pathogenic mechanisms in periodontitis part 1

Question 1

Etiology

Answer 1

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.

Question 2

Pathogenesis

Answer 2

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.

Question 3

What is the definition of inflammation?

Answer 3

local response to cellular injury, marked by capillary dilation, leukocytic infiltration, redness, heat, and pain. It serves to eliminate noxious agents and damaged tissue.

Question 4

What causes destructive changes in periodontal tissue?

Answer 4

subtle disruption of the delicate balance between tissue defense mechanisms and pathogenic plaque.

Question 5

What is the primary etiology of periodontal disease?

Answer 5

bacterial plaque

Question 6

What causes tissue destruction in periodontal disease?

Answer 6

Tissue destruction, including pocket formation, attachment loss, and bone loss, is primarily due to the inflammatory response.

Question 6

What is periodontitis characterized by?

Answer 6

Microbially-associated, host-mediated inflammation that results in loss of periodontal attachment

Question 7

What characterizes the bacteria that are considered periodontal pathogens?

Answer 7

virulence properties that allow them to survive
promote inflammatory pathology
contain antigens that trigger immune responses that can be protective

Question 7

How does the threshold between stable and active periodontal disease vary?

Answer 7

person to person, depending on individual factors

Question 7

How can the dose–response curve for periodontal disease shift?

Answer 7

based on genetic and environmental changes

Question 8

How is the immune response protective in periodontal disease?

Answer 8

protective by controlling the bacterial infection, involving antibodies and PMNs (polymorphonuclear neutrophils).

Question 9

How can the immune response become destructive in periodontal disease?

Answer 9

becomes destructive with continued inflammation, leading to excessive quantities of destructive enzymes, inflammatory mediators, and immunopathology.

Question 10

Why is the immune-inflammatory response in periodontal disease considered a “two-edged sword”?

Answer 10

because, while it aims to protect against bacterial plaque, it can also cause tissue destruction when inflammation persists.

Question 11

What is a marked determinant of inflammation in periodontal disease?

Answer 11

substantial recruitment of neutrophils

Question 11

What are pro-inflammatory cytokines in periodontal disease

Answer 11

IL-1, IL-6, IL-8, TNF-ɑ, and PGE2

Question 12

What do proinflammatory cytokine cause?

Answer 12

vasodilation of blood vessels,
release of serum proteins into surrounding periodontal tissues
absorption of histamine and neuropeptides into blood vessels.

Question 12

What is the source of the cytokines and mediators in the periodontium?

Answer 12

LPS can trigger into fibroblasts and monocytes to form

Question 13

Matrix Metalloproteinases (MMPs)
and Osteoclasts cause what?

Answer 13

Tissue Destruction

Question 14

slide 24

Question 14

What regulates the differentiation of osteoclasts in periodontal disease?

Answer 14

inflammatory cytokines and lipid mediators, including IL-1, IL-6, TNF-a, and PGE2

Question 14

Which anti-inflammatory cytokines and peptides regulate osteoclast differentiation?

Answer 14

IL-10 and IL-4

Question 15

How does chronic inflammation in periodontitis contribute to alveolar bone loss?

Answer 15

alveolar bone loss by uncoupling bone formation from resorption, mediated by spatial and temporal considerations

Question 16

What is the role of spatial and temporal considerations in bone loss in periodontitis?

Answer 16

Spatially, bacteria release bone-resorbing mediators to induce osteoclastogenesis and bone loss.

Temporally, increased inflammatory mediators prolong the resorption phase of bone remodeling.

Question 17

Osteoimmunology: crosstalk between the immune and bone systems

Answer 17

Inflammatory cytokines
then
Stromal cells, osteoblasts upregulate RANK-L
then
Osteoclast differentiation
then
Bone resorption

Question 18

How does the signaling occur with innate immunity?

Answer 18

LPS reacts directly with Toll-like receptors (TLRs), which are pattern recognition receptors (PRRs).

