Pathology And Mechanisms Of Destruction Flashcards
LO
Periodontitis and gingivitis are both examples of what type of inflammation
Chronic inflammation
What are Histological features of the inflammatory lesion
- Extensive collagen loss
- Epithelial proliferation
- Bone Loss
- Cellular Inflammatory infiltrate:
Neutrophils
Macrophages
T lymphocytes
Plasma cells
(Loss of collagen from pdl - attachment loss occurs and apical migration of junctional epithelium)
Overview of pathogenesis of periodontal disease
Aka how does disease progress
Bacteria can lead to inflammatory response or tissue damage
Inflammatory response can lead to further growth of bacteria, tissue damage or repair
Tissue damage can lead to repair or heighten Inflammatory response
Molecular Mediators of Disease Activity
Aka what are the molecules involved in disease progression
- Bacterial virulence factors
- Signalling molecules controlling host response
Bacterial virulence factors
What are they?
What can bacterial virulence factors be produced by?
- Substances produced by bacteria that cause disease progression (for understanding)
Bacterial virulence factors can be produced by:
- secreted by the bacteria - eg enzymes and leukotoxin
- metabolites
- structural components of the bacteria
- released during growth or death of the bacteria - eg endotoxins, fimbriae
What are 4 things Bacterial Virulence Factors can do?
Bacterial Virulence Factors can:
• Breakdown host tissues directly (enzymes - eg collagenase)
• Damage / kill host cells (toxins)
• Stimulate host - mediated tissue breakdown (e.g. bone resorption)
• Stimulate inflammatory / immune responses
How do bacterial virulence factor lead to host response
• Bacterial virulence factors have PAMPs - “Pathogen Associated Molecular Patterns” (eg LPS)
• these Bind to cell surface receptors on macrophages - eg TLRs ( Toll-like receptors)
• Results in cytokine stimulation and immune activation
Give 3 characteristics of host response
Host responses are:
- essential to prevent serious progressive infection
• may also result in local tissue damage
• also stimulate attempts at tissue repair
Molecular Mediators of Host Responses include:
Give 3 examples
Aka what are the Molecules produced by host cells as part of immune response
• Vasoactive Inflammatory Mediators eg. Histamine
• Cytokines (inter-cellular soluble protein messengers ) include : IL-1, IL-6, IL-8, IL-10, TNF, Interferons
• Prostaglandins and Leukotrienes
Overall make a complex interacting network of pro- and anti-inflammatory signals to allow an appropriate inflammatory response
IF HOST RESPONSES ARE PROTECTIVE, WHY DO THEY CAUSE LOCAL TISSUE DAMAGE
Some Tissue damage necessary for effective host response eg in gingivitis
collagen breakdown within gingival connective tissue is required to allow passage of cells eg neutrophils and macrophages and lymphocytes to get to areas necessary to fight bacterial invasion , and some epithelial proliferation
Overall - Local tissue damage provides access for the inflammatory response
How does tissue damage occur in periodontal disease?
What is most tissue damage caused by?
How does connective tissue damage occur
Connective Tissue Damage
•Bacterial enzymes can damage tissues directly.
What is Most damage is mediated by?
What are the mediators produced by?
Matrix Metalloproteinases
What are they?
Produced by?
Stimulated by?
Important in?
Inhibited by?
What are the types of MMPs
What’s responsible for bone resorption in periodontal disease
Osteoclast formation and the RANKL/OPG system
Osteoclasts break down bone
Osteoclasts formation is controlled by RANKL and OPG
RANKL - tells cells to become osteoclasts
OPG - blocks them becoming osteoclasts
Premonocytes have receptor RANK
OsteoBLASTS have RANKL on their surface - When RANK binds to RANKL, leads to osteoclasts formation and bone resorption
In periodontitis, there’s inflammation and inflammation causes MORE RANKL to be secreted by neutrophils, causing increased osteoclasts and excessive bone breakdown
The RANK /RANKL /OPG system
What is RANKL essential for
Where is RANKL found?
What determines whether bone resorption occurs?
What is RANKL blocked by ?
RANKL in Periodontitis
In health are there high or low levels of OPG
What happens to levels of OPG in periodontitis?
What is RANKL expression induced by in periodontitis?
What is associated with bone resorption in periodontitis
Attempts at repair
How does the host respond for tissue repair
Regulated by?
What are Major risk factors for progressive periodontitis
• Smoking
• Diabetes
• Genetics
• Specific bacteria
Pathological factors associated with progressive periodontitis?
• Microbial variation - Pathogenic bacteria present
• Neutrophil Function -abnormalities in neutrophil function - eg impaired phagocytosis
• Hyper-inflammatory response - susceptible ppl may have exaggerated response
Microbial variation
1 - Which species are associate with destructive periodontal disease?
2 - what are the virulence factors of P gingivalis and AA?
(What about them enhances disease)
3- amount of bacteria/bacterial load?
Neutrophils - Why are they important?
Defective neutrophil function leads to what?
What factors affects neutrophil migration?
Neutrophils are essential in fighting bacterial infections - phagocytose bacteria + perpetuate adaptive immune response IL 17 - key in bone resorption
Defective neutrophil function leads to SEVERE PERIODONTAL BREAKDOWN
Neutrophil migration may be impaired in SMOKING + DIABETES
Hyper-inflammatory” responses
Nature and magnitude of host responses will be regulated by :
• Type of bacteria / virulence factors
• Genetics (normal individual variation)
• Systemic conditions such as diabetes
• Smoking
Potential therapeutic implications
What are Adjunctive therapies for specific susceptible patients ?
Aka what can be given TO THEM?
• Antimicrobial
• Specific inflammatory inhibitors (anti-cytokine therapies, NSAIDS)
• Anti-tissue damage - MMP inhibitors
• Anti-bone resorption - OPG
THIS IS ALL IN ADDITION TO REMOVAL OF BIOFILM
Summary
