Inflammation is a physiological response to injuries or insults, including bacterial infections. Acute inflammation is short-term, while chronic inflammation is nonphysiological and pathologic. Chronic inflammation activates adaptive immune responses, involving cellular and non-cellular mechanisms. Innate and adaptive immunity must coordinate to restore tissue homeostasis. Periodontal diseases are caused by bacteria, with the host-microbe interaction determining disease severity. Unlike many infectious diseases, periodontal diseases are caused by the overgrowth of commensal organisms rather than exogenous pathogens. Immune mechanisms that maintain commensal balance must adapt to preserve homeostasis. Periodontal diseases include gingivitis (inflammation of the gums) and periodontitis (inflammation of supporting tissues). Both are common globally, with significant prevalence in the US. The disease is associated with bacterial accumulation at the dento-gingival margin, though the exact causative organisms are unclear. The host responds to microbial challenge by generating an inflammatory cell infiltrate in the periodontal pocket. The initial inflammation is a physiological defense, not pathology. Clinical signs include plaque formation, calculus, and gingival inflammation. If plaque is removed, homeostasis is restored; if not, it becomes pathology. The initial lesion involves resident leukocytes and endothelial cells responding to bacterial biofilm. No clinical inflammation is present, but histological changes are observed. Bacterial metabolic products trigger cytokine production and neuropeptide release, leading to vasodilation and neutrophil migration. The early lesion follows, with increased neutrophils, macrophages, and lymphocytes. Complement proteins are activated, and epithelial proliferation occurs. The established lesion is a transition from innate to adaptive immunity, with increased blood flow and collagen production. The advanced lesion is the destructive phase, with irreversible attachment and bone loss. Innate immunity includes epithelial cells, phagocytes, and the complement cascade. Neuropeptides contribute to the initial immune response. The complement cascade is activated through three pathways: classical, lectin, and alternative. The alternative pathway is dominant in periodontal diseases, suggesting that even with pathogen-specific antibodies, most complement activation is via this pathway. Neuropeptides modulate inflammation, with substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) playing key roles. Substance P causes vasodilation and increases microvascular permeability. CGRP has vasodilator and immunosuppressive effects. VIP regulates both proinflammatory and anti-inflammatory mediators. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, triggering intracellular events leading to cytokine and chemokine production. TLRs are expressed on various immune cells, including dendritic cells, macrophages, and lymphocytes. TLR signaling pathways involve adapter proteins like MyD88, leading to cytokine production and immune responses. AntigenInflammation is a physiological response to injuries or insults, including bacterial infections. Acute inflammation is short-term, while chronic inflammation is nonphysiological and pathologic. Chronic inflammation activates adaptive immune responses, involving cellular and non-cellular mechanisms. Innate and adaptive immunity must coordinate to restore tissue homeostasis. Periodontal diseases are caused by bacteria, with the host-microbe interaction determining disease severity. Unlike many infectious diseases, periodontal diseases are caused by the overgrowth of commensal organisms rather than exogenous pathogens. Immune mechanisms that maintain commensal balance must adapt to preserve homeostasis. Periodontal diseases include gingivitis (inflammation of the gums) and periodontitis (inflammation of supporting tissues). Both are common globally, with significant prevalence in the US. The disease is associated with bacterial accumulation at the dento-gingival margin, though the exact causative organisms are unclear. The host responds to microbial challenge by generating an inflammatory cell infiltrate in the periodontal pocket. The initial inflammation is a physiological defense, not pathology. Clinical signs include plaque formation, calculus, and gingival inflammation. If plaque is removed, homeostasis is restored; if not, it becomes pathology. The initial lesion involves resident leukocytes and endothelial cells responding to bacterial biofilm. No clinical inflammation is present, but histological changes are observed. Bacterial metabolic products trigger cytokine production and neuropeptide release, leading to vasodilation and neutrophil migration. The early lesion follows, with increased neutrophils, macrophages, and lymphocytes. Complement proteins are activated, and epithelial proliferation occurs. The established lesion is a transition from innate to adaptive immunity, with increased blood flow and collagen production. The advanced lesion is the destructive phase, with irreversible attachment and bone loss. Innate immunity includes epithelial cells, phagocytes, and the complement cascade. Neuropeptides contribute to the initial immune response. The complement cascade is activated through three pathways: classical, lectin, and alternative. The alternative pathway is dominant in periodontal diseases, suggesting that even with pathogen-specific antibodies, most complement activation is via this pathway. Neuropeptides modulate inflammation, with substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) playing key roles. Substance P causes vasodilation and increases microvascular permeability. CGRP has vasodilator and immunosuppressive effects. VIP regulates both proinflammatory and anti-inflammatory mediators. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, triggering intracellular events leading to cytokine and chemokine production. TLRs are expressed on various immune cells, including dendritic cells, macrophages, and lymphocytes. TLR signaling pathways involve adapter proteins like MyD88, leading to cytokine production and immune responses. Antigen