TARRSON FAMILY ENDOWED CHAIR IN PERIODONTICS

UCLA SCHOOL OF DENTISTRY

Presents Presents
Dr. E. Barrie Kenney
Professor & Chairman
Section of Periodontics
E. Barrie Kenney B.D.Sc., D.D.S., M.S., F.R.A.C.D.S.
Tarrson FamiIy Endowed Chair in Periodontics.
Professor and Chairman Division of Associated CIinicaI SpeciaIties UCLA
SchooI of Dentistry Pathogenesis of
PeriodontaI Disease
ingivitis is widespread with 54 percent of the popuIation
13 years or oIder having bIeeding on probing.
The most common type of gingivitis is caused by DentaI PIaque products
such as Exotoxins and Endotoxins initiating infIammation of gingivaI
tissues.
'TS
SubgingivaI bacteriaI biofiIm (pIaque) initiates gingivaI
infIammation (ingivitis).
This in some patients may extend apicaIIy to become periodontitis
ROLE OF
PLAQUE
The first bacteria that form a biofiIm on cIeaned tooth surfaces are
Streptococci species (ram positive cocci)
ithin two days ram negative bacteria aIso appear in the subgingivaI
biofiIm and gingivaI infIammation begins
Exotoxins are secreted by many ram positive and ram
negative bacteria.
Endotoxins are onIy seen with ram negative bacteria
ExampIes of Exotoxins produced by sub gingivaI bacteria
Further exampIes of Exotoxins
Some Exotoxins directIy inhibit the protective effects of infIammatory
ceIIs and heaIing
BacteriaI Leukotoxin from some strains of ActinobacciIus
Actinomycetemcomitans (A.a) cause necrosis and apoptosis of
Ieukocytes
Endotoxin is an important cause of gingivaI tissue damage by ram
negative bacteria in the subgingivaI biofiIm.
Endotoxins directIy destroy gingivaI ceIIs. They enhance tissue
destruction due to stimuIation of the immune response associated with
gingivaI infIammation
STMULATO OF
MMUE
RESPOSE
EstabIished ingivitis present in Iower incisor region.
Signs of acute infIammation, redness, and sweIIing
SubgingivaI bacteria initiate ingivitis by their Exotoxins and Endotoxins
changing the epitheIiaI ceIIs Iining the gingivaI crevice
Scanning EIectron Microscopic view of a heaIthy gingivaI suIcus.
The epitheIiaI ceIIs form an intact surface which acts as a barrier to
subgingivaI bacteria and their toxins.
BacteriaI Exotoxins such as HyaIuronidase destroy the
interceIIuIar connections between epitheIiaI ceIIs Iining
the gingivaI suIcus.
This is one of the first stages of initiation of gingivitis
The barrier effect of epitheIiaI ceIIs is reduced by a widening
of interceIIuIar spaces.
This aIIows penetration of other bacteriaI products
through the epitheIium to the underIying gingivaI
connective tissue
Transmission EIection Micrograph of epitheIiaI ceIIs from a heaIthy
gingivaI suIcus with narrow interceIIuIar spaces.
Transmission EIection Micrograph of an epitheIiaI ceII from earIy
ingivitis.
The interceIIuIar spaces are widened and the epitheIiaI barrier has
become more porous.
Scanning EIectron Micrograph of epitheIiaI from EarIy ingivitis.
CeIIs of gingivaI suIcus showing normaI areas of quiescence, other areas
of widened interceIIuIar spaces with Ieukocytes passing out from the
connective tissue.A area of normaI quiescent epitheIium.B bacteria.C
widened interceIIuIar spaces.

High powered view with obvious widened interceIIuIar spaces and hoIes
through the epitheIium.
Other bacteriaI Exotoxins such as coIIagenase can
now penetrate through the epitheIiaI ceII barrier of the
gingivaI suIcus.
This resuIt in destruction of the basement membrane and
areas of Ioss of the epitheIiaI ceII Iayer with uIcer formation.
E is area of normaI intact epitheIiaI ceIIs, U is Ioss of epitheIiaI ceIIs and
uIceration.A area of uIceration.E normaI epitheIium.
EnIargements seen beIow show direct exposure of gingivaI connective
tissue coIIagen to subgingivaI bacteria at the base of the
uIcerated epitheIium. C coIIagen fibers of connective tissue.
A E
E
C
C
Transmission EIection Micrograph of ingivitis.
