Brigandi R A, Rotman H L, Yutanawiboonchai W, Leon O, Nolan T J, Schad G A, Abraham D
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Exp Parasitol. 1996 Apr;82(3):279-89. doi: 10.1006/expr.1996.0035.
Mice immunized against Strongyloides stercoralis L3 were shown to kill greater than 90% of challenge larvae contained within diffusion chambers. The objective of the present study was to identify the host components responsible for immunity. Serum from unprotected, control mice and protected, immune mice in doses of 25-500 microliters was transferred into naive mice at the same time and location as larval challenge. Transfer of as little as 50 microliters of immune serum was able to confer protective immunity. The serum-transferred immunity was ablated by excluding cells from the larval microenvironment or by depleting granulocytes through monoclonal antibody treatment in the recipient mice. Specific antibody isotypes were isolated using protein G and isotype-specific affinity columns. The resulting transfer experiments identified IgM as the isotype responsible for protective immunity to S. stercoralis L3. Antibody binding studies in vivo were performed and only IgM bound to the surface of infective L3 and host-derived L3 (L3+) in immune animals. Elevated levels of C3 were also found bound to the surface of L3/L3+ in immune mice. Cobra venom factor treatment of immunized mice to deplete complement completely eliminated C3 binding to the surface of L3/L3+ and ablated immunity. Therefore, IgM, complement, and granulocytes are necessary for immune elimination of S. stercoralis L3/L3+. Identification of antigens recognized by IgM may help select possible vaccine candidates.
经免疫的抗粪类圆线虫L3期幼虫的小鼠能够杀死扩散小室内90%以上的攻击幼虫。本研究的目的是确定负责免疫的宿主成分。将来自未受保护的对照小鼠和受保护的免疫小鼠的血清,以25 - 500微升的剂量,在与幼虫攻击相同的时间和地点转移到未接触过该幼虫的小鼠体内。仅转移50微升免疫血清就能赋予保护性免疫。通过排除幼虫微环境中的细胞或通过在受体小鼠中用单克隆抗体处理来耗尽粒细胞,血清转移的免疫被消除。使用蛋白G和同型特异性亲和柱分离特定的抗体同型。由此产生的转移实验确定IgM是对粪类圆线虫L3期幼虫具有保护性免疫的同型。进行了体内抗体结合研究,在免疫动物中只有IgM与感染性L3期幼虫和宿主来源的L3期幼虫(L3+)的表面结合。还发现免疫小鼠中L3/L3+表面结合的C3水平升高。用眼镜蛇毒因子处理免疫小鼠以完全耗尽补体,完全消除了C3与L3/L3+表面的结合并消除了免疫力。因此,IgM、补体和粒细胞对于粪类圆线虫L3/L3+的免疫清除是必需的。鉴定被IgM识别的抗原可能有助于选择可能的疫苗候选物。