Periodontal Immunology - Immunopathogenesis Flashcards

1
Q

What are the hallmark signs of periodontitis

A

Attachment loss - manifests as increased pocket depth

Alveolar bone destruction

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2
Q

What species in the biofilm can cause tissue destruction and how

A

Gingipains can clean and degrade host proteins to make them available as an energy source which can contribute to destruction of the connective tissues and attachment loss

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3
Q

How is gingivitis first initiated

A

The host detects an accumulation of plaque bacteria, detected by TLR expressed within the gingival epithelium
This will lead to upregulation and the release of pro-inflammatory mediators which will trigger the clinical signs of inflammation allowing immune cells to migrate into the tissues to try and control the infection

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4
Q

Which cells migrate to the gingival tissue during gingivitis and how do they do this

A

Mainly neutrophils and monocytes
They follow the chemokine and cytokine gradient that is produced upon activation of TLRs and they migrate through the gingival tissue towards the gingival margins

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5
Q

What is the role of neutrophils and monocytes in the gingival tissue

A

They can either phagocytose any microbes invading the tissue or they can release their degredative enzymes into the GCF and those enzymes will bathe the biofilm attached to the subgingival tissues

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6
Q

How does gingivitis affect the gingival crevicular fluid

A

There is increased flow of the GCF

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7
Q

What is the role of lymphocytes during gingivitis

A

T cells help to coordinate the responses and B cells can differentiate into plasma cells and then start releasing antibodies into the GCF and saliva

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8
Q

What are the possible outcomes of gingivitis

A

Biofilm is controlled as the threat is removed so there is resolution of inflammation and return to health
or
Periodontal pathogens in the biofilm drive dysbiosis preventing the return to homeostasis while evading the immune response so over time, the immune response will become chronic, damaging the host tissues

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9
Q

Describe the role of neutrophils in periodontal health

A

Neutrophils continually track through the gingival tissue and towards the gingival margin where they degranulation and release their contents into the GCF
Occurs constantly and is crucial for maintaining health and to suppress the expression of virulence

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10
Q

Why is periodontitis so aggressive in patients with lost neutrophil function

A

Neutrophils aren’t available and aren’t functioning correctly so they’re not available to control bacterial growth giving particular species a competitive advantage, invading the gingiva tissues leading to widespread inflammation

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11
Q

How can the presence of neutrophils lead to destruction of tissues

A

Within the degradation enzymes designed to control the biofilm, there is a major source of MMPs which are host enzymes important for clearing damaged tissues after infection
The vast number of MMPs during periodontitis contribute to tissue destruction

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12
Q

Describe the protective role adaptive immunity plays in periodontitis

A

Prevents the biofilm trafficking through the tissue and gaining access to the circulation, preventing systemic infection

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13
Q

Why is the adaptive immune response during periodontitis destructive

A

The sustained activation of inflammation contributes to alveolar bone absorption

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14
Q

Describe monocytes differentiation in health

A

Monocytes, given the right signals, can either differentiate into macrophages or osteoclasts
In health the balance between bone formation and absorption is balanced, old bone is placed with new bone

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15
Q

How is monocytes differentiation regulated

A

By a triad of cytokines, RANKL, its receptor RANK and the decoy receptor OPG

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16
Q

How is RANKL present in periodontitis

A

Activated B and T cells within the gingival tissue release RANKL into the periodontal lesion

17
Q

Describe how inflammation leads to bone loss

A

There is high levels of RANKL and low levels of OPG
OPG isn’t available to inhibit RANKL from binding to RANK
Monocytes are being recruited in large numbers
RANKL will bind to RANK causing the monocytes to differentiate into osteoclasts which will resorb the surrounding bone leading to alveolar bone resorption and eventually tooth loss

18
Q

Describe how pro-inflammatory cytokines contribute to bone resorption

A

Different types of cytokines containing TNFa (IL-1, IL-6 IL-17) inhibit osteoblasts and bone formation resulting in bone resorption