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Pathogenesis of Periodontitis Environmental and acquired risk factors Microbial Challenge Host Immunoinflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Genetic risk factors Page, Ann Periodontol 1998 Pathogenesis of Periodontitis Microbial Challenge Host Immunoinflammatory response Clinical signs of disease initiation and progression Bacteria attacking the body • Antigens • Lipopolysaccharides • Other virulence factors Page, Ann Periodontol 1998 Pathogenesis of Periodontitis The body defense: • Antibodies • Neutrophils Microbial Challenge Host Immunoinflammatory response Clinical signs of disease initiation and progression Bacteria attacking the body • Antigens • Lipopolysaccharides • Other virulence factors Page, Ann Periodontol 1998 Pathogenesis of Periodontitis Inflammatory response releases: • Cytokines • Prostanoids • Matrix Metalloproteinases Microbial Challenge Host Immunoinflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Page, Ann Periodontol 1998 In Patient A, who is NOT susceptible to periodontitis: Microbial Challenge Host Immunoinflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Tissue and bone repair/healing Page, Ann Periodontol 1998 In Patient B, who is susceptible to periodontitis: Tissue destruction and bone loss Microbial Challenge Host Immunoinflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Page, Ann Periodontol 1998 In Patient B, who is susceptible to periodontitis: Microbial Challenge Host Immunoinflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Deepening of periodontal pockets, furcation involvement, contaminated cementum… Page, Ann Periodontol 1998 Pathogenesis of Periodontitis Environmental and acquired risk factors Microbial Challenge Host Immunoinflammatory response Connective tissue and bone metabolism Clinical signs of disease initiation and progression Genetic risk factors Page, Ann Periodontol 1998 In periodontitis, what is actually occurring in a periodontal pocket… Periodontal Pathogens has invaded: • Periodontal pocket • Cementum • Gingival tissue In a patient susceptible to periodontitis, how does the body react? IL-8/ICAM-1 1. Epithelial Cells produce IL-8 and ICAM-1 in response to bacteria & antigens 2. IL-8 and ICAM-1 are chemotactic signals for neutrophils, which are recruited to the sulcus Neutrophils Bacteria/Antigens 3. Neutrophils control bacterial assault by phagocytosis but also secrete matrix metalloproteinases or collagenases (MMP-8) which results in collagen degradation MMP-8 T-cell Plasma Cell B-cell 4. Interaction of antigens with B cells lead to production of antibodies and complements, which contribute to phagocytosis 5. In response to bacterial LPS, various cells produce IL-1, TNF-, and PGE2 Activated B-Cell IL-1 TNF- Macrophage LPS PGE2 Fibroblast Activated B-Cell IL-1 TNF- Macrophage PGE2 Fibroblast Osteoclast activation 6. Production of IL-1, TNF-, and PGE2 leads to osteoclast activation, proliferation and differentiation Major Mediators Disease Health Higher amounts of IL-1, TNF-, PGE2, MMPs • • Proinflammatory Destructive Lower amounts of IL-10, TGF-, IL1ra, TIMPs Disease Health Higher amounts of IL-10, TGF-, IL1ra, TIMPs Lower amounts of IL-1, TNF-, PGE2, MMPs • • Anti-inflammatory Protective