Lectins in Insect Immunity

描述：(申请人提供)：非自我认可是必要的 昆虫防御系统的组成部分，用于抵抗感染。认识到 昆虫的非我主要是通过一套模式识别来完成的 受体，是与细胞表面多糖结合的蛋白质 病原体或寄生虫。这种识别启动了各种免疫系统 反应，包括原酚氧化酶(PPO)的激活和包膜。PPO 激活涉及丝氨酸蛋白酶级联，导致TC黑化 后生动物和原生动物寄生虫的封装。在人类的昆虫媒介中 疾病、寄生虫的检测和杀灭可能不是很有效 因为某些识别受体缺失或不与其他受体相互作用 刺激足够的保护性反应的分子。人们对此知之甚少 脑内任何一种模式识别受体介导的识别过程 昆虫，或启动各种免疫反应的机制 通过识别过程。 凝集素是模式识别受体的主要候选者，因为它们 能与细胞表面糖蛋白和糖脂的末端糖结合 很多病原体。四种新的C型凝集素IMMULECTINS(IMLS)已经被 分离自烟草天牛Manduca sexta。IML参与PPO 激活和封装。另外，两种IML-2相关丝氨酸蛋白酶 Sexta中鉴定的同系物(SPH)是PPO激活所必需的 酚氧化酶原激活酶(PAP)。这项提案旨在测试一个 一般假设IML-2与病原体或 寄生虫的功能是将酚氧化酶(P0)的激活定位到该区域 包围着入侵的有机体。这一假设的一部分是IML-2 结合到寄生虫表面参与了血浆复合体的组装 导致PPO活化的蛋白质，特别是在细胞表面 入侵者。 其具体目的是：1.研究IML-2的结合特异性。装订 IML-2对病原体或寄生虫表面碳水化合物的作用触发 免疫反应。需要进一步的研究来确定碳水化合物 IML-2的结合特异性。2.研究IML-2-SPH启动的 在PPC激活过程中表面的蛋白质复合体。血淋巴的形成 寄生虫表面的蛋白质复合体可能定位于PPO的激活 入侵地点入侵的地点或在入侵寄生虫的表面实验将会 旨在研究IML-2、SPH、PPO、 和PAP。

DESCRIPTION: (provided by the applicant): Non-self recognition is an essential component of the insect defense system to fight infection. Recognition of non-self in insects is mainly accomplished by a set of pattern recognition receptors, which are proteins that bind to polysaccharides in the surface of pathogens or parasites. Such recognition initiates a variety of immune responses, including prophenoloxidase (PPO) activation and encapsulation. PPO activation involves a serine proteinase cascade, leading tc melanotic encapsulation of metazoan and protozoan parasites. In insect vectors of human diseases, detection and killing of parasites are not highly effective, perhaps because certain recognition receptors are lacking or do not interact with othei molecules to stimulate an adequate protective response. Little is known about the recognition process mediated by any pattern recognition receptors in insects, or the mechanisms by which a variety of immune responses are initiated by the recognition process. Lectins are primary candidates as pattern recognition receptors because they can bind to terminal sugars of glycoproteins and glycolipids on the surface of many pathogens. Four novel C-type lectins, immulectins (IMLs), have been isolated from the tobacco hornworm, Manduca sexta. IMLs are involved in PPO activation and encapsulation. Also, two IML-2-associated serine proteinase homologs (SPHs) identified in M. sexta are necessary for PPO activation by prophenoloxidase-activating proteinase (PAP). This proposal aims to test a general hypothesis that binding of IML-2 to the surface of a pathogen or parasite functions to localize phenoloxidase (P0) activation to the area surrounding the invading organism. A part of this hypothesis is that IML-2 bound to a parasite surface participates in assembly of a complex of plasma proteins that results in activation of PPO specifically at the surface of the invader. The specific aims are: 1. Investigate binding specificity of IML-2. The binding of IML-2 to carbohydrates on the surface of pathogens or parasites triggers immune responses. Further research is needed to determine the carbohydrate binding specificity of IML-2. 2. Study IML-2-SPH initiated assembly of a protein complex at a surface during PPC activation. Formation of hemolymph protein complexes on the surface of parasites may localize PPO activation on the site of invasion or on the surface of invading parasites. Experiments will be designed to investigate protein-proteil interactions among IML-2, SPH, PPO, and PAP.