Immunopathogenisis Of Periodontal Disease

Question 1

What are two hallmark clinical sign of periodontitis?

Answer 1

1. Attachment loss
2. Alveolar bone loss

= increased pocket depth

Question 2

What causes attachment loss and alveolar bone loss?

Answer 2

Combination of pathogens (P. gingivalis) and host immune response

Question 3

What sequence of events caused by hosts immune response leads to the manifestation of swollen, red, bleeding gums?

Answer 3

1. Increased TLR stimulation
2. Increased production of pro-inflammatory mediators (cytokines, chemokines)
3. Triggers acute inflammatory response
   - redness, swelling, bleeding
   - increased vasodilation, cell migration

Question 4

What immune cells respond to gingivitis?

Answer 4

1. Neutrophils Remain predominant cell type in the initial lesion
2. Monocytes are recruited, activated and differentiate into macrophages
3. Lymphocytes are recruited to fine-tune the immune response

Question 5

What are the possible outcomes following hosts immune response to gingivitis?

Answer 5

1. Biofilm is controlled, inflammation is resolved, periodontal tissues return to health (homeostasis achieved)
2. Response is ineffective (due to perio pathogen creasing response), dysbiosis persists and chronic inflammation ensues. Immune reaction becomes destructive and host tissues are destroyed

Question 6

How do neutrophils contribute to tissue destruction in periodontal disease?

Answer 6

1. Crucial for maintaining healthy periodontium
2. Numbers increase during gingivitis
   - return to health
   - predispose to disease progression
3. Excessive infiltration associated with chronic inflammation
   - microbial subversion (Pathogen easily avoids immune response)
   - degradative enzymes (major source of matrix metalloproteinases ‘MMPs’)
   - inflammatory cytokines and oxygen radicals contribute to hypoxic environment
   - connective tissue destruction manifests clinically as loss of attachment

Question 7

What disease can result from an under immune reaction due to leukocyte adhesion deficiency?

Answer 7

Early onset (aggressive) periodontitis

Question 8

How does adaptive immunity contribute to destruction of tissue in periodontal disease?

Answer 8

1. Defence cells and immunoglobulins present are unable to regulate dysbiotic biofilm
2. Protective - prevents systemic infection
3. Destructive - inflammation induced alveolar bone loss

Question 9

What cells that are part of adaptive immunity are present in periodontal disease?

Answer 9

1. T and B lymphocytes present in early lesion
2. Aggregates rich in CD4 T cells and B cells evident as lesion progresses
3. B cell/plasma cells predominate advanced lesions

Question 10

What immunoglobulins are present in periodontal disease?

Answer 10

IgG

Question 11

Where are osteoclasts derived from?

Answer 11

Monocytes/macrophage lineage

Question 12

What signalling molecules regulate bone remodelling?

Answer 12

1. RANKL
2. RANK
3. OPG triad

Question 13

How does inflammation leas to bone loss?

Answer 13

1. Activated T and B cells in periodontal lesion secrete RANKL
2. Low level of OPG present means RANKL is not inhibited from binding to RANK
3. Monocytes recruited one large numbers
4. RANKL/RANK binding results in differentiation into osteoclasts
5. Uncontrolled alveolar bone resorption

Question 14

What cytokines contribute to bone resorption by inhibiting bone formation?

Answer 14

Pro inflammatory cytokines:

1. IL-1
2. IL-6
3. IL-17
4. TNFa

Question 15

How does Matrix Metalloproteinase activation affect host tissues?

Answer 15

1. Elevated and dysregulated MMP activation contributes to tissue destruction (manifests as attachment loss)