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Pathogenesis of Periodontal Disease (Host defence mechanisms (PMNs (If…
Pathogenesis of Periodontal Disease
Essential factors for Colonization of sub gingival species
For a pathogen to cause disease it must be able to:
Colonize sub-gingival area
Compete against other species for habitat
Defend itself from host defences
Multiplication, bacteria must reach a threshold population b/f being able to cause disease
Attachment to one or more surface (enamel pellicle, early colonizers, secondary colonizers)
Produce damaging factors to the host
LPS by Gram -, leukotoxins from Aa. etc...
Host defence mechanisms
Desquamation of epithelial cells
some bacteria overcome this by invading subjacent cells
Flow of GCF + Saliva help to clear away bacteria and prevent binding
Abs in sub gingival area
Prevent bacterial attachment (neutralization)
Opsonize bacteria + facilitate phagocytosis
Overcome by Ab proteases secreted by P .gingivalis, P. Intermedia (also holds early and late colonizers in biofilm), Capnocytophaga
PMNs
Phagocytosis
Releasing lysosomal enzymes into crevice/pocket
Bacteria counteract by:
Production of leukotoxin (Aa)
Production of capsules –> P. gingivalis –> inhibit phagocytosis
If bacteria enter CT:
PMNs, macrophages and lymphocytes act as antagonistic cells against bacteria (any disease that affects immune f(x) will increase susceptibility to PD regardless of age)
E selectin expression on the vascular epithelium + IL-8 (chemotactic) helps PMNs reach infected tissue
Bacteria like Aa produce leukotoxin
Kills PMNs, monocytes, mature T and B lymphocytes
Facilitates non-lethal suppression of immune cells
P intermedia and T. denticola produce immunosuppressants
4 Lesions of Gingivitis + Periodontitis
Shift from health (above to disease)
Reduced host defences + normal microbial challenge
disease
Early lesion (gingivitis)
b/w 12-21days of plaque accumulation, lesion becomes clinically evident
by 21d, lymphocytes make up 70% , PMNs and plasma cells < 10% total infiltration
forms after 4-7 days of plaque accumulation
Mechanism:
If bacteria not destroyed in initial phase, they penetrate JE to enter CT
In response to increased #s of bacteria, epithelial cells release chemokines to attract more PMNs, macrophages and lymphocytes
Increased bv permeability allows large #s of PMNs to rush to the site
The increased # of PMNs destroy additional gingival CT as they head towards bacteria
PMNs form a wall of cells b/w biofilm and tissue
PMNs phagocytize bacteria in the sulcus in an effort to protect the host tissues from bacteria
Macrophages release cytokines, PGE2 and MMPs, these recruit more immune cells to get rid of bacteria. If the infection is brought under control, the body is able to repair the damage
Established Lesion (gingivitis)
Lymphocytes produce lots of antibodies to fight bacteria
More immune cells are recruited, more toxic chemicals released, more tissue is destroyed (macrophages in contact with G- produce cytokines, PGE2 and MMPs
PMNs continue to battle in the sulcus
Cytokines recruit more macrophages and lymphocytes
Macrophages + B cells and plasma cells become most numerous
PGE2 + MMPs cause more collagen destruction in CT
Sub gingival plaque extends in sulcus, disrupts the coronal portion of JE
PGE2 stimulates gingival fibroblasts to produce more PGE2 and MMPs, battle continues until resolution or disease progresses
The formation of a gingival pocket seen in gingivitis results from:
The presence of edema pushing the margin of the gingiva coronally
The partial detachment of the coronal end of the JE
however, gingival CT b/w CEJ and crest of alveolar bone remain intact
Not every gingivitis will progress to periodontitis, the rate of periodontal tissue destruction varies
*
Advanced lesion
∆ from previous phases to a stage where bacterial challenge is not well controlled and tissue destruction is evident
Plaque biofilm grows laterally and apically along root surface, periodontitis is initiated
Immune system tries to eliminate bacteria, but cannot, more immune cells are recruited and tissue destruction ensues
immune response overwhelms tissue repair
macrophages produce > [cytokines, IL-1, PGE2, and MMPs] resulting in destruction of CT + alveolar bone
gingival fibroblasts take on a fibroclast activity and destroy gingival CT + PDL fibres
PMNs and lymphocytes produce MMPs, this causes destruction of gingival CT + PDL fibres
Osteoclasts, stimulated by PGE2, destroy crest of alveolar bone
JE extends rete ridges into CT and migrates apically along root
Clinical outcome: formation of PD pocket/attachment loss and bone loss (always ask yourself where the gingival margin is relative to CEJ)
Attachment loss: distance of CEJ to the base of the periodontal pocket is the ATTACHMENT LOSS
measured from the CEJ to the tip of the probe clinically
Normal host defences + increased microbial challenge
Initial (subclinical gingivitis phase)
occupies 5-10% of CT, not evident clinically
Early colonizers (Streptococci) near gingival margin
occurs 2-4 days following plaque accumulation
Mechanism
Bacteria + MB products/lipoteichoic acid of G+ trigger host response
Cells of sulcular + JE release inflammatory mediators (PGE2, TNF, MMPs)
Blood vessels dilate and release cytokines to attract more PMNs
PMNs pass from bv into CT to get to the sulcus, destroying CT in their path with proteases (collagenase etc...)
PMNs migrate into JE from CT
PMNs reach sulcus and phagocytize bacteria
body repairs CT
Pathogenesis of Periodontitis
Susceptible individuals or susceptible sites that are breached, exposing tissues and cells to bacterial components
Cellular components including monocytes, and fibroblasts are stimulated by bacterial components (LPS) to produce many or all of cytokines
Up-regulated IL-1B, TNF, PGE2 and enzymes (MMP) activate fibroblasts and degrade CT and bone matrix directly
IL-8
Epithelial cells
PMN chemotaxis + transepithelial migration
PGE2
Monocytes/macrophages, fibroblasts
Osteoclast stimulation
Increased MMP production
IL-6
T cells, Monocytes/macrophages, fibroblasts , epithelial cells
Pro inflammatory: increased IL-1, PGE2, MMP
Th2 response (B cell differentiation)
MMP-1
Fibroblasts,monocytes/macrophages, epithelial cells
Collagenase
IL-1, TNF-a
Produced by Monocytes, macrophages, T cells
Osteoclast stimulation
Pro inflammatory: Leukocyte chemotaxis, monocyte/macrophage activation
Increased MMP production
Activation of T cells
Increased production of IL-1 and PGE2
MMP-8
PMNs
Collagenase
Activated fibroblasts also destroy collagen by MMPs
LPS activates macrophages via LBP binding to CD14 receptors
Bone resorption results directly (by macrophages) or indirectly through stimulate of osteoclasts
Virulent microorganisms must be present in local lesion at critical minimal infective dose (not in all cases, non inflammatory destructive PD)
Bacterial threshold load is 10^5-10^8 microorganisms per site
Red complex, mostly G - anaerobic organisms and Aa
Cytokines alone or in concert stimulate inflammation, bone resorption, collagen destruction via MMPs