ANTIGEN HANDLING IN MUCOSAL IMMUNITY TO TOXINS AND PILI

免疫粘膜表面的最佳技术还没有 都是设计出来的。非复制疫苗，如毒素和菌毛 (菌毛)具有安全性和特异性的优点，但 通常没有足够的免疫原性。早期的研究表明 霍乱毒素(CT)及其B亚单位(CT-B)的免疫原性。 B)基于给药途径、剂量、受体结合 刺激环状AMP的能力、分子大小和能力。 由于CT有几个独特的属性，该项目建议 将CT检查结果概括为大肠杆菌菌毛研究 RDEC-1株病兔模型的建立。因此，不同形式的 RDEC-1菌毛(AF/R1)抗原(完整菌毛、菌毛、亚单位和 活菌毛杆菌)将通过以下方式免疫兔子 不同的途径和剂量，以及IgA和Ig G特异性的粘膜 全身反应将在血清、胆汁和 肠道灌洗标本。 我们最近的研究试图区分不同的特征 基于宿主如何处理从宿主吸收的抗原 肠腔。我们发现CT是从管腔中吸收的 进入胸腔导管淋巴，而且淋巴转运更大 而不是门脉血液运输。有证据表明，在非免疫系统中 大鼠淋巴携带CT与其膜受体的络合 GM1神经节苷脂，可能通过Peyer‘s进入淋巴 帕奇斯。CT免疫率模型的进一步研究将 寻求通过Peyer‘s补片确认CT的摄取，以及 确认淋巴中存在CT-神经节苷脂复合体。至 检测淋巴携带抗原的相关性、数量和形态 十二指肠内给药后淋巴中发现CT的 静脉输注给非免疫接受者，并随后 测量了免疫力。 一项主要的努力将涉及CT的不同抗原形式(CT- B、类毒素、前霍乱原)和它们对Peyer‘s的摄取 补丁及其免疫原性。菌毛抗原也将是 用放射性标记亲和纯化的方法在Peyer‘s斑块中寻找 杂交瘤和单抗，包括杂交瘤 辨认出毛状物的四元结构。 该项目的最终目标是 抗原处理的特点，如抗原吸收 进入Peyer的补片和淋巴，以及粘膜免疫 不可复制的疫苗抗原。

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.