Pathogenesis of

periodontal disease-
Host Response to
Periodontal
Pathogens
 the word pathogenesis is defined as “the origination and development
of a disease.

 ” Essentially, this refers to the step-by-step processes that lead to the

development of a disease and that result in a series of changes in the
structure and function , in this case, the periodontium.

 In broad terms, the pathogenesis of a disease is the mechanism by

which a causative factor (or factors) causes the disease.

 The word itself is derived from the Greek roots pathos (meaning
“suffering”) and genesis (meaning “generation or creation”).
 it is clear that the bacteria in dental plaque are the cause of both
gingivitis and periodontitis,

 however, not all individuals with gingivitis will progress to

periodontitis, and not all individuals with periodontitis will progress to
tooth loss.

 The development of gingivitis can be considered to be a

well‐controlled immunologic response.

 However, in some people, due to environmental factors, their own

innate susceptibility or both, there is loss of connective tissue and
bone, apical migration of the junctional epithelium, and development
of periodontitis
 Over the past two decades it has become established that
periodontitis results from the interaction of the host’s defense
mechanisms with biofilms containing complexes including
Porphyromonas gingivalis,Tannerella forsythia, and Treponema
denticola.

 Aggregatibacter actinomycetemcomitans has been implicated in

aggressive periodontitis in some populations.
 it is now recognized that many people carry the organisms without
manifesting disease progression.

 In this context, it is clear that most people are in balance with their
biofilm for most of the time and it is only when this balance is
disturbed that disease results.

 Such disturbances may occur as a result of environmental

influences leading to an opportunistic increase in the numbers of
organisms, or a depression of the host’s defense mechanisms or
indeed both.
The presence of periodontal pathogens alone is
insufficient to cause the tissue destruction seen in
periodontitis .

 It is the body's response to the periodontal

pathogens that is the cause of nearly all the
destruction seen in periodontitis .
The way that the body responds to periodontal
pathogens is known as the host response .

 The prime purpose of the human immune system

defend the life of the individual ( host ) .
In the instance of periodontal disease , the immune
system strives to defend the body against periodontal
pathogens .
The body's defenses are employed to save the life of
the host , NOT to preserve the tooth or its
supporting periodontal tissues .
Inflammatory Responses in the Periodontium

Microbial Virulence Factors Host-Derived Inflammatory Mediator

 The molecules that play a role in the pathogenesis of

periodontitis can be broadly divided into two main groups:
1. those derived from the subgingival microbiota (i.e., microbial
virulence factors)
2. and those derived from the host immune–inflammatory
response.
 In terms of the relative importance of each, it is now clear that
most of the tissue breakdown results from the host’s
inflammatory processes.
 Microbial Virulence Factors

 The subgingival biofilm initiates and perpetuates inflammatory

responses in the gingival and periodontal tissues.

 The subgingival bacteria also contribute directly to tissue damage

by the release of noxious substances, but their primary importance
in periodontal pathogenesis is that of activating immune–
inflammatory responses.

 that in turn, result in tissue damage, which may well be beneficial

to the bacteria located within the periodontal pocket by providing
nutrient sources.
Lipopolysaccharide

 Lipopolysaccharides (LPSs) are large molecules composed of a

lipid component (lipid A) and a polysaccharide component.

 They are found in the outer membrane of gram-negative

bacteria.

 They act as endotoxins (LPS is frequently referred to as

endotoxin).

 they elicit a strong immune responses.

 The interaction of the immune system cells (as macrophages,
monocytes, dendritic cells, and B cells) with LPS triggers a series of
intracellular events.

 The net results of which are the increased production of

inflammatory mediators and the differentiation of immune cells
(e.g., dendritic cells) for the development of effective immune
responses against the pathogens.

 LPS is of key importance for initiating and sustaining inflammatory

responses in the gingival and periodontal tissues
 lipoteichoic acid

 A component of gram-positive cell walls.

 stimulates immune responses, although less potently than LPS.

 Both LPS and lipoteichoic acid are released from the bacteria present
in the biofilm and stimulate inflammatory responses in the tissues,
thereby resulting in increased vasodilation and vascular permeability,
the recruitment of inflammatory cells by chemotaxis, and the release
of proinflammatory mediators by the leukocytes that are recruited to
the area.
 Bacterial Enzymes and Noxious Products

 Plaque bacteria produce several metabolic waste products that contribute

directly to tissue damage.

 These include noxious agents such as ammonia (NH3) and hydrogen

sulfide (H2S), as well as short-chain carboxylic acids such as butyric acid
and propionic acid.

 These acids are detectable in GCF and are found in increasing

concentrations as the severity of periodontal disease increases.

