病毒感染与自身免疫病课件.ppt

Exogenous viral agents have also been implicated as potential triggers or pathogenic agents of autoimmune conditions. Viruses which have been linked to the pathogenesis of SLE include ： Epstein-Barr Virus (EBV) Cytomegalovirus (CMV), parvovirus (细小) B19 Human Papilloma Virus (HPV), Human Herpes Virus (HHV-6), HHV-7, HHV-8, Dengue virus HIV human T cell lymphotropic virus (HTLV,人类嗜T细胞病毒 ) LMP1 LMP1 expression has been implicated in making important contributions to a variety of human malignancies, as well as to autoimmune diseases. LMP1 alters B-cell biology and the molecular mechanisms by which it exerts these effects by LMP1-mediated signaling pathways Epitope Spreading（表位扩展） 抗原刺激免疫系统，首先针对免疫优势表位产生免疫应答，如果抗原没有及时清除，免疫应答持续时，机体可相继针对隐蔽表位产生应答--表位扩展。 Polyspecific B-cell Activation Accumulation of EBV-specific CD8+ T-cells in Sites of Inflammation EBV specific CD8+ T-cells are enriched in or near the diseased organs of patients with RA and MS . EBV-specific CD8+ T-cells have also been reported to accumulate in synovial fluid (滑液)from patients with psoriatic arthritis, osteoarthritis and Reiter’s syndrome 局部炎症部位EBV特异性CTL细胞的集聚，加剧了局部的炎症反应 Transactivation of Human Endogenous Retroviruses EBV 诱导内源性逆转录病毒---产生 HERV-K18 HERV-K18编码--超抗原--激活--- T细胞 HERV-K18表达产物---在RA的外周血和关节液中出现 ，但SLE尚未报道。 已经证明EBV 在体外可激活---HERV-W（MS相关逆转录病毒（MSRV）），在MS患者的星形胶质细胞，B细胞和单核细胞中存在MSRV MSRV 体内外均可激活T-cells 并诱导产生 cytokines. Human Endogenous Retroviruses （HERV） 随着研究的深人，人们发现少部分HERV保留了产生逆转录病毒产物和病毒颗粒的能力 HERV与人类的进化关系密切，是哺乳动物生殖所必需的，并且影响哺乳动物胎盘发育，是妊娠所不可或缺的基因。同时和胎盘共同构建了一个防止微生物感染胎盘的屏障。 HERV还参与人体多种自身免疫性疾病和肿瘤的发生和发展过程。 HERV抗体在睾丸肿瘤、乳癌和黑素瘤中很常见。 HRES-1 two Gag-related products : 28-kD nuclear autoantigen (p28) ： HRES-1/p28 24-kD small GTP-ase (termed HRES-1/Rab4) higher titres of autoantibodies to HRES-1/p28