perio immunology Flashcards

1
Q

gingivitis vs periodontitis

A

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

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2
Q

hallmark sign of periodontitis

A

attachment loss
alveolar bone loss

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3
Q

what are the immune defences in our oral cavity?

A

GCF, oral mucosa barrier, saliva

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4
Q

how does saliva serve its immune purpose

A

has antimicrobial peptides and proteins

but it cannot remove accumulated biofilm, requires mechnical brushing

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5
Q

how does oral mucosa protect the oral environment

A

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

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6
Q

igg and iga function in the mouth

A

IgG => bind to pathogen and triggers immune reaction

IgA => coat and prevent binding of pathogens to tooth surfaces

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7
Q

aetiological factors of periodontal diseases

A
  • 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
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8
Q

what types of bacteria are present in perio patients

A

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

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9
Q

what factors shape the composition of oral microbiome?

A

by interactions with the host (genetics, diet, lifestyle, behaviours)

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10
Q

virulence factors of P. gingivalis

A

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.

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11
Q

where are red complex bacteria most commonly found

A

areas of pocket depth and bleeding on probing

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12
Q

What is Polymicrobial dysbiosis

A

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.

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13
Q

what occurs in gingivitis

A

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

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14
Q

what are gingipains

A

protein produced by P.gingivalis that mediates the interaction between P. gingivalis bacteria and hosts

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15
Q

what is the role of neutrophils in periodontitis? what happens when there is too much or too little neutrophils?

A

crucial for maintaining healthy periodontium

too little neutrophils => immune under reaction => leukocyte adhesion deficiency

too many neutrophils => immune over reaction and chronic inflammation

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16
Q

LAD

A

leukocyte adhesion deficiency

17
Q

what is LAD associated with

A

Aggressive periodontitis

neutrophils cannot leave the blood to enter tissues and protect the gum, certain pathogens can thrive and invade

18
Q

what causes chronic inflammation of the gums

A

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…
19
Q

what is the role of adaptive immunity in periodontal destruction

A

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

20
Q

How does inflammation lead to bone loss?

A
  1. Activated T and B cells in periodontal lesion secrete RANKL
  2. RANKL binds RANK to induce osteoclast differentiation
  3. High levels of RANKL
  4. Low levels of OPG
  5. Monocytes recruited in large numbers
  6. Differentiate into osteoclasts
  7. Bone resorption results
21
Q

what is the function of opg and rankl

A

opg - inhibits rankl, inhibiting osteoclast differentiation

rankl- induces osteoclast differentiation -> bone resorption

22
Q

what produces opg

A

osteoblast

OPG promotes bone formation, inhibits RANKL

23
Q

what produces rankl

A

osteoblasts

promotes osteoclastogenesisie bone resorption

24
Q

Cellular and molecular events linking bacterial-induced inflammation with pathologic tissue destruction

A

Bacterial products bind to TLRs on epithelium, stimulating secretion of cytokines, chemokines and AMPs.

  1. Vasodilation and selective recruitment of leukocytes (predominantly neutrophils, also monocytes and lymphocytes)
  2. Bacterial products activate neutrophils, further release of pro-inflammatory mediators. Amplification loop of neutrophil infiltration.
  3. Activated lymphocytes express RANKL. RANKL/OPG balance disrupted
  4. RANKL binds RANK on osteoclast precursors (monocytes). Activates osteoclastogenesis leading to alveolar bone resorption.
  5. Pro-inflammatory cytokines (IL-1, IL-6, IL-17, TNFa) contribute to bone resorption by inhibiting bone formation.
  6. Elevated and dysregulated MMP activation contributes to connective tissue destruction (manifests as attachment loss).
25
Q

What are examples of pro inflammatory mediators?

A

IL 1
IL 6
IL 17
TNF alpha

26
Q

Examples of anti inflammatory mediators

A

IL 10
TGF BETA
PDGF
VEGF