女性生殖道黏膜免疫通过固有免疫和适应性免疫不仅可抵抗致病菌的入侵,还有助于成功受精及妊娠,从而维持女性生殖健康。女性生殖道固有免疫系统包括黏膜上皮的机械屏障、共生菌的微生物屏障、固有免疫细胞及其受体的免疫屏障,适应性免疫包括B细胞介导的体液免疫及T细胞介导的细胞免疫。女性生殖道黏膜免疫不仅参与局部炎症,还可能具有抗肿瘤免疫应答的作用。此外,女性生殖道黏膜免疫受性激素的调节,从而有利于维持局部微环境的稳态。本文就近年有关女性生殖道黏膜免疫的研究进展进行总结。     

大面积深度烧伤感染的防治

全身性感染或脓毒症是严重烧伤患者面临的最大威胁，因为大面积深度烧伤造成体表和体腔的天然屏障破坏，全身免疫功能失衡，烧伤创面坏死组织本身又成为微生物生长的培养基。机体与微生物间的相对平衡失调，不仅对高度致病菌易感性增加，而且对致病力很弱的病原菌易感性亦增加。北京积水潭医院烧伤科1958年-1995年共收治烧伤面积80％TBSA以上患者314例，     

烧伤患者高压氧治疗过程中sIL-2R和Fn含量变化

本文报道严重烧伤患者血中可溶性白介素２受体（ｓＩＬ ２Ｒ）和纤维连接蛋白（Ｆｎ）的含量变化，并观察高压氧治疗（ＨＢＯＴ）对其含量的影响，籍以探讨ＨＢＯＴ对机体免疫功能的作用和它在防治烧伤感染上的可能机理。１对象和方法选择首治严重烧伤患者４２例，烧伤总...     

白色念珠菌感染免疫应答的研究进展北大核心CSCD

白色念珠菌是人体条件致病菌,当人体免疫力下降或病原菌侵入非正常寄居部位可引发严重感染。机体通过各种免疫应答机制防御与清除白色念珠菌感染,而后者的免疫逃避机制是临床上治疗白色念珠菌感染的重大挑战。本文就白色念珠菌感染免疫应答的研究进展进行综述。     

关于肠道免疫耐受与经口诱导耐受DNA疫苗的研究

粘膜免疫系统是机体抵抗病原体感染的第一道重要防线.粘膜经常暴露于病原体并与之接触.因此,在病原体侵入部位产生免疫应答,对于清除病原体保护机体是必需的.     

中性粒细胞在结核病免疫中的作用及其研究进展

多形核中性粒细胞(PMN)作为机体重要的固有免疫效应细胞,是机体抵抗病原微生物感染的第一道防线。早期的研究认为PMN仅作为吞噬细胞在结核分枝杆菌(Mtb)感染的早期参与抗结核病的固有免疫应答,但近年来的研究显示PMN还参与了结核病适应性免疫的诱导和调节,对结核病免疫的发展有重要的影响。目前,人们对其在结核病免疫过程中发挥的确切功能、对结核发生发展的影响及相关机制还未完全明了,然而近年来越来越多的研究正逐步加深我们对PMN在结核病免疫中的作用的认识。现就近年来有关PMN在结核病免疫中的研究进展进行综述。     

危重烧伤患者的肠道复苏

以往危重烧伤患者休克期复苏多以静脉液体复苏为主,虽能恢复有效循环血容量,但胃肠道仍处于隐匿性休克状态。由于严重烧伤后肠道屏障功能受损害、机体高代谢状态及免疫功能紊乱等病理生理变化,肠道复苏引起临床医师的重视,并且动物实验及临床研究都证实其可行性和有效性。本文结合作者前期研究工作以及多年危重烧伤救治经验,同时复习国内外有关文献,就肠道复苏在危重烧伤治疗中的作用进行深入探讨,以对今后危重烧伤的救治有所裨益。     

烧伤后淋巴细胞活性的变化——抑制细胞的作用

严重烧伤并发致命败血症的高发生率以及败血症是烧伤后最主要的死亡原因这一事实,被认为是机体免疫功能丧失的结果。烧     

病原菌影响巨噬细胞极化的研究进展

巨噬细胞作为固有免疫系统中的重要一员,具有吞噬、抗原呈递、杀伤病原体等功能,在早期控制病原菌感染中发挥重要作用。病原菌可诱导巨噬细胞发生M1/M2型极化而参与机体对病原菌感染的免疫应答。病原菌运用不同的策略诱导巨噬细胞极化,对感染性疾病转归产生重要的影响。     

