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流行 世界各地。疟疾和疟疾有效疫苗的研制 新出现的巴贝斯虫在一定程度上受到了缺乏 相关的近亲繁殖动物模型。牛的免疫调节机制 比起老鼠，它们更像人类，所以这种繁殖出来的大型动物 物种提供了一种可供选择的系统来研究 对原生动物寄生虫的保护性免疫。巴贝西亚的病理学 牛的牛感染与疟原虫引起的非常相似 恶性疟原虫在人类中的感染，其特点是普遍存在 日本血吸虫寄生虫红细胞的循环障碍和隔离 毛细血管床，尤其是在大脑中。从天然中恢复的牛 或实验性感染活的扁虱或血液传播阶段的B。 牛发展出针对后续暴露的长期保护性免疫力 对同源和异源寄生虫菌株，这与 与Th1反应的体外发展有关。灭活免疫 寄生虫或分离的裂殖子抗原也导致了变量 对同源和异种的保护性免疫程度 挑战，这与特定的体液反应无关。 此外，基于血清学选择疫苗抗原的尝试 免疫优势未能识别保护性免疫原。因为 细胞介导的免疫效应机制是诱导 对许多细胞内寄生虫的保护性免疫和诱导 1型(T1或Th1)辅助细胞与免疫牛黄杆菌和 对于相关的疟疾寄生虫，我们提出了一种替代方法 基于能力的原生动物保护性寄生虫抗原识别 在免疫动物中诱导T1反应。我们假设抗原 选择在体外刺激T1反应将刺激 体内保护性免疫。Th1细胞将被用作探针，以识别 牛分枝杆菌潜在保护性抗原。TH细胞系和克隆 源自免疫牛，以细胞因子表达为特征 模式将被用于增殖分析，以确定生化 分离的寄生虫抗原。部分抗这些抗体的抗血清 纯化的蛋白质将被用来鉴定编码 通过筛选牛分枝杆菌表达文库来刺激T细胞蛋白。 或者，T细胞系和克隆将被直接用于筛选 图书馆。然后将对选定的重组蛋白进行测试 诱导牛保护性免疫的能力和表征 体外和体外T细胞、巨噬细胞和抗体反应的性质 在体内对抗免疫原。这些研究将为我们提供对 保护性免疫的细胞和分子基础 自然刺激免疫牛的Th1反应，这将是 直接适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.