Chap 13 Host Repsonse PART 1

Inflammatory Response

Activated by immune system in response to offending agent or injury

• Traps offending agents or starts healing injured tissue 

• Not meant to be activated for long time 

• When tissue does not go through resolution phase, result is chronic inflammation—destruction of the periodontum (when something should not be there REBOUST), tissue can NOT repair or resolve

Periodontal Disease

• Biofilm-induced infection that precipitates complex immunoinflammatory response, Multiple factors can cause disease, Biofilm alone can not cause the disease,

• Presence of periodontal pathogens alone insufficient to cause tissue destruction seen in periodontitis

• Host immunoinflammatory response, triggered by presence of microbial biofilm, is direct cause of nearly all destruction seen in periodontal disease

Inflammatory Response and Resolution: image

Image: 2 pathways

1. Biofilm microbial invasion to the host and triggers - Acute inflammation( reversable

2. Chronic inflammation- permanent tissue damage

Factors Enhancing the Microbial Challenge:

Virulence Factor?

Primary Factor (3)

Virulence factor ?

• Mechanisms that enable biofilm bacteria to colonize and damage tissues of periodontium- how pathogenic colonizing

• Factors Can be Proteins on cell membrane, Toxins substances called endotoxins

Primary virulence factors:

1. KNOW*** Presence of lipopolysaccharide (LPS) (Activation of the complement pathway get immune system involved and go after the bacteria)

• BECAUSE OF Gram negative bacteria in mature is a lot more pathogenic because of LPS( endotoxin) it can initate the inflammtion process

2. Ability to invade host tissues, allow bacteria to escape this host defense

3. Ability to produce enzymes(collagene)

Factors Modulating the Host Immunoinflammatory Response

Genetic factors?

• Ex?

Genetic factors

• Affect formation of biochemical mediators >> impact host’s susceptibility to periodontal disease

Example: Papillon-Lefèvre syndrome (genetic origin)

Factors Modulating the Host Immunoinflammatory Response

• Acquired factor?

• Decreases?

• Increases ?

Acquired factors

Example: diabetes mellitus: known risk factor for periodontal disease >>significant effect on the immune & inflammatory responses

• Decreases PMNs

• Increases TNF-a, IL-1b & PGE levels

Environmental factors? 

Example: tobacco smoking: known risk factor for periodontal disease >> significant effect on the immune & inflammatory responses

• Decreases PMNs phagocytic activity

• Decreases vascularity

• Microbial shift to pathologic bacteria

Acute Inflammation (6 Types of cells involve) ?

Host response to microbes involves cells including:

1. Inflammatory cells

2. PMNs

3. Antigen-presenting cells

4. T- and B- lymphocytes

5. Fibroblasts

6. Epithelial cells

Acute inflammation has host-protective effect: 4 effects?

Must dampen after microbial challenge eliminated

1. First line of defense against microbial invasion

2. Eliminates harmful stimuli

3. Replaces injurious host cells

4. Creates environment favorable to tissue repair

Resolution of Acute Inflammation Following Removal of Microbial Challenge: 

• Effectiveness?

 Acute inflammation and resolution must work together

• Effectiveness of acute inflammation determines whether inflammation favor or detrimental

• Recent studies indicate resolution of inflammation and return to noninflammatory state is actively regulated biologic process

Catabasis?

• It is what?

• Proinflammation mediators in periodontitis ex?

Return to homeostasis after inflammatory process

• Thought to be biologic process just as complicated as onset of inflammation

Proinflammation mediators in periodontitis:

• Prostaglandins, thromboxanes, prostacyclins, and leukotrienes

Catabasis:

• Periodontitis lipid mediators associated with?

• Over-recruitment or overactivity of PMNs can?

Periodontitis lipid mediators associated with:

• Recruitment of PMNs

• Destruction of connective tissue matrix

• Resorption of alveolar bone

Over-recruitment or overactivity of PMNs can amplify inflammatory process

If host unable to tamp down inflammation then its called? 

• Can have pathologic effects on? 

