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Cytokines & Diseases

Cytokines & Diseases. Start. 资料 : 郭爽 王智娜 邰莹 翻译 : 郭爽 王智娜 邰莹 整理 : 王 凡 制作 : 莫文思. 2005 级临床七年制四班. CONCEPT. Cytokines are a family of low molecular weight proteins mediating innate and adaptive immune response. Classification: — interleukins, — interferons,

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Cytokines & Diseases

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  1. Cytokines & Diseases Start 资料:郭爽 王智娜 邰莹 翻译:郭爽 王智娜 邰莹 整理:王凡 制作:莫文思 2005级临床七年制四班

  2. CONCEPT Cytokines are a family of low molecular weight proteins mediating innate and adaptive immune response. Classification: — interleukins, — interferons, — tumor necrosis factors, — colony-stimulating factors, — chemokines — transforming factors.

  3. CHARACTERISTICS Cytokines are mainly synthesized in response to inflammatory or antigenic stimuli. The same cytokines may be produced by many cell types, and individual cytokines are often produced by diverse cell types. Mode of secretion: autocrine, paracrine , endocrine.

  4. Biological Function • Take part in nonspecific immunity — anti-bacteria , anti-virus • Take part in specific immunity • Stimulate hematopoiesis • Take part in inflammatory reaction

  5. Diseases we’ll mention TSLP & Allergic Diseases IL-18 & Type 1 Diabetes BACK

  6. The relationship between thymic stromal lymphopoietin (TSLP) and allergic diseases

  7. ? Why human body produces strongly Th2 immune response when contact with allergen? ? Why human body produce too many IgE?

  8. consists IL-7R-a chain TSLPR- γchain. • Thymic stronmal lymphopoietin • Originally cloned from thymic stromal epithelium • Structurally related to IL-7 • Four alpha helical bundie cytokine Structure of tslp

  9. Il-7 structure in 3d Romano T. Kroemer Stephen W. Doughty, Prediction of Three Dimensional Structure of Human Interleukin-7 By Homology Modeling; Protein Engineering vol.9,no.6;pp493-496,2006

  10. TSLP gene location 5q31 5q22.1 TSLP Cytokine cluster IL-7 is encoded on 8q12-8q13 • Human TSLP is encoded on chromosome 5q22.1 next to the atopic cytokine cluster on 5q31 (IL-7 is encoded on 8q12-q13)

  11. TSLP Expression • epithelial cells • 1.respiratory epithelial cells • 2.keratinocytes(角化细胞） • 3.thymic epithelial cells within the Hassal corpuscles • mast cells activated by cross-linking FcεR1 • smooth muscle cells • fibroblasts. • human myeloid dendritic cells (mDC)

  12. MHC-Ⅰ, MHC-Ⅱ on the surface of DC co-receptor: CD40, CD80 Mature sign: CD83 TSLP Th (IL-4, 5,13) CD4+ T cell TSLP-DC MECHANISM produce B cell ,Ig E

  13. BACK

  14. Answer to question 1: TSLP-DC express OX40L OX40(T cell)+OX40L(TSLP-DC) T cell Th2 BACK

  15. MECHANISM • IL-4 • IL-5 • TSLP-DC IL-4 actives B cell through decreasing expression of inhibit receptor on the surface of allergen specific B cell. IL-5 induces B cell proliferation, promotes respiratory tract epithelial cells expressing eosinophilic granulocyte . TSLP-DC reacts with naïve CD8+ T cell to produce effect cell, products quantity of INF-a to enhance tissue destroyed. Answer to question 2

  16. DC & monocyte Mast cell TSLP Th2 IL-4, 5,13 B cell proliferation Ab IgE Positive regulation BACK

  17. IL-18 and type I diabetes

  18. History • IL-18 is a new cytokine found by Okamura in 1995 . • It can induce T cell to produced IFN-g, then named IL18 . • IL-18 is a related IL-1 is formed by the precursor of a wide range of cells, such as T, B cells, monocytes and so on.

  19. composition IL-18 is composed by 192 amino acids, containing a 35 amino acid sequence as the guide sequence. In a cell , pro-IL-18 use ICE (also known as Cas Pase-1) to cut off 35 amino acid residues in the N terminal, then become the active IL-18.

  20. Lead to injury and death of Island B cell. Type I diabetes The mechanism of il-18 lead to type 1 diabetes Promote the secretion of cytokines ----- IFN-g Enhancement of NK cell cytotoxicity Enhancement of FasL mediated cytotoxicity BACK

  21. THE END THANK YOU

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