 These substances have profound effects on host cells (e.g., butyric acid
induces apoptosis in T cells, B cells, fibroblasts, and gingival epithelial
cells).
 The short-chain fatty acids may aid P. gingivalis infection through
tissue destruction, and they may also create a nutrient supply for the
organism by increasing bleeding into the periodontal pocket.

 The short-chain fatty acids also influence cytokine secretion by immune

cells.
 Plaque bacteria produce proteases, which are capable of
breaking down structural proteins of the periodontium such as
collagen, elastin, and fibronectin.

 Bacteria produce these proteases to digest proteins and thereby

provide peptides for bacterial nutrition.

 Bacterial proteases disrupt host responses, compromise tissue

integrity, and facilitate the microbial invasion of the tissues
 Microbial Invasion

 Microbial invasion of the periodontal tissues has long been a contentious

topic.

 In histologic specimens, bacteria (including cocci, filaments, and rods)

have been identified in the intercellular spaces of the epithelium.

 Periodontal pathogens such as P. gingivalis and Aggregatibacter

actinomycetemcomitans have been reported to invade the gingival tissues
including the connective tissues.

 Fusobacterium nucleatum can invade oral epithelial cells, and bacteria

that routinely invade host cells may facilitate the entry of noninvasive
bacteria by coaggregating with them
 The clinical relevance of these various findings is unclear

 more recent studies have reported that although species such as

P. gingivalis can be found located within the tissues, they are
mainly within the epithelium, and it is unusual for the bacteria to
reach the connective tissue until extensive tissue destruction has
occurred, and even then it is as a result of inflammation rather
than “invading” bacteria.
 Is bacterial invasion of the tissues a valid concept, and does it
have implications for therapy?

 Good evidence indicates that certain species of subgingival bacteria are

able to invade epithelial cells, thereby providing a shelter from the host
defense

(highlighting the important role of epithelium in host defenses by release

of cytokines to activate inflammatory responses).

 However, invasion of the deeper connective tissues by live bacteria such

as Porphyromonas gingivalis seems to occur (if it occurs!) at a much later
stage in advanced disease, probably as a result of inflammation and
resultant tissue destruction
 Reports of bacteria present in the tissues (described as a “reservoir of
infection”) have sometimes been used to justify the use of antibiotics
for treatment of periodontitis as a means to try to eliminate those
organisms that are located in the tissues and that are therefore
“protected” from mechanical disruption by root surface debridement.

 However, until the clinical relevance of the presence of bacteria in the

tissues is better defined, it is inappropriate to make clinical treatment
decisions (e.g., whether to use adjunctive systemic antibiotics) on this
premise alone.
 Host-Derived Inflammatory Mediators
 Biochemical mediators are biologically active
compounds secreted by the immune cells that activate
the body's inflammatory response .

Inflammatory mediators of importance in periodontal disease are

- Cytokines
-Prostaglandins
-Matrix metalloproteinases ( MMPs )
Cytokines

Powerful mediators produced by immune cells

 Influence the behavior of other cells

 Signal to immune system to send more

phagocytes to site of infection
 Cytokines ( cont . )

Produced by many different cells — PMNs , macrophages , B

lymphocytes , epithelial cells , gingival fibroblasts , and
osteoblasts

 Produced in response to tissue injury

 Cytokines important in periodontal disease include IL -1,

IL-6, IL-8, and TNF-alpha.
 Cytokines are small secreted proteins released by cells have a specific
effect on the interactions and communications between cells.

 Cytokine is a general name; other names include:

 lymphokine (cytokines made by lymphocytes),
 monokine (cytokines made by monocytes),
 chemokine (cytokines with chemotactic activities),
 interleukin (cytokines made by one leukocyte and acting on other
leukocytes).

 Cytokines may act on the cells that secrete them (autocrine action), on
nearby cells (paracrine action), or on distant cells (endocrine action).

 There are both proinflammatory cytokines and anti-inflammatory cytokine

 Functions of Cytokines

Recruit cells ( PMNs and macrophages ) to infection site

 Increase vascular permeability that increases movement

of immune cells into the tissues

 Can initiate tissue destruction and bone loss in

chronic infections , such as periodontal disease.
 Prostaglandins

Powerful inflammatory mediators

 Series of prostaglandins - D , E , F , G , H , I

Most cells can produce prostaglandins

Functions of Prostaglandins

Increase permeability and dilatation of blood vessels to

promote increased movement of immune cells and
complement to the infection site.

 Trigger osteoclasts - bone - consuming cells - to

destroy the alveolar bone.
Promote the overproduction of destructive MMP
enzymes.

