Host Immune Response to Plaque Biofilm (PDF)

# Chapter 15 Host Immune Response to Plaque Biofilm ## Section 1 The Host Response in Periodontal Disease - **Factors Enhancing the Microbial Challenge** - **Presence of lipopolysaccharide (LPS)**: Gram-negative bacteria are a component of mature plaque biofilm. Gram-negative bacteria are virule...

# Chapter 15 Host Immune Response to Plaque Biofilm ## Section 1 The Host Response in Periodontal Disease - **Factors Enhancing the Microbial Challenge** - **Presence of lipopolysaccharide (LPS)**: Gram-negative bacteria are a component of mature plaque biofilm. Gram-negative bacteria are virulent because of lipopolysaccharide (LPS), an endotoxin present on the outer membrane of the bacteria. LPS can be responsible for initiating inflammation in periodontal tissues. - **Ability to invade tissues**: There is good evidence that several subgingival bacteria can invade epithelial cells. Some of the periodontal bacteria - such as *Porphyromonas gingivalis (P.g)* and *Aggregatibacter actinomycetemcomitans (A.a)* - can invade host tissues. Penetration of tissues can, to some degree, allow the bacteria to escape host defense mechanisms. - **Ability to produce enzymes**: Several periodontal bacteria produce enzymes such as collagenases and proteases that can directly degrade host proteins that are a basic part of the structure of the periodontium. - **Factors Affecting the Host Immune Response** - **Genetic Factors**: Genetic factors appear to contribute to periodontal disease. Studies in twins and families indicate an association between periodontal disease and genetic factors. Diseases with genetic origin such as Papillon-Lefèvre syndrome and leukocyte adhesion deficiency (LAD) are associated with aggressive types of periodontal diseases. Also, variations in genes controlling formation of biochemical mediators can modify the immune response to plaque biofilm, increasing the susceptibility to periodontal disease. - **Environmental Factors**: Tobacco smoking is a known risk factor for periodontal diseases. It has a significant effect on the immune and inflammatory system. Smoking has been shown to decrease polymorphonuclear neutrophil (PMN) phagocytic capacity, decrease vascularity of gingival tissues, and affect both T- and B-lymphocyte response to periodontal pathogens. - **Acquired Factors**: Diabetes mellitus is a known risk factor for periodontal diseases and its progression. Abnormal blood glucose levels seen in diabetes mellitus affects the host response by reducing PMN function, increasing interleukin (IL)-1, tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) levels in gingival crevicular fluid and reducing growth and proliferation of periodontal ligament fibroblasts and osteoblasts in periodontium. ## Section 2 Histologic Stages in the Development of Periodontal Disease **Bacterial Accumulation (Initial Lesion)** - **Bacterial Features**: Bacteria colonize the tooth surface near the gingival margin. - **Cellular Features**: The presence of gram-negative bacteria and their metabolic products initiates the host immune response. - **Cytokines**: released by the junctional epithelial cells stimulate the immune response, recruiting polymorphonuclear leukocytes (PMNs) to the site - **PMNs**: pass from blood vessels into the gingival connective tissue. - They need to reach the sulcus to fight the bacterial infection - As they pass into the gingival connective tissue they release cytokines. - The goal of the PMNs is to reach the bacteria in the sulcus and destroy them. - **Complement System** Activated - **Tissue Level Features** - Initial location of the plaque biofilm is supragingival. - Vascular dilatation of arterioles, capillaries, and venules in the dentogingival complex. - Gingival crevicular fluid increases in volume. - **Clinical Features** - The gingiva looks healthy clinically. - This initial lesion phase develops 2 to 4 days following plaque biofilm accumulation. - **Outcome of Host Response** - The host response is successful, if most of the bacteria are destroyed. - If the bacterial infection is brought under control - through the efforts of the immune system and effective plaque biofilm control - the body can repair the destruction caused by the immune response. - If the bacterial pathogens are not controlled, however, early gingivitis develops. **Early Gingivitis (Early Lesion)** - **Bacterial Features**: Bacterial accumulation