2016wl-第6章细胞因子.pptVIP

同源多聚体 * * Chemokine receptors are G Protein-Coupled Receptors. 趋化因子受体是表达在一些特定的细胞表面的G蛋白偶连的七跨膜域受体。这些受体与细胞外的配体趋化因子结合。与特异的趋化因子结合后，趋化因子受体引发钙离子内流而产生细胞趋化反应，从而诱导细胞到生物体的特定部位。 * X-linked severe combined immunodeficiency(X-SCID) is an?immunodeficiency?disorder, stemming from a mutated (abnormal) version of the?IL2-Rγ?gene located at xq13.1 on the X-chromosome, which is shared between receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. /wiki/X-linked_severe_combined_immunodeficiency * * * * * * Pleiotropism refers to the ability of one cytokine having multiple effects on diverse cell types. Redundancy refers to the property of multiple cytokines having the same or overlapping functional effects. * Synergy refers to the property of two or more cytokines having greater than additive effects. Antagonism refers to the ability of one cytokine inhibiting the action of another. 100多年前,就有人发现肿瘤常因感染而出现坏死，现在知道是TNF引起炎症和肿瘤血管栓塞所致。 * Septic shock is characterized by vascular collapse, disseminated intravascular coagulation, and metabolic disturbances and it can be reproduced in experimental animals by administration of LPS or TNF. Antagonists of TNF can prevent mortality in the experimental models, but clinical trials with anti-TNF antibodies or with soluble TNF receptors have not shown benefit in patients with sepsis. The cause of this therapeutic failure is not known, but it may be because other cytokines elicit the same responses as TNF, an example of redundancy. * * Roles of cytokines in hemopoiesis CSF=Colony stimulating factor * * Therefore, it was possible to add various substances to cultures of hemopoietic stem cells and then examine which kinds of colonies (if any) were stimulated by them. * Supplement or addition therapy Blocking or antagonist therapy * 局部性：细胞因子通常以自分泌(autocrine)和旁分泌(paracrine)方式发挥作用。某些细胞因子在一定条件下可以内分泌(endocrine) 方式作用于全身。 复杂性 多效性与重叠性 协同性与拮抗性 网络性 TH1 Mj IL- 4 marrow stroma cell IL-1 IL-6 IL-7 SCF HSC IL-1 IL-6 IL-11 TNF-a GM-CSF G-CMF M-CSF monocyte TH