IMMUNE RESPONSES TO PLASMODIUM IN ANOPHELES GAMBIAE

疟疾是大多数国家的主要病媒传播寄生虫病， 发展中国家，也威胁到军事人员，游客， 商人和其他在非洲、亚洲和拉丁美洲工作的人。 由于寄生虫和蚊子对药物和杀虫剂的抗药性， 需要控制策略。研究的长期目标 是了解蚊子的生理学、生物化学和遗传学 对疟疾感染有抵抗力。这可能会提出一些方法， 用遗传转化的非媒介生物取代自然种群 蚊子一种特殊类型的抵抗力存在于基因- 冈比亚按蚊的选择菌株，其以黑色素包裹 许多疟疾物种的动合子。一个完全敏感的菌株， 选择比较。拟议的研究将侧重于审查 抵抗力的生化和遗传基础。 一个新发现的模型系统的阻力，使用离子交换 珠粒将用于遗传和生物化学研究。疟原虫- 抗性蚊子使带负电荷的C-25珠变黑， 易感蚊子则不会。这一制度将极大地促进 抗性基因的数量性状位点定位，因为没有寄生虫 需要被介绍并且雄性可以被评分。标记用于 作图包括一个酯酶基因座，该基因座已显示与 带有抗性和微卫星标记。137颗微型卫星 标记现在可从所有常染色体和X染色体获得。在 除了这些绘图研究之外， 抗性蚊子和易感蚊子缺乏黑化 并会检查蚊患。将C-25微珠接种至敏感 蚊子，然后解剖并引入抗性蚊子， 没有被黑化。这种保护的性质将由 在接种之前用各种酶处理珠粒 抵抗蚊子。SDS PAGE将用于检查 几种类型的珠子注定要在抗性菌株中黑化 和未黑化的珠粒上。相关的蛋白 与黑化或与保护性反应， 蚊子将被纯化并用于多克隆抗体生产。

Malaria is the major vector-borne parasitic disease for much of the developing world and also threatens military personnel, tourists, business people and others who work in Africa, Asia and Latin America. Because of parasite and mosquito resistance to drugs and pesticides, new control strategies are needed. The long-term objective of the research is to understand the physiology, biochemistry, and genetics of mosquitoes that are resistant to malaria infections. This may suggest ways to replace natural populations with genetically transformed nonvector mosquitoes. A specific type of resistance is found in a genetically- selected strain of Anopheles gambiae which melanotically encapsulates ookinetes of many malaria species. A fully susceptible strain was also selected for comparison. The proposed research will focus on examining the biochemical and genetic basis for resistance. A newly-discovered model system of resistance that uses ion exchange beads will be used for genetic and biochemical studies. Plasmodium- resistant mosquitoes melanize negatively charged C-25 beads while susceptible mosquitoes do not. This system will greatly facilitate quantitative trait loci mapping of resistance genes, since no parasites need to be introduced and males can be scored. Markers to be used for mapping include an esterase locus which has been shown to be associated with resistance and microsatellite markers. A total of 137 microsatellite markers are now available from all autosomes and the X-chromosome. In addition to these mapping studies, the biochemistry of melanization in resistant mosquitoes and the lack of melanization in susceptible mosquitoes will also be examined. C-25 beads inoculated into susceptible mosquitoes and then dissected and introduced into resistant mosquitoes are not melanized. The nature of this protection will be studied by treatment of the beads with various enzymes prior to inoculation into resistant mosquitoes. SDS PAGE will be used to examine proteins on several types of beads destined to be melanized in the resistant strain and on unmelanized beads in the susceptible strain. Proteins associated with melanization or with the protective response in susceptible mosquitoes will be purified and used for polyclonal antibody production.