Massimo Costalonga DMD, PhD DENT5301

Healthy
gingiva
Pathogenesis of Periodontitis
Normal
Current Thinking Tooth chrown gingival
sulcus
Gingiva is 2 to 3
millimeters
Massimo Costalonga D.M.D., Ph.D. deep
Root
Department of Developmental
and Surgical Sciences Periodontal
ligament

Alveolar bone

Advanced Background
periodontitis
Periodontal diseases:
Bleeding
Infection of the gingiva Infectious diseases that results in
Calculus chronic inflammation of the soft tissue
Gingival recession
Loss of bone surrounding the gingival pockets.
Tooth mobility
Halitosis (bad breath) Destroys the bone and soft tissue
connection between the gingiva and
the root of the tooth (Kornman 1987,
Disease that is not
reversible but ONLY Suzuki 1988)
controllable

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Massimo Costalonga DMD, PhD DENT5301

Chronic periodontitis is Cultivable

associated with a variety of microorganisms
bacterial species
Bacteriological and immunological studies
implicated a number of subgingival
organisms associated with chronic adult
periodontitis. (Red, Orange, Green, Purple
and Yellow complexes) (Socransky et al. 1997)
In advanced adult periodontitis, gram-
negative bacteria may compose 75% of the
bacteria (Robertson 1985)

Modified from Socransky S. et al. 1997

Most microorganisms are

uncultivable
Do you think we can culture
all bacteria in periodontal
pocket ?

Talk with the person next to you

about this NOW

Kumar PS et al. 2005

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Massimo Costalonga DMD, PhD DENT5301

Bacterial biofilm
16S RNA sequences separated
health and disease
Bacterial
challenge
Epithelium
Innate PMNs
Chemokines
immunity Cytokines

first

Kumar PS et al. 2005 Korman KS et al. Periodontology 2000 Vol. 14 1997, 33-53

Initial
Gingivitis How are these microbes
sensed or detected by our
Acute body?
inflammation
Talk with the person next to you
about this NOW

Korman KS et al. Periodontology 2000 Vol. 14 1997, 33-53

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Massimo Costalonga DMD, PhD DENT5301

PRRs
INNATE
Neutropenia = Low PMN counts cellular response
Monocytes/macrophages
Neutrophils
Natural Killer (NK)

Recognition of
Pathogen Associated
Molecular Patterns
(PAMPs) by Pattern
Recognition Receptors
(PRRs)
Downloaded from: Carranzas Clinical Periodontology (on 4 August 2006 06:34 PM)

IL-8 Lipid mediators

of inflammation

Increase
Increase vascular
vascular
permeability
permeability
Increase
Increase smooth
smooth muscle
muscle
contraction
contraction

Increase
Increase smooth
smooth muscle
muscle
contraction
contraction

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Massimo Costalonga DMD, PhD DENT5301

Linoleic acid in plasma membrane

Phospholipase C Inhibited by Lipid mediators of
STEROIDS

Inhibited by Inflammation Resolution

NSAID

Prostaglandins Lipoxins
Thromboxans Resolvins
Leukotrienes Protectins

T-cell and B-cell mediated immunity Toll-like receptors

in periodontal tissues
(TLRs)
INNATE
IMMUNITY
PENETRATION LYMPHOCYTE
MICROBIAL DC and ANTIBODY
AND ACTIVATION
ADHERENCE Macrophages Activated
INFECTION
MACROPHAGES

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Massimo Costalonga DMD, PhD DENT5301

Exogenous pathway T helper cells (CD4+)

1. Extracellular In the
microorganisms are lymph nodes
phagocytosed T cells
recognize
2. Destroyed and such
reduced in peptides microbial
3. Presented to T cells peptides via
via MHC class II the T cell
molecules receptor
and

T helper 1 (Th1) T helper 2 (Th2)

Interferon- Interleukin-4
(IFN) (IL-4)

Cell-mediated Antibody
immunity immunity

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Massimo Costalonga DMD, PhD
Th1 vs. Th2
in periodontal disease
T helper 1 cytokine IFN
protects from disease
T helper 2 cytokine IL-4
does not protect from disease
WHY ???
DENT5301
Immune response and
periodontitis in humans
In individuals resistant to periodontitis, neutrophils
and cell-mediated immunity (Th1) limit attachment
loss (Page et al. 1997).
Lack of cell-mediated immunity (IL-12, IFN and
TNF-) promotes susceptibility to periodontitis
(Chapple C. 1998).
Antigen Presenting Cells from patients susceptible
to periodontitis may have a bias towards a Th2
response and thereby promoting an ineffective
humoral immunity in periodontitis (Fokkema S.
2002).
Cells in Periodontal Tissues
Gingivitis lesion: mainly T helper 1
lymphocytes (Th1)
Periodontitis lesion: mainly activated
B cells and plasmacells
Activation of B cells is dependent
on T helper 2 lymphocytes (Th2)
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Massimo Costalonga DMD, PhD DENT5301

Destruction phase
Cytokine production most important IL- Induction of bone loss
1 but also TNF-, IL-6, IL-8, IL-12, IL-15 Osteoclast progenitors express the
and chemokines MCP-1 and RANTES receptor activator of NF-B (RANK)
Cytokine-induced alteration of the Activated T cells express the receptor
connective tissue metabolism activator of NF-B Ligand (RANKL)
Imbalance between collagenases and RANK / RANKL interaction + M-CSF
matrix metalloproteinases (MMPs) generates Tartarate-Resistant Acid
activity and collagen synthesis Phosphatase positive (TRAP+)
osteoclasts => BONE RESORPTION
IL-1 and IL-6 induce fibroblast and
osteoclast activation

Tissue Working Model T helper 2

Macrophage IL-4 and
IL-10
T helper 1 B220 B cell T cell CD4
IgG2a
IgG2a
mRANKL sRANKL
B220
B220 B cell T cell CD4
CD4
IgG1, IgA RANK
IFN
IFN Osteoclast
mRANKL sRANKL UNPROTECTIVE
Precursor
Precursor
RANK
++ M-CSF
M-CSF
Osteoclast
Osteoclast
Precursor
Precursor
TRAP++
Osteoclast
Bone Bone
Bone
Destruction

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Massimo Costalonga DMD, PhD DENT5301

Potassium channel
blocker (kaliotoxin) T helper 2
Induced Protection and
Therapeutic Future B220 B cell T cell CD4

Osteoprotegrin (OPG) is a decoy mRANKL sRANKL

receptor that binds membrane RANK

Osteoprotegrin
bound and soluble RANKL on (OPG) Osteoclast
Precursor
activated T and B cells Precursor

++ M-CSF
M-CSF
Potassium channel blocker
(Kaliotoxin) reduce the TRAP++
Osteoclast
expression of RANKL on T cells Bone
Destruction

Conclusion
Th1 type response IFN-mediated protects
from disease progression.
Th2 type response IL-4 and IL10-mediated
are inefficient at controlling microbial
biofilm.
Interference with RANK - RANKL
interaction of affects the degree of bone
loss
Cytokines and lipid mediators may mediate
systemic effects that increase the risk of
preterm birth and/or low birth weight