Periodontal immunology

Question 1

What is a discription of gingivitis

Answer 1

Inflammation localised to gingival tissues

Acute inflammation

Normal physiological response to infection or injury

Question 2

What is periodontitis

Answer 2

Inflammation of the gingival tissues and supporting periodontal structures ​

Chronic inflammation​

Pathological inflammatory response associated with tissue destruction

Question 3

How are gingivitis and periodontitis differentiated

Answer 3

Gingivitis - Gingival localised ACUTE inflammation (response to this is normal)

Periodontitis - CHRONIC Inflammation of all tissue and structures (pathological inflammatory response which adds to destruction)

Question 4

What is the trigger for inflammation

Answer 4

Oral biofilm - specifically the amount present (build up of plaque and calculus)

Question 5

What biofilm cannot be accessed by our cell mediated immune response

Answer 5

Biofilm formed above the gumline

Question 6

What does the GCF possess to defend against bacteria

Answer 6

AMPs
Cytokines
Chemokines
Lactoferrin
IgG

Question 7

Is poor oral hygiene an aetiological factor in periodontitis?

Answer 7

Yes, poor oral hygiene is one of the predominant factors that causes gingival inflammation
BUT not everyone with gingival inflammation get attachment loss

Question 8

What are early bacteria colonisers usually classed as

Answer 8

Commensal species

Question 9

What category do late colonisers usually fall into

Answer 9

Gram negative bacteria

Question 10

What is polymicrobial dysbiosis

Answer 10

Community of micro-organisms that work together to actively disrupt the normal homeostatic balance in the oral cavity for their own benefit

Question 11

How does polymicrobial dysbiosis occur

Answer 11

Inflammation happens with plaque and calculus build up, leading to a competition between bacteria in which species compatible with health (inflammaphobic bacteria) are elliminated while periodontal pathogens thrive. (inflammophilic)

Question 12

How can P.gingivalis evade the immune response

Answer 12

Due to its many virulence factors that both activate and subvert the immune resposes allowing it to thrive in flammatory environments such as:
-Gingipains (proteases with broad specificity)
-Inflammophilic
-Atypical LPS (TLR4 antagonist)

Question 13

What are the aetiological factors associated with periodontal disease

Answer 13

Accumulated plaque bacteria (oral hygeine)

Presence of periodontal pathogens ​

Polymicrobial dysbiosis

Question 14

What are the hallmark clinical signs of periodontitis?

Answer 14

Attachment loss - manifests as increased pocket depth​

Alveolar bone destruction​

The persistent inflammation directed towards the dysbiotic oral biofilm causes this destruction (bystander damage).

Question 15

How does the immune system react to an altered microbial colonisation resulting in gingivitis

Answer 15

Increased TLR stimulation​

Increased production of pro-inflammatory mediators​

Triggers acute inflammatory response​
-Increased vasodilation​
-Redness, swelling, bleeding ​
-Increased immune cell migration​

Increase flow of GCF
Influx of neutrophils, increased lymphocytes and monocytes

Question 16

How can neutrophils (which are crucial for periodontal health) end up becoming destructive

Answer 16

Numbers increased during gingivitis​
-Return to health ​
-Predispose to disease progression​

Excessive infiltration associated with chronic inflammation

Question 17

Why do immune over reaction and under reaction both cause periodontal destruction

Answer 17

A balance is needed between too few and too many neutrophils being present as they are crucial for a healthy periodontium while detrimental in large numbers

Question 18

What is the method by which neutrophils can cause tissue destruction in large numbers

Answer 18

Neutriphils release degradative enzymes that can degrade our tissues and contribute to attachment loss (this provides new attachment sites for the dysbiotic biofilm which colonises deeper into the subgingival margin)

Question 19

How can the adaptive immune system also cause damage

Answer 19

T and B lymphocytes present in early lesion ​

Aggregates rich in CD4 T cells and B cells evident as lesion progresses​

Unable to regulate dysbiotic biofilm​

Protective – limits systemic infection​

Destructive – inflammation induced alveolar bone loss

Question 20

Why does inflammation lead to bone loss

Answer 20

The B and T cells fighting the bacteria secrete RANKL
This binds tp RANK inducing the osteoclast differentiation from monocytes

Usually the OPG prevents this/monitors levels to maintain balance

Due to the high levels of T and B cells both secreting RANKL and recruiting many monocytes the OPG levels become vastly outnumbered by RANKL and in turn too many osteoclasts are produced (bone resorption occurs)

Question 21

What are the steps which together link bacterial induced inflammation to pathological tissue destruction

Answer 21

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 (manifests as attachment loss).