血脑屏障PPT参考幻灯片.pptVIP

* * T cells, B cells and antigen-presenting cells (APCs), including macrophages, enter the central nervous system (CNS), where they secrete certain chemicals known as cytokines that damage the oligodendroglial cells. These cells manufacture the myelin that insulates the neuronal axon. The injured myelin cannot conduct electrical impulses normally, just as a tear in the insulation of a wire leads to a short circuit. Lymphocytes diapedese into the CNS through use of a surface receptor known as?4-integrin. This step is impeded by antibodies specific for?4-integrin or by interferon-?(IFN-). Once the blood–brain barrier is breached, other inflammatory cells accumulate in the white matter. Inside the brain, T cells and accompanying macrophages and microglial cells release osteopontin (OPN), interleukin-23 (IL-23), IFN-?and tumour-necrosis factor (TNF), all of which damage the myelin sheath. Also, the presence of OPN might lead to the attraction of T helper 1 (TH1) cells. T-cell activation can be blocked by altered peptide ligands (APLs), such as copaxone, or by statins. Concomitantly, B cells (plasma cells) produce myelin-specific antibodies, which interact with the terminal complex in the complement cascade to produce membrane-attack complexes that further damage oligodendroglial cells. DNA vaccination can be used to tolerize T- and B-cell responses to myelin. * T cells and antigen-presenting cells (APCs) such as macrophages produce glutamate, a toxic substance, which injures oligodendroglial cells and underlying axons. The activation of T cells can be blocked by various approaches, including statins and altered peptide ligands (APLs). Statins also inhibit the secretion of metalloproteases, and it has been suggested that they might, therefore, also act to block T cells from entering the central nervous system (CNS). Antibodies specific for?4-integrin also block the movement of T cells into the brain. OPN, osteopontin. * HIV脑病的病理改变是以脑沟增宽、脑室扩大为特征的脑萎缩，也会出现脑膜纤维化。组织病理的标志是病毒所导