权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Immunological Studies on The Prevention and Diagnoses of Protozoan Infection

原虫感染预防和诊断的分子免疫学研究

基本信息

批准号：
03556041
负责人：
SUZUKI Naoyoshi
金额：
$ 10.62万
依托单位：
OBIHIRO UNIVERSITY, RES.CENTER FOR PROTOZOAN MOLECULAR IMMUNOLOGY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

Using newly synthesized peptides on the activity units which were isolated from lymphokines as an immunoregulator, Obiopeptide, the effect of immunosuppression caused by cyclophosphamide to animals cronically infected with Toxoplasma gondii was examined. Mice chronically infected with Toxoplasma, were treated with cyclophosphamide or anti-CD4 monoclonal antibody to identify the effect of these immunosuppressive reagents on the cysts in the brain of infected mice. The effect of obiopeptide as an immunomodulator treatment of the immunosuppressed mice was also analyzed. In the brain of non-treated and cyclophosphamide-treated, chronically Toxoplasma infected mice mainly typicallarge tissue cysts, and sometimes divided cysts, were detected after staining with anti-Toxoplasma ABC technique. In contrast, the brain from anti-CD4 treated, chronically infected mice, contained multiple deeneated Toxoplasma tissue cysts of different size in some partialregions in the brain. Mice chronicaly infect … More ed with Toxoplasma and treated with a combination of cyclophosphamide and obiopeptide showed a significantly higher survival rate than those treated with cyclophosphamide alone. The percentage of neutrophils and lymphocytes in mice treated with a combination of Obiopeptide and anti-CD4, or obiopeptide and cyclophosphamide, was higher than that of mice treated with anti-CD4 or cyclophosphamide alone. These results indicate that reactivaion or rupture of tissue cysts in mice treated with cyclophosphamide, chronically infected with Toxoplasma, might be mainly mediated by CD4 positive cells rather than other immunocomponent cells. The increase of neutrophilic leukocytes might contribute tothe induction of the resistance to Toxoplasma gondii in mice, after treatment with obiopeptide and cyclophosphamide in combination.On the other hand, an immunopotentiator such as TLA (Toxoplasma Lysate Antigens) was tested in our experimental studies. Growth of the tumor autoinduced by 20-methylcholantherne (MC) in rats was inhibited after administration of TLA.The antitumor activity of TLA was most obvious in the early stage of tumoral growth. When TLA was administered to rats before the appearance of tumor, tumor formation was delayd slightly. According to the immunohistological examination of tumor tissue with anti-Thy-a antibody, the rats treated with TLA showed large Thy-1 positive or Lymphokine-Activated Killer (LAK) cells, whereas the untreated rats indicated only a few small Thy-a positive or NK cells. These observation indicate that TLA is a useful modifier of biological responses to MC-induced tumors. In a series of these studies, TLA induces NK cells, cytotoxic T-lymphocytes and LAK cells in animals after injection, however, the induction of these killer cells needs to combine with monocyte-macrophages in in vivo. Less

利用从淋巴因子中分离的活性单元上新合成的多肽作为免疫调节剂Obiopeptide，研究了环磷酰胺对弓形虫慢性感染动物的免疫抑制作用。用环磷酰胺或抗cd4单克隆抗体治疗慢性弓形虫感染小鼠，观察免疫抑制试剂对感染小鼠脑内囊肿的影响。并分析了生物肽作为免疫调节剂对免疫抑制小鼠的治疗作用。在未处理和环磷酰胺处理的小鼠大脑中，经抗弓形虫ABC技术染色，发现慢性弓形虫感染的小鼠主要是典型的大组织囊肿，有时是分裂的囊肿。相比之下，经抗cd4治疗的慢性感染小鼠的大脑，在大脑的某些部分区域含有多个不同大小的缺牙弓形虫组织囊肿。慢性弓形虫感染小鼠，环磷酰胺和生物肽联合治疗的存活率明显高于单用环磷酰胺治疗的存活率。生物肽与抗cd4或生物肽与环磷酰胺联合治疗小鼠的中性粒细胞和淋巴细胞百分比高于单独抗cd4或环磷酰胺治疗小鼠。这些结果表明，慢性弓形虫感染小鼠经环磷酰胺处理后，组织囊肿的再激活或破裂可能主要由CD4阳性细胞介导，而不是由其他免疫成分细胞介导。生物肽与环磷酰胺联合用药后，小鼠体内嗜中性白细胞的增加可能是诱导小鼠对弓形虫产生耐药性的原因之一。另一方面，免疫增强剂如TLA（弓形虫裂解抗原）在我们的实验研究中进行了测试。给药后，20-甲基胆碱（MC）诱导的肿瘤在大鼠体内的生长受到抑制。TLA的抗肿瘤活性在肿瘤生长早期最为明显。大鼠在肿瘤出现前给予TLA，肿瘤形成略有延迟。用抗Thy-a抗体对肿瘤组织进行免疫组织学检查，经TLA处理的大鼠肿瘤组织中有大量的Thy-1阳性或淋巴因子活化杀伤细胞（LAK），而未经TLA处理的大鼠肿瘤组织中只有少量的Thy-a阳性或NK细胞。这些观察结果表明，TLA是一种有用的mc诱导肿瘤生物反应调节剂。在这一系列的研究中，TLA在动物体内注射后诱导NK细胞、细胞毒性t淋巴细胞和LAK细胞，但这些杀伤细胞的诱导需要在体内与单核巨噬细胞结合。少