ICP-25 Aetiology and Pathogenesis of Periodontal Disease Flashcards
What are the clinical features of good periodontal health
Gingiva are:
- Pink
- Firm
- Stippled
- “knife-edge” papillae
What are the clinical features of gingivitis
- Bleeding from gingiva
- Marginal redness
- Gingivae swollen
- No bone loss/attachment loss
- No mobility
- No recession
- No gaps
What are the clinical features of periodontitis
- Recession
- Mobility
- Increased probing depths (pocket formation)
- Sensitivity
- Drifting
- Gaps (black triangles)
- Bone loss (radiographs)
- Long teeth
What is the weak point in the periodontal barrier during inflammation
the junctional epithelium
What is calculus and where can it be found
Mineralised plaque from calcified bacterial matrix and pellicle
Can be found Supra and Subgingivally
Describe Supragingival calculus
Creamy/Yellow
Precipitation of mineral salts from saliva (calcium phosphate/hydroxyapatite)
Describe Subgingival calculus
- Brown
- Precipitation of mineral salts from crevicular fluid (whitelockite) - difficult to remove
Where does calculus attach to and what covers it
Attaches to enamel, dentine and cementum
Covered by unmineralised bacterial plaque
What are the stages of periodontal lesion and what disease are they associated with
Initial lesion - gingivitis
Early lesion - gingivitis
Established lesion - established gingivitis
Advanced lesion - periodontitis
Describe the features of an initial lesion
Subclinical
- Dental plaque accumulation
- Increased neutrophil migration
- Gingival crevicular flow increases
Describe the features of Early lesion
- Dental plaque accumulation more extensive
- Increasing neutrophils followed by monocytes/macrophages and then lymphocytes
- Increased vascularity
- Collagen destruction to create space for infiltrate
- Rete peg proliferation
Describe the features of Established lesion
- Neutrophils continue to migrate into the tissues and into the gingival crevice
- Extensive sub gingival plaque
- Plasma cell predominate in the inflammatory infiltrate
- No loss of CT attachment
- No bone loss
- This lesion may remain stable for some time or may progress to a destructive lesion
Describe the feature of an advanced lesion
- Gingival recession with fibrosis in CT
- Continued extension of subgingival plaque
- Extension of inflammatory infiltrate into CT
- Apical Migration and ulceration of JE
- Periodontal ligament loss
- Alveolar bone resorption by osteoclasts
What immune cells can be involved with periodontal lesions
- Dendritic cells
- Macrophages
- Mast cells
- Neutrophils
- Monocytes
- T cells
- B cells
What triggers the inflammatory and immune response in periodontitis
Bacterial products secreted:
- Enzymes: collagenase, protease, hyaluronidase
Bacterial Membrane:
- LPS
- Lipoteichoic acid (LTA)
- Capsular material
Metabolic Products:
- Buytric acid
- Propionic acid
What are some types of Sentinel cells
- Macrophages
- Dendritic cells
- Mast cells
What are Pattern Recognition Receptors (PRRs) on sentinel cells activated by
PAMPs - Pathogen Associated Molecular Patterns (on surface of pathogens)
DAMPs - Damage Associated Molecular Patterns (Indicate cell damage - inside of cells externalised)
What are released by sentinel cells and what do they do
They release alarm molecules (alarmins) - pro-inflammatory mediators that trigger inflammation
What kinds of pro inflammatory mediators are released by sentinel cells
- Histamine
- Pro-inflammatory cytokines
- Prostaglandins
What happens when histamine is released
- Mast cells release histamine - microvasculature produce PGI2, dilates BVs
- Endothelial contraction - open up vasculature
What are some pro-inflammatory cytokines
- Tumour Necrosis Factor Alpha
- Interleukin - 1Beta
- Interleukin - 6
- Interleukin - 8
What are some prostaglandins
Prostaglandins (PGE2)
Prostacyclin (PGI2)
Describe type 1 inflammation
Activation by histamine in minutes
- Vasodilation and endothelial cell contraction (redness and heat)
- Inflammatory exudate move into tissues (oedema)
- Leukocyte extravasation - neutrophils brought in from blood into the gingival tissues initially
What causes Type 2 inflammation and what happens in it
Activation by TNF-alpha and IL-1B in hours
- More pronounced type 1 activation
- Monocyte recruitment (macrophages in tissues)
Where are neutrophils recruited from
Recruited early from the blood into the tissues
What are the functions of neutrophils
- Phagocytosis
Produces: - Chemokines (to attract other immune cells)
- Pro-inflammatory cytokines (IL-1B, TNF-a, IL-8)
- Anti-inflammatory cytokines (IL-10)
- Granule derived antimicrobial molecules and enzymes (lysozymes)
- Reactive oxygen species and matrix metalloproteases (MMPs) (enzymes that break down tissues)
- Substances that help B cells survival
- Neutrophil extracellular traps (NETs)
- Express RANKL on surface and contribute to bone destruction
- Regulate other immune cells T cells/DCs/NK cells/ Macrophages
What are some neutrophil defects that are often associated with periodontitis
- Leukocyte Adhesion Deficiency (LAD) - recruitment deficient
- Lazy Leukocyte Syndrome - Neutrophil function affected
- Neutropenia - low numbers of neutrophils
- Cyclic neutropenia - levels fluctuate over time form normal to low
- Produce too many pro-inflammatory cytokines (IL-1B, TNF-a, IL-8)
What are the functions of Macrophages
- Antigen presenting cell
- Phagocytosis
- Produce Proinflammatory cytokines (MI macrophages)
- Anti-inflammatory cytokines (M2 macrophages)
What is the complement system and what is it activated by
Cascade of circulating blood proteins Activated by: - Antigen-antibody complexes - Bacterial endotoxin LPS on bacterial outer membranes - Lectin pathway
What are the functions of the complement system
- Opsonisation - stick to and mark antigen for phagocytosis
- Cell lysis - ruptures bacterial cell walls
- Chemotaxis - neutrophils and macrophages attracted to antigen
- Mast cell activation - Histamine release
What kinds of T helper cells are there and what do they do
Th1 = cytotoxic cells
Th2 = mediate humoral immunity (B cells)
Th17 - important in mediating bone loss
What kinds of T-regulatory cells are there and what do they do
Tregs = anti-inflammatory (IL-10)
What do B cells do and when are they predominant in periodontal lesions
- Produce antibodies
- Predominate in established and advanced lesions
- 60% of lymphocytes in periodontal lesions
- Express and produce RANKL - drives bone loss
Describe the resolution of inflammation of periodontal tissues
- Removes plaque
- Reversal of inflammation
- Reduction in pro-inflammatory mediators
- Resolvins (lipid mediators of inflammation)
- Repair CT to produce new collagen forming new CT
What is the RANKL-OPG pathway of bone loss
- Mechanism by which the immune system regulates bone turnover
- Balance between RANKL and OPG important in controlling bone loss
- Balance between the bone forming and bone resorbing cells
Describe how the RANKL-OPG pathway works
- Receptor activator of nuclear factor kappa-B ligand (RANKL) - expressed by osteoblasts - important in osteoclast formation, function and survival
- Receptor activator of nuclear factor kappa-B (RANK) - located on osteoclast precursors and mature osteoclasts
- Osteoprotegerin (OPG) - binds to RANKL and competitively inhibits RANKL - expressed by osteoblasts and other tissues - protective against bone loss
- Oesteogen - limits release of RANKL
What ratio of RANKL:OPG causes bone formation/loss
Low RANKL:OPG ratio = bone formation
High RANKL:OPG ratio = bone loss