Toll-like receptors and their role in experimental models of microbial infection

Effective host defense against microbial infection depends upon prompt recognition of pathogens, activation of immediate containment measures, and ultimately the generation of a specific and definitive adaptive immune response. The innate immune system of the host is responsible for providing constant surveillance against infection; when confronted by pathogens it deploys a series of rapidly acting antimicrobial effectors while simultaneously instructing the adaptive immune system as to the nature and context of the infectious threat. Pathogen recognition and activation of innate immunity is mediated by members of the Toll-like receptor (TLR) family through detection of conserved microbial structures that are absent from the host. Experimental models of infection using TLR-deficient mice, as well as limited human studies, have clearly demonstrated the critical role of TLRs in host defense against most major groups of mammalian pathogens.     

Transcriptomic profiling revealed the signatures of intestinal barrier alteration and pathogen entry in turbot (Scophthalmus maximus) following Vibrio anguillarum challenge

The mucosal immune system serves as the frontline barriers of host defense against pathogen infection, especially for the fishes, which are living in the pathogen rich aquatic environment. The intestine constitutes the largest surface body area in constantly contact with the external pathogens, and plays a vital role in the immune defense against inflammation and pathogen infection. Previous studies have revealed that fish intestine might serves as the portal of entry for Vibrio anguillarum. To characterize the immune actors and their associated immune activities in turbot intestine barrier during bacterial infection, here we examined the gene expression profiles of turbot intestine at three time points following experimental infection with V. anguillarum utilizing RNA-seq technology. A total of 122 million reads were assembled into 183,101 contigs with an average length of 1151 bp and the N50 size of 2302 bp. Analysis of differential gene expression between control and infected samples at 1 h, 4 h, and 12 h revealed 2079 significantly expressed genes. Enrichment and pathway analysis of the differentially expressed genes showed the centrality of the pathogen attachment and recognition, antioxidant/apoptosis, mucus barrier modification and immune activation/inflammation in the pathogen entry and host immune responses. The present study reported the novel gene expression patterns in turbot mucosal immunity, which were overlooked in previous studies. Our results can help to understand the mechanisms of turbot host defense, and may also provide foundation to identify the biomarkers for future selection of disease-resistant broodstock and evaluation of disease prevention and treatment options.     

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis.     

The contribution of mast cells to bacterial and fungal infection immunity

Mast cells are hematopoietic progenitor-derived, granule-containing immune cells that are widely distributed in tissues that interact with the external environment, such as the skin and mucosal tissues. It is well-known that mast cells are significantly involved in IgE-mediated allergic reactions, but because of their location, it has also been long hypothesized that mast cells can act as sentinel cells that sense pathogens and initiate protective immune responses. Using mast cell or mast cell protease-deficient murine models, recent studies by our groups and others indicate that mast cells have pleiotropic regulatory roles in immunological responses against pathogens. In this review, we discuss studies that demonstrate that mast cells can either promote host resistance to infections caused by bacteria and fungi or contribute to dysregulated immune responses that can increase host morbidity and mortality. Overall, these studies indicate that mast cells can influence innate immune responses against bacterial and fungal infections via multiple mechanisms. Importantly, the contribution of mast cells to infection outcomes depends in part on the infection model, including the genetic approach used to assess the influence of mast cells on host immunity, hence highlighting the complexity of mast cell biology in the context of innate immune responses.     

Interleukin-17 in host defence against bacterial,mycobacterial and fungal pathogens

The mammalian immune system is intricately regulated, allowing for potent pathogen-specific immunity to be rapidly activated in response to infection with a broad and diverse array of potential pathogens. As a result of their ability to differentiate into distinct effector lineages, CD4 T cells significantly contribute to pathogen-specific adaptive immune responses. Through the production of effector cytokines, CD4 T helper (Th) cells orchestrate the precise mobilization of specific immune cells to eradicate infection. The protective effects of the newly identified lineage of Th17 cells against pathogens like Klebsiella pneumoniae, Citrobacter rodentium and Candida albicans indicate the capacity of Th17 cells to confer protection against extracellular bacterial and fungal pathogens, filling a critical void in host immunity not covered by the classically described Th1 lineage that activates immunity to intracellular pathogens or the Th2 lineage that is important in protection against mucosal parasitic pathogens. Host defence by Th17 cells extends beyond protection against extracellular bacterial and fungal pathogens, as demonstrated in infections against intracellular bacteria like Listeria monocytogenes and Salmonella enterica, as well as Mycobacterium tuberculosis. Herein, we summarize both experimental data from mouse infection models and epidemiological studies in humans that demonstrate the protective effects of interleukin-17 and Th17 CD4 T cells in immunity to bacterial, mycobacterial and fungal pathogens.     

