Host responses to oral biofilms Flashcards
How is periodontitis different to different health conditions?
Bacterial load is located generally “outside” the body making it a challenge for immune-inflammatory response to take action.
Plaque is a biofilm
Periodontitis is a result of dysbiosis of the normal microbiome
Where are biofilms located in periodontitis and gingivitis?
In gingivitis: Supragingivally
In periodontitis: Subgingivally
What risk factors tip the homeostasis towards dysbiosis? What factors favour resistance?
Resistance: Innate and adaptive immune response, inflammation, and other structural components.
Risk factors: Environmental factors such as smoking, dental plaque accumulation, socioeconomic status as well as host-specific factors such as genetic factors and overall inflammatory burden.
How does the epithelium provide a barrier to entry of microorganisms?
It forms a physical and biological barrier:
Physical barrier via turnover + peeling
Biological barrier via defensins, IL-8, adesion mols, and PMNs
How does GCF protect against inflammation?
Consists of plasma derived substances such as antibodies, cytokines and enzymes. Also composed of epithelium and immune cells.
GCF volume and flow increase with increasing inflammation.
What are the first defense cells against periodontitis?
Neutrophils
What innate immune system structures are protective?
Saliva: Prevents drying of gingiva and teeth with antimicrobial effects.
Epithelium: Physical barrier, inflammatory response via keratinocytes, and immune response via langerhans’ cells
Inflammatory response: Fluid component (GCF) and cellular components such as neutrophils and macrophages
What adaptive immune system structures are protective?
Humoral response
Cell-mediated response
What does LPS do to periodontium?
It stimulates macrophages to produce MMPs, IL-1b, and TNF-a
It stimulates fibroblasts to produce more MMPs
It stimulates IL-1b production as well as TNF-a by B cells and macrophages.
What are the histopathological classifications of clinical presentation of gingivitis?
Pristine: Histological perfection
Initial: Clinically healthy gingiva
Early: Early gingivitis
Established: Chronic or established gingivitis
Advanced: Periodontitis
What are the features of pristine gingiva?
Super healthy gingiva with no infiltrate
No bleeding
Pink, firm, scalloped outline, stippled and knife edge margin
Shallow gingival sulcus up to 3mm deep
Free of histological inflammation is extremely rare
What are the features of clinically healthy (not pristine) gingiva?
Healthy with infiltrate
Neutrophils and macrophages in JE
Lymphocytes in connective tissue
Collagen reduction not detectable clinically
Increase in vascular structures
Exudate and transudative fluid from vessels to tissues (GCF)
What does the initial lesion look like in periodontitis?
Change in microvascular plexus JE (vessels remain dilated and increase in number)
Arteriolas capillaries, and venules dilation
Hydrostatic pressure increase
Increased permeability
Exudate of fluids and proteins
Increased GCF
Enhanced PMNs migration
PMNs accumulate in JE and sulcus
VERY FEW PLASMA CELLS
What are the commonly seen features of ginigvitis?
10 to 20 days of plaque accumulation
Clinical signs of gingivitis
Redness, swelling, Blood on probing
Reversible after plaque removal
When does the early lesion from gingivitis form?
One week after plaque accumulation
What are the histological features of gingivitis?
Connective Tissue infiltrate 15% of volume
Fibroblasts degenerate
Collagen destruction
Clinically detectable inflammation
Proliferation of basal and JE cells
Coronoal rete ridges
What are the features of an established lesion?
Increased fluid and leukocyte migration
More edematous swelling clinically
Plasma cells 10% on coronal connective tissue
Collagen loss in apical and lateral directions
Inflammatory cell infiltrate expands
Extension of rete pegs into connective tissue
JE detatched from tooth structure
Pocket epithelium with heavy cell infiltrate PMNs
Permeable and ulcerated pocket epithelium
What are the clinical features of advanced periodontitis?
Pocket gets deeper
Apical plaque growth
Lateral and apical extension of infiltrate
Alveolar bone loss starts
Extensive fiber damage
Apical migration of JE from CEJ
Plasma cells predominate
What is the function of antibodies?
Neutralization directly of antigens
Opsonization for Fc receptor-mediated phagocytosis
And complement activation
What does complement activation do?
Leads to bacterial lysis
Inflammation
Phagocytosis of C3b-coated bacteria
What do CD4+ helper T cells do?
Release various cytokines which lead to antibody response
Activate macrophages via IFN-gamma
Activate inflammation via TNF
How does the humoral response provide protection against the bacteria from dental plaque?
- Plaque antigens diffuse through the JE
- Langerhan cells within epithelium capture and process the antigens
- APCs leave gingiva in lymphatics
- APCs go to lymph node and begin to stimulate lymphocytes to produce a specific immune response
- Antibodies are produced specific to the microbe
- Antibodies leave the circulation and are carried to the crevice in the transudate from the inflamed and dilated blood vessels
- Antibody action on microbes in the crevice can result in killing, aggravation, precipitation, detoxification, opsonization, and phagocytosis of bacteria
How does cell mediated immunity protect in periodontitis?
Antigen penetration of JE contact to connective tissue
T-helper cells proliferate and release cytokines which activate other cells such as macrphages, B cells or T cells to stimulate, inhibit or kill.
T-helper cells on reexposure proliferate and produce cytokines.
What do immune mediators do in periodontitis?
Cytokines induced by host response play a critical role in periodontal tissue breakdown.
Periodontal bone loss due to bacteria, high levels of cytokines, prostaglandins, MMPs, RANKL and low levels of IL-10 TGF-B, TIMPs and OPG
IL-6 and IL-8 are high inperiodontitis patients.
What does IL-1 do in periodontitis?
Stimulates proresorptive cytokines, RANKL and TNF-alpha
What does TNF-alpha do?
TNF-alpha accelerates bone destruction
What does osteoclast activation result in?
RANKL and OPG stimulate osteoclasto-genesis and one resorption
If the RANKL/OPG ratio is high then it is proresorptive
If the RANKL/OPG ratio is low then it is antiresorptive
IFNgamma and IL-17 increase RANKL
IL-4 and IL-10 reduce RANKL/OPG ratio
Which lymphocytes are antiresorptive?
TH2 and Tregs and antiresorptive
Which lymphocytes are proresorptive?
Lymphocyte subsets TH1 and TH17 are proresorptive