continues and biofilm maturation occurs. This results in the production of bacterial toxins and byproducts that penetrate the junctional epithelium. - **Cellular Features: Migration and Chemotaxis of PMNs** - **Cytokines**: released by the junctional epithelial cells in response to the increased bacterial challenge - attract additional cellular defenders to the site. - **Increased permeability**: of the blood vessels allows larger numbers of PMNs to move into the gingival connective tissue near the infection site. - **PMNs**: migrate through the junctional epithelium to form a “wall of cells” between the biofilm and the sulcus wall. They comprise the most important component of the local defense against bacteria. - **Cytokines**: released by the PMNs cause localized destruction of the connective tissue. This tissue destruction allows more PMNs to migrate through the connective tissue toward the sulcus. PMNs phagocytize bacteria in the sulcus in an effort to protect the host tissues from the bacterial challenge. - **Migration of Additional Cellular Defenders** - **Macrophages**: recruited to the connective tissue. These cells release biochemical mediators including cytokines, PGE2, and MMPs. These biochemical mediators recruit additional immune cells to the infection site. MMP is responsible for the excessive loss of collagen in the affected connected tissue zone. - **T-lymphocytes**: migrate to the connective tissue and produce cytokines and antibodies. The early lesion is predominantly a T-cell lesion. - **Tissue Level Features** - **Sulcular epithelium**: and the adjacent connective tissue are affected the most: collagen loss of 60% to 70% is noted at this stage. - **Sulcular epithelium**: starts forming epithelial ridges (epithelial extensions that protrude into connective tissue) due to inflammatory changes. - **Junctional epithelial cells**: start to proliferate. - **Clinical Features** - Inflammatory changes such as edema and redness of gingival marginal tissue can be observed clinically. - Early lesion phase develops 4 to 7 days following plaque biofilm accumulation. Duration of early gingivitis can vary between individuals. - **Outcome of Host Response at the Stage** - The large number of PMNs, macrophages, and T-lymphocytes may control the bacterial pathogens. - Initiation of good patient self-care can disrupt the plaque biofilm – and result in a return to health – if the bacterial infection is brought under control – through the efforts of the immune system and effective plaque biofilm control – the body can repair the destruction caused by the immune response. - If the host immune response fails to "hold the line," the early lesion will progress to the "established gingivitis”—the next phase of disease progression. **Established Gingivitis (Established Lesion)** - **Bacterial Features**: Plaque biofilm extends subgingivally into the gingival sulcus, disrupting the attachment of the coronal-most portion of the junctional epithelium from the tooth surface. - **Cellular Features: Migration of Additional Cellular Defenders to the Site** - **Large numbers**: of subgingival bacteria stimulate the epithelial cells to secrete more cytokines, resulting in greater recruitment of additional PMNs, macrophages, and lymphocytes. - **The established lesion**: is predominated by the presence of plasma cells (leukocytes that produce antibodies) in the affected connective tissue zone. Hence, the established lesion is considered to be a plasma cell lesion. PMNs, macrophages, and lymphocytes continue to assist in fighting the bacteria in the sulcus. - **Plasma cells**: produce large quantities of antibodies to assist in controlling the bacterial challenge - **The immune system**: sends more immune cells to fight the bacteria. More toxic chemicals are released and additional healthy connective tissue is destroyed. - Cytokines, PGE2, and MMPs are produced by macrophages exposed to gram-negative bacteria. - Cytokines recruit additional macrophages and lymphocytes to the area. - PGE2 and the MMPs initiate collagen destruction. - Gingival fibroblasts are stimulated to produce additional PGE2 and MMPs. - **Tissue Level Features**: - **Epithelial ridges**: extend deeper in connective tissue to maintain epithelial integrity. - **Junctional epithelium**: loosens its attachment to the root surface and starts to transform into pocket epithelium. Pocket epithelium is thinner and more permeable compared to