粘膜免疫系统与粘膜免疫应答的诱导

粘膜免疫系统是机体抵抗病原体入健的第一道免疫屏蔽,同机体的系统免疫相比,粘膜免疫系统的淋巴细胞总数远远超过存在于骨髓,胸,腺,脾脏以及淋巴结中的淋巴细胞数量,粘膜表面分泌性免疫球蛋白A（sIgA)的量显高于循环IgG的总量,而且粘膜分泌物中的抗体以IgA抗体为主,由于粘膜免疫系统的区域性分布,诱导系统免疫的免疫途径和免疫佐剂不能诱导粘膜免疫应答,经消化道,呼吸道和生殖道免疫可有效地诱导粘膜免疫应答,霍乱毒素是良好的粘膜免疫,佐剂,能有效地诱导粘膜免疫应答,粘膜免疫的上述特点可能是某些疫苗经系统免疫后,尽管能诱导血液中产生高滴度的IgG抗体,但不能预防疾病的原因。     

乳酸菌与肠粘膜免疫

1　乳酸菌在胃肠道的分布胃肠道由复杂的生态系统组成 ,至今已被分离、鉴定的菌种有 40 0多种 ,以严格厌氧菌为主。据统计 :人体的微生物数目达到 10 1 3～ 10 1 4 个 ,超过了人体细胞总数 ,而肠道中的微生物又是最重要的。表 1　胃肠道中乳酸菌的分布 [1 ]部位组成菌体浓度 (CFU/ml)胃十二指肠、空肠回肠结肠StreptococcusLactobacillus与胃相似BacteriodesClostridiumStreptococci LactobacillusBacteriodesEubacteriumClostridium PeptococcusBifidobacteriumFusobacterium Streptococcus10 1～ 10 2*10 2 ～ 10 410 6～ 10 8***1…     

粘膜免疫

细心的读会发现,在本书涉及的16种细菌性感染中,除一种(Borrelia burgdorferi)是通过节肢动物叮咬皮肤传播以外,其它都是直接伤害或经粘膜表面侵入。这种情况很普遍,因为绝大多数细菌和病毒感染都是这种方式,但由原生动物感染的疟疾是个最重要的例外。免疫系统与大多数物质的接触都是在粘膜(图1),     

粘膜免疫佐剂研究进展

粘膜免疫佐剂在新型疫苗的设计中具有重要作用。常用的粘膜免疫佐剂主要包括细菌性物质、细胞因子以及抗原递送系统。本文综述了这些佐剂的研究进展,以期为新型疫苗研究提供参考。     

M细胞--启动粘膜免疫应答的入口

粘膜免疫系统是机体免疫系统的重要组成部分,外来抗原可选择性的与M细胞相结合并被内吞入M细胞以诱导粘膜免疫应答或造成机体的感染.本文介绍了M细胞的结构、分化来源、生物学功能、与微生物感染的关系、及其在粘膜疫苗、药物传送中的应用.     

哺乳类动物和人的粘膜免疫系统与生育力调节

皮肤和粘膜是哺乳类动物和人体的内外环境之间的第一道屏障或第一道防线。粘膜是消化道,呼吸道和泌尿生殖道的重要组成部份。在粘膜系统大约集中了70%的淋巴组织。哺乳类动物的配子成熟。运输,精卵子的结合和融合,受精卵的运输,胚泡着床等等,都是在生殖道内进行的。因此,研究生殖道的粘膜免疫系统在不育的诊断和治疗,性传染疾病的控制,避孕疫苗的研究等方面,都有很重要的意义。粘膜免疫系统有几个显著的特点：首先,在抗体成份方面,以IgA为主,IgA的分泌量约占全身各种抗体成份的60%以上。为了刺激粘膜的体液免疫反应,局部免疫的效果最佳。参与粘膜免疫调节的细胞有T辅助细胞,T杀伤和抑制细胞,反抑制细胞,抗抑制细胞。其次在细胞免疫方面,粘膜系统有许多TCR1 T细胞,它们在粘膜免疫方面可能具有重要的功能。粘膜系统的免疫细胞的特有分布是通过细胞表面的许多受体和配体的相互作用来实现的。雌性生殖道的粘膜免疫系统的反应常与激素水平有关,如雌二醇的升高常伴随IgA的升高,孕酮的存在常有抑制IgA产生的作用。此外,在妊娠子宫内发现有许多特殊的抑制细胞和其他许多抑制因子。在某些不孕患者的精浆内可测定到抗精子的IgA和IgG。精浆内存在许多免疫细胞抑制因子和许多免疫细胞。不育患者的免疫细胞的数量增高。雌性生殖道内IgA型抗精子抗体的存在与不育的关系十分密切。以单克隆IgA研究抗精子局部免疫的作用是很重要的课题。通过控制粘膜免疫系统来调节生育力。应用免疫抑制药物可以治疗某些免疫性不育。对于免疫避孕来说,口服避孕疫苗的研制不仅是必要的,也是可能的。动物实验表明,口服疫苗可以刺激局部IgA和IgG的产生。基因工程细菌也许是最简便有效的抗精子避孕疫苗的载体。其它一些口服疫苗的投药系统也正在研制之中。口服疫苗同时也是某些性传播疾病（如艾滋病、乙肝等）的重要预防手段。     

