Periodontal immunology Flashcards
Pathological differences between gingivitis and periodontitis
Gingivitis
- Inflammation localised to gingival tissues
- Acute inflammation
- Normal physiological response to infection or injury
Periodontitis
- Inflammation of the gingival tissues and supporting periodontal structures
- Chronic inflammation
- Pathological inflammatory response associated with tissue destruction
Aetiological factors of periodontal diseases
- poor OH
- biofilm composition (esp P. gingivalis, T. forsythia and T. denticola)
- host/pathogen interaction
- genetic
- environmental and acquired risk factors
Describe the concept of pathogenicity
Microbial pathogenicity is the outcome of host-bacterial interactions
both microbial and hosts put selective pressures on each other via antigens and virulence factors (microbial) and innate and adaptive immunity (host)
selective pressures from both are influenced by environment and genetics
How host-bacterial interactions contribute to periodontitis pathogenesis
Virulence factors of P. gingivalis
- asaccharolytic (nutrients from breakdown of proteins and peptides)
- gingipains (proteases with broad specificity)
- atypical LPS (TLR4 antagonist)
- inflammophilic (inflammatory environment favours expression of virulence)
Factors which trigger gingival inflammation: (changes in the oral biofilm) - accumulation - composition - expression of virulence
Key immune defences in the oral cavity and describe their primary function
- Gingival crevicular fluid
- AMPs
- Cytokines
- Chemokines
- Lactoferrin
- IgG - Oral mucosa
- AMPs
- cytokines
- chemokines - Saliva
- S-IgA
- Lysozyme
- Peroxidase
- Lactoferrin
- Mucins
- Agglutinins
- Cystatins
- Histatins - Neutrophils
- plasma cells
The involvement of host immune responses to periodontal tissue destruction
Gingivitis
- increased TLR stimulation
- increased production of pro-inflammatory mediators
- acute inflammatory response triggered (redness, swelling, bleeding, increased vasodilation, cell migration)
Periodontitis
- neutrophils remain predominant cell type in initial lesion
- monocytes are recruited, activated and differentiate into macrophages
- lymphocytes are recruited to fine-tune the immune response
Factors that may cause dysbiosis of the oral microbiome
- smoking
- diet
- OH
- innate/adaptive immune factors
- salivary flow rates
- activity of salivary proteins
- genetic differences
- diseases e.g. diabetes
- antibiotics/ antimicrobial agens
Describe the role of neutrophils in periodontal destruction
- crucial for maintaining healthy periodontium
- Numbers increased during gingivitis
- contain infection = return to health
- unable to contain infection = predispose to disease progression - excessive infiltration associated with chronic inflammation
- degradative enzymes (MMPs)
- inflammatory cytokines and oxygen radicals contribute to hypoxic environment
- connective tissue destruction manifests clinically as loss of attachment
Describe the role of adaptive immunity in periodontal destruction
- T and B lymphocytes present in early lesion
- Aggregates rich in CD4 T cells, B cells and dendritic cells evident as lesion progresses
- Unable to regulate dysbiotic biofilm
- B cell/plasma cells predominate advanced lesions
- IgG fails to regulate dysbiotic biofilm
Protective - prevents systemic infection
Destructive - inflammation induced alveolar bone loss
How does inflammation lead to bone loss
- high levels of RANKL (favours bone resorption via osteoclasts)
- low levels of OPG (doesn’t favour bone formation via osteoblasts)
- inflammation induced bone resorption
- pathological bone destruction
- activated T and B cells in the periodontal lesion secrete RANKL
- RANKL binds RANK to induce osteoclast differentiation
- OPG prevents
How does inflammation lead to bone loss
- high levels of RANKL (favours bone resorption via osteoclasts)
- low levels of OPG (doesn’t favour bone formation via osteoblasts)
- inflammation induced bone resorption
- pathological bone destruction
- activated T and B cells in the periodontal lesion secrete RANKL
- RANKL binds RANK to induce osteoclast differentiation leading to bone resorption
(3. OPG prevents RANKL binding RANK - OPG inhibits osteoclast differentiation)
What are the cellular and molecular events linking bacterial-induced inflammation with pathologic tissue destruction
- Bacterial products bind TLRs on epithelium, stimulating secretion of cytokines, chemokines and AMPs
- Vasodilation and selective recruitment of leukocytes (predominantly neutrophils, also monocytes and lymphocytes)
- Bacterial products activate neutrophils, further release of pro-inflammatory mediators. Amplification loop of neutrophil infiltration.
- Activated lymphocytes express RANKL. RANKL/OPG balance disrupted
- RANKL binds RANK on osteoclast precursors (monocytes). Activates osteoclastogenesis leading to alveolar bone resorption.
- Pro-inflammatory cytokines (IL-1, IL-6, IL-17, TNFa) contribute to bone resorption by inhibiting bone formation.
- Elevated and dysregulated MMP activation contributes to connective tissue destruction
