Oral Cavity Defense Mechanisms: Saliva and Its Antibacterial Factors

ORAL CAVITY DEFENSE
MECHANISM
CONTENTS
 INTRODUCTION
 CLASSIFICATION
 MUCOUS MEMBRANE
 SALIVA
 MECHANISM OF ACTION
 GCF
 LEUKOCYTES IN DENTOGINGIVAL
AREA
INTRODUCTIO
N
The first section of the mouth
is known as the oral cavity, or
the mouth cavity.
This space is bordered in the

front and to the sides by the two
alveolar arches, which contain
the teeth. Toward the back it is
bordered by the isthmus of the
fauces.
ORAL MUCOUS
MEMBRANE
SALIVA
GCF
ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION

ORAL MUCOUS MEMBRANE
The oral mucosa is continuous with the skin

of the lip through the vermillion border
Posteriorily : mucosa of the pharynx
ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION A

ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION A
FUNCTION
 DEFENCE: impermeable to bacterial toxins.
 LUBRICATION: oral cavity moist and thus prevent the mucosa

from drying and cracking.
 SENSORY: sensitive to touch, pressure, pain and temperature
 PROTECTION

The gingival epithelium consists of a continuous
lining of stratified squamous epithelium ,and
the three different morphologic and functional
points of view; the oral or outer epithelium
,sulcular epithelium and junctional epithelium.

CELLS
Langerha
ns cells
keratin
ocytes
melanocy Merkel
tes cells
PROLIF
ERATIO
N
DIFFER
ENTATI
ONN
Differentiation of keratinocyte by keratinization
process which leads to production of an ortho
keratinized superficial horny layer which is made up
of mainly keratin protein.
This layer makes intact barrier between the oral
environment and deep layers.

Langerhans cells located among the
keratinocytes at supra basal levels belong to the
mononuclear phagocyte system as modified
monocytes.
They have an important role in the immune
reaction as antigen presenting cells for
lymphocytes

physical barrier to infection, it also has an active role in innate
host defense.
they secrete interleukin-8 (IL- 8) and other chemokines and

cytokines to alert various cell types and to attract neutrophils
natural antimicrobial peptides in response to bacterial plaque.
increased proliferation, by alteration of cell signaling events,

and by changes in differentiation and cell death altering tissue
homeostasis.

SALIVA
According to Stedman’s
medical dictionary 27th
edition
Saliva is a clean, tasteless,

odourless, slightly acidic ,
viscous fluid