perio immunology Flashcards
gingivitis vs periodontitis
Inflammation localised to the gingival tissues and Normal physiological response to infection or injury
Inflammation of the gingival tissues and supporting structure (PDL and alveolar bone) and Pathological inflammatory response associated with tissue destruction that does not resolve
hallmark sign of periodontitis
attachment loss
alveolar bone loss
what are the immune defences in our oral cavity?
GCF, oral mucosa barrier, saliva
how does saliva serve its immune purpose
has antimicrobial peptides and proteins
but it cannot remove accumulated biofilm, requires mechnical brushing
how does oral mucosa protect the oral environment
physical barrier preventing microbes from entering
functional barrier that expresses TLR that detect PAMPs
epithelial cells on oral mucosa release cytokines, chemokines and antimicrobial peptides. These signals recruit immune cells into the gingival tissues
igg and iga function in the mouth
IgG => bind to pathogen and triggers immune reaction
IgA => coat and prevent binding of pathogens to tooth surfaces
aetiological factors of periodontal diseases
- Accumulated plaque bacteria from poor OH
- Presence of periodontal pathogens (orange red complex)
- Polymicrobial dysbiosis
- In susceptible hosts (immune system plays a role)
- Host-pathogen interactions determine susceptibility
what types of bacteria are present in perio patients
Red complex
- Porphyromonas gingivalis
- Tannerella forsythia
- Treponema denticola
late colonizers
o gram negative anaerobic
o or facultative ie can survive with or without oxygen, uses up oxygen and breeds more anaerobes
what factors shape the composition of oral microbiome?
by interactions with the host (genetics, diet, lifestyle, behaviours)
virulence factors of P. gingivalis
o Immune evasion
o Asaccharolytic - nutrients from breakdown of proteins and peptides
o Gingipains - proteases with broad-specificity
o Atypical LPS –TLR4 antagonist - P.gingivalis can change its LPS, blocks signalling
o Inflammatory environment favours expression of virulence
o Drives dysbiosis in susceptible hosts
o factors simultaneously activate and subvert immune responses – thrive in inflammatory environments.
where are red complex bacteria most commonly found
areas of pocket depth and bleeding on probing
What is Polymicrobial dysbiosis
community of pathogens, work together to actively disrupt the normal homeostatic balance in the oral cavity for their own benefit
perio pathogens thrive in inflammatory conditions , changing the biofilm composition – healthy species are lost and disease-causing species thrive – this is polymicrobial dysbiosis.
what occurs in gingivitis
altered microbial colonisation
increased flow of GCF
influx of neutrophils
monocytes and lymphocytes
Increased TLR stimulation
Increased production of pro-inflammatory mediators
- Increased vasodilation
- Redness, swelling, bleeding
- Increased immune cell migration
what are gingipains
protein produced by P.gingivalis that mediates the interaction between P. gingivalis bacteria and hosts
what is the role of neutrophils in periodontitis? what happens when there is too much or too little neutrophils?
crucial for maintaining healthy periodontium
too little neutrophils => immune under reaction => leukocyte adhesion deficiency
too many neutrophils => immune over reaction and chronic inflammation
LAD
leukocyte adhesion deficiency
what is LAD associated with
Aggressive periodontitis
neutrophils cannot leave the blood to enter tissues and protect the gum, certain pathogens can thrive and invade
what causes chronic inflammation of the gums
immune over reaction, too many neutrophils
- Neutrophils 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)– and so it progresses…
what is the role of adaptive immunity in periodontal destruction
CD4 T cells and B cells evident as lesion progresses, they release mediators to regulate the immune response but are unable to regulate biofilm, instead they cause destruction and inflammation -> bone loss
How does inflammation lead to bone loss?
- Activated T and B cells in periodontal lesion secrete RANKL
- RANKL binds RANK to induce osteoclast differentiation
- High levels of RANKL
- Low levels of OPG
- Monocytes recruited in large numbers
- Differentiate into osteoclasts
- Bone resorption results
what is the function of opg and rankl
opg - inhibits rankl, inhibiting osteoclast differentiation
rankl- induces osteoclast differentiation -> bone resorption
what produces opg
osteoblast
OPG promotes bone formation, inhibits RANKL
what produces rankl
osteoblasts
promotes osteoclastogenesisie bone resorption
Cellular and molecular events linking bacterial-induced inflammation with pathologic tissue destruction
Bacterial products bind to 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 are examples of pro inflammatory mediators?
IL 1
IL 6
IL 17
TNF alpha
Examples of anti inflammatory mediators
IL 10
TGF BETA
PDGF
VEGF
