Nash T E
Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Philos Trans R Soc Lond B Biol Sci. 1997 Sep 29;352(1359):1369-75. doi: 10.1098/rstb.1997.0122.
Giardia lamblia, a protozoan parasite of the small intestine of humans and other animals, undergoes surface antigenic variation. The antigens involved belong to a family of variant-specific surface proteins (VSPs), which are unique, cysteine-rich zinc finger proteins. The patterns of infection in humans and animals fail to show the expected cyclical waves of increasing and decreasing numbers of parasites expressing unique VSPs. Nevertheless, changes in VSP expression occur within the population in vivo owing to selection of VSPs by both immune and non-immune mechanisms. After inoculation of a single G. lamblia clone (able to persist in the absence of immune pressure) expressing one VSP (> or = 90%) into mice or humans, the original VSP continues to be expressed until 2 weeks post inoculation (p.i.), when many other VSPs gradually replace it. Selection by immune-mediated processes is suggested because switching occurs at the same time that humoral responses are first detected. In most mouse strains, switching also occurs at about two weeks. Almost all trophozoites are eliminated at three weeks (p.i.), but a barely detectable infection persists over months. In neonatal mice, apparent self-cure is delayed until the sixth or seventh week. Antigenic switching does not occur in adult or neonatal severe combined immunodeficiency disease (SCID) mice, but does occur in neonatal nude mice, thus implicating B-cell-mediated mechanisms in immune switching. Not all VSPs are expressed to the same degree in vivo. Some VSPs appear to be preferentially selected whereas others are eliminated on a non-immune basis. In infections in which immunity does not play a role, such as in SCID mice, and during the first week of infection in immunocompetent mice or gerbils, persisting VSPs are preferentially expressed and maintained whereas non-persisting VSPs are replaced within the first week of infection. The purpose of antigenic variation may be presentation of a wide assortment of VSPs to hosts, increasing the chance of a successful initial infection or reinfection. Immune selection of variants comes into play following biological selection.
蓝氏贾第鞭毛虫是人和其他动物小肠内的一种原生动物寄生虫，会发生表面抗原变异。所涉及的抗原属于一个变异特异性表面蛋白（VSP）家族，这些蛋白是独特的、富含半胱氨酸的锌指蛋白。人和动物的感染模式并未显示出表达独特VSP的寄生虫数量呈预期的周期性增减波动。然而，由于免疫和非免疫机制对VSP的选择，体内群体中会发生VSP表达的变化。将表达一种VSP（≥90%）的单个蓝氏贾第鞭毛虫克隆（能够在无免疫压力的情况下持续存在）接种到小鼠或人体内后，最初的VSP会持续表达至接种后2周，之后许多其他VSP会逐渐取代它。由于在首次检测到体液反应的同时发生了转换，提示存在免疫介导过程的选择。在大多数小鼠品系中，转换也发生在大约两周时。几乎所有滋养体在接种后三周被清除，但仍有难以检测到的感染持续数月。在新生小鼠中，明显的自愈会延迟到第六或第七周。抗原转换在成年或新生严重联合免疫缺陷病（SCID）小鼠中不发生，但在新生裸鼠中会发生，因此表明B细胞介导的机制参与免疫转换。并非所有VSP在体内的表达程度都相同。一些VSP似乎被优先选择，而其他的则在非免疫基础上被清除。在免疫不起作用的感染中，如在SCID小鼠中，以及在免疫健全的小鼠或沙鼠感染的第一周内，持续存在的VSP会被优先表达和维持，而非持续存在的VSP会在感染的第一周内被取代。抗原变异的目的可能是向宿主呈现各种各样的VSP，增加初次感染或再次感染成功的机会。变异体的免疫选择在生物学选择之后发挥作用。
