MECHANISMS OF NONSTERILIZING IMMUNITY IN MALARIA

疟疾的非灭菌免疫机制

• 批准号: 3125258
• 负责人: WILLIAM Paul WEIDANZ
• 金额: $ 19.62万
• 依托单位: HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-06-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3125258
• 关键词: B lymphocyte; Plasmodium; T lymphocyte; active immunization; immunity; immunosuppression; macrophage; malaria; microorganism disease chemotherapy; protozoal antigen

Resistance to acute Plasmodium chabaudi adami malaria in mice is mediated by non-antibody mechanisms of immunity. Adoptive cell transfer studies demonstrate that T cells are required for both the induction and expression of this form of immunity. The purpose of the proposed study is to determine which Lyt subsets of splenic T cells are involved. Lyt subsets of spleen cells from euthymic mice prepared by selective killing with anti-Lyt monoclonal antibody in the presence of complement or by panning rat anti-mouse Lyt coated spleen cells on petri plates coated with anti-rat Ig will be injected into histocopatible athymic nude mice prior to challenge with P. chadaudi adami. The resulting parasitemias will be plotted against time in order to see which Lyt subset(s) suppress infection. Also, Lyt subsets of spleen cells prepared from the spleens of P. chabaudi adami immune B-cell deficient mice as well as immunologically intact mice will be tested for their ability to adoptively transfer immunity to P chabaudi adami infection to irradiated homologous recipients. In order to define mechanisms of nonantibody immunity to P. chabaudi adami T-cell clones and T-cell hybrids constructed with spleen cells of immune mice will be tested for their capacity to protect nude mice against challenge infection. Similarly, soluble factors from protective cell lines will be characterized and tested for their ability to mediate protection in nude mice. Two additional parameters will be investigated in order to determine whether they can be correlated with protection achieved with Lyt fraction T-cell clones and T-cell hybrids. These are splenic macrophage activation as determined by chemiluminescence and the activation of splenic reticular cells. Finally, P. chabaudi adami antigens will be fractionated and characterized in terms of their ability to activate protecting cell populations as well as to induce protection in mice by immunization. This approach, which will attempt to correlate protection with cell function, factor-production, and effector cell activation, may provide a coherent physiologic picture of events which must transpire for the expression of antibody-independent immunity.

介导小鼠对急性夏波蒂疟原虫疟疾的抗性