The mucosal immune system of the upper respiratory tract and development of nasal vaccine for upper respiratory tract infection

A. A.实验研究1。Mucosal immune function of NALTSelected Th2-type cytokine expressing CD4_D1+_D1T cells were induced in intranasally-immunized mice NALT。M细胞被观察到在老鼠NULT。在Nasal洗涤中，抗基因特异性IgA抗体标题在没有Peyers补丁的老鼠免疫后增加。这些发现强烈地认为NALT功能是Nasal IgA响应的一个诱导性站点。微生物体内免疫诱导抗基因特异性IgA在微生物体内免疫。最大的抗基因IgA反应被观察到在微生物体内免疫，一种非典型的嗜酸乳杆菌感染（NTHi）的抗原，它是奥蒂斯媒体的主要病原体。这一反应并不只是在鼻子上，但也是在中间的耳朵里。在体内，微免疫性地与牙龈卟啉单胞菌的固定蛋白质相结合，是一种在周期性炎症中用于破坏性慢性炎症、抗原-特异性IgA抗体在Nasal mucosae和salivary地被诱导。Thus， int ... More Ranasal vaccination可能是上呼吸道追踪中抗原-特定微生物免疫反应的最有效的指标。预防病毒感染通过内爆免疫炎症反应导致感染老鼠和Rs病毒在内爆免疫后进入纳爆洞穴。针对RS病毒的Fab antibodies的Nasal管理员被限制的病毒传播和降解的炎症反应。这些发现也导致了我们对内源性免疫的结合，可以用于在上呼吸道中预防病毒感染的有效性。Clinical Study 1。P6-特定IgA-秘密细胞的数量在tonsil显示出比细菌样本中的NTHi更大的数量。Tonsil中的P6-特定IgA保密细胞的数目与IgA抗体标题中的nasal secrets相关。内通子就像OK-432的内通免疫一样，增加了质子和抗原特异性抗体活性中M-蛋白-特异性抗体保密细胞的数目。CD4-D1+-D1T cells produced Th2-and Th1-type cytokines in response to stimulation with P6 or M-protein。这些发现建议，Palatine tonsil对一个效应器站点很重要。在otitis介质与效应（OME）中的腺素入侵NTHi经常从患者中培养出更多的腺素，而不是在没有OME的患者中。一种趋势是增加了高度稳定的块状表皮素是配备的，而视网膜表皮素的扩展是与OME患者的大部分。数据提出的是，腺体炎症在OME的病理学中被隐含了。Antigen specific-antibody responses in otitis-prone children exhibited reduced IgG D22-D2 responses to S.肺炎和IgG对NTHi的反应。Otitis的表现与数字免疫学缺陷有关。Less（低）

A. Experimental Study1. Mucosal immune function of NALTSelected Th2-type cytokine expressing CD4ィイD1+ィエD1 T cells were induced in intranasally-immunized mice NALT. M cells were observed in rat NALT. Antigen-specific IgA antibody titers in nasal wash were increased after immunization of mice without Peyers patches. These findings strongly suggest that NALT functions as an inductive site of nasal IgA response.2. Induction of antigen-specific IgA by intranasal immunization in miceThe greatest antigen-specific IgA response was observed in mice intranasally immunized with P6, an antigen of nontypeable Haemophilus influenzae (NTHi) that is a major pathogen of otitis media. This response was induced not only in the nose but also in the middle ear. In mice immunized intranasally with fimbrial protein of Porhyromonas gingivalis, a causative agent for destructive chronic inflammation in the periodontium, antigen-specific IgA antibodies were induced in nasal mucosae and salivary glands. Thus, int … More ranasal vaccination may be the most effective means for induction of antigen-specific mucosal immune responses in the upper respiratory tract.3. Prevention of virus infection by intranasal immunizationInflammatory reaction was mild in mice with Rs virus injected into the nasal cavity after intranasal immunization with vaccina virus. Nasal administrations of Fab antibodies against RS virus restricted viral proliferation and decreased the inflammatory reaction. These findings also lead us to the conclusion that intranasal immunization is useful for prevention of virus infection in the upper respiratory tract.B. Clinical Study1. The number of P6-specific IgA-secreting cells was greater in the tonsils showing no NTHi than in the samples with the bacteria. The number of P6-specific IgA-secreting cells in tonsils was correlated with IgA antibody titers in nasal secretions. Intratonsillar as well as intranasal immunization with OK-432 increased the number of M-protein-specific antibody-secreting cells in tonsils and antigen-specific antibody activity in nasal secretions. CD4ィイD1+ィエD1 T cells produced Th2-and Th1-type cytokines in response to stimulation with P6 or M-protein. These findings suggest that the palatine tonsils are important as an effector site.2. Adenoid involvement in otitis media with effusion (OME)NTHi was cultured more frequently in adenoids from patients with OME than in patients without OME. A tendency toward increased stratified squamous epithelium was apparent, and reticular epithelium extension was greater in patients with OME. The data suggest that adenoid inflammation is implicated in the pathogenesis of OME.3. Antigen specific-antibody responses in otitis-prone childrenOtitis-prone children exhibited reduced IgGィイD22ィエD2 responses to S. pneumoniae and IgG responses to NTHi. Otitis proneness appears to be related to numerous immunological deficiencies. Less