Prostaglandins of the E series (PGE) initiate most

of the alveolar bone destruction in periodontitis.
Matrix Metalloproteinases ( MMPs )

Family of at least 12 different enzymes

 Produced by various cells of the body – PMNs,

macrophages , fibroblasts , JE cells

 Enzymes act together to breakdown connective tissue

matrix
Function of MMPs in Health

In health , MMPs facilitate normal turnover of the

periodontal connective tissue matrix .
MMPs - Chronic Bacterial Infection

MMPs are released in an attempt to kill invading

bacteria

Overproduction of MMPs results in breakdown of

connective tissue of the periodontium .
 High MMP levels result in extensive collagen destruction
in the periodontal tissues .

 Without collagen , the tissues of the gingiva , periodontal

ligament , and supporting alveolar bone degrade .

 This results in gingival recession , pocket formation , and

tooth mobility .
Recap - Host Response

 Cytokines - recruit PMNs and macrophages to the

infection site

 Prostaglandins - increase vascular permeability allowing

immune cells and complement to move to the infection site

 MMPs - facilitate normal turnover of the connective

tissue matrix
Recap - Host Response ( cont . )

Cytokines - initiate tissue destruction and bone loss

 Prostaglandins ( PGE ) -alveolar bone destruction

 MMPs - collagen destruction

Host and Bacteria
Characteristics of Host Response

The presence of periodontal pathogens does not

necessarily mean that an individual will experience
periodontitis
Some people with abundant bacterial plaque exhibit
only mild disease .
 Others with light bacterial plaque suffer from severe
disease
 Untreated gingivitis does not always lead to
periodontitis .
 Everyone infected with pathogens will not get
periodontal disease .
The Host Response

Pathogenic bacteria infect the periodontium .

 The body responds by mobilizing defensive cells .

 Cells release a series of chemicals to fight bacteria .

In Periodontal Disease

 The body's immune system causes tissue destruction in

an attempt to stop bacterial infection .

 Complex interactions between periodontal pathogens

and host response determine the onset and severity of
periodontal disease
 Bacteria colonize the tooth near
the gingival margin.
 Bacteria initiate host response.
 PMNs pass from bloodstream
into the gingival connective
tissue
 PMNs release cytokines that
destroy gingival connective
tissue , allowing PMNs to move
quickly through the tissue .
 PMNs migrate into the sulcus
and phagocytize bacteria
 Bacteria penetrate into the
connective tissue .

 More PMNs are attracted to

the site : they release more
cytokines causing more
localized destruction of the
connective tissue .

 Macrophages are recruited

to the connective tissue
They release cytokines ,
PGE2 , and MMPs .
 Established
Gingivitis – Subgingival
Plaque Phase
 Plaque biofilm extends subgingivally

 Macrophages and lymphocytes become

more numerous in the connective tissue ,
PMNs continue to fight bacteria in the
sulcus .

 Host cells produce more toxic chemicals

- cytokines , PGE2 , and MMPs .

 the attachment of the coronal- most

portion of the JE start to be disrupted
 Plaque biofilm grows along the root surface .

 The immune response becomes chronic ;

intense inflammation begins to harm
the periodontium .

 Cytokines destroy the connective tissue and

PDL fibers .

 Cytokines , PGE2 , and MMPs

destroy the connective tissue and bone .
 Mechanism of bone
destruction

 Macrophages produce cytokines , PGE2 , and

MMPs

 These mediators stimulate fibroblasts to

secrete PGE2 and MMP .

 Mediators from the macrophages and

fibroblasts result in destruction of the
connective tissue .

 PGE2 stimulates osteoclasts to resorb the

crest of the alveolar bone .
Recap - Pathogenesis

 Periodontal disease is a bacterial infection of the

periodontium .

 The presence of bacteria , however , does not

necessarily mean that an individual will experience
periodontitis .
 The body responds to periodontal pathogens by
mobilizing defensive cells and releasing chemicals to
combat the bacteria .

 This body defense mechanism is referred to as the host

defense
 The microscopic changes in the periodontium have 4
distinct phases:

- Early bacterial accumulation phase (initial stage)

- Early gingivitis - plaque overgrowth phase
- Established gingivitis - subgingival plaque phase
- Periodontitis - tissue destruction phase
 The junctional epithelium migrates apically along the root
surface into the collagen-depleted areas to maintain an
intact epithelial barrier.

 Osteoclastic bone resorption starts, and the bone retreats

from the advancing inflammatory front as a defense
mechanism to the prevent the spread of bacteria into the
bone.
Periodontitis
 Recap - Host Response

 For the periodontium to remain healthy , the

bacterial infection must be controlled so as not to
trigger a chronic , exaggerated host immune
response .

 The body's immune response to the bacteria causes

most of the tissue destruction in the periodontal
tissues.
THANK YOU