If host unable to tamp down inflammation soon after removal of microbial challenge:

• Acute inflammation progresses to uncontrolled, unresolved chronic inflammation

• Can have pathologic effects on host tissue

Inflammatory Biochemical Mediators of the Host Response:

• “Middlemen” sent by?

• Important biochemical mediators (3)?

Def

• In response to bacterial challenge, host immune cells secrete biologically active compounds >> activate the body’s inflammatory response

• “Middlemen” sent by host cells to activate inflammatory response

Important biochemical mediators:

1. Cytokines

2. Prostaglandins (PG)

3. Matrix metalloproteinases (MMPs)

1. Cytokines:

• what is it?

• Released by?

• 2 main things it does?

• Produced by (6)

What is it: Powerful regulatory proteins released by host immune cells that influence behavior of other cells

• Transmit information or signals between cells

• Alert and activate immune system for help

Produced by

1. PMNs,

2. macrophages,

3. B-cells,

4. epithelial cells,

5. gingival fibroblasts,

6. osteoblasts

1. Cytokines Functions & Key Periodontist

• 4 functions?

• Key cytokines in periodontitis- 4 Types

Function to:

1. Recruits cells (PMNs and macrophages) to infection site

2. Bind to specific cell surface receptors on target cells

3. Increase vascular permeability – increases movement of immune cells of site of infection

4. Can initiate and perpetuate irreversible tissue destruction and bone loss in chronic inflammatory diseases

Key cytokines in periodontitis:

1. Interleukin-1 (IL-1β)

2. Interleukin-6 (IL-6)

3. IL-8

4. Tumor Necrosis Factor – (TNF-α)

2. Prostaglandins:

• What is?

• Important prostaglandins- ( start from d…6 letters)

• Prostaglandins of E series play huge role in?

• Macrophage: major source of PGEs

Def:

• Powerful biochemical mediators derived from fatty acids expressed on surface of most cells

Important prostaglandins:

• Prostaglandins D, E, F, G, H, and I

Prostaglandins of E series :

• (PGEs) play important role in bone destruction in periodontitis

Macrophage a major source of PGEs

• Also produced by PMNs and gingival fibroblasts

2. Prostaglandins Functions:

• Increase? 

• Trigger? 

• Promote? 

Functions: 

• Increase permeability and dilation of blood vessels 

• Trigger osteoclasts to destroy alveolar bone 

• Can promote overproduction of destructive MMP enzymes

3. Matrix Metalloproteinases (MMPs)

• Proteolytic enzymes breaksdown:

• Produced by (4):

• Major source of MMPs in Periodontitis:

MMPS IS:

• Family of at least 12 proteolytic enzymes that breakdown connective tissue matrix

Produced by

1. PMNs

2. macrophages,

3. gingival fibroblasts

4. junctional epithelial cells

Major source of MMPs in Periodontitis

1. PMNs

2. Gingival fibroblasts

MMPs Effects in Health and Chronic Infection: 

In Health

• Facilitate

• Overactivity of MMPs tightly regulated by? 

• MMP-TIMP balance helps the? 

Health 

1. Facilitate normal turnover of periodontal connective tissue matrix 

2. Overactivity of MMPs tightly regulated by host-derived tissue inhibitors of matrix metalloproteinases (TIMP)

3. MMP-TIMP: balance helps maintain integrity and health of connective tissue

Current Theory of Pathogenesis Image

1. Gingival health associated with symbiotic biofilm

• Mediated by proportionate immunoinflammatory response

2. Traditional pathogenic bacteria accumulate when bacterial biofilm not disturbed

• Interferes with normal tissue function and host response

• Balance remains stable in people not susceptible

3. In susceptible individuals, dysbiotic biofilm activates host response to produce excessive cytokines, reactive oxygen species, and MMPS, leading to:

• Collagen breakdown

• Bone resorption

• Periodontal tissue damage

Current Theory of Pathogenesis

1.  Removal of bacterial biofilm, 

2.  Risk factor- Alter host, Impacts what? 

1. Removal of bacterial biofilm can help reestablish health-promoting biofilm 

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

• Alter host immuno-inflammatory response to biofilm 

• Impact individual’s susceptibility to periodontal disease