Perio Ch. 13: Host inflammatory response to dental biofilm

The presence of periodontal pathogens alone are

not sufficient enough to cause the destruction seen in periodontitis

What is the inflammatory response?

activated by the immune system system in response to injury or offending agent, traps them and starts to heal tissue, not meant to be activated for a long time

When tissue does not go through resolution phase the result is

chronic inflammation

What is the host immunoinflammatory response triggered by?

the presence of microbial biofilm and its response causes nearly all the destruction seen in perio disease

What is the cause of nearly al the destruction seen in periodontitis?

the body's response to the periodontal pathogens

Immunoinflammatory response

activation of leukocytes and release of pro and anti-inflammatory mediators

The way the body responds to periodontal pathogens is known as the

host response

the prime purpose of the human immune system is to

defend the life of the host

The body's defenses are employed to save the

life of the host, not to preserve the tooth or its supporting periodontal tissues

What are factors enhancing microbial challenges?

virulence factors

Virulence factor

all the mechanisms that enable biofilm bacteria to colonize and damage tissues

Virulence factors may be either:

structural characteristics of bacteria or substances produced by bacteria

Examples of virulence factors

presence of lipopolysaccarides, ability to invade tissues, ability to produce enzymes

Virulence factors: lipopolysaccaride

mature biofilm contains gram negative bacteria which have LPS on their outer membrane and LPS initiatives inflammation in periodontal tissues

host response to microbes involves cells including:

neutrophils, antigen presenting cells, T and B lymphocytes, fibroblasts, epithelial cells

Acute inflammation

has host protective effect, first line of defense, replaces host cells and removes harmful stimuli, created favorable environment for tissue repair

Resolution of Acute Inflammation Following Removal of Microbial Challenge

acute inflammation and resolution most work together and effectiveness of acute inflammation determines whether inflammation is favorable or detrimental

What is catabasis?

return to homeostasis after inflammatory process - complicated process

pro inflammation mediators in periodontitis:

prostaglandins, thromboxanes, prostacyclins and leukotrienes

periodontitis lipid mediators are associated with

recruitment of neutrophils, destruction of connective tissue matrix and resorption of alveolar bone

Over-recruitment or overactivity of PMNs can amplify the

inflammatory process

In catabasis, pro-resolving lipid mediators work in programmed systemic process to

terminate neutrophils to the site, stimulate macrophages to remove dead cells, promote antibacterial activities, promote tissue repair and regeneration

Chronic inflammation

Acute inflammation progresses to uncontrolled, unresolved chronic inflammation - can lead to permanent tissue damage

What is the most numerous perio pathogen that we see?

P. gingivalis

Virulence factor: ability to invade tissue

penetration of bacteria into host tissues allows bacteria to escape host defense mechanisms

Which pathogens can invade most tissues?

P. gingivalis and A.A (both have LPS on cell membrane)

gram negative bacteria tend to be

anaerobic (no oxygen)

Virulence factors: ability to produce enzymes

several bacteria produce enzymes such as collagenases and proteases that can directly degrade host structures in the periodontium

what do collagenases do?

break down collagen

What do proteases break down?

proteins

Certain factors can modulate the hosts susceptibly to periodontal disease such as

genetic factors, environmental factor and acquired factors

genetic factors

age sex etc - non modifiable

environmental factors

smoking - modifiable

acquired factors

diabetes (can be modifiable if uncontrolled and non modifiable if controlled)

Mediators =

the middlemen

What are the mediators?

biochemical sent by host cells to activate the inflammatory response

Inflammatory mediators of importance

cytokines, prostaglandins, matrix mallatoproteinases (MMP's)

First response are

neutrophils which then recruit leukocytes and phagocytes

Biochemical mediator: cytokine

allows cells to talk, many of body cells release cytokines in response to tissue injury or bacteria, signal the immune system to send more phagocytes

Cytokines that are important in periodontitis include:

IL-1 IL-6 IL-8 and TNF -alpha

Cytokines are produced by

neutrophils, macrophages, B cells, epithelial cells, gingival fibroblasts and osteoblasts

What is the function of cytokines?

bind to specific cell surface receptors on target cells and increases vascular permeability, can initiate and perpetuate irreversible tissue destruction in chronic inflammation

Biochemical mediatory: prostaglandins

powerful inflammatory mediators derived from fatty acids that have a large role in initiation of bone destruction in periodontitis which triggers osteoclasts, increase permeability and dilation of blood vessels to promotion increased movement of immune cells to infection site, causes overproduction of destructive MMP enzymes

Important prostaglandins include

D E F G H and I - prostaglandins PGE2 play important role in destruction in perio

What are a major source of PGE's?

macrophage

metalloproteinases role in chronic bacterial infections

without collagen the tissues of the gingiva, pal and alveolar bone degrade which results in gingival recession, pockets and mobility

Biochemical mediators: matrix metalloproteinases

12 different enzymes that break down the connective tissue matrix ; in health they facilitate normal turnover of connective tissue matrix

Overacitvity of MMP's are tightly regulated by

tissue inhibitors of matrix metalloproteinases (TIMP) - helps maintain balance and health of connective tissue

MMPs effects in chronic infection and inflammation:

cytokines and prostaglandins stimulate leukocytes and fibroblasts to release MMPs and releases excessive amounts with intense inflammation

What can inhibit MMP activity?

periostat - 20mg doxycycline

What are a major source of MMP's in periodontitis ?

