临床免疫学（鲁林荣）第1讲 自身免疫病.pptVIP

* Molecular Mimicry，中文称之为分子模拟，主要是指病毒抗原被T细胞识别产生应答之后，由于某些病毒编码的抗原和人体自身抗原高度类似，使得这些应答T细胞能同时交叉识别自身抗原，从而导致对自身组织的攻击 * 这里是一些类似抗原肽的例子。 * 病毒感染诱导自免的另一种方式是By stander activation， 一种方式是感染促使TLR分泌炎症因子直接损伤组织；组织损伤后组织恶意新抗原被释放和识别。 * 这里还涉及到一个表位扩展的现象，是自免发展进程的一个主要特征。。。 * * Corticosteroid Corticosteroid 环氧合酶 膜联蛋白 前列腺素白三烯 Cyclosporin Cyclosporin Immune Therapy of Autoimmune diseases Therapeutic approaches for immune disorders Therapeutics based on the B7:CD28/CTLA-4 family 1. Costimulatory blockade Therapeutics based on the B7:CD28/CTLA-4 family 2. Inhibiting the inhibitor – anti-tumor immune therapy Anti-CD11a antibody (efalizumab) inhibits the migration of dendritic cells and T cells into psoria skin lesions Anti-CD3 mAb Treatment for Autoimmunity Suppression of autoimmunity with anti-CD3 Results of Herold anti-CD3 Phase I/II trial in Type 1 Diabetes ? Tumor Necrosis Factor-α (TNF-α) ? TNFα is a multifunctional pro-inflammatory mediator a) Induction of further cytokine production b) Activation or expression of adhesion molecules c) Growth stimulation ?Overproduction of TNF α is associated with a wide range of pathological conditions. ?Effort to find ways to down-regulate production or inhibit its effects. TNFα Crohn’s Disease (CD) ? Inflammatory Bowel Disease (IBD) ? Chronic inflammation of areas of the gastrointestinal tract. ? Can affect all layers of the bowel wall with possible abscesses and fistulas（脓肿和瘘） (~30% of patients). ? Common symptoms Abdominal pain Diarrhea Weight Loss Loss of appetite Fever Fatigue Excruciatingly painful – may require morphine Increased risk of colorectal cancer Unknown cause No known cure Difficult to treat. ? Imbalance of pro- and anti-inflammatory mediators ? Enhanced Th1 response (IFNγ, TNFα) ? TNFα is a pro-inflammatory cytokine produced by monocytes, macrophages and T cells ? Local production is thought to have a key role in the initiation and propagation of Crohn’s disease ?Production of TNF