pathogenic mechanisms in periodontitis part 1 Flashcards
Etiology
the study or theory of the factors that cause disease and how they are introduced to the host. It focuses on the cause or origin of a disease or disorder.
Pathogenesis
the process that causes the disease, including the origin and the chain of events leading to the disease, specifically the cellular events, reactions, and other pathological mechanisms involved in disease development.
What is the definition of inflammation?
local response to cellular injury, marked by capillary dilation, leukocytic infiltration, redness, heat, and pain. It serves to eliminate noxious agents and damaged tissue.
What causes destructive changes in periodontal tissue?
subtle disruption of the delicate balance between tissue defense mechanisms and pathogenic plaque.
What is the primary etiology of periodontal disease?
bacterial plaque
What causes tissue destruction in periodontal disease?
Tissue destruction, including pocket formation, attachment loss, and bone loss, is primarily due to the inflammatory response.
What is periodontitis characterized by?
Microbially-associated, host-mediated inflammation that results in loss of periodontal attachment
What characterizes the bacteria that are considered periodontal pathogens?
virulence properties that allow them to survive
promote inflammatory pathology
contain antigens that trigger immune responses that can be protective
How does the threshold between stable and active periodontal disease vary?
person to person, depending on individual factors
How can the dose–response curve for periodontal disease shift?
based on genetic and environmental changes
How is the immune response protective in periodontal disease?
protective by controlling the bacterial infection, involving antibodies and PMNs (polymorphonuclear neutrophils).
How can the immune response become destructive in periodontal disease?
becomes destructive with continued inflammation, leading to excessive quantities of destructive enzymes, inflammatory mediators, and immunopathology.
Why is the immune-inflammatory response in periodontal disease considered a “two-edged sword”?
because, while it aims to protect against bacterial plaque, it can also cause tissue destruction when inflammation persists.
What is a marked determinant of inflammation in periodontal disease?
substantial recruitment of neutrophils
What are pro-inflammatory cytokines in periodontal disease
IL-1, IL-6, IL-8, TNF-ɑ, and PGE2
What do proinflammatory cytokine cause?
vasodilation of blood vessels,
release of serum proteins into surrounding periodontal tissues
absorption of histamine and neuropeptides into blood vessels.
What is the source of the cytokines and mediators in the periodontium?
LPS can trigger into fibroblasts and monocytes to form
Matrix Metalloproteinases (MMPs)
and Osteoclasts cause what?
Tissue Destruction
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What regulates the differentiation of osteoclasts in periodontal disease?
inflammatory cytokines and lipid mediators, including IL-1, IL-6, TNF-a, and PGE2
Which anti-inflammatory cytokines and peptides regulate osteoclast differentiation?
IL-10 and IL-4
How does chronic inflammation in periodontitis contribute to alveolar bone loss?
alveolar bone loss by uncoupling bone formation from resorption, mediated by spatial and temporal considerations
What is the role of spatial and temporal considerations in bone loss in periodontitis?
Spatially, bacteria release bone-resorbing mediators to induce osteoclastogenesis and bone loss.
Temporally, increased inflammatory mediators prolong the resorption phase of bone remodeling.
Osteoimmunology: crosstalk between the immune and bone systems
Inflammatory cytokines
then
Stromal cells, osteoblasts upregulate RANK-L
then
Osteoclast differentiation
then
Bone resorption
How does the signaling occur with innate immunity?
LPS reacts directly with Toll-like receptors (TLRs), which are pattern recognition receptors (PRRs).
How do TLRs recognize pathogens?
TLR-4 recognizes lipopolysaccharides (LPS) and activates NF-kB downstream, leading to the production of pro-inflammatory cytokines.
What is the role of activated T cells in adaptive immunity?
produce interferon-gamma (INF-γ)
What is the function of INF-gamma in the immune response?
activates macrophages, enhancing their ability to combat pathogens.
How are macrophages activated in innate immunity?
Bacterial lipopolysaccharides (LPS) from Gram-negative bacteria (e.g., P. gingivalis) activate macrophages to produce inflammatory cytokines.
What additional processes are triggered by bacterial LPS?
Complement activation
Release of chemotactic lipids and cytokines
Engagement of Toll-like receptors (TLRs)
What is the downstream effect of inflammatory cytokines and arachidonic acid metabolites?
Stromal cells and osteoblasts upregulate RANK-L.
RANK-L promotes osteoclast differentiation, leading to bone resorption.
What do macrophages from patients with severe periodontitis secrete when stimulated with LPS in vitro? (Offenbacher and Salvi, 1999)
They secrete much higher levels of PGE2
What is a major pathway to bone and PDL destruction in periodontitis?
Macrophages
What evidence supports the role of macrophages in periodontitis?
Macrophages from patients with chronic periodontitis secrete higher levels of TNF-ɑ when stimulated with LPS in vitro. Some studies also show increased IL-1𝛃 secretion (Baqui et al. 1998; Cheng et al. 2020).
How does inflammation in the terminal dentition relate to macrophage activity?
In the “terminal dentition,” GCF (gingival crevicular fluid) levels of IL-1 and TNF-ɑ are elevated. Additionally, peripheral blood monocyte secretion of inflammatory cytokines is also increased (Salvi et al. 1998).
How does adaptive immunity influence periodontal disease pathology?
T cell contribution to pathogenesis
How is the cross talk between innate and adaptive immune responses mediated?
Natural Killer cells (examples: APCs and Langerhan Cells.)
What are the roles of Th-cell differentiation?
Promotion of cell-mediated immunity: Increases macrophage function.
Promotion of humoral immunity: Enhances antibody production.
Promotion of inflammatory and autoimmune responses: Increases the PMN (polymorphonuclear neutrophil) response.
How do Th1 and Th2 cells differ in their roles?
Th1 cells: Induce cell-mediated immunity and enhance inflammation through their cytokines.
Th2 cells: Induce humoral immunity through their cytokines.
How are Th1 or Th2 effector cells induced?
During the first interaction of naive CD4+ T cells with antigen-presenting cells (APC), cytokines from the APC induce either Th1 or Th2 differentiation.
What role do neutrophils play in Th-cell differentiation?
induce the recruitment of interleukin-17 (IL-17)-producing CD4-positive Th17 cells to sites of infection or inflammation.
How does a dysbiotic microbiome affect Th17 cells in periodontal disease?
triggers the pathogenic Th17/IL-17 response, which is associated with periodontal tissue destruction and bone loss.
What effect does interleukin-17 have in periodontal tissue?
induces RANKL and inhibits osteoprotegerin expression in human periodontal ligament cells, contributing to bone resorption.
What is the RANKL/RANK/OPG pathway?
pathway regulates osteoclast maturation, bone modeling, and remodeling
What is RANK?
Receptor activator of NF-Kb
What is RANKL?
Receptor activator of NF-kB ligand
What is OPG?
Osteoprotegerin
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What did the murine model of P. gingivalis-induced periodontitis show about adaptive immunity?
periodontal adaptive immune response is potentially destructive in periodontitis. Specifically, severe combined immunodeficient mice, which lack both T and B cells, developed less P. gingivalis-induced bone loss than immunocompetent controls.
What did the study by Baker PJ (1994) suggest regarding adaptive immunity and periodontitis?
adaptive immunity, specifically T and B cells, may contribute to the severity of bone loss in periodontitis, as immunocompetent mice exhibited more bone loss compared to immune-deficient mice.
What does anti-collagenase activity do?
inhibits MMP (matrix metalloproteinase) activity and decreases connective tissue (C.T.) breakdown.
Efficacy data shows benefits after 3 to 9 months of use, while safety data supports continued use for up to 12 months.
