Ch. 13: Host Immunoinflammatory Response to Biofilm

Question 1

Inflammatory Response

Answer 1

activated by immune system to offending antigen/injury
Not meant to be activated for a long time!
When tissue does not go through resolution phase, the result is chronic inflammation
Host immunoinflammatory responses is direct cause of nearly all destruction seen in perio disease

Question 2

Virulence Factor

Answer 2

mechanism that enable biofilm to colonize and damage tissues
Presence of lipopolysaccharide (LPS), ability to invade tissues, ability to produce enzymes

Question 3

Acute Inflammation

Answer 3

Host protective effect, 1st line of defense
must resolve after the microbial challenge is eliminated!

Question 4

Catabasis

Answer 4

return to homeostasis after inflammatory process
Pro-resolving lipid mediators work to terminates PMN recruitments, stimulate macrophages to remove dead cells, promote antibacterial activities, promote tissue repair and regeneration

Question 5

Chronic Inflammation

Answer 5

can have pathological effects on host tissue

Question 6

Important Biochemical Mediators

Answer 6

cytokines, prostaglandins, MMPs

Question 7

Cytokines

Answer 7

any protein secreted by cells that affects behavior of nearby cells

Question 8

Cytokines produced by

Answer 8

PMNs, macrophages, B-cells, epithelial cells, gingival fibroblasts, osteoblasts

Question 9

Effects of cytokines

Answer 9

Bind to specific cell surface receptors on target cells
Increases vascular permeability
Can initiate and perpetuate irreversible tissue destruction in chronic inflammatory disease

Question 10

Cytokine Examples

Answer 10

Can initiate and perpetuate irreversible tissue destruction in chronic inflammatory disease

Question 11

Prostaglandins

Answer 11

powerful biochemical mediators from fatty acids expressed on surfaces of most cells
Important: D, E, F, G, H, I

Question 12

E series (PGE)

Answer 12

play important role in bone destruction during periodontitis

Question 13

Source of PGEs

Answer 13

Macrophages major source of PGE’s, as well as PMNs and gingival fibroblasts

Question 14

Prostaglandin function

Answer 14

increase permeability, dilate blood vessels, triggers osteoclasts to destroy bone, can promote overproduction of destructive MMP enzymes

Question 15

MMPs (Matrix Metalloproteinases)

Answer 15

enzymes that break down CT matrix

Question 16

Sources MMPs

Answer 16

PMNs, macrophages, fibroblasts, epithelial cells of JE (PMNs and fibroblasts major source)

Question 17

MMPs in health

Answer 17

facilitates normal turnover of perio CT matrix

Question 18

TIMP

Answer 18

helps regulate overactive to prevent CT breakdown (MMP-TIMP balance)

Question 19

Release of MMPs

Answer 19

Cytokines and prostaglandins stimulate leukocytes and fibroblasts to release excessive amounts

Question 20

Periostat

Answer 20

can inhibit MMP activity

Question 21

Current Theory of Pathogenesis

Answer 21

gingival health associated w/ symbiotic biofilm
Traditional pathogenic bacteria accumulate when biofilm not disturbed
In susceptible individuals, dysbiotic biofilm activates host response to produce excessive cytokines, ROS, MMPS leading to CT breakdown, bone resorption, perio tissue damage
Removal of bacterial biofilm can help reestablish health promoting biofilm

Question 22

Initial Lesion (Bacterial Accumulation)

Answer 22

bacteria colonize tooth near gingival margin *biofilm is supragingival
2-4 days after plaque biofilm accumulation
Gram negative bacteria initiate release of cytokines, BGE2, MMPS, TNF-a
PMNs recruited to site, migrate sulcus, phagocytize bacteria
Gram negative bacteria activate complement system, vascular dilation occurs in dentogingival complex
Gingival crevicular fluid increases in volume
Clinically, gingiva looks healthy
Host responses successful if most bacteria destroyed
If controlled, body can repair damage, if not, early gingivitis develops

Question 23

Early Lesion (Early Gingivitis)

