GENETIC CONTROL OF IMMUNITY TO HELIGMOSOMOIDES POLYGYRUS

这项建议的主要目标是评估所发挥的作用 H-2连锁基因在控制幽门螺杆菌免疫应答中的作用 小鼠的多回，以定位与H-2相关的基因，并 进行基因特征的比较免疫学研究 耐药和敏感品系的小鼠，以鉴定 对这种寄生虫免疫的功能性效应器。目标 将通过研究H-2同源品系小鼠的感染来解决 它们只在主要组织相容性复合体内的基因上有所不同，以及 在拥有共同H-2连锁基因但表达 不同的遗传背景。我们将比较全身抗体和局部抗体 耐药品系和敏感品系小鼠对多回螺旋体的反应 用寄生虫特异性的酶联免疫吸附试验(ELISA)检测 Ig G、Ig M、Ig A和Ig E抗体，并将比较抗体产生 通过测试选定的淋巴细胞群在斑块形成中的潜力 体内和体外(Mishell-duton)抗原后的细胞(PFC)检测 引爆。参与这些反应的细胞的特征是 抑制或消除这些细胞中的特定功能细胞类型 使用针对H-2、Ia和Ly抗原的抗血清培养表达 免疫活性细胞的功能亚群。我们还将使用这些 抗血清用于表征引起标记的细胞群 易感但不敏感的抗体反应性抑制 受感染小鼠的抗药性品系。除了研究幽默之外 对多脑回的免疫反应，我们将研究细胞免疫反应 在具有遗传特征的耐药和敏感品系的小鼠中。 控制显著的L3剂量依赖性脾肿大的细胞群 耐药但不敏感的小鼠品系也会表现出 特色化的。然后我们将量化细胞对这两种幼虫的反应 和成虫多回抗原使用敏感和特异的耳肿胀 实验和体外淋巴细胞刺激实验。最后，我们 将决定细胞或体液免疫反应是否易感 小鼠的品系在多脑回感染期间被特异性抑制。 这将通过选择性地耗尽抑制细胞来实现 通过注射针对I-J编码基因产物的抗血清或 从使用特定Ia和Ly抗血清的细胞培养中提取。

The principal objectives of this proposal are to evaluate the role played by H-2-linked genes in controlling immune responsiveness to Heligmosomoides polygyrus in the mouse, to map the H-2-linked genes involved, and to conduct comparative immunological studies between genetically characterized resistant and susceptible strains of mice in order to identify the functional effectors of immunity against this parasite. The objectives will be addressed by studying infections in H-2 congenic strains of mice which differ only at genes within the major histocompatibility complex, and in strains of mice which share common H-2-linked genes but express different genetic backgrounds. We will compare systemic and local antibody responses to H. polygyrus in resistant and susceptible strains of mice using a parasite-specific enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, IgA, and IgE antibody, and will compare antibody production potential by testing selected lymphoid cell populations in plaque forming cell (PFC) assays after both in vivo and in vitro (Mishell-Dutton) antigen priming. The cells involved in these responses will be characterized by inhibiting or eliminating specific functional cell types from these cultures using antisera specific for the H-2, Ia, and Ly antigens expressed on functional subsets of immunocompetent cells. We will also use these antisera to characterize the cell populations responsible for the marked suppression of antibody responsiveness exhibited by susceptible but not resistant strains of infected mice. In addition to studying the humoral immune responses to H. polygyrus, we will study cellular immune responses in genetically characterized resistant and susceptible strains of mice. The cell populations controlling the marked L3 dose-dependent splenomegaly exhibited by resistant but not susceptible strains of mice will also be characterized. We will then quantitate cellular responses to both larval and adult H. polygyrus antigens using a sensitive and specific ear swelling assay as well as by in vitro lymphocyte stimulation assays. Finally, we will determine if the cellular or humoral immune response in susceptible strains of mice is specifically suppressed during H. polygyrus infection. This will be accomplished by selective depletion of suppressor cells from the host by injection of antisera specific for I-J coded gene products or from cell cultures using specific Ia and Ly antisera.