粘膜免疫的研究进展

粘膜免疫研究始于本世纪初，１９６３年Ｃｈｏｄｉｒｋｅｒ和Ｔｏｍａｓ关于人体粘膜粘液中免疫球蛋白类型的研究，开辟了粘膜免疫研究的新时期。随后，生化、遗传、细胞及分子生物学领域不断取得的进展，极大地丰富了粘膜免疫的研究。现将有关的研究作一综述。１粘膜免疫...     

寄生虫的粘膜免疫研究进展

粘膜免疫是机体抗感染的第一道免疫屏障，寄生虫的粘膜免疫，对于寄生虫病发病机制的了解及免疫预防方法的优选有重要的意义。本文着重对弓形虫、隐孢子虫、血吸虫的粘膜免疫及粘膜疫苗的研究进展进行综述。     

寄生虫的粘膜免疫研究进展

粘膜免疫是机体抗感染的第一道免疫屏障 ,寄生虫的粘膜免疫 ,对于寄生虫病发病机制的了解及免疫预防方法的优选有重要的意义。本文着重对弓形虫、隐孢子虫、血吸虫的粘膜免疫及粘膜疫苗的研究进展进行综述     

粘膜免疫相关佐剂研究进展

覆盖在胃肠道、呼吸道、泌尿生殖道及一些外分泌腺的粘膜具有丰富的免疫细胞,这些细胞被归入粘膜相关淋巴组织(MALT),MALT包括集合淋巴小结和弥散免疫细胞,是粘膜免疫系统的主要组成部分。机体的粘膜组织是外界抗原入侵和定居的易感场所,由抗原诱导产生的局部粘膜免疫反应是粘膜表面重要的体内防御机制。而诱导粘膜免疫,特     

霍乱毒素与粘膜免疫

霍乱毒素 (CT)是霍乱弧菌产生的一种不耐热肠毒素 ,是霍乱弧菌引起腹泻的致病因子 ,CT具有很好的免疫原性 ,也是霍乱弧菌疫苗开发中考虑的一个重要候选抗原。另外 ,CT是很好的粘膜佐剂 ,在粘膜免疫研究中具有很重要的作用。本文将对CT的粘膜免疫诱导作用作一综述。1　CT的分子结构和致病机理CT是由A和B亚单位组成的AB5型结构的六聚体蛋白。A亚单位 (CTA)能被蛋白酶裂解为两个片段 :A1和A2 ,二者以二硫键相连。A1具有ADP -核糖基转移酶的作用 ,它能由B亚单位 (CTB)介导透过细胞膜 ,是CT的毒力活性部分 ;A2的主要功能是连接A1和…     

老年胃肠道感染和粘膜免疫

虽然老年对免疫活性的影响已有很多研究,但对分泌性或者粘膜免疫系统尚未引起足够重视。监于该系统起着防卫许多抗原和病原体第一线的关键作用,因此不能忽视。许多研究资料表明,老年人粘膜表面如呼吸道和胃肠道显示对感染性疾病的易感性增加,这反映分泌性免疫系统分泌的主要免疫球蛋白A(lgA)与衰老相关的下降。除流行病学资料证实免疫反应降低、呼吸和胃肠道感染性疾病的发病率增高与衰老相关之外,分泌性免疫系统与衰老相关的资料则不多见。许多研究者报告,人类和啮齿动物抗体形成能力、总抗体和/或特异性抗体滴度与衰老呈相关性降低。但其他一些研究者报告,不同种类动物血清lgA水平随年龄增长     

粘膜免疫与艾滋病的预防和控制

粘膜是大多数病原微生物侵入机体的门户。粘膜免疫系统的特异和天然免疫机制阻止了绝大部分粘膜感染的发生。世界范围内约有90%的人类免疫缺陷病毒(HIV)感染是通过粘膜发生的。与HIV-1粘膜传播有关的粘膜包括泌尿生殖系统和消化系统粘膜。消化道粘膜不仅在HIV-1侵入机体的过程中作为病毒入侵的门户,而且在HIV-1感染后为病毒的繁殖提供场所。HIV-1感染导致粘膜中CD4 T淋巴细胞不断减少,可能在HIV-1感染后的病理过程中发挥重要作用。通过杀微生物制品或艾滋病疫苗阻断或限制HIV-1跨越粘膜屏障,可能是控制HIV/AIDS粘膜传播的最有效的生物学干预措施。     

阿尔茨海默病患者嗅粘膜免疫病理观察

目前阿尔茨海默病 (Ａｌｚｈｅｉｍｅｒｄｉｓｅａｓｅ,ＡＤ)的临床诊断主要依赖临床神经心理学检查 ,通过排除法得出。国外报道嗅粘膜 (ｏｌｆａｃｔｏｒｙｍｕｃｏｓａ ,ＯＭ)免疫病理染色可能成为ＡＤ诊断的客观指标 ,为此我们对ＯＭ免疫病理特点及其对ＡＤ的临床诊断价值进行了探讨。　　一、对象和方法　　 1997年至 1999年收治的 9例ＡＤ患者、10例血管性痴呆 (ｖａｓｃｕｌａｒｄｅｍｅｎｔｉａ ,ＶＤ)患者以及 10例健康老年人 (ｎｏｒｍａｌｅｌｄｅｒｌｙｃａｓｅｓ ,ＮＥＣ)的ＯＭ进行免疫病理检查 ,所有研究对象均来自生活在广州…     