Intracellular infections in Drosophila melanogaster: Host defense and mechanisms of pathogenesis

The fruit-fly Drosophila melanogaster has emerged as a powerful model to study innate immunity against intracellular pathogens. To combat infection, the fly relies on multiple lines of defense, many of which are shared with mammals and arthropod vectors of human diseases. In addition to conserved immune pathways, the ease of performing sophisticated genetic screens has allowed the identification of novel host immune factors and novel pathogen virulence factors. Recently, some groups have exploited this to simultaneously analyze the host and pathogen genetics of intracellular infection. This review aims to unravel the Drosophila immune response against intracellular pathogens, highlighting recent discoveries.     

Trained immunity from the perspective of Plasmodium infection

The immune system of vertebrates includes innate immunity and adaptive immunity, and the network between them enables the host to fight against invasions of various pathogens. Recently, studies discovered that immune memory is one of the features of innate immunity, breaking the previous opinion that immune memory exists only in adaptive immunity. Immune memory supports innate immune cells to respond efficiently upon reinfection or restimulation. During the Plasmodium infection, the innate immune system is the first to be triggered, and innate immune cells are activated by components from Plasmodium or Plasmodium-infected red blood cells. Innate immune cells could be induced to develop memory after the activation and may play an important role in the subsequent infection of Plasmodium or other pathogens and stimulation. This review will discuss the recent findings relevant to trained immunity and Plasmodium infection, facilitating the understanding of the role of trained immunity in malaria and other diseases and the development of therapeutic strategies based on trained immunity.     

Shaping the immune response to parasites: role of dendritic cells

Parasites represent a diverse group of pathogens that often trigger highly polarized immune responses that become tightly regulated during chronic infection. Recent studies have implicated the parasite-dendritic-cell interaction as a key determinant of the host response to these eukaryotic invaders. Dendritic cells appear to be pivotal in the initiation of cellular immunity against parasites as well as in directing Th1/Th2 effector choice. Moreover, there is increasing evidence that parasites regulate dendritic-cell function for the purposes of evading host immunity. This regulation also benefits parasites by protecting their host niche from the potentially lethal consequences of an uncontrolled inflammatory response.     

Microbiota and metabolites in rheumatic diseases

As a gigantic community in the human body, the microbiota exerts pleiotropic roles in human health and disease ranging from digestion and absorption of nutrients from food, defense against infection of pathogens, to regulation of immune system development and immune homeostasis. Recent advances in “omics” studies and bioinformatics analyses have broadened our insights of the microbiota composition of the inner and other surfaces of the body and their interactions with the host. Apart from the direct contact of microbes at the mucosal barrier, metabolites produced or metabolized by the gut microbes can serve as important immune regulators or initiators in a wide variety of diseases, including gastrointestinal diseases, metabolic disorders and systemic rheumatic diseases. This review focuses on the most recent understanding of how the microbiota and metabolites shape rheumatic diseases. Studies that explore the mechanistic interplay between microbes, metabolites and the host could thereby provide clues for novel methods in the diagnosis, therapy, and prevention of rheumatic diseases.     

Innate immunity in experimental SIV infection and vaccination

Innate immunity represents the first line of defence to pathogens besides the physical barrier and seems to play a role in protection against HIV/SIV infection and disease progression. High production of beta-chemokines and CD8+ T cell anti-viral factors in naive as well as in vaccinated macaques has been associated with complete or partial protection against SIV infection indicating that genetic or environmental factors may influence their production. This innate immunity may help in generating HIV/SIV-specific responses upon the first exposure to HIV/SIV. SIV subunit vaccines given by the targeted iliac lymph node route have been shown to induce an increased production of CD8+ T cell suppressor factors and beta-chemokines. Only a few vaccine studies have focused on enhancing the innate immune response against HIV/SIV. The use of unmethylated CpG motifs, HSP and GM-CSF as adjuvants in SIV vaccines has been shown to induce production of HIV/SIV-inhibiting cytokines and beta-chemokines, which seem to be important in modulating and steering the adaptive immune responses. HSP has also been shown to induce gammadelta+ T cells, which contribute to the innate immunity. More knowledge about the interplay between the innate and adaptive immune responses is important to develop new HIV/SIV vaccine strategies.