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The 2005 Nobel Prize Helicobacter pylori

The 2005 Nobel Prize Helicobacter pylori. 64 陳冠伃 62 陳治郡 80 楊昀達 91 鄭惟仁 60 陳安婕 75 黃俊諺 71 陳穎鈞 63 陳泊儒 59 郭人碩. 指導助教 : 林博雅. Contents. 得獎者簡介 幽門桿菌介紹 VacA 致病機制 急性慢性胃炎 CagA 致病機轉 Helicobacter 致癌機制 Helicobacter 檢驗與治療 影片總結. About the Laureates --- before they met.

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The 2005 Nobel Prize Helicobacter pylori

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  1. The 2005 Nobel PrizeHelicobacter pylori 64陳冠伃 62陳治郡 80楊昀達 91鄭惟仁 60陳安婕 75黃俊諺 71陳穎鈞 63陳泊儒 59郭人碩 指導助教:林博雅

  2. Contents • 得獎者簡介 • 幽門桿菌介紹 • VacA致病機制 • 急性慢性胃炎 • CagA致病機轉 • Helicobacter致癌機制 • Helicobacter檢驗與治療 • 影片總結

  3. About the Laureates--- before they met

  4. 1951 1981 1979 Barry J. Marshall J. Robin Warren • 1968 1981 1979

  5. After they met---heading toward the Nobel prize

  6. 1981 Campylobacter-like organisms, CLO • 1982 tissue culture & animal model • 1984 human model • 1989 Helicobacter pylori • 2005 Nobel prize 1981 1984 2005 1982 1989

  7. Helicobacter pylori • about 3 μm in length and 0.5 μm in diameter • Gram-negative and microaerophilic • Use flagella for motility

  8. Stomach acid • Secrete urease for surviving in acid environment. • Spread from person to person through fecal-oral or oral-oral routes. Gastric epithelium

  9. Urease 1.使Hp能在胃部生存 2.尿素檢驗法-胃是否有Hp 1.Adhesion 2.TFSS系統 Flagella Secreted proteins VacA & CagA 1.胃部黏膜細胞的毀損 2.造成胃癌 3.引起一連串的免疫機制

  10. Virulence factor • flagellin（鞭毛蛋白） • urease（尿素酶） • adhesin（黏附素） • vacuolating cytotoxin,VacA（空泡毒素） • cytotoxin associated gene A,CagA（細胞毒素相關蛋白）

  11. Flagellin • The principal flagellum substituent • Switch between multiple flagellin genes • Activity＆Toxicity

  12. Urease

  13. Adhesin Adhere to stomach cell Releases protease and phospholipase degrades the hydrophobic layer gastric acid erodes stomach

  14. VacA Vacuolating cytotoxin A 30nm 87kD 1980 Timothy Cover H.pylori infects epithelial cells→vacuolation Oligomer Double layer。12-14 Single layer。 6-7

  15. Vacuolation Apoptosis VacA pathways Tight junction

  16. Apoptosis

  17. Vacuolation Oligomerization H+ V-ATPase Cl- Channel Apoptosis

  18. Tight junction Inhibit T cell activation

  19. Acute gastritis Chronic gastritis

  20. Acute gastritis Release INF(Interferon)-γ → attract more macrophages to the infected epithelial cells → inflammation INF- γ Microphage Bcell Dendritic cell Activate B cell (little) Release IL-2 → activate TC Positive feedback Release IL-12 (Interleukin 細胞間白素) → activate TH1 cells IL-12

  21. Chronic gastritis Release INF-γ → attract more macrophages to the infected epithelial cells → inflammation INF- γ IL-4 Microphage Dendritic cell Release IL-4 → activate more B cells B cell Release IL-10 → activate TH2 cells → inactivate TH1 cells IL-10 IL-12 Release IL-12 → activate TH1 cells

  22. Comparison IL-10 released by TH2 cells will inactivate TH1 cells → By contrast, TH1 cells in chronic gastritis are less → Reduce the level of inflammation

  23. CagA(cytotoxin associated gene A) an H. pylori virulence factor 1a 120–145-kDa protein exists in 60%~70% H. pylori. CAG PATHOGENICITY ISLAND (PAI) 2cagA-positive and cagA-negative strains. 3 TYPE IV SECRETION SYSTEM(TFSS)

  24. TFSS

  25. SH2 protein tyrosine phosphatase 2 (SHP-2) SH2：src homology 2 domains PTP：protein tyrosine phosphatase CagApathways

  26. IL-8 assembles monocytes, neutrophils and ROS Leukocytes secrete a. IL-1β ---proinflammatory cytokines b. TNFα ---Tumer necrosis factor

  27. Secrete gastric juice↓ Hp exists Cag A White blood cells release cytokines Gastric epithelial cells More serious inflammation IL-1β TNFα IL-8 Arachidonic acid (花生四烯酸) in the cell membrane turns into prostaglandin (前列腺素) COX-2↑ ROS aggregation White blood cells aggregation + Gastrin ↑ Affect cell physiolgy Activate oncogene Growth factors↑ More white blood cells aggregation Too less gastric juice, too much gastrin → Atrophic gastritis → Abnormal cells proliferation massively Chronic gastritis

  28. VEGF Cag A EGFR Vessels proliferation

  29. After Hp disappears 常見 罕有

  30. Diagnosis & Cure • Ⅰ. Invasive examination 1.Cell cultivation 2.Urease test 3.Tissue examination • Ⅱ. Noninvasive examination 1. Urea breath test 2. Serum examination • Ⅲ. Cure Proton and potassium pump inhibitor amoxicillin, clarithromycin metronidazole.

  31. Conclusion

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