Bacteria have penetrated into the connective tissue.E epitheIiaI ceII
cytopIasm BM basement membrane .C connective tissue.B bacteria.
E
B
C
BM
Bacteria Iirst contact with immune system occurs in epithelium with Langerhams
cells which process antigens.
EpitheIiaI uIceration provides a portaI for subgingivaI
bacteria and their products to the gingivaI connective
tissue.
Most subgingivaI bacteria that penetrate into connective
tissue in gingivitis do not proIiferate in the tissue.
Bacteria may now enter bIood vesseIs and cause a
bacteremia.
This is because they are anaerobic and the tissues are
aerobic.
BacteriaI products that contact gingivaI connective
tissue initiates an acute infIammatory response with
vasodiIatation, edema and poIymorphonucIear
Ieukocyte (P.M.) activation.
ingivitis is seen cIinicaIIy as acute infIammation with
redness and edema of tissues and exudates of infIammatory
fIuid from the gingivaI suIcus.
EarIy ingivitis.
There is bIeeding from the gingivaI suIcus with probing, brushing or
mastication.
This is a resuIt of epitheIiaI uIceration in the gingivaI suIcus and acute
infIammation of the connective tissue.
ingivaI bIeeding on probing is seen as earIy as the
second day of initiation of ingivitis.
BIeeding on probing is a sign of active tissue destruction.
t may persist through to the Iater stages of
Periodontitis
f ingivitis is treated, the epitheIium can heaI and bIeeding
can disappear after seven to ten days.
One of the first effects of bacteriaI contact with
gingivaI tissue is activation of Mast ceIIs
Mast ceIIs are infIammatory ceIIs of the BasophiI series of
granuIar Ieukocytes
Mast ceIIs have ToII Iike receptors which initiate prodution of vasoactive
substances such as Histamine which induce vascuIar permeabiIity and
vasodiIatation.
This vasodiIatation and increased permeabiIity of capiIIaries is associated
with edema and diapedesis of Ieukocytes from the bIood vesseIs into the
connective tissue of the gingiva.
Mast ceIIs produce other infIammatory mediators such as SIow- Reacting
Substance of AnaphyIaxis, Leukotriene C4, Tumor ecrosis factor aIpha
(TF).and L6. These activate the acute infIammatory response.
Light Micrograph of connective tissue in ingivitis vasodiIatation, edema,
and migration of Leukocytes.
'ascuIar tree of normaI gingivaI tissue.
PeripheraI vesseIs aIIow rapid movement of bIood from the arterioIes
through the capiIIaries to the venuIus.
ingiva coIor in heaIth is paIe pink
ith vasodiIatation in ingivitis terminaI circuIation is more convoIuted
so gingiva appears red and often has a purpIish coIor
'asodiIatation resuIts in more compIex pathways of bIood fIow so that
circuIation is sIowed through gingivaI tissues.
This resuIts in redness as weII as increased reduced HemogIobin giving a
purpIish coIor to the gingiva.
PoIymorphonucIear Ieukocytes (P.M..s) are the characteristic dominant
infIammatory ceIIs of acute infIammation of the gingiva
n ingivitis PMs and edema fIuid appear in the connective tissue and
pass through the damaged epitheIiaI ceIIs into the gingivaI suIcus and
then into the mouth. PMS move to the L8 chemoattractant seen in
junctionaI epitheIium and are attached by CAM 1-TERCELLULAR
ADHESO MOLECULE from Langerhams ceIIs.
ngivaI fIuid is an indicator of gingivaI infIammation and it carries
PMSand antibodies into the pocket
ne to two percent oI PMNS pass through
junctional epithelium each day.
Scanning EIectron Micrograph of PM (L) passing from connective tissue
(CT) through epitheIium (E).
L
l
L
C
L
E
T
PMs are abIe to migrate through tissue towards
chemotaxic substances such as peptides from
bacteria, saIiva, Endotoxin,L8 and activated
compIement.
PMs are abIe to enguIf bacteria by a process of
phagocytosis.
This chemotaxis brings PMs out of bIood vesseIs
and they accumuIate in connective tissue and
epitheIium and eventuaIIy pass into the pocket to be
moved by gingivaI fIuid into the mouth.
EnguIfed bacteria are destroyed by oxidative production of
toxic reduced oxygen metaboIites such as superoxide
anion. on oxidative IysosomaI enzymes such as defensins
and proteases found in IysosomaI granuIes,
aIso kiII bacteria .n the increasing anaerobiosis of the
pocket oxidative kiIIing is impaired.
