Periodontal immunology

Question 1

what is the difference between gingivitis and periodontitis?

Answer 1

gingivitis
* inflammation localised to gingival tissues
* acute inflammation
* normal physiological response to infection or inury

periodontitis
* inflammation of the gingival tissues and periodontal structures (alveolar bone, periodontal ligament)
* chronic inflammation
* pathological inflammatory response associated with tissue destruction

Question 2

what is polymicrobial dysbiosis in periodontitis?

Answer 2

community of microorganisms that work together to actively disrupt the normal homeostatic balance in the oral cavity for their own balance

they work together to evade the immune system

Question 3

what is the aetiology of periodontology associated with?

Answer 3

• accumulated plaque bacteria
• presence of periodontal pathogens
• polymicrobial dysbiosis

Question 4

what are the hallmark signs of periodontitis?

Answer 4

• attachment loss
• alveolar bone desctruction

Question 5

describe the formation of gingivitis

Answer 5

• increased TLR (toll-like receptor) stimulation by PAMPs (pathogen associated molecular patterns) e.g. LPS (lipopolysaccharides - endotoxins) and peptodoglycans
• occurs on macrophages, dendritic cells and neutrophils
• leads to the production of cytokines and chemokines which attract more monocytes, neutrophils and dendritic cells
• monocytes are activated and differentiate into macrophages - phagocytosis
• dendritic cells are APCs which present to T lymphocyte cells which fine-tune the immune response

acute inflammatory response is triggered:
* increased vasodilation
* redness, swelling, bleeding
* increased immune cell migration

Question 6

what is the role of neutrophils in periodontal health?

Answer 6

• they are first line defence against bacterial plaque in the gingival sulcus
• migrate from the blood stream into the gingival crevice in response to bacterial biofilm
• neutrophils phagocytose periodontal pathogens and release antimicrobial substances to control infection

Question 7

what is the role of neutrophils in periodontal tissue destruction?

Answer 7

excessive or dysregulated neutrophil response leads to chronic inflammation and tissue damage
* neutrophils become overactivated when TLRs recognise PAMPs such as LPS (lipopolysaccharides)
* neutrophils release MMPs (matrix metalloproteinases) and other reactive oxygen species which degrade collagen leading to bone loss and attachment loss
* inflammation persists and more neutrophils are recruited, worsening the tissue damage

Question 8

what is aggressive periodontitis and how does it occur?

Answer 8

• when neutrophils show impaired chemotaxis leading to bacterial overgrowth
• there is an immune under-reaction

Question 9

what is the role of adaptive immunity in periodontal destruction?

Answer 9

• T cells are activated by APCs such as dendritic cells, then activate B cells
• periodontal pathogens trigger an excessive immune response
• T and B cells secrete soluble RANKL
• RANKL binds with RANK to induce osteoclast differentiation on a monocyte (pre-osteoclast)
• OPG prevents RANKL from binding with RANK so inhibits osteoclast differentiation
• in periodontitis, there are high levels of soluble RANKL and low levels of OPG
• monocytes are recruited in large numbers and can differentiate into osteoclasts which cause bone destruction

Question 10

describe the overall cellular and molecular events linking bacterial-induced inflammation with pathologic tissue destruction

Answer 10

1. bacterial products bind TLRs on epithelium, stimulating secretion of cytokines and chemokines
2. vasodilation and selectrive recruitment of leukocytes (neutrophils, monocytes, lymphocytes) occurs
3. bacterial products activate neutrophils, further releasing pro-inflammatory mediators - amplification loop of neutrophil infiltration
4. activated lymphocytes express RANKL and the RANKL/OPG balance is disrupted
5. RANKL binds to RANK on monocytes, activating osteoclastogenesis leading to alveolar bone resorption
6. pro-inflammatory cytokines (IL-1, IL-6, IL-7, TNFa) contribute to bone resorption by inhibiting bone formation
7. elevated MMP activation from neutrophils contributes to connective tissue destruction which manifests as attachment loss