肝片吸虫对抗百日咳杆菌保护性Th1应答的抑制

百日咳杆菌感染或百日咳疫苗免疫后可诱导较强的抗原特异性Th1应答,对宿主抗感染起关键作用,其中IFN-γ在控制百日咳杆菌感染以及抑制细菌在粘膜部位寄生起重要作用。肝片吸虫感染的宿主主要产生Th1应答。本文的研究目的在于探讨体内细菌病原体诱导的Th1和寄生虫诱导的Th1的相互影响。 实验中所用的抗原包括经甲醛处理的百日咳杆菌的超声粉碎物(BPS),百日咳杆菌     

儿童哮喘与百日咳关系机制的研究进展

支气管哮喘是常见的慢性气道疾病,其主要病理机制为气道炎症及气道重塑,与多种呼吸道病原感染相关。由于近年来全球范围出现“百日咳重现”,百日咳与哮喘的关系也引起了学者们的广泛关注。大量的临床研究提示百日咳与哮喘之间具有相关性,但其相关机制尚未明确。作者对两者之间的相关机制研究在分子、细胞和组织水平进行了综述。在分子水平,百日咳感染可以导致气道炎症及气道重塑。在细胞水平,百日咳感染后可通过百日咳毒素诱导细胞骨架重组,丧失细胞连接的完整性,引发气道炎症,促进气道重塑。在组织水平,百日咳毒素和气管细胞毒素均可引起明显的呼吸道组织学改变,包括气管细胞毒素对纤毛呼吸上皮的挤压和破坏,导致气道炎症及气道重塑。     

细胞因子信号转导抑制因子在呼吸道合胞病毒感染支气管上皮细胞免疫失衡中的表达

呼吸道合胞病毒(respiratory syncytial virus,RSV)是婴幼儿下呼吸道感染的重要病原体之一,流行病学调查发现,婴幼儿期患过RSV毛细支气管炎的患儿中50％ ～ 70％可发生反复喘息,甚至支气管哮喘(简称哮喘)[1].Th1/Th2失衡是哮喘患儿气道炎症和气道高反应性发生和发展的关键[2],细胞因子信号转导抑制因子(suppressor of cytokine signaling,SOCS)与Th1/Th2分化有密切关系[3].本研究通过在体外构建RSV持续感染人气道上皮细胞(human bronchial epithelial cells,HBEC)的模型,并与淋巴细胞共培养,观察干扰素-γ(IFN-γ)和IL-4以及SOCS3和SOCS5的表达,为RSV感染引起Th免疫失衡的机制及SOCS与Th分化的关系提供证据.     

呼吸道病毒与老年人支气管哮喘急性发作期的关系

支气管哮喘的病因目前尚不十分清楚,但考虑与遗传和环境因素引起有关.近年来随着对哮喘病因研究的逐渐深入,呼吸道病毒所引起的哮喘发作或病情恶化受到临床医生的重视.目前研究比较多的是病毒与儿童哮喘的关系[1,2],病毒与老年人哮喘的关系研究的相对较少,本实验进一步明确呼吸道病毒与老年人哮喘的关系.     

B7-1阻断剂对实验性小鼠支气管哮喘的治疗作用

支气管哮喘（简称哮喘）最重要的免疫学异常是Th1／Th2亚群数目和（或）功能比例失衡，表现为Th2亚群数目增多和功能亢进，Th1亚群数目减少和功能降低。抗原递呈细胞（APC）能刺激CD4^＋T淋巴细胞向Th2细胞分化，是诱导哮喘发病的第一步，APC／T淋巴细胞相互识别中，B7家族协同刺激信号和其配体的结合是诱导Th2效应的关键，分子中与哮喘关系最密切的是B7-1（CD80）和B7-2（CD56），其中B7-1／CD28是激活T淋巴细胞最重要的协同刺激通路是B7-1／CD28通路，其在哮喘的发病和治疗中具有重要研究价值。我们的实验以小鼠哮喘模型为研究对象，观察阻断B7-1／CD28协同刺激通路对哮喘的治疗作用，为探讨哮喘治疗的新途径提供实验资料。     

卡介苗预防支气管哮喘的研究进展

支气管哮喘（哮喘）是一种免疫性疾病，目前还缺乏有效的预防手段，在人类应用卡介苗（BCG）预防结核病的80多年中，有证据表明BCG能预防哮喘，认为BCG作为一种免疫刺激剂，可以诱导Th1型免疫反应，抑制Th2型免疫应答，调控Th1／Th2型细胞之间的平衡，从而抑制气道高反应性、减轻气道炎症。但是最近很多研究表明，BCG与哮喘防治无明显关系，不能从根本上减轻哮喘的症状，对哮喘无防治作用。现就近年来国内外应用BCG预防哮喘的两种不同观点以及造成两者偏差的可能原因做一综述。     

