Periodontal immunology Flashcards
What is a discription of gingivitis
Inflammation localised to gingival tissues
Acute inflammation
Normal physiological response to infection or injury
What is periodontitis
Inflammation of the gingival tissues and supporting periodontal structures
Chronic inflammation
Pathological inflammatory response associated with tissue destruction
How are gingivitis and periodontitis differentiated
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)
What is the trigger for inflammation
Oral biofilm - specifically the amount present (build up of plaque and calculus)
What biofilm cannot be accessed by our cell mediated immune response
Biofilm formed above the gumline
What does the GCF possess to defend against bacteria
AMPs
Cytokines
Chemokines
Lactoferrin
IgG
Is poor oral hygiene an aetiological factor in periodontitis?
Yes, poor oral hygiene is one of the predominant factors that causes gingival inflammation
BUT not everyone with gingival inflammation get attachment loss
What are early bacteria colonisers usually classed as
Commensal species
What category do late colonisers usually fall into
Gram negative bacteria
What is polymicrobial dysbiosis
Community of micro-organisms that work together to actively disrupt the normal homeostatic balance in the oral cavity for their own benefit
How does polymicrobial dysbiosis occur
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)
How can P.gingivalis evade the immune response
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)
What are the aetiological factors associated with periodontal disease
Accumulated plaque bacteria (oral hygeine)
Presence of periodontal pathogens
Polymicrobial dysbiosis
What are the hallmark clinical signs of periodontitis?
Attachment loss - manifests as increased pocket depth
Alveolar bone destruction
The persistent inflammation directed towards the dysbiotic oral biofilm causes this destruction (bystander damage).
How does the immune system react to an altered microbial colonisation resulting in gingivitis
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
How can neutrophils (which are crucial for periodontal health) end up becoming destructive
Numbers increased during gingivitis
-Return to health
-Predispose to disease progression
Excessive infiltration associated with chronic inflammation
Why do immune over reaction and under reaction both cause periodontal destruction
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
What is the method by which neutrophils can cause tissue destruction in large numbers
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)
How can the adaptive immune system also cause damage
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
Why does inflammation lead to bone loss
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)
What are the steps which together link bacterial induced inflammation to pathological 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 (manifests as attachment loss).
What do TLR recognise
PAMPs or MAMPs
What drives the pathology of periodontitis
Immune response to the bacteria
