免疫学教学课件-9-免疫调节-new.pptxVIP

第十二章 免疫调节;第一节 固有免疫应答的调节;第一节 固有免疫应答的调节 一、TLR信号转导的反馈调节;防止内毒素休克发生的反馈调节机制： ;;Soluble TLRs: sTLR2 and sTLR4;Intracellular negative regulators;IRAK-M (interleukin-1 receptor-associated kinase M) 激活性IRAK: IRAK and IRAK4, 抑制性IRAK: IRAK-2 and IRAK-M ;SOCS-1 (Suppressor of cytokine signaling 1);A20: TNF-a induced protein containing Zinc Finger domain. Target: RIP1, TRAF6. N-terminal DUB domain, C-terminal Zinc fingers. Modulate both Myd88 dependent and independent pathways.;TLR通路的负反馈调节;具有负反馈作用的膜蛋白;Regulation of TLRs by apoptosis;二、通过抑制信号途径调控细胞因子的激活;IFNg + IL-12;Negative Regulation of JAK-STAT signaling pathway in the immune system;The regulation of JAKs: mainly at the translational level ;SOCS ;Inhibition of STAT activity by PIAS (Protein inhibitor of activated STAT);PTP (protein-tyrosine phosphatase) family: About 90 members. Structure: Classic PTPs contain a PTP domain for hydrolyze phospho-tyrosine. ;PTK与PTP之间拮抗性的作用;Regulation of STATs by PTPs.;;Regulation of JAKs by ubiquitylation and ISGylation.;三、补体效应的调节 补体调节蛋白（complement regulatory protein） ;;（2）抑制补体转化酶的形成和促进其解离;C4BP: 取代2b与4b结合；dissociating C2b from the C4b, blocking the formation of C3 Convertase.;;（3）抑制膜攻击复合物的形成;2. 补体调节蛋白作用的同源性;四、免疫-内分泌-神经系统的相互作用和调节;Estrogen receptor is expressed by immune cells;Androgen receptor is expressed by immune cells;Gender difference in immune responses: Severity of infectious disease Response to vaccines and medications Incidence and pathogenesis of autoimmune diseases. Possible reason: X- or Y- linked genes Sex hormones ;Male more susceptible: Cutaneous leishmaniasis （黑热病）, TB, Lepromatous leprosy（麻风）;Cellular mechanisms: pDC: ER expression on pDC mediated the pathogenicity of pDC in SLE (produce IFN-a). ER expression on macrophages also auguments the production of pro-inflammatory cytokines. ER expression on iNKT cells mediates enhanced IFN-g expression by iNKT cells. ERa and ERb expression on T cells---Th1 response. Pregnancy: susceptible to infection and resistant to autoimmunity