PMN's and gingival fibroblasts

What is our best response to removal of biofilm ?

mechanical removal NOT antibiotics

some people with abundant biofilm exhibit only

mild disease

others with light biofilm

suffer severe disease

untreated gingivitis does not always

progress to periodontitis ; everyone infected with pathogens will not get periodontal disease

The bone remodeling cycle

osteoclasts - bone resorbing

osteoblasts - bone building

4 phases of bone homeostasis:

resorption, reversal, formation, resting

resorption

break down the bone creating an erosion cavity

reversal

attraction of osteoblasts to build bone

formation

new mineralized bone develops

resting

lengthy, waiting period until next cycle

What is RANKL?

cytokine that activates osteoclasts and promotes bone resorption that is produced and released on the membrane of an osteoblast

Full name of RANKL

receptor activator of nuclear factor kappa - b ligand

Ligand is a

receptor

When does bone resorption occur?

RANKL binds to RANK expressed on the cells surface of osteoclastic precursor cells which then stimulates the precursor cells to differentiate into mature osteoclasts

What is osteoprotegerin (OPG) ?

another protein signaling molecule produced by osteoblasts but unlike RANKL it protects bone from excessive resorption by binding to RANKL which blocks the binding of RANKL to RANK this preserves bone and stablizes the bone remodeling process

Bone metabolism

homeostatic condition occurs when the body can stabilize levels of alveolar bone only when RANKL and OPG are in balance

osteoprotegerin

produced by osteoblasts

bone resorption occurs when

osteoclasts are stimulated to resorb alveolar bone

when the OPG to RANKL levels are out of balance what happens?

osteoclasts resorb alveolar bone

Homeostatic conditions exist when

levels OPG and RANKL are in balance in periodontal tissues and alveolar bone levels stay stable

What are the 4 phases of microscopic changes in periodontal disease?

1. initial lesion - bacterial accumulation

2. early lesion - early gingivitis

3. established lesion - established gingivitis

4. advanced lesion - periodontitis

current theory of pathogenesis: Gingival health is associated with __________ biofilm

symbiotic

current theory of pathogenesis: traditional pathogenic bacteria accumulate when bacterial biofilm is

not disturbed

current theory of pathogenesis: in susceptible individuals what happens?

dysbiotic biofilm activates host response to produce excessive cytokines, MMPs, which lead to collagen breakdown, bone resorption and tissue damage

Risk factors are associated with dysbiotic dental biofilm communities and can:

alter host immunoinflammatory response and impact individuals susceptibility

which prostaglandin is most responsible for alveolar bone destruction?

PGE2

What activates osteoclasts?

RANKL

Who created the histologic stages of development in periodontal disease?

page and Schroeder 1976

Initial lesion/bacterial accumulation

bacteria colonization near gingival margin, increased vascular dilation and crevicular fluid, neutrophils migrate to the sulcus and at this stage gingiva looks healthy and changes that are occurring are microscopic, initial biofilm accumulation is supra gingival, gram negative bacteria activate complement system

Early gingivitis gingivitis/early lesion

biofilm overgrowth phase, bacteria penetrate connective tissue, more neutrophils attracted to the site and release more cytokines causing more destruction of connective tissue, can see erythema and swelling clinically, good self care can return to health, sucular epithelium and connective tissue most affected and starting forming epithelial ridges and junctional epithelial cells start to proliferate , can return to health w good self care

Initial lesion develops ________ days after accumulation

2 to 4

increased gingival crevicular fluid can cause a

pseudopocket

Early lesion develops ______ days after the accumulation of biofilm.

4-7

Established gingivitis/established lesion

subgingival plaque phase, biofilm extends subgingival and disrupts attachment of the coronal most portion of the JE, macrophages and lymphocytes are most numerous in the connective tissue and neutrophils continue to fight in the sulcus, host cells produce more toxic chemicals - cytokines, pge2 and mmp's, transforms into deeper pocket, collagen lost, deeper epithelial ridges

It is impossible to know when established gingivitis

will progress to periodontitis bc it is still histologic

Established gingivitis appears ______ days after bacterial accumulation

21

established gingivitis can be reversed with

periodontal instrumentation and pt education and home-care

Advanced lesion/periodontitis

tissue destruction phase ; irreversible damage to the periodontium which is the hallmark of periodontitis, Tissue destruction becomes the main outcome of the immune system response.

The immune response becomes chronic; intense inflammation begins to harm the periodontium.

Cytokines, PGE2, and MMPs destroy the connective tissue, PDL fibers & bone - pocket, biofilm growing laterally and apical on root surface

Advanced lesion phase characterized by:

BOP, pockets, destroyed PDL, been loss, furcation and mobility

Factors influencing host's failure to control bacterial challenge:

abnormal PMN function (HIV), acquired, environmental and systemic factors, virulence of bacteria in biofilm