PMs IysosomaI granuIes can destroy bacteria intraceIIuIarIy.
They can be reIeased and cause connective tissue and bacteriaI
destruction extraceIIuIarIy.
Light microscopic view of ingivitis.
PMs seen in connective tissue and migrating through epitheIium into
gingivaI suIcus.
High power view of PMs in gingivaI fIuid of gingivaI crevice
Scanning EIectron Micrograph of PMs passing through epitheIium.
ote bacteria attached to PMs in process of being phagocytosed
High power view of PM and bacteria attached undergoing phagocytosis.
B bacteria
B
Light Microscopic view of PMs from gingivaI fIuid showing evidence of
phagocytosis.
hite spheres inside PMs have been enguIfed.
PMs form a protective Iayer in regions where epitheIium of the gingivaI
suIcus has been disrupted in ingivitis
CIinicaI exampIe of estabIished ingivitis with emphasis on the acute
infIammatory reaction
The BasophiI series are seen in ingivitis as Mast ceIIs, eutrophiIs as
PMs.
EosinophiIs are not significant contributors to pIaque induced ingivitis
nfIammatory ceIIs of the AgranuIar series of Leukocytes are aIso seen in
gingivitis
Monocytes become Macrophages in infIamed gingivaI tissue.
They exhibit chemotaxis, phagocytosis, enzyme production and bacteriaI
kiIIing simiIar to PMs. They are activated by bacteriaI products Iike
LPOPOLYSACCHARDE LPS.
They aIso produce cytokines such as L1 and TUMOR ECROSS
FACTOR TF which have a wide infIammatory infIuence as weII as
stimuIating osteocIast proIiferation,differentiation and activation.
PROSTALAD E PE another infIammatory and osteocIast activator
is aIso secreted in response to L1,TF And LPS.
Macrophages interact with Lymphocytes by assisting in BacteriaI Antigen
presentation to Lymphocytes which then produce specific antibodies (B
ceIIs)or cytokines (T ceIIs). Macrophages then cIean up the destroyed
bacteriaI remnants by phagocytosis.
As ingivitis deveIops the initiaI acute infIammatory response continues
and a chronic infIammatory response is added.
Lymphocytes and capiIIary proIiferation characterize this chronic
infIammation.
B ceIIs are Lymphocytes derived from Bone Marrow and produce
antibodies to bacteriaI antigens.
T ceIIs are Iymphocytes derived from the Thymus and initiate ceII
mediated immunity by producing Iymphokines
B ceIIs interact with macrophages in gingivaI tissue and become pIasma
ceIIs which produce antibodies.
There are aIso B ceIIs series that carry the memory of a particuIar antigen
and can quickIy produce antibodies, this memory is dependant on
interactions with T ceIIs.
PIasma ceIIs (B ceIIs) produce immunogIobuIins within gingivaI tissue
which bind to and inactivate bacteriaI antigens incIuding Exotoxins.
Antibody - Antigen compIexes aIso activate CompIement
PIasma ceIIs produce a variety of immunogIobuIins with each one being
specific for a particuIar bacteriaI antigen and have memory to become
quickIy activated.
Patients with periodontaI disease have high serum IeveIs of g specific
for pIaque bacteria.
Activation of compIement is another part of the immune response seen in
ingivitis
Activation of compIement produces moIecuIes such as
C2a C5b that are cytotoxic, increase vascuIar
permeabiIity and are chemotactic for PMs and
Macrophages.
Activation of compIement can occur directIy due to antibody
antigen compIexes.
BacteriaI inactivation by antibodies is aIso enhanced
by C3b an opsonin from compIement which coats
bacteria and enhances phagocytosis.
ndirectIy compIement is activated by Endotoxin,
poIysaccharides and other bacteriaI products.
Mast cells are activated by C3a and C5a.
T Lymphocytes are very common in gingivitis. They interact with bacteriaI
Antigens processed by Macrophages.
