A Recent Perspective on Alcohol, Immunity, and Host Defense

Background:  Multiple line of clinical and experimental evidence demonstrates that both acute, moderate, and chronic, excessive alcohol use result in various abnormalities in the functions of the immune system.
Methods:  Medline and Pubmed databases were used to identify published reports with particular interest in the period of 2000–2008 in the subject of alcohol use, infection, inflammation, innate, and adaptive immunity.
Results:  This review article summarizes recent findings relevant to acute or chronic alcohol use-induced immunomodulation and its consequences on host defense against microbial pathogens and tissue injury. Studies with in vivo and in vitro alcohol administration are both discussed. The effects of alcohol on lung infections, trauma and burn injury, liver, pancreas, and cardiovascular diseases are evaluated with respect to the role of immune cells. Specific changes in innate immune response and abnormalities in adaptive immunity caused by alcohol intake are detailed.
Conclusion:  Altered inflammatory cell and adaptive immune responses after alcohol consumption result in increased incidence and poor outcome of infections and other organ-specific immune-mediated effects.     

Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Tuberculosis (TB) is known to be fueled by HIV as well as social and economic factors. With progression of the diabetes mellitus (DM) pandemic in countries where TB is also endemic, focus is increasing on the potential links between DM and TB. Despite the magnitude of the DM-TB association woldwide, it is striking how little we know about the underlying biology that promotes this association which is a major concern to public health. In this review we summarize current findings regarding the alterations in the innate and adaptive immune responses of DM patients to Mycobacterium tuberculosis (Mtb). Current findings suggest underperforming innate immunity followed by a hyper-reactive cellular response to Mtb, but the contribution of these altered responses to TB susceptibility or to the more adverse clinical outcomes of TB patients with DM remains unclear. Elucidating the basic mechanisms underlying the higher susceptibility of DM patients to TB should lead to a strategy for stratification of the millions of DM patients worldwide into those with the highest TB risk for targeted TB prevention.     

Innate immune responses to M. tuberculosis infection

A prerequisite for successful establishment of Mycobacterium tuberculosis in the host is its ability to survive after internalization in alveolar macrophages that they encounter after inhalation. The innate immune response protects some individuals to the extent that they remain uninfected. In others, the innate immune system is not sufficient and an adaptive immune response is generated. This is usually protective, but not sterilizing, and individuals remain latently infected. In susceptible individuals, M. tuberculosis successfully escapes immune surveillance. The interplay between the host innate immune response and the bacterial mechanisms in play to offset this response, is of considerable importance in dictating the course of the disease. In order to gain an understanding of this interplay it is of importance to analyze how M. tuberculosis interacts with innate immune receptors and makes its entry into macrophages, how it subverts the bactericidal effects of macrophages, and dampens processes required for protective immunity, including cytokine and chemokine induction. This review will focus on some of the Indian efforts in these areas, concentrating mainly on the interaction of M. tuberculosis with macrophages and dendritic cells (DCs). The role of the PE/PPE family of proteins in regulating the immune response, will not be discussed in this chapter. The genome-wide approaches of analyzing host-M. tuberculosis interactions will also be discussed elsewhere.     

Primary biliary cirrhosis: From bench to bedside

Primary biliary cirrhosis(PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient's genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed.     

免疫系统的衰老及其机制

免疫系统随着年龄的增加而功能退化,出现免疫系统衰老.免疫系统衰老与老年人群感染的易感性、疫苗的低效性、自身免疫性疾病增加以及肿瘤多发性密切相关.免疫系统衰老的特征表现为细胞介导的免疫功能下降以及抗体介导的体液免疫应答的降低.在衰老过程中,T细胞和B细胞功能的下降与先天性免疫系统功能的降低同时存在.本文就免疫系统随年龄衰老的改变及其内在机制进行综述.     

Immunology of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system(including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells(e.g., dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.     

Immunotherapy exploiting the versatility of dendritic cells

Dendritic cells (DC) are the most potent antigen-presenting cells that initiate T cell-mediated immune responses. The development of methods to generate a large number of DC in vitro has facilitated their application to immunotherapy. Adding tumor antigens to DC in vitro and administering them to cancer patients is expected to induce effective immune responses to cancers, which are poorly immunogenic in most cases. There are several parameters that need to be optimized to improve the efficacy of DC-based immunotherapy. Because the immune system has developed in order to eliminate microbial pathogens and is thus well equipped with machinery for that purpose, reproducing events occurring during anti-infection immune responses for antitumor immunity may lead to the development of effective tumor immunotherapy.     

Vitamin D and Innate Immunity

This chapter will examine the role of vitamin D in the innate immune system as a mediator of human host defense mechanisms microbial disease, focusing on tuberculosis. The first section will examine tuberculosis and the innate immune response to the intracellular pathogen, Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis. This is followed by a discussion of the known associations, genetic and mechanistic, between the vitamin D pathway and tuberculosis susceptibility. Finally, the chapter will conclude with a discussion on the potential for adjuvant treatment of tuberculosis with vitamin D.     

慢性阻塞性肺疾病的细胞与分子机制研究进展

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)以不完全可逆的气流受限为特征,它在世界范围内的高发病率和病死率是导致巨大经济和社会负担的主要原因.COPD肺部慢性炎症由炎症细胞及其分泌的细胞因子和趋化因子等相互作用而发生发展的,并可触发先天性和获得性免疫反应,进一步加重炎症反应.本文就炎症细胞及细胞因子在COPD形成机制中的作用,以及先天性和获得性免疫机制在COPD肺部炎症的作用作一综述,以期提高对本病发病机制的认识.     

Toll样受体及其在抗结核感染免疫中的作用

Toll样受体(Toll-like receptors,TLR)是表达在哺乳动物细胞表面的一类重要的模式识别受体,是进化中比较保守的一个受体家族,TLR能特异地识别病原体相关分子模式,不仅在激活天然免疫中发挥着莺要的作用,而且还调节获得性免疫,是连接天然免疫与特异性免疫的主要桥梁.研究表明,TLR是介导宿主对结核杆菌的识别及抗结核免疫反应的关键分子,与抗结核感染免疫有关的主要是TLR2和TLR4.对TLR的研究有助于阐明结核病的发病机制并为其治疗提供崭新的策略.     

Iron overload and immunity

Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage.Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes,will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.     

Immune reaction and colorectal cancer: Friends or foes?

The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.     

炎性树突状细胞的功能特性及在支气管哮喘发病机制中的作用

树突状细胞是功能最强的专职抗原递呈细胞,作为机体免疫应答的启动者在免疫应答中占有重要地位.研究显示在感染或炎症状态下由炎性单核细胞分化而来的一种树突状细胞亚型——炎性树突状细胞,参与调节免疫应答.近来,炎性树突状细胞在支气管哮喘发生机制中的作用备受关注,现就炎性树突状细胞在不同类型免疫应答的作用及其与支气管哮喘的关系作一综述.