M细胞—启动粘膜免疫应答的人口

粘膜免疫系统是机体免疫系统的重要组成部分,外来抗原可选择性的M细胞相结合并被内吞入M细胞以诱导粘膜免疫应答或造成机体的感染。本文介绍了M细胞的结构、分化来源、生物学功能、与微生物感染的关系、及其在粘膜疫苗、药物传送中的应用。     

禽流感与禽流感病毒研究进展

对禽流感的症状、传播、感染、流行规律、疾病发生历史、流行监测、诊断、防治以及禽流感病毒的分类地位、命名、病毒粒子形态结构、病毒基因组结构、病毒复制、病毒变异的研究进展作了综合评述,并对该领域的研究热点和方向作了探讨。     

Avian influenza virus

Recent outbreaks of highly pathogenic avian influenza in chickens and ducks that occurred in 9 Asian countries including Japan alarmed to realize that there is no border for infections and gave a rise to great concern for human health as well as for agriculture. This H5N1 virus jumped the species barrier and caused severe disease with high mortality in humans in Viet Nam and Thailand; 15 deaths of 22 cases and 8 of 12, respectively. A second concern was the possibility that the situation could give rise to another influenza pandemic in humans since genetic reassortment may occur between avian and human influenza viruses when a person is concurrently infected with viruses from both species. This process of gene swapping inside the human body can give rise to a new subtype of the influenza virus to which humans would not have immunity. The outbreaks also emphasized the need to continue active surveillance on avian influenza throughout the year to undertake aggressive emergency control measures as soon as an infection is detected.     

肠道黏膜免疫与炎症小体的研究进展

肠道是机体消化器官,为机体生命活动提供所需要的营养。肠道免疫系统有独特的功能,在抵抗潜在病原体侵入机体过程中发挥至关重要的作用。炎症小体是机体天然免疫系统中重要的蛋白复合体感受器,参与病原体引起的宿主防御反应,并在维持肠道免疫稳态中发挥关键作用。本文综述了肠道黏膜免疫系统及炎症小体在肠道免疫中的作用。     

Toxoplasma gondii and mucosal immunity

Toxoplasma gondii, an intracellular parasite infects the host through the oral route. Infection induces a cascade of immunological events that involve both the components of the innate and adaptative immune responses. Alteration of the homeostatic balance of infected intestine results in an acute inflammatory ileitis in certain strains of inbred mice. Both the infected enterocytes as well as the CD4 T cells from the lamina propria produce chemokines and cytokines that are necessary to clear the parasite whereas CD8 intraepithelial lymphocytes secrete transforming growth factor beta that reduces the inflammation. In this review, we describe the salient features of this complex network of interactions among the different components of the gut-associated lymphoid tissue cell population that are induced after oral infection with T. gondii.     

Stimulation of protective and cross-protective immunity against influenza B virus after adjuvant mucosal immunization of mice

Intratracheal immunization of mice with inactivated influenza B virus and delipidated Bacillus firmus as adjuvant increases protection of mice against infection with the homologous virus strain and induces cross-protection: mice immunized by influenza virus B/Yamanashi 166/98 were protected even against phylogenetically distant virus drift variant B/Lee/40 lethal for mice.     