T ceIIs then undergo proIiferation and differentiation into the different
types of T ceIIs.
n EarIy gingivitis, T ceIIs are the dominant Lymphocytes, but eventuaIIy
B ceIIs dominate.T ceIIs have dense round nucIei with very IittIe
cytopIasm.B ceIIs (pIasma ceIIs) are Iarger than T Iymphocytes and have
an eccentric Iighter staining nucIeus with an aImost equaI sized
cytopIasm
EIectron Micrograph of pIasma ceII (B ceII) with eccentric nucIeus and
prominent endopIasmic reticuIum for protein antibody production
Activated T Lymphocytes produce cytokines. These are bioactive
moIecuIes that enhance infIammation and aIso can cause damage to
gingivaI and periodontaI ceIIs.
Two important cytokines are nterIeukin-1 (L-1) and Tumor ecrosis
Factor (TF).
ith chronic infIammation gingivaI bIood vesseIs and infIammatory ceIIs
proIiferate into the areas of destroyed connective tissue.
EstabIished ingivitis around Iower incisors.
Acute infIammatory changes are superimposed on chronic infIammation
charges.
The combined acute and chronic infIammation seen in ingivitis and
periodontitis is destructive of bacteria.
t aIso causes damage to the connective tissue of gingiva and the
periodontaI tissues
Another mechanism of breakdown of connective tissue in PeriodontaI
disease invoIves Matrix MetaIIoproteinases (M.M.P).
These are produced by PMs, Macrophages ,FibrobIasts and EpitheIiaI
ceIIs. MMP8comes from PMS MMP1 comes from resident ceIIs.
ingival Metalloproteins can be reduced by systemic administration
oI low dose Doxycycline--20mg.every 12 hours .This is the basis Ior
the use oI Periostat to treat Periodontal disease,
ExampIes of MMP
The bacteriaI induced infIammation of ingivitis can
spread apicaIIy and invoIves the destruction of
connective tissue of the Periodontium incIuding bone.
The damaged epitheIium of the gingivaI suIcus proIiferates
apicaIIy.
This is Periodontitis
As Ioss of attachment of connective tissue fibers to
cementum occurs the pocket epitheIium migrates to Iine the
root surface.
Light microscope view of Iower incisor with Periodontitis.
ingivaI nfIammation has spread apicaIIy and bone destruction has
occurred.
There is apicaI migration of epitheIium causing attachment Ioss and
increase of pocket depth.
High power view with epitheIium E migrated apicaI to bone crest B, and
infIammation causing bone Ioss
B
E
OSTEOBLAST -
OSTEOCLAST
TERACTO
Bone Loss Due to
nhibition of OsteobIasts,
StimuIation of
OsteocIasts.
High power view of osteocIast causing bone Ioss in periodontitis
Macrophages produce prostagIandin E (PE) and (L-1) and Iymphocytes
produce nterIeukin-1 (L-1) which activate osteocIasts by interacting with
osteobIasts.
The mechanisms causing bone Ioss in Periodontitis
are not weII documented.
Activated osteocIasts destroy the inorganic bone
components by reIease of acid hydroIases.
Bone destruction is a resuIt of osteobIasts or
infIammatory ceIIs signaIing osteocIasts activation via
cytokines such as L-1 and TF and ProstagIandins
(PE).
MMPs from osteobIasts destroy the organic coIIagenous
components.
PossibIe mechanisms of bone Ioss in Periodontitis
incIude:
Other mechanisms of bone Ioss:
Suppression of osteobIasts by infIammation with
Iowered bone production
Up reguIation of cytokine and PE secretion by
infIammatory ceIIs and
osteobIasts
Loss of coIIagen attachment with reduction of tensiIe
forces on bone
Direct bacteriaI toxicity on osteobIasts and coIIagen
Up reguIation of MMPs from infIammatory and connective
tissue ceIIs.
CIinicaI exampIe of Periodontists with emphasis on chronic infIammatory
changes.
There were 7mm pockets after initiaI therapy.
Same case being treated with fIap surgery. ote bone Ioss.
Radiograph of advance Periodontitis with evidence of interproximaI bone
Ioss
Same case with fIap surgery. Extensive bone Ioss due to pIaque induced
Periodontitis.
For further information use the text Carranzas CIinicaI
PeriodontoIogy
9
th
Edition
B Saunders 10. 2002
Chapter 7
mmunity and nfIammation
Chapter 8
MicrobiaI nteractions with the host in PeriodontaI
Diseases
Chapter 9
MoIecuIar BioIogy of the host-microbe interaction in
PeriodontaI Diseases.
Chapter 16
ingivaI nfIammation
Chapter 17
CIinicaI features of ingivitis
Chapter 22
The PeriodontaI Pocket