junctional epithelium - **Continued collagen loss**: in the infiltrated connective tissue zone. - **Clinical Features**: - All the usual clinical features of gingivitis are evident in this phase, but are more accentuated compared to the initial stage and early stage. - Established gingivitis is generally observed 21 days after plaque biofilm accumulation. - **Outcome of Host Response**: - In many individuals, the host response is adequate to contain the bacterial challenge during this phase. - Periodontal instrumentation and patient education, at this point, can be helpful in controlling the bacterial challenge. The combination of professional treatment and good patient self-care can stop the bacterial challenge and return the periodontium to health. - In certain susceptible individuals if the bacterial infection is not controlled, established gingivitis progresses to periodontitis. Unfortunately, no one can predict when and if established gingivitis will progress to periodontitis. Current research is directed to trying to determine which individuals are at risk for developing periodontitis. **Periodontitis (Advanced Lesion)** - **Bacterial Features**: Plaque biofilm grows laterally and apically along the root surface. The periodontal pocket provides an ideal protected environment for continued growth of subgingival bacteria presenting a chronic, repeated challenge to the host. - **Cellular Features: Host Response Intensifies**: - The bacterial infection becomes chronic, leading to chronic inflammation. The immune response becomes so intense that it begins to harm the periodontium. - **Cellular defenders**: intensify their defense against the bacterial pathogens - PMNs, macrophages, and epithelial cells produce cytokines that cause destruction of the gingival connective tissue and periodontal ligament fibers. - Macrophages produce high concentrations of cytokines, PGE2, and MMPs that result in destruction of connective tissue and alveolar bone. - MMPs mediate destruction of the extracellular matrix of the gingiva, collagen fibers attached at the apical edge of the junctional epithelium, and the periodontal ligament. - PGE2 mediates bone destruction by stimulating large numbers osteoclasts to resorb the crest of the alveolar bone. The gingival pocket progresses to become a periodontal pocket. - The tissue destruction caused by the host immune response now overwhelms any tissue repair. Tissue destruction becomes the main outcome of the immune system response. - **Tissue Level Features (Destruction of Periodontal Tissues Ensues)**: - **Cells**: of the junctional epithelium migrate apically on root surface resulting in the development of a periodontal pocket. - **Gingival fibroblasts**: shift to a state that favors the destruction of the gingival connective tissue and periodontal ligament fibers. - **Osteoclasts**: destroy the crest of the alveolar bone. - **Clinical Features**: - This advanced lesion phase is characterized by periodontal pocket formation, bleeding on probing, destruction of the periodontal ligament, alveolar bone loss, furcation involvement, and tooth mobility. - These tissue changes (such as apical migration of junctional epithelium, connective tissue destruction, periodontal ligament destruction, and alveolar bone loss) are not reversible. - **Outcome of Host Response**: - Chronic infection by the periodontal pathogens induces a chronic inflammatory response. The chronic inflammation destroys periodontal tissues and causes more damage to the periodontium than the bacterial infection. Irreversible tissue damage is the hallmark of periodontitis. - **Factors influencing the host's failure to control the bacterial challenge may include:** - Abnormal PMN function. - Persistence and virulence of bacteria in the biofilm. - Acquired and environmental factors such as smoking and stress. - Systemic factors such as uncontrolled diabetes mellitus or genetic factors. ## Section 3 The Impact of Host Response on Bone Homeostasis ## Section 4 Focus on Patients - **Clinical Patient Care** - **Evidence in Action** - **Ethical Dilemma** ## Key Terms - Biochemical mediators - Cytokines - Prostaglandins - Host response - Virulence factor - Catabasis - Pro-resolving lipid mediators - MMP - PGE - TIMP - RANKL - Homeostatic condition - Pathogenesis - Bone Remodeling - Osteoblasts - Osteoclasts - OPG - Bone resorption --- This markdown document accurately describes the information from the image.