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The Nobel Prize in Physiology or Medicine 2005

The discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease. The Nobel Prize in Physiology or Medicine 2005. Class A Group 4 王彥昇、何長軒、吳庭瑜、呂庭毅、卓韋儒、林欣聖、林庭蔚、張剛瑋. Content. Discoverers Helicobacter pylori Virulence factors Immunoreactions Gastritis

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The Nobel Prize in Physiology or Medicine 2005

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  1. The discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease The Nobel Prize in Physiology or Medicine 2005 Class A Group 4 王彥昇、何長軒、吳庭瑜、呂庭毅、卓韋儒、林欣聖、林庭蔚、張剛瑋

  2. Content Discoverers Helicobacter pylori Virulence factors Immunoreactions Gastritis Gastric cancer Diagnosis & Cure Summary

  3. Drs. Barry Marshall and Robin Warren • Successfully cultivated H. pylori • Showed below Robin Warren • Proved H. pylori the pathogen • Invented C13 urea breath test Barry Marshall

  4. Helicobacter Pylori • Gram negative • Spiral shaped • Microaerophilic bacterium • 2~4 um • Inhabit in stomach and duodenum

  5. Epidemiology 90% 80% 20% • 50% affection rate • socio-economic status<race • Oralaffection • Reduce obese Ashma GERD(Gastroesophageal Reflux Disease)

  6. Virulence Factors Pathogenic Factors Flagellin Urease Adhesin VacA Secret TFSS HOST CELL Injection CagA

  7. Mucus Urease PH<4 4<PH<8.2 H2O CO2 Urea Urease NH3 Neutralize gastric acid 空泡變性 Epithelial cells

  8. Adherence of H. pylori • Adhesin - BabA(histo-blood group antigen binding adhesion) - SabA (sialic acidbinding adhesion) • LPS(lipopolysaccharide) -- Lex(Lewis x) -- Ley(Lewis y) • Lewis blood group antigen • Related ABO antigens

  9. Persistence infection and chronic inflammation(gastritis) BabA Leb s-Lex SabA H. pylori use BabA for recognition of Leb H. pylori triggers the host to retailor mucosal glycosylation patterns to up-regulate s-Lex Vigorous inflammantory response H. pylori might have gain local advantage In the prepared of escaping of intimate contact with lymphocyte or other defensive cells.

  10. cagA (cytotoxin associated gene A) • Cag PAI (Cag pathogenicity island ) a. cagA( exists in 60%~70% H. pylori) b. TFSS • Translate to protein CagA (cytotoxin associated antigen A ) a.a 120–145-kDa protein

  11. cag PAI TFSS

  12. SH2(N-SH2 C-SH2 ) protein tyrosine phosphatase

  13. NF-κB TFSS IL-8(interlukin-8) Neutrophil、Monocyte NF-kB TNFα、IL-1 pH increased IL-8

  14. VacA(Vacuolating cytotoxin A) -Discovery: 1980 -Subunits: p37&p58 -Oligomer complex

  15. 3. Increase paracellular epithelial permeability 2. Apoptosis 1.Vacuolation 4.T-lyphocyte Immunosuppression

  16. H. pylori induced gastric ulcer

  17. Acute gastritis Chronic gastritis

  18. Acute gastritis INF-γ： 1.Increase antigen presenting of macrophage 2.Attract more macrophage to the epithelial cells ↓ inflammation Macrophage INF-γ B cell DC= dendritic cell TH1 activate little B cells IL-2 T cell→Tc INF-γ IL-12

  19. Chronic gastritis INF-γ IL-4 Macrophage Dendritic cell TH2 cell release IL-4 ↓ B cell proliferation B cell TH2 cell IL-10 Stimulate TH2 cell Inhibit TH1 cell IL-12

  20. Comparison between acute and chronic gastritis Persistent colonization of Hp in presence of mild gastritis High level of inflammation

  21. Gastric Cancer Benign gastric ulcer

  22. Cox2cyclooxygenase-2 Cox2 PG Arachidonic acid 花生四烯酸 PGE2 15d-PGj2 in the cell membrane PPAR-γ G-protein coupled receptor EGFR Activate transcription of anti-apoptotic genes Protein kinase cascade VEGF BCL2↑ Apoptosis Angiogenesis

  23. ROS NO Angiogenesis VEGF Reactive oxygen species(自由基) Tissue DNA damage Mutation activation of host signaling pathways (carcinogen) Angiogenesis(血管新生)

  24. Oncogene K-Ras p53 Mutated K-Ras Mutated p53 Protein kinase cascade Cox2 mRNA transcription↑ Cannot repair Cox2↑

  25. Diagnoses Invasive testing： Histological examination Culture P.C.R. Rapid urease test Non-invasive testing： Serology test Scatological examination C13-urea breath test

  26. 13 C13 Urea 13 13 Urease • NH2C13ONH2NH3　＋　H2C13O3 • H2C13O3→ H2O+C13O2

  27. Cures Triple therapy 三合一療法 & 飲食控制 1.Antibiotics + bismuth subsalicylate(鉍鹽) 2.Antibiotics + proton pump inhibitors Curability 80%~90%. And it’s permanent! Nobel prize get!

  28. Summary Helicobacter pylori Virulence factors Immunoreactions Gastritis Gastric cancer Nobel prize get!!!

  29. Thanks to this pioneering discovery, peptic ulcer disease is no longer a chronic, frequently disabling condition, but a disease that can be permanently cured. Gastric cancer →Nobel prize get!!!!!!!!

  30. Thanks for your listening~

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