ANTIGEN HANDLING IN MUCOSAL IMMUNITY TO TOXINS AND PILI

免疫粘膜表面的最佳技术还没有 被设计了。 非复制型疫苗，如毒素和皮利 （菌毛）提供了安全性和特异性的优点，但 通常免疫原性不足。 早期的研究表明 霍乱毒素（CT）及其B亚单位（CT- B）基于给药途径、剂量、受体结合 能力、分子大小和刺激环AMP的能力。 由于CT有几个独特的属性，本项目建议 将CT所见与E.大肠杆菌皮利， RDEC-1株病兔模型。 因此，不同形式的 RDEC-1菌毛（AF/R1）抗原（完整的皮利、菌毛、亚单位， 活的纤毛杆菌）将用于免疫兔子， 各种途径和剂量，以及伊加和IgG特异性粘膜 并且将在血清、胆汁和 肠道灌洗标本。 我们最近的研究试图找出 基于宿主如何处理从细胞中吸收的抗原， 肠腔 我们发现CT从管腔吸收 进入胸导管淋巴，淋巴转运更大 比门静脉血液运输更重要 有证据表明，在非免疫性 大鼠淋巴传递的CT与其膜受体复合 GM 1神经节苷脂，可能通过派伊尔氏淋巴管进入淋巴 补丁. 对CT免疫率模型的进一步研究， 通过派尔集合淋巴结确认CT摄取，以及 证实淋巴中存在CT-神经节苷脂复合物。 到 检测淋巴抗原的相关性， 十二指肠内给药后在淋巴中发现的CT 静脉输注给非免疫受体， 免疫力测量 一个主要的努力将涉及不同的抗原形式的CT（CT- B、类毒素、类霍乱原），并将其摄取到派尔氏淋巴结中 贴片及其免疫原性。 菌毛抗原也将是 使用放射性标记的亲和纯化的 异源血清和单克隆抗体，包括杂交瘤 识别菌毛四级结构。 该项目的最终目标是 抗原处理的特征，如抗原吸收 派伊尔淋巴结和淋巴，以及粘膜免疫， 非复制型疫苗抗原。

Optimal techniques to immunize mucosal surfaces have not yet been devised. Nonreplicating vaccines, such as toxins and pili (fimbriae) offer the advantages of safety and specificity, but are often not sufficiently immunogenic. Earlier studies have shown that immunogenicity of cholera toxin (CT) and its B subunit (CT- B) is based on route of administration, dose, receptor-binding ability, molecular size and ability to stimulate cyclic AMP. Because CT has several unique properties, this project proposes to heneralize the findings on CT to a study of E. coli pili using the rabbit model of RDEC-1 strain disease. Thus, different forms of the RDEC-1 pilus (AF/R1) antigen (intact pili, pilus, subunits, and the live piliated bacillus) will be used to immunize rabbits by various routes and doses, and the IgA- and IgG-specific mucosal and systemic responses will be measured in serum, bile and intestinal lavage specimens. Our recent studies have sought distinguishing features between antigens based on how the host handles antigen absorbed from the intestinal lumen. We found that CT was absorbed from the lumen into thoracic duct lymph and that lymph transport was greater than portal blood transport. There is evidence that in nonimmune rats lymph-borne CT was complexed to its membrane receptor GM1 ganglioside, and probably entered lymph through Peyer's patches. Further studies in the rate model of CT immunity will seek to confirm uptake of CT through Peyer's patches, and confirm the presence of CT-ganglioside complexes in lymph. To test the relevance of lymph-borne antigen, the quantity and form of CT found in lymph after intraduodenal administration will be infused intravenously into nonimmune recipients and subsequent immunity measured. A major effort will relate the different antigen forms of CT (CT- B, toxoid, procholeragenoid) with their uptake into Peyer's patches and their immunogenicity. Pilus antigen will also be sought in Peyer's patches using radiolabelled affinity-purified heterosera and monoclonal antibodies, including a hybridoma recognizing the pilus quaternary structure. The ultimate goal of the project is the correlation between the characteristics of antigen handling, such as antigen absorption into Peyer's patches and lymph, and mucosal immunity to nonreplicating vaccine antigens.