IDENTIFICATION OF BABESIA IMMUNOGENS WITH TH CEL

血液寄生虫病在大多数热带和亚热带地区仍然是地方病 世界上的一些地区。研制有效的疟疾疫苗， 新出现的巴贝斯虫寄生虫在一定程度上受到缺乏 相关的远系繁殖动物模型。牛的免疫调节机制 比老鼠更像人类，所以这种远系繁殖的大型动物 物种提供了一个替代系统来研究的机制， 对原生动物寄生虫的保护性免疫。巴贝氏病的病理学 牛的牛感染与疟原虫引起的感染非常相似 恶性疟原虫感染的人类，其特征是广泛的 寄生红细胞的循环障碍和隔离 毛细血管床，尤其是大脑从自然恢复的牛 或实验性感染活蜱或血液传播阶段的B。 牛对随后的暴露产生长期的保护性免疫力 同源和异源寄生虫菌株， Th1反应的体外发展。灭活疫苗接种 寄生虫或分级的裂殖子抗原也导致可变的 对同源和异源的保护性免疫程度 挑战，这与特定的体液反应无关。 此外，尝试基于血清学特性选择疫苗抗原， 免疫优势未能鉴定出保护性免疫原。因为 细胞介导的免疫效应机制对于诱导 对许多细胞内寄生虫的保护性免疫， 1型（T1或Th1）辅助细胞与对B的免疫相关。虱和牛 相关的疟疾寄生虫，我们提出了一种替代方法， 基于能力鉴定保护性原生动物寄生虫抗原， 在免疫动物中诱导T1反应。我们假设抗原 选择用于体外刺激T1反应的细胞将刺激 体内保护性免疫Th1细胞将被用作探针以鉴定 B的潜在保护性抗原。牛Th细胞系和克隆 来源于免疫牛并表征细胞因子表达 模式将用于增殖试验，以生物化学方式识别 分离的寄生虫抗原。抗血清针对这些部分 纯化的蛋白质将用于鉴定编码 通过筛选B.牛表达文库。 或者，T细胞系和克隆将直接用于筛选T细胞。 图书馆然后将测试选定的重组蛋白的 在牛中诱导保护性免疫的能力， T细胞、巨噬细胞和抗体应答的性质， 在体内对抗免疫原。这些研究将提供深入了解 保护性免疫的细胞和分子基础， 自然刺激免疫牛的Th1应答， 直接应用于人类的相关巴贝斯虫和疟疾寄生虫。

Hemoparasitic diseases remain endemic in most tropical and semitropical areas of the world. Development of effective vaccines for malarial and newly emerging babesial parasites has been partly constrained by the lack of relevant outbred animal models. Immunoregulatory mechanisms in cattle are much more like those of humans than mice, so this outbred large animal species provides an alternative system to study the mechanisms of protective immunity against protozoan parasites. The pathology of-Babesia bovis infection in cattle is very similar to that caused by Plasmodium falciparum infections in humans, and is characterized by a generalized circulatory disturbance and sequestration of parasitized erythrocytes in the capillary beds, especially in the brain. Cattle recovered from natural or experimental infection with viable tick- or blood-borne stages of B. bovis develop long-lived protective immunity against subsequent exposure to both homologous and heterologous parasite strains, which correlates with the in vitro development of a Th1 response. Immunization with killed parasites or fractionated merozoite antigen has also resulted in variable degrees of protective immunity against homologous and heterologous challenge, which does not correlate with a specific humoral response. Furthermore, attempts to select vaccine antigens based on serological immunodominance have failed to identify protective immunogens. Because cell-mediated immune effector mechanisms are crucial for the induction of protective immunity against many intracellular parasites, and induction of Type 1 (T1 or Th1) helper cells correlates with immunity to B. bovis and related malarial parasites, we propose an alternative method for identifying protective protozoan parasite antigens based on the capacity to induce T1 responses in immune animals. We hypothesize that antigens selected for in vitro stimulation of T1 responses will stimulate protective immunity in vivo. Th1 cells will be used as probes to identify potentially protective antigens of B. bovis. Th cell lines and clones derived from immune cattle and characterized for cytokine expression patterns will be used in proliferation assays to identify biochemically fractionated parasite antigens. Antisera raised against these partially purified proteins will be used to identify the genes encoding the stimulatory T cell proteins by screening a B. bovis expression library. Alternatively, T cell lines and clones will be used directly to screen the library. Selected recombinant proteins will then be tested for the capacity to induce protective immunity in cattle and to characterize the nature of the T cell, macrophage and antibody responses both in vitro and in vivo against the immunogen. These studies will provide insight into the cellular and molecular basis of protective immunity against antigens that naturally stimulate a Th1 response in immune cattle, which will be directly applicable to related babesial and malarial parasites of humans.