Answer 23

bacteria accumulation continues, biofilm matures
4-7 days after biofilm accumulation
Toxins and byproducts penetrate JE
Cytokine attract additional cells to site, more PMNs move into gingival CT (forms wall of cells between biofilm and sulcus, releases more cytokines)
Macrophages recruited to CT and release biochemical mediators
T-cells migrate to CT and produce cytokines and antibodies
Sulcular epithelium and adjacent CT effect most (60-70% collagen loss)
Sulcular epithelium starts forming epithelial ridges, JE cells start to proliferate
Inflammatory changes observed clinically
Larger number of PMNs, macrophages, and T-cells may control bacterial pathogens
Can disrupt plaque biofilm w/ good patient self care

Question 24

Established Lesion (Established Gingivitis)

Answer 24

biofilm extends into sulcus, disrupting JE attachment at coronal most portion
Epithelial cell secrete more cytokines
Predominated by presence of plasma cells in CT zone
Immune system send more immune cells
Epithelial ridges extend deeper in CT
JE loosens attachment to root and starts to transform into pocket epithelium
Continued collagen loss in CT
Clinical features of gingivitis more evident, 21 days after accumulation
Host response can often contain bacteria, perio instrumentation and patient ed. can help as well

Question 25

Advanced Lesion (Periodontitis)

Answer 25

biofilm grows laterally and apically along root Perio pocket ideal environment for subgingival bacterial growth Infection becomes chronic, tissue destruction exceeds hosts ability to repair damage JE cells migrate apically on root and perio pocket forms Fibroblasts shift to state that favors destruction of CT and PDL fibers Osteoclasts destroy crest of alveolar bone Tissue changes NOT reversible Chronic infection induces chronic inflammatory response that destroys peri tissues and causes damage to periodontium Characterized by: pocket formation, BOP, destruction of PDL, bone loss, furcation involvement, tooth mobility Factors influencing host: abnormal PMN function, persistence/virulence of bacteria, acquired and environment factors, systemic factors

Question 26

Bone Remodeling

Answer 26

osteoclasts (bone resorbing) are multinucleated Activation mediated by cell surface receptor activator of nuclear factor Kappa-B (RANK) Osteoblasts are bone-forming cells, synthesize collagen and other bone proteins, involvement in mineralization

Question 27

Resorption

Answer 27

osteoclasts break down bone and matrix, creating erosion cavity

Question 28

Reversal

Answer 28

mononuclear cells prepare bone for new osteoblasts to begin building bone

Question 29

Formation

Answer 29

osteoblasts form a matrix to replace resorbed bone w/ new bone

Question 30

Resting

Answer 30

prolonged resting period follows until a new remodeling cycle begins

Question 31

Regulation of Bone Remodeling Cycle

Answer 31

receptor activator of nuclear factor kappa-b (kB0 and ligand (RANKL) Protein catalysts expression on osteoblasts membrane Osteoclastic differentiation factor Resorption occurs when RANKL binds w/ RANK (stimulate precursor cells to differentiate into osteoclasts)

Question 32

Osteoprotegerin (OPG)

Answer 32

protein signaling molecule produced by osteoblasts Protects bone from excessive resorption by binding to RANKL, blocks binding w/ RANK

Question 33

RANKL and OPG in balance

Answer 33

homeostatic condition of alveolar bone

Question 34

Resorption occurs when

Answer 34

osteoblasts stimulated by RANKL to resorb bone

Question 35

OPG levels decreased w/

Answer 35

perio inflammation, stimulating resorption

Question 36

Stimulates Resorption

Answer 36

RANKL, IL-1b, TNF-a, IL-6, IL-11, IL-17, PGE2

Question 37

Inhibits Resorption

Answer 37

OPG, IL-4, IL-10, IL-12, IL-13, IFN-y

Question 38

Link between Perio and RANKL bone resorption

Answer 38

proinflammatory mediators protect host from microbes but also stimulate osteoblasts, fibroblasts, T-cell, and B-cells to produce RANKL RANKL activates osteoclasts If unstopped/unabated, host response leads to irreversible destruction of alveolar bone