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实验性仓鼠内脏利什曼病中早期高亲和力特异性 IgG 的产生。

Early high avidity specific IgG production in experimental hamster visceral leishmaniasis.

机构信息

Instituto de Medicina Tropical-Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Protozoology Laboratory, Instituto de Medicina Tropical de São Paulo, Avenida Doutor Enéas de Carvalho Aguiar 470, São Paulo, SP, 05403-000, Brazil.

出版信息

Parasitol Res. 2020 Nov;119(11):3881-3885. doi: 10.1007/s00436-020-06851-9. Epub 2020 Aug 14.

Abstract

Visceral leishmaniasis (VL) by Leishmania (Leishmania) infantum is epidemic in Brazil. Hypergammaglobulinemia appears early in patients with VL and is ineffective. Usually, high-affinity IgG B cells are selected during most infections, a critical step for an effective humoral response. The avidity of IgG antibodies in VL is unexplored due to the absence of temporal parameters in most patients, associated to low clinical significance. Experimental infection models overcome this fact, allowing the monitoring of the disease temporal evolution. In this study, the avidity of IgG antibodies was evaluated in experimental models, in infection in hamsters, and in immunization in rabbits. Specific IgG antibodies were detected by ELISA, using chaotropic solution to determine avidity, as reported for viral infections. The levels of IgG antibodies correlated with the progression of experimental infection in hamsters or antigenic stimulation in immunized rabbits. However, IgG avidity was high early in infected animals, even in early periods (> 80%), while in immunized rabbits, they had early antibodies of low avidity with progressive maturation, similar as other infections. These data suggest that the affinity maturation of the avidity of anti-Leishmania IgG antibodies promoted at an early stage, influencing the appropriate interaction between antigens and affecting the disease progression. This fact could be associated to monovalent immune complexes, as reported in human and experimental VL. This scenario may be related to an independent process of immune cell activation by the parasite but absent in antigen preparation used as immunogens.

摘要

内脏利什曼病(VL)由利什曼原虫(Leishmania)感染引起,在巴西流行。高免疫球蛋白血症在 VL 患者中早期出现,但无效。通常,在大多数感染中,高亲和力 IgG B 细胞被选择,这是有效体液反应的关键步骤。由于大多数患者缺乏时间参数,并且与低临床意义相关,因此 VL 中 IgG 抗体的亲合力尚未得到探索。实验感染模型克服了这一事实,允许监测疾病的时间演变。在这项研究中,通过实验感染的仓鼠模型和免疫接种的兔模型评估了 IgG 抗体的亲合力。使用离液剂通过 ELISA 检测特异性 IgG 抗体,以确定如报道的病毒感染中的亲合力。在感染的仓鼠或免疫接种的兔子的抗原刺激中,IgG 抗体的水平与实验感染的进展相关。然而,在感染的动物中,IgG 亲合力在早期就很高,甚至在早期(>80%),而在免疫接种的兔子中,它们具有早期低亲合力的抗体,随着时间的推移逐渐成熟,类似于其他感染。这些数据表明,抗利什曼原虫 IgG 抗体的亲合力成熟在早期被促进,影响抗原和抗体之间的适当相互作用,并影响疾病的进展。这种情况可能与单价免疫复合物有关,如在人类和实验性 VL 中报道的那样。这种情况可能与寄生虫对免疫细胞的激活过程有关,但在用作免疫原的抗原制剂中不存在。

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