CUTANEOUS IMMUNE RESPONSE TO PARASITIC INFECTION

对寄生虫感染的皮肤免疫反应

• 批准号: 2672650
• 负责人: RAMASWAMY KALYANASUNDARAM
• 金额: $ 10.25万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672650
• 关键词: Langerhans' cell; Schistosoma mansoni; antigen antibody reaction; antigen presentation; cell migration; cell type; cellular immunity; electron microscopy; flow cytometry; host organism interaction; human tissue; immunity; immunization; immunocytochemistry; immunoregulation; interleukin 10; laboratory mouse; lymph nodes; molecular cloning; molecular pathology; monoclonal antibody; nucleic acid sequence; organ culture; polymerase chain reaction; schistosomiasis; skin

The principal objective of this proposal is to identify the potential role of skin in initiating a protective immune response against Schistosoma mansoni infection in human and mice. The skin is the only site of entry for this parasite into human. It is now well established that in addition to acting as a major physical barrier against invading organisms, the skin functions as an important immunological organ. Therefore, migration of the parasite (schistsosomulae) through various layers of the skin (which lasts for over 48 hrs) should provide ample opportunity for the skin immune system to interact and initiate a T cell (Th1 or Th2 type) response in the skin and its associated lymph nodes. Yet, we know very little of the cutaneous immune responses to schistosomes. Given the fact that skin is also probably the only major site for future vaccination against schistosomiasis in human, it is highly important that we identify and characterize the local responses that might play a crucial role in the generation of protective immune responses. Therefore, in this project we are initially proposing studies that will analyze the immune responses generated in the skin and draining axillary lymph nodes of mice, following infection or immunization. Our preliminary RT-PCR studies show generation of a differential cytokine response in the skin within hours after immunization (IFN-gamma) or infection (IL-4 and IL-10) suggesting that the skin immune system may play a major role in directing the immune responses to appropriate pathways leading to protection or infection. The experiments proposed in this project will further identify the role of various cells in the skin, in initiating this differential response. These studies are thus, important in understanding ways to immunomodulate responses at the local site of immunization or infection in order to generate a strong protective immune response in the host. Our preliminary studies also show that migrating schistosomulae elaborate a low molecular weight factor that modulate the inflammatory and immune response in the skin of mouse and human. Possibly the parasite uses this mechanism to escape immune detection in the skin. Interestingly, schistosomulae of Trichobilharzia ocellata a bird schistosome which induces an acute allergic inflammatory response in the skin (commonly called 'swimmer's itch') do not appear to produce this low molecular weight factor. Therefore, in this study we are also proposing experiments to characterize and clone this factor, develop antibodies and test their ability in potentiating the protective responses. Thus, the studies proposed in this five year project will provide us with clear answers on the (1) role of skin in the generation of a protective immune response against S. mansoni (2) how migrating schistsosomulae escape this mechanism and, (3) possible ways by which we can modulate this response to help predict the success of an immunization protocol.

该提议的主要目的是确定潜力 皮肤在发起保护性免疫反应中的作用 人类和小鼠中的曼氏血吸虫感染。皮肤是唯一的 该寄生虫进入人类的入境地点。现在已经建立了 除了充当反对入侵的主要物理障碍之外 生物体，皮肤充当重要的免疫器官。 因此，寄生虫（schistsomulae）迁移各种 皮肤层（持续48小时）应提供充足的 皮肤免疫系统相互作用和启动T细胞的机会 （Th1或Th2型）皮肤及其相关淋巴结的反应。 然而，我们对皮肤免疫反应几乎没有 血块。鉴于皮肤也可能是唯一的主要 未来针对人类血吸虫病的未来疫苗接种的地点，这是 我们识别并表征本地响应非常重要 这可能在保护性免疫的一代中起着至关重要的作用 回答。因此，在这个项目中，我们最初是在建议研究 这将分析皮肤中产生的免疫反应和排水 感染或免疫后，小鼠的腋窝淋巴结。我们的 初步RT-PCR研究表明差异细胞因子的产生 免疫后几个小时内皮肤反应（IFN-GAMMA）或 感染（IL-4和IL-10）表明皮肤免疫系统可能 在指导免疫反应中发挥重要作用 导致保护或感染的途径。提出的实验 该项目将进一步确定各种细胞在皮肤中的作用， 在启动这种差异响应时。因此，这些研究是 在理解当地免疫调节反应的方法中很重要 免疫部位或感染部位，以产生强大的 宿主中的保护性免疫反应。 我们的初步研究还表明，迁移的序列详细迁移 低分子量因子，可调节炎症和免疫 小鼠和人的皮肤反应。可能是寄生虫使用的 避免皮肤中免疫检测的机制。 有趣的是， Trichobilharzia ocellata的斑点斑点是鸟斑点 在皮肤中诱导急性过敏性炎症反应（通常 称为“游泳者的痒”）似乎不会产生这种低分子 重量因子。因此，在这项研究中，我们还提出了实验 为了表征和克隆这个因素，开发抗体并测试其 能够增强保护性反应的能力。因此，研究 在这个五年项目中提出的建议将为我们提供明确的答案 （1）皮肤在保护性免疫反应产生中的作用 反对S. Mansoni（2）迁移的实体如何逃脱 机制和（3）我们可以调节此响应的可能方法 帮助预测免疫协议的成功。