粘膜免疫与反复发作性尿路感染

尿路感染 (ｕｒｉｎａｒｙｔｒａｃｔｉｎｆｅｃｔｉｏｎ ,ＵＴＩ)是指尿路内有致病微生物繁殖而引起的尿路炎症。主要致病微生物为细菌 ,偶尔也可为真菌或病毒等。尿路感染属于粘膜相关疾病 ,临床上易反复发作。反复发作的原因除尿路梗阻、畸形、机体免疫功能低下外 ,粘膜屏障破坏、粘膜免疫功能紊乱也是重要原因。1　尿路粘膜的屏障作用与反复尿路感染 (ＲＴＵＩ)尿路上皮细胞表面有一层粘液 ,系由上皮细胞、杯状细胞粘液腺分泌的高分子糖蛋白、溶菌酶、浆蛋白组成 ,可以保持尿路粘膜表面光滑 ,减少物质沉积 ,对抗粘膜表面酸、酶及细菌的…     

肝纤维化的研究进展

肝纤维化的形成,与病因、肝脏炎症有关.肝纤维化的消散,与胶原酶的活性有关.但是在上述肝纤维化的整个代谢过程中,最重要的是肝星状细胞(HSC)的活化、转化和凋亡等事件.     

霍乱毒素黏膜免疫佐剂作用研究进展

霍乱(cholera)是由霍乱弧菌(vibrio cholerae)引起的急性传染病,属三大国际检疫传染病之一,也是我国法定管理的甲类传染病.其病理变化主要由霍乱弧菌的肠毒素所致,临床表现为不同程度的腹泻、呕吐、失水,少数患者出现肌肉痉挛、代谢性酸中毒、循环衰竭等.     

The effect of route of immunization on mucosal immunity and protection

In macaques, the route of immunization has a profound effect on the immune response. Augmenting rectal or vaginal immunization with oral or nasal immunization enhanced the secretory IgA, serum IgG, and T cell responses. However, targeted iliac lymph node (TILN) immunization with recombinant simian immunodeficiency virus (SIV) gp120 and p27 elicited the most consistent mucosal antibody responses in the rectum, vagina, urine, seminal fluid, and blood. Both mucosal and TILN immunization induced specific CD4+ T cell proliferative responses in the iliac lymph nodes, which drain these mucosal surfaces, and in the splenic and circulating T cells. Rectal mucosal challenge with cell-free SIV induced total protection in 4 of 7 macaques that were immunized by the TILN route, and, compared with unimmunized macaques or those immunized by the mucosal route (P<.001), it induced a >90% decrease in virus load in 3 of them. Protection from mucosal rectal infection with SIV was significantly associated with an increase in the CD8 suppressor factor (which was generated by the iliac lymph node), RANTES, and MIP-1beta (P<.01).     

糖尿病血脂异常研究新进展

糖尿病血脂异常危害严重,但我国对该病的防治还不尽人意,临床实践与指南仍有较大差距.降低低密度脂蛋白胆固醇是糖尿病血脂异常防治的首要目标.生活方式调整和他汀类仍是糖尿病血脂异常治疗的基石,但在大剂量使用他汀类时应注意其不良反应,如肌酶的升高以及发生糖尿病风险的增加等.他汀类联合其他降脂药能否降低残留心血管风险,仍需进一步研究证实.     

糖皮质激素抵抗的研究进展

糖皮质激素（glucocorticoid，GC）由肾上腺皮质束状带合成和分泌，受下丘脑-垂体-肾上腺轴的调节，具有调节碳水化合物、蛋白质、脂肪和水、盐、电解质的代谢，维持机体内环境平衡，以及抑制免疫／炎症反应等多项生理功能。GC是治疗支气管哮喘、原发性肾病综合征、溃疡性结肠炎、系统性红斑狼疮、多发性肌炎等风湿、免疫性疾病的主要药物，多数患者经GC治疗能取得满意疗效，但有少数患者对大剂量GC治疗反应很差或无反应，称为激素抵抗（glucocorticoid resistance），可分为原发性激素抵抗综合征和获得性激素抵抗综合征。尽管激素抵抗发病率较低，但可致治疗棘手和病人预后较差。因此，了解GC抵抗的发生机制，对诊治GC抵抗型患者是十分重要的，现就GC抵抗近年的相关研究进展综述如下。     

Use of recombinant virus-vectored tuberculosis vaccines for respiratory mucosal immunization

Recombinant virus-vectored TB vaccines represent the most promising vaccine platform for boosting the protective immunity mediated by parenteral BCG prime immunization. A major advantage associated with virus-vectored vaccines is that they are potent respiratory mucosa-deliverable vaccines. A recombinant replication-deficient adenoviral (Ad) vector was engineered to express Mycobacterium tuberculosis (M.tb) Ag85A. Single administration of this Ad vaccine via the intranasal, but not intramuscular, route provided potent immune protection from pulmonary M.tb challenge. Respiratory mucosal boosting immunization with Ad vaccine was effective in enhancing T-cell activation and immune protection following parenteral DNA or BCG prime immunization. We have also recently developed a recombinant vesicular stomatitis virus-vectored (VSV) TB vaccine. Ad and VSV vector systems will be complementary to each other for BCG prime-virus vaccine boost immunization protocols.     

