MECHANISMS OF ENHANCEMENT OF INNATE IMMUNITY

增强先天免疫力的机制

• 批准号: 2767680
• 负责人: CHRISTOPHER JEFFREY BAYNE
• 金额: $ 3.16万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-28 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2767680
• 关键词: SDS polyacrylamide gel electrophoresis; Saccharomyces cerevisiae; Vibrio; Vibrionaceae; acute phase protein; alternatives to animals in research; bacteria infection mechanism; bacterial genetics; bactericidal immunity; cooperative study; gene expression; genetic regulation; genetic transcription; genetic translation; inflammation; messenger RNA; protein sequence; recombinant DNA; trout /salmon

Support is requested to enable the candidate to conduct collaborative research with Dr. Tomoki Yano, Kyushu University, in 1999, remaining there for 9 months. One return trip to the U.S. will be made to coordinate research at the home university. The visit (part of a sabbatical) is for a dual purpose: initiation of a collaboration that addresses basic aspects of immunity (see below), and equipping the applicant with expertise to benefit subsequent research. Research to understand mechanisms of action of adjuvants and immuno-potentiators has contributed to our knowledge of the roles of accessory cells and cytokines in orchestration of immune responses. Potentiation of innate immunity, by means of macrophage activation or induction of the hepatic acute phase response, when achieved in advance of an infection, may influence the outcome of that infection. Indeed, rational manipulation of innate immunity prior to vaccination may prove to be a means of achieving desirable outcomes in immunization programs. The long-term objectives of the research include achievement of a fuller understanding of the evolution of the hepatic acute phase response (as reflected in altered concentrations of specific plasma proteins), and its induction. Specific aims include the cloning and sequencing of genes for two positive acute phase proteins in the model organism (rainbow trout), and determination of the kinetics of transcription and translation of these genes following stimulation by different agents. At the present, acute phase proteins in plasma are used diagnostically in relation to tissue damage and septicemia, but their potential medical utility as therapeutants is under-realized. By knowing the full functional repertoire of these protective proteins in more primitive species (in which the adaptive immune system is less well developed), we anticipate insights that will lead to such therapeutic uses in human medicine, after validation in veterinary species.

要求候选人于1999年与候选人与Tomoki Yano博士进行合作研究，并于1999年与京都大学进行合作研究，并在那里呆了9个月。 将进行一次回到美国的回程，以协调家庭大学的研究。访问（休假的一部分）是出于双重目的：启动协作，该协作解决免疫的基本方面（请参见下文），并为申请人提供专业知识，以使后续研究受益。 了解辅助和免疫受损的作用机制的研究为我们了解了辅助细胞和细胞因子在免疫反应编排中的作用。 通过巨噬细胞激活或诱导肝急性相反应的增强，在感染之前实现肝急性相反应的增强可能会影响该感染的结果。实际上，在接种疫苗之前对先天免疫的合理操纵可能被证明是实现免疫计划中理想结果的一种手段。 该研究的长期目标包括实现对肝急性期反应的演变的更深入的了解（如特定的血浆蛋白的变化反映）及其诱导。 具体目的包括模型生物体中两个阳性急性相蛋白的基因的克隆和测序，以及在不同药物刺激后的转录动力学和这些基因转录动力学的测定。 目前，血浆中的急性相蛋白与组织损伤和败血病有关，但其潜在的医疗用途是治疗剂的潜在医疗用途。 通过了解这些保护性蛋白在更原始物种中的全部功能曲目（自适应免疫系统的发育不佳），我们预计在验证兽医物种后，会导致人类医学中这种治疗用途的见解。