Genetic immunity and influenza pandemics

In addition to the great number of publications focused on the leading role of virus mutations and reassortment in the origin of pandemic influenza, general opinion emphasizes the victim side of the epidemic process. Based on the analysis and integration of relevant ecological, epidemiological, clinical, genetic and experimental data, the present article is focused on the evolution of 'virus - victim' ecological systems resulting in the formation of innate (i.e. genetic, constitutional) immunity in the involved species and populations. This kind of immunity functions today as the greatest natural barrier to the pandemic spread of influenza among humans and ecologically related kinds of animals. Global influenza pandemics can arise when the worldwide population contains at least a minimum number of people susceptible to a known or mutant influenza virus. Special attention is paid in this article to individual tests for the presence of this barrier, including the implications of specific findings for public health policy. Such tests could be based on in vitro observation of the action of relevant virus strains on primary cell cultures or on their cellular or molecular components extracted from individuals. The resources of the Human Genome Project should also be utilized.     

Salmonella-mediated mucosal cell-mediated immunity.

Oral immunization with the recombinant Salmonella typhimurium strain (BRD 847) expressing the C fragment of tetanus toxin (TT) induces brisk Ag-specific mucosal S-IgA and serum Ab responses characterized by strong IgG2a Abs to the encoded antigen. We have constructed an attenuated Salmonella typhimurium (aroA- aroD-) strain that expresses chicken egg albumin (OVA) to further elucidate the role of Salmonella-induced Th1 cell phenotype on mucosal cell-mediated immunity (CMI). Peyer's patches and spleen lymphocytes from mice that received the oral Salmonella-OVA vaccine showed dramatic increases in the percent cell lysis of the H-2b restricted EG7.OVA tumor cell line. These results indicate that a single dose of rSalmonella vaccine antigen vector is required to illicit systemic and mucosal Th1-type responses and CTLs. These results also support the existence of a highly regulated relationship between specific cell-mediated immunity and a branch of the humoral immune system, i.e. mucosal IgA responses.     

NALT- versus Peyer's-patch-mediated mucosal immunity

Recent studies indicate that the mechanism of nasopharynx-associated lymphoid tissue (NALT) organogenesis is different from that of other lymphoid tissues. NALT has an important role in the induction of mucosal immune responses, including the generation of T helper 1 and T helper 2 cells, and IgA-committed B cells. Moreover, intranasal immunization can lead to the induction of antigen-specific protective immunity in both the mucosal and systemic immune compartments. Therefore, a greater understanding of the differences between NALT and other organized lymphoid tissues, such as Peyer's patches, should facilitate the development of nasal vaccines.     

Interleukin-1 family cytokines as mucosal vaccine adjuvants for induction of protective immunity against influenza virus

A safe and potent adjuvant is needed for development of mucosal vaccines against etiological agents, such as influenza virus, that enter the host at mucosal surfaces. Cytokines are potential adjuvants for mucosal vaccines because they can enhance primary and memory immune responses enough to protect against some infectious agents. For this study, we tested 26 interleukin (IL) cytokines as mucosal vaccine adjuvants and compared their abilities to induce antigen (Ag)-specific immune responses against influenza virus. In mice intranasally immunized with recombinant influenza virus hemagglutinin (rHA) plus one of the IL cytokines, IL-1 family cytokines (i.e., IL-1α, IL-1β, IL-18, and IL-33) were found to increase Ag-specific immunoglobulin G (IgG) in plasma and IgA in mucosal secretions compared to those after immunization with rHA alone. In addition, high levels of both Th1- and Th2-type cytokines were observed in mice immunized with rHA plus an IL-1 family cytokine. Furthermore, mice intranasally immunized with rHA plus an IL-1 family cytokine had significant protection against a lethal influenza virus infection. Interestingly, the adjuvant effects of IL-18 and IL-33 were significantly decreased in mast cell-deficient W/W(v) mice, indicating that mast cells have an important role in induction of Ag-specific mucosal immune responses induced by IL-1 family cytokines. In summary, our results demonstrate that IL-1 family cytokines are potential mucosal vaccine adjuvants and can induce Ag-specific immune responses for protection against pathogens like influenza virus.