幽门螺杆菌粘膜疫苗的研究进展

胃窦部幽门螺杆菌(Helicobacter pylori,Hp)感染可引起许多胃十二指肠疾病,包括B型(胃窦)胃炎、消化性溃疡、胃粘膜相关淋巴组织淋巴瘤和胃癌.临床上对Hp感染的治疗主要采用以抗生素为主的治疗方案,虽可在一定程度治愈Hp感染,但不能预防Hp再感染,同时抗生素的使用可导致Hp耐药菌株的产生和带来许多严重的副作用.而Hp疫苗可以解决这一难题,使得Hp疫苗接种成为了根治Hp感染和预防再感染的唯一方法.目前,Hp疫苗的研究进展迅速,粘膜疫苗以其有效的保护性免疫效果成为这一研究的热点.我们对Hp粘膜疫苗的组成、接种途径、免疫效果及保护性免疫机制等方面的研究进展加一综述.     

Controlled analysis of nanoparticle charge on mucosal and systemic antibody responses following pulmonary immunization

Pulmonary immunization enhances local humoral and cell-mediated mucosal protection, which are critical for vaccination against lung-specific pathogens such as influenza or tuberculosis. A variety of nanoparticle (NP) formulations have been tested preclinically for pulmonary vaccine development, yet the role of NP surface charge on downstream immune responses remains poorly understood. We used the Particle Replication in Non-Wetting Templates (PRINT) process to synthesize hydrogel NPs that varied only in surface charge and otherwise maintained constant size, shape, and antigen loading. Pulmonary immunization with ovalbumin (OVA)-conjugated cationic NPs led to enhanced systemic and lung antibody titers compared with anionic NPs. Increased antibody production correlated with robust germinal center B-cell expansion and increased activated CD4⁺ T-cell populations in lung draining lymph nodes. Ex vivo treatment of dendritic cells (DCs) with OVA-conjugated cationic NPs induced robust antigen-specific T-cell proliferation with ∼100-fold more potency than soluble OVA alone. Enhanced T-cell expansion correlated with increased expression of surface MHCII, T-cell coactivating receptors, and key cytokines/chemokine expression by DCs treated with cationic NPs, which were not observed with anionic NPs or soluble OVA. Together, these studies highlight the importance of NP surface charge when designing pulmonary vaccines, and our findings support the notion that cationic NP platforms engender potent humoral and mucosal immune responses.The lung is a primary site of pathogen entry and is therefore a critical target for mucosal vaccination. Conventionally administered vaccines (e.g., s.c. or intramuscular injection) provide strong humoral protection, but often fail to generate mucosal immunity, especially in the form of IgA (1). Mucosal vaccines not only provide local protection, but also confer systemic immunity, including distal mucosal sites (1–3). Mucosal and systemic antibody responses require complex cross-talk between innate and adaptive immune cells. Antigens are first encountered by professional antigen presenting cells (APCs), such as dendritic cells (DCs), at the site of infection or injury. Activated DCs migrate to the draining lymph node (dLN), where they present antigenic peptides on MHCII, which allows for activation of antigen-specific CD4⁺ T cells. Activated T cells instruct antigen-specific B cells to form germinal centers (GC) in the dLN where B cells expand, undergo affinity maturation, and Ig class switch recombination, resulting in production of highly specific antibodies with specialized functions (4). All three cell types (DCs, CD4⁺ T cells, and B cells) are required for GC formation, because T-cell–deficient mice fail to form GCs and DC depleted mice exhibit reduced antibody production (5–7).Nanoparticle (NP) formulations are being engineered to improve subunit vaccine approaches that induce pathogen mimicry while still maintaining the safety of subunit vaccines (8, 9). In the lung, NP formulations offer potential solutions to overcome biological barriers and target APCs (2, 10–13). Cationic NP formulations have been shown to increase mucosal antibody production following pulmonary or intranasal administration (14, 15), whereas independent studies using anionic NP approaches show only minimal improvement in antibody production compared with immunization with soluble protein alone (16, 17). To date, no direct evaluation of NP surface charge on mucosal immune responses has been performed, likely due to limitations in NP formulation that prevent such a comparison without dramatically changing NP composition. Our studies used the unique Particle Replication in Non-Wetting Template (PRINT) process to exquisitely control all other nanoparticle characteristics and specifically investigate the role of NP charge on vaccine responses.     

阿尔茨海默病的最新研究进展

阿尔茨海默病(AD)是老年期痴呆最常见的疾病之一,是现代老龄化社会面临的严峻问题, 也是生物医学研究者面对的重大课题.