Pathology: Tissue Damage

Question 1

Name some histological features of the inflammatory lesion

Answer 1

• Epithelial proliferation of the junctional and sulcular epithelium
• Extensive collagen loss
• Progresses to loss of bone and collagen from PDL
• Attachment loss and apical migration of JE
• Activation of adaptive immune response activating neutrophils, macrophages, T lymphocytes and plasma cells

Question 2

What are the two main sources of molecules that can instigate tissue damage?

Answer 2

1) Bacterial virulence factors
2) Signalling molecules from host response

Question 3

What are the three main classes of bacterial virulence factors?

Answer 3

1) Bacterial secretion: bacterial virulence factors that break down collagen or ground substance. Production of enzymes or leukotoxin.
2) Metabolites produced by bacteria which ingress into the connective tissue and enhance degradation of the collagenous molecules
3) Structural components of the bacteria e.g. LPS and endotoxin effects on the periodontal tissues

Question 4

What are the roles of bacterial virulence factors?

Answer 4

Breakdown of host tissue directly.
Damage / kill host cells.
Stimulate the host - endotoxin causing bone resorption.
Inflammation - pro-inflammatory cytokines.

Question 5

How does the host recognise bacteria?

Answer 5

Bacteria are recognised by host cells such as dendritic cells via PAMP molecules.
PAMPA molecules on bacterial cells bind to Toll like receptors on macrophages.
This instigates cytokine stimulation and activates the immune response.

Question 6

Name some molecules that are involved in the host response

Answer 6

1) Vasoactive inflammatory mediators - histamine
2) Cytokines - TNFalpha, IL1, IL6, IL8
3) Lipid-derieved molecules - prostaglandins, leukotrienes

Question 7

Why does the host response cause damage to periodontal tissues?

Answer 7

Collagen breakdown required to facilitate the passage of immune cells to get to the area where the bacteria are.

Question 8

What enzymes do bacteria produce to undergo direct damage to the tissues?

Answer 8

Collagenase, elastinase

Question 9

What is the role of matrix metalloproteinases in periodontal disease?

Answer 9

Group of enzymes with a metallic ion as part of their structure.
When there is an inflammatory response, there is an increased level of these enzymes which facilitates breakdown of collagen and movement of inflammatory cells.
They are stimulated by pro-inflammatory cytokines or components.
Examples: collagenases (MMP1, MMP8)

Question 10

Explain the RANKL/OPG system leading to bone resorption in periodontal disease

Answer 10

• Osteoclasts form from pre-monocytes
• In order for them to differentiate to osteoclasts, they need RANK receptor
• Osteoblasts are in control of secreting RANK ligand binding to RANK on osteoclasts
• Osteoblasts have RANKL on their surface which binds to RANK receptor to lead to osteoclast formation and bone resorption
• OPG counteracts RANK action by preventing RANKL binding to RANK. This means no osteoclast activation so less bone resorption
• During periodontitis, we get an increase in RANK ligand produced by pro-inflammatory cytokines so more osteoclast activation and get more resorption

Question 11

What are the attempts at repair that the body undergoes after tissue damage?

Answer 11

• New mature tissue formation occurs such as granulation tissue and fibrosis
• If there is loss of attachment of the PDL, in most cases there is healing by fibrosis (Scaring)

Question 12

What are the attempts at repair that the body undergoes after tissue damage?

Answer 12

• New mature tissue formation occurs such as granulation tissue and fibrosis
• If there is loss of attachment of the PDL, in most cases there is healing by fibrosis (Scaring)

Question 13

What are the three main factors that make an individual more susceptible to periodontitis compared to another individual?

Answer 13

1) Microbial variation - increase in number of P.Gingivalis. Certain bacteria produce specific virulence factors making them more damaging
2) Neutrophil function - patients with neutropenia have an increased risk of severe periodontal breakdown. Smoking and diabetes affects chemotaxis of neutrophils and phagocytic function
3) Hyper-inflammatory response - instigated by types of bacteria or their virulence factors.

Question 14

Name some adjunctive therapies that can be used alongside removing the biofilm

Answer 14

1. Antimicrobials to target certain bacteria
2. Specific inflammatory inhibitors - to dull the affects of the host response
3. Inhibiting MMPS and inhibiting RANKL
4. Finding MMPs may be used as a biomarker