Humoral Immunity of Long-lived Invertebrates

MCB9726771阿姆斯特朗，彼得·奎格利，詹姆斯·奎格利长寿无脊椎动物的体液免疫任何动物的生存都需要有效的手段来阻止无数不同的潜在病原体的入侵。因此，大多数动物都进化出了各种不同的防御策略来保护它们。这些包括哺乳动物非常复杂的适应性免疫系统，以及在低等动物中经常出现的不太复杂的先天防御机制。本研究以无脊椎动物的一种特殊的防御系统为研究对象，以美洲河蟹为模型系统。这种动物缺乏抗体和淋巴细胞，这是适应性免疫系统的核心元素，但它的血液系统中有对病原体提供抵抗力的组件。一种系统涉及血浆蛋白(2-巨球蛋白)，它能够与血流中的微生物蛋白酶结合。结合的(2-巨球蛋白)不仅能抑制蛋白水解酶，还能识别、去除和降解由此形成的复合体。第二个系统涉及第二种血浆蛋白--血红蛋白，它能够与进入血流的外来细胞结合并溶解。这两个系统在功能上是相互关联的，因为酶反应(2-巨球蛋白可以增强血红蛋白的裂解活性)。本研究包括三个目标，以确定这些系统的基本特征。(1)分离和鉴定与蛋白-(2-巨球蛋白)复合体结合的血细胞上的受体。(2)描述影响细胞对络合物的结合和摄取途径的因素。(3)明确了蛋白水解酶-2-巨球蛋白复合体和其他因子调节红蛋白裂解活性的分子机制。这些研究不仅可以帮助我们了解这些系统，还可以预测在更复杂、更高等生物的血液中发现的相关蛋白质具有类似的功能。

MCB9726771 Armstrong, Peter Quigley, James Humoral Immunity of Long-lived Invertebrates Lay Abstract Survival of any animal requires efficient means to thwart the invasion of a myriad of different potential pathogens. As a result, most animals have evolved a variety of different defense strategies for their protection. These include the very complex adaptive immune system of mammals as well as less complex, innate defense mechanisms represented frequently in lower animals. The present research focuses on a particular defense system of invertebrates and utilizes the American horseshoe crab (Limulus polyphemus) as a model system. This animal, which lacks the antibodies and lymphocytes that are the core elements of adaptive immune systems, nevertheless has within its blood system components that provide resistance to pathogens. One system involves the plasma protein, (2-macroglobulin, which is able to bind to microbial proteases in the blood stream. Not only does the bound (2-macroglobulin inhibit the proteases, but also blood cells recognize, remove and degrade the complexes thus formed. A second system involves a second plasma protein, limulin, which has the ability to bind to and lyse foreign cells that enter the blood stream. The two systems are functionally interrelated since protease-reacted (2-macroglobulin can enhance the lytic activity of limulin. The present studies include three objectives to define basic features of these systems. (1) The receptors on the blood cells that bind the protease-(2-macroglobulin complexes will be isolated and characterized. (2) Factors that effect the binding and pathway of uptake of the complexes by the cells will be described. (3) The molecular mechanism by which protease-(2-macroglobulin complexes and other factors regulate the lytic activity of limulin will be defined. These studies will not only allow us to understand these systems in Limulus but may also lead to predictions of similar functions for related proteins found in the b lood of more complex, higher organisms.