影响支气管哮喘Th1/Th2失衡的因素及治疗的新视点

支气管哮喘(简称哮喘)是由嗜酸粒细胞、肥大细胞和T细胞等多种炎性细胞参与的气道慢性炎症性疾病,其发病机制极为复杂,近来研究发现Th1/Th2失衡是哮喘免疫学发病机制中的一个重要环节,本文就Th1/Th2失衡与哮喘的关系,Th1/Th2平衡的调节及其在哮喘治疗中的价值作一综述.     

影响支气管哮喘Th1／Th2失衡的因素及治疗的新视点

支气管哮喘（简称哮喘）是由嗜酸粒细胞、肥大细胞和T细胞等多种炎性细胞参与的气道慢性炎症性疾病，其发病机制极为复杂，近来研究发现Th1／Th2失衡是哮喘免疫学发病机制中的一个重要环节，本文就Th1／Th2失衡与哮喘的关系，Th1／Th2平衡的调节及其在哮喘治疗中的价值作一综述。     

细胞信号转导在Th细胞分化中的作用

支气管哮喘(哮喘)是由多种细胞(如嗜酸粒细胞、肥大细胞、T细胞、中性粒细胞、气道上皮细胞等)和细胞组分参与的气道慢性炎症性疾患[1]。气道高反应性和可逆性气流受限是其病理特征。目前研究表明:Th1和Th2之间平衡失调是哮喘发病的重要机制。并认为Th2优势应答是哮喘发病的始动因素和维持因素,而对Th1优势应答在哮喘中的作用意见尚未统一。Kavita[2]研究表明:STAT4介导的细胞信号转导对由变态反应原诱导的气道反应的加重起着重要作用,而且Th1优势应答诱导产生的对嗜酸性粒细胞有趋化功能的趋化因子可引起哮喘患者气道极大的损伤。因此…     

γδT细胞与支气管哮喘关系的研究进展

支气管哮喘（哮喘）是以气道嗜酸粒细胞、淋巴细胞等炎症细胞浸润为主、气道高反应性增高为特征、Th1/Th2反应失衡并表现为Th2优势应答的疾病.关于淋巴细胞与哮喘的关系大部分研究仅限于αβT细胞,对γδT细胞在支气管哮喘发生发展中的作用是近十多年来才开始关注的.本文就γδT细胞的免疫学特性及与哮喘的关系作一综述.     

Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production

Acute exacerbations are the major cause of asthma morbidity, mortality, and health-care costs and are difficult to treat and prevent. The majority of asthma exacerbations are associated with rhinovirus (RV) infection, but evidence supporting a causal relationship is weak and mechanisms are poorly understood. We hypothesized that in asthmatic, but not normal, subjects RV infection would induce clinical, physiologic, and pathologic lower airway responses typical of an asthma exacerbation and that these changes would be related to virus replication and impaired T helper 1 (Th1)/IL-10 or augmented Th2 immune responses. We investigated physiologic, virologic, and immunopathologic responses to experimental RV infection in blood, induced sputum, and bronchial lavage in 10 asthmatic and 15 normal volunteers. RV infection induced significantly greater lower respiratory symptoms and lung function impairment and increases in bronchial hyperreactivity and eosinophilic lower airway inflammation in asthmatic compared with normal subjects. In asthmatic, but not normal, subjects virus load was significantly related to lower respiratory symptoms, bronchial hyperreactivity, and reductions in blood total and CD8⁺ lymphocytes; lung function impairment was significantly related to neutrophilic and eosinophilic lower airway inflammation. The same virologic and clinical outcomes were strongly related to deficient IFN-γ and IL-10 responses and to augmented IL-4, IL-5, and IL-13 responses. This study demonstrates increased RV-induced clinical illness severity in asthmatic compared with normal subjects, provides evidence of strong relationships between virus load, lower airway virus-induced inflammation and asthma exacerbation severity, and indicates augmented Th2 or impaired Th1 or IL-10 immunity are likely important mechanisms.     

