THE MUCOSAL AND SERUM IGA SYSTEMS IN AIDS

艾滋病中的粘膜和血清 IGA 系统

• 批准号: 3136563
• 负责人: SUSAN JACKSON
• 金额: $ 16.5万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3136563
• 关键词: AIDS; HIV infections; antiantibody; antibody formation; antibody neutralization test; antiviral antibody; autoantibody; blood proteins; bone marrow; chromatography; enzyme linked immunosorbent assay; human immunodeficiency virus 1; human subject; human tissue; immune complex; immunochemistry; immunoglobulin A; immunoglobulin isotypes; intestinal mucosa; radiotracer; rheumatoid factor; saliva; secretory immune system; serology /serodiagnosis; tissue /cell culture; ultracentrifugation; virus antigen

Although impressive progress has been made toward understanding the biology of the etiologic agent of AIDs as well as the basis of its pathogenicity, new cases of the disease continue to increase worldwide at logarithmic rates, with no currently available means of either prevention or cure. AIDS is earmarked by a multitude of immune abnormalities, some of which are poorly understood. One of the relatively uncharacteracterized disorders of immune function in AIDS is an apparent dysfunction of IgA regulation. This is typified by inversely affected levels of serum and secretory IgA (often in the absence of alterations in the levels of other immunoglobulin isotypes), as well as elevated levels of IgA- containing immune complexes and IgA rheumatoid factor (RF). Understanding these often IgA-specific immunopathologies as well as the IgA immune system in general is imperative in a disease that is so often mucosally acquired as well as associated with multiple secondary infections at mucosal surfaces. Therefore, we will use the known serological and structural differences of serum and secretory IgA to elucidate the origin and function of IgA produced by the systemic and mucosal IgA systems in AIDS. At the cellular level we will study the immunoglobulin isotypes, including subclasses and molecular form of IgA, produced by peripheral blood lymphocytes, bone marrow, and lymphoid cells of sigmoid colon of AIDS patients; we will perform similar analyses on HIV-specific antibodies produced by the same cell populations. Since serum IgA is normally produced primarily in the bone marrow, we will examine the regulation of IgA synthesis by bone marrow cells of AIDS patients. We will examine the functional role of IgA antibodies, specifically with regard to: antibody-mediated enhancement of HIV infectivity; role in mediation or inhibition of ADCC and HIV neutralization; and identification of IgA autoantibodies. Other Studies will aim at identifying the cellular origins of IgA RF, using the same cell populations defined above. We will also characterize both serum and secretory (salivary) IgA and IgA antibodies specific for HIV with respect to IgA subclass and molecular form. Finally, we will further analyze the IgA- containing immune complexes in the sera of AIDS patients and correlate the composition and levels of these complexes with clinical status. These studies will answer basic questions as to the role of IgA, an immunoglobulin isotype generally considered incapable of protecting the host by classical mechanisms, in the pathogenesis of AIDS, a disease characterized by notable aberrations in IgA regulation.

尽管在理解人类的进化过程中 艾滋病病原体的生物学及其治疗的基础 致病性，新发病例不断增加 世界范围内的对数增长率，目前没有可用的手段 预防或治疗的方法。 艾滋病是由众多的 免疫异常，其中一些是知之甚少。 之一 相对不典型的免疫功能障碍 在艾滋病中是伊加调节的明显功能障碍。 这是 典型表现为血清和分泌伊加水平的负向影响 （通常在其他水平没有变化的情况下） 免疫球蛋白同种型），以及伊加- 含有免疫复合物和伊加类风湿因子（RF）。 了解这些IgA特异性免疫病理学 因为伊加免疫系统通常在疾病中是必需的， 通常是通过粘膜获得的， 粘膜表面继发感染。 因此，我们将使用 已知的血清学和血清结构的差异， 分泌型伊加，以阐明伊加产生的起源和功能 通过系统和粘膜伊加系统。 在细胞 水平，我们将研究免疫球蛋白同种型，包括 伊加的亚类和分子形式，由外周血产生 淋巴细胞、骨髓和乙状结肠的淋巴样细胞 艾滋病患者;我们将对艾滋病毒特异性 由相同的细胞群产生的抗体。 由于血清伊加 通常主要在骨髓中产生，我们将检查 艾滋病骨髓细胞伊加合成调节 患者 我们将研究伊加抗体的功能作用， 特别是关于：抗体介导的HIV增强 传染性;在ADCC和HIV的介导或抑制中的作用 中和;和伊加自身抗体的鉴定。 其他 研究的目的是确定伊加RF的细胞起源， 使用上面定义的相同细胞群。 我们还将 表征血清和分泌（唾液）伊加和伊加 伊加亚类的HIV特异性抗体，和 分子形式 最后，我们将进一步分析伊加- 在艾滋病患者的血清中含有免疫复合物， 将这些复合物的组成和水平与 临床状态 这些研究将回答基本问题， 伊加是一种免疫球蛋白同种型， 不能通过经典机制保护宿主， 艾滋病的发病机制，一种疾病的特点是显着 伊加调节异常。