Armstrong Peter B
Marine Biological Laboratory, Woods Hole, MA 02543, USA.
Immunobiology. 2006;211(4):263-81. doi: 10.1016/j.imbio.2006.01.002. Epub 2006 Apr 18.
The immune system is the collection of effector molecules and cells of the host that act against invading parasites and their products. Secreted proteases serve important roles in parasitic metabolism and virulence and the several families of protein protease inhibitors of the plasma and blood cells play an important role in immunity by inactivating and clearing the protease virulence factors of parasites. The protease inhibitors are of two classes, the active-site inhibitors and the alpha2-macroglobulins. Inhibitors for the first class bind and inactivate the active site of the target protease. Proteins of the second class bind proteases by a unique molecular trap mechanism and deliver the bound protease to a receptor-mediated endocytic system for degradation in secondary lysosomes. Proteins of the alpha2-macroglobulin family are present in a variety of animal phyla, including the nematodes, arthropods, mollusks, echinoderms, urochordates, and vertebrates. A shared suite of unique functional characteristics have been documented for the alpha2-macroglobulins of vertebrates, arthropods, and mollusks. The alpha2-macroglobulins of nematodes, arthropods, mollusks, and vertebrates show significant sequence identity in key functional domains. Thus, the alpha2-macroglobulins comprise an evolutionarily conserved arm of the innate immune system with similar structure and function in animal phyla separated by 0.6 billion years of evolution.
免疫系统是宿主中针对入侵寄生虫及其产物起作用的效应分子和细胞的集合。分泌型蛋白酶在寄生虫代谢和毒力中发挥重要作用，血浆和血细胞中的几类蛋白质蛋白酶抑制剂通过使寄生虫的蛋白酶毒力因子失活和清除，在免疫中发挥重要作用。蛋白酶抑制剂分为两类，即活性位点抑制剂和α2-巨球蛋白。第一类抑制剂结合并使靶蛋白酶的活性位点失活。第二类蛋白质通过独特的分子捕获机制结合蛋白酶，并将结合的蛋白酶递送至受体介导的内吞系统，以便在次级溶酶体中降解。α2-巨球蛋白家族的蛋白质存在于多种动物门类中，包括线虫、节肢动物、软体动物、棘皮动物、尾索动物和脊椎动物。脊椎动物、节肢动物和软体动物的α2-巨球蛋白已被证明具有一套共同的独特功能特征。线虫、节肢动物、软体动物和脊椎动物的α2-巨球蛋白在关键功能域中显示出显著的序列同一性。因此，α2-巨球蛋白构成了先天免疫系统中一个进化上保守的分支，在经历了6亿年进化分离的动物门类中具有相似的结构和功能。