Asthma: new developments concerning immune mechanisms, diagnosis and treatment

PURPOSE OF REVIEW: This brief review discusses how recent research may modify our understanding of the immunology of asthma. Consideration is given to the possible impact that these observations may have upon diagnostic and therapeutic strategies. RECENT FINDINGS: New studies indicate that current conceptions regarding the balance between Th1 and Th2 systems may need modification. The relationship between infection and the development of asthma in children has proven to be much more complex than originally suggested by the 'hygiene hypothesis'. In addition, important genetic differences have been found in the response of asthmatic patients to therapeutic agents. SUMMARY: Greater insight into the mechanisms responsible for asthma and the introduction of new drugs will depend in part upon the development of reliable and simple methods for detecting airway inflammation. As the immunologic aspects of asthma are dissected, we can expect that many more potential targets for treatment will be discovered, but treatment may have to be individualized for genetic differences between different individuals.     

Relationship of complete respiratory dysfunction: one linked airway. A selective clinical discussion.

There is increasing clinical, immunologic, and pathophysiological consensus that allergic rhinitis (AR) and asthma are different manifestations of a single condition: inflammation of the upper and lower airways characterized by nasal and bronchial hyperresponsiveness. Most patients with asthma have AR and asthma is present in a large percentage of patients with AR. Rhinitis is a major riskfactor for asthma. Treating rhinitis in patients with AR and asthma improves not only the rhinitis but also the asthma. It is becoming clinically evident and studies have confirmed that improving the upper airway also helps the lower airway. There appears to be a connection between upper and lower airway dysfunction, suggesting one linked airway. There also seems to be a relationship between AR and asthma, suggesting that the two conditions are manifestations of one syndrome of complete respiratory dysfunction. The evidence is compelling but it is not completely established.     

Eosinophilic airway disorders

Diseases of the airway are common and make up a significant proportion of the respiratory physician's workload. The major contributors to this situation, such as asthma, chronic obstructive pulmonary disease (COPD), and chronic cough, all result from airway inflammation and often have an overlapping clinical picture, which in some instances makes accurate clinical diagnosis difficult. Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness, and airway inflammation, which is usually eosinophilic. However, the relationship between eosinophilic inflammation and asthma is complex, with only a weak correlation between the severity of airway inflammation and the markers of the severity of asthma, such as Pc20 and FEV1. Eosinophilic bronchitis is characterized by a chronic cough and sputum eosinophilia without airway hyper-responsiveness or variable airflow obstruction. The asthma phenotype is characterized by microlocalization of mast cells in the airway smooth muscle, emphasizing the importance of airway smooth muscle dysfunction in asthma. COPD has generally been considered to be a neutrophilic disease, in contrast to asthma. However, there is increasing evidence that a significant subgroup exists consisting of patients with stable COPD who have chronic airway eosinophilia with a more steroid-responsive disease. This article covers the role of eosinophils in the airway disorders asthma, COPD, and eosinophilic bronchitis.     

Roles of hyperresponsiveness and airway inflammation in bronchial asthma

Bronchial hyperresponsiveness is one important feature of bronchial asthma, and evidence has been accumulated that airway inflammation contributes to the specific airway response in asthmatic patients. Increase in airway responsiveness following viral infection, exposure to allergen, ozone or chemical sensitizers supports the evidence for a link between hyperresponsiveness and airway inflammation. However, as only some respiratory tract infections induce an increase in hyperresponsiveness, and patients with chronic bronchitis and cystic fibrosis have less airway hyperresponsiveness than asthmatics, airway inflammation is considered to be only one of many factors contributing to the hyperresponsiveness of asthmatic airways.     

Viral infections in asthma and COPD

Airway viral infections are associated with the pathogenesis of asthma and COPD. It has been argued that respiratory syncytial virus (RSV) infection in infancy is a probable causal factor in the development of pediatric asthma. RSV infections tend to induce Th2-biased immune responses in the host airways. RSV infection, atopy, and low pulmonary function in neonates may work synergistically toward the development of pediatric asthma. Human rhinovirus (HRV) is a representative virus associated with the exacerbation of asthma in both children and adults. Viral infections trigger innate immune responses including granulocytic inflammation and worsen the underlying inflammation due to asthma and COPD. The innate immune responses involve type-I and -III interferon (IFN) production, which plays an important role in anti-viral responses, and the airway epithelia of asthmatics reportedly exhibit defects in the virus-induced IFN responses, which renders these individuals more susceptible to viral infection. A similarly impaired IFN response is seen in COPD, and several investigators propose that latent adenoviral infection may be involved in COPD development. Persistent RSV infections were detected in a sub-population of patients with COPD and were associated with the accelerated decline of lung function. The virus-induced upregulation of co-inhibitory molecules in the airway epithelium partly accounts for the persistent infections. Experimental animal models for virus-asthma/COPD interactions have shed light on the underlying immune mechanisms and are expected to help develop novel approaches to treat respiratory diseases.     

Respiratory infections: their role in airway responsiveness and pathogenesis of asthma

A clear relationship between viral upper respiratory infections and exacerbations of asthma has been established in numerous clinical studies. However, a unifying concept to explain how respiratory viruses bring about these changes has not been established unless it is the ability of viral illnesses to promote the inflammatory process. These changes in inflammation potentially encompass several organ systems: airway epithelium, the autonomic nervous system, and immediate hypersensitivity reactions. Thus, enhanced airway reactivity in viral respiratory infections represents a complex orchestration of many factors and functions to create the end result of bronchial hyperresponsiveness. Insight into precisely how the respiratory virus initiates these changes should provide valuable and new information into the pathogenesis of asthma. Therefore, not only is virus-induced asthma an important clinical problem, but it may also serve as a window to mechanisms of airway hyperreactivity and asthma.     

Invariant natural killer T (iNKT) cells in asthma: a novel insight into the pathogenesis of asthma and the therapeutic implication of glycolipid ligands for allergic diseases.

Allergic bronchial asthma is a complex inflammatory diseases originated from dysregulated immune responses in the respiratory mucosa. The inflammatory state in asthmatic lung is characterized by massive infiltration with eosinophils, lymphocytes, and mast cells in the airway mucosa leading to airway hyperseisitivity, goblet cell hyperplasia and mucus overproduction. The inflammatory process is thought to be the result of intensive T helper (Th) 2-biased immune response. Over the past several years, there has been enormous progress in understanding the mechanisms for development of Th2-biased responses after inhaled exposure to allergens and the characteristics of CD4+ T cells prominently involved in this process. Recently, a new population of T cells, invariant natural killer T (iNKT) cells has been shown to play an important role in the pathogenesis of mouse model of allergic airway inflammation. iNKT cells are one of the most potent immune modulators through a massive production of a various cytokines including IL-4 and IFN-gamma upon activation, and are involved in a variety of immunoregulations including infection, autoimmunity, and tumor surveillance. The potent pathogenic role of iNKT cells in the development of bronchial asthma is due to their ability to produce predominant Th2 cytokines in a given condition. The involvement of iNKT cells in the pathogenesis of asthma might have been underestimated in the past studies demonstrating the involvement of CD4+ T cells in asthma because of the difficulty in the detection of iNKT cells. Meanwhile, growing evidences have demonstrated that iNKT cells could be a promising target for immune-based therapies for autoimmune diseases, tumor, and infection due to the invariance of their TCR usage, the restriction to the evolutionally-conserved non-polymorphic antigen-presenting molecule CD1d, and their outstanding ability to produce both Th1- and Th2-cytokines. In this review, we will overview current understanding of the pathophysiological roles of iNKT cells in asthma. We would also discuss on possible therapeutic approaches to bronchial asthma employing glycolipid ligands for iNKT cells.     

Viral infection and asthma: Respiratory syncytial virus and wheezing illness

A strong link between bronchiolitis and asthma has been indicated. Bronchiolitis that occurs in infants is manifested physiologically by a widespread narrowing of the air passages and, clinically, by asthma-like symptoms.The major cause of bronchiolitis is respiratory syncytial virus infection. While the precise pathophysiologic sequences of infection are incomplete, many observations have suggested that there is an infiltration of eosinophils in the airways. Current studies have shown that the respiratory syncytial virus penetrates the pulmonary defenses and initiates immunologic responses. The histamine and leukotriene mediators that are released produce an inflammatory reaction and the chemotactic factors bring eosinophils to the site of the reaction. Degranulation of eosinophils can release eosinophil cationic protein into the airways. Our finding that chemoattractants for eosinophils, interleukin-8 and RANTES (regulated upon activation, normal T cell expressed and presumably secreted) were detected in nasopharyngeal aspirates of infants with bronchiolitis suggests that such chemokines from epithelial cells may induce an eosinophil infiltration in the airway. Similar allergic inflammatory changes have been observed in asthma and in epithelial cells infected with respiratory viruses. Future investigation of the mechanism by which bronchiolitis can induce asthma will provide benefits in the treatment and prevention of asthma in sensitive individuals.