Question 19

How do TLRs recognize pathogens?

Answer 19

TLR-4 recognizes lipopolysaccharides (LPS) and activates NF-kB downstream, leading to the production of pro-inflammatory cytokines.

Question 19

What is the role of activated T cells in adaptive immunity?

Answer 19

produce interferon-gamma (INF-γ)

Question 20

What is the function of INF-gamma in the immune response?

Answer 20

activates macrophages, enhancing their ability to combat pathogens.

Question 21

How are macrophages activated in innate immunity?

Answer 21

Bacterial lipopolysaccharides (LPS) from Gram-negative bacteria (e.g., P. gingivalis) activate macrophages to produce inflammatory cytokines.

Question 21

What additional processes are triggered by bacterial LPS?

Answer 21

Complement activation Release of chemotactic lipids and cytokines Engagement of Toll-like receptors (TLRs)

Question 22

What is the downstream effect of inflammatory cytokines and arachidonic acid metabolites?

Answer 22

Stromal cells and osteoblasts upregulate RANK-L. RANK-L promotes osteoclast differentiation, leading to bone resorption.

Question 23

What do macrophages from patients with severe periodontitis secrete when stimulated with LPS in vitro? (Offenbacher and Salvi, 1999)

Answer 23

They secrete much higher levels of PGE2

Question 24

What is a major pathway to bone and PDL destruction in periodontitis?

Answer 24

Macrophages

Question 25

What evidence supports the role of macrophages in periodontitis?

Answer 25

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).

Question 25

How does inflammation in the terminal dentition relate to macrophage activity?

Answer 25

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).

Question 25

How does adaptive immunity influence periodontal disease pathology?

Answer 25

T cell contribution to pathogenesis

Question 26

How is the cross talk between innate and adaptive immune responses mediated?

Answer 26

Natural Killer cells (examples: APCs and Langerhan Cells.)

Question 26

What are the roles of Th-cell differentiation?

Answer 26

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.

Question 26

How do Th1 and Th2 cells differ in their roles?

Answer 26

Th1 cells: Induce cell-mediated immunity and enhance inflammation through their cytokines. Th2 cells: Induce humoral immunity through their cytokines.

Question 27

How are Th1 or Th2 effector cells induced?

Answer 27

During the first interaction of naive CD4+ T cells with antigen-presenting cells (APC), cytokines from the APC induce either Th1 or Th2 differentiation.

Question 28

What role do neutrophils play in Th-cell differentiation?

Answer 28

induce the recruitment of interleukin-17 (IL-17)-producing CD4-positive Th17 cells to sites of infection or inflammation.

Question 29

How does a dysbiotic microbiome affect Th17 cells in periodontal disease?

Answer 29

triggers the pathogenic Th17/IL-17 response, which is associated with periodontal tissue destruction and bone loss.

Question 30

What effect does interleukin-17 have in periodontal tissue?

Answer 30

induces RANKL and inhibits osteoprotegerin expression in human periodontal ligament cells, contributing to bone resorption.

Question 31

What is the RANKL/RANK/OPG pathway?

Answer 31

pathway regulates osteoclast maturation, bone modeling, and remodeling

Question 31

What is RANK?

Answer 31

Receptor activator of NF-Kb

Question 32

What is RANKL?

Answer 32

Receptor activator of NF-kB ligand

Question 32

What is OPG?

Answer 32

Osteoprotegerin

Question 33

slide 48

Question 34

What did the murine model of P. gingivalis-induced periodontitis show about adaptive immunity?

Answer 34

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.

Question 35

What did the study by Baker PJ (1994) suggest regarding adaptive immunity and periodontitis?

Answer 35

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.

Question 35

What does anti-collagenase activity do?

Answer 35

inhibits MMP (matrix metalloproteinase) activity and decreases connective tissue (C.T.) breakdown.

Answer 36

Efficacy data shows benefits after 3 to 9 months of use, while safety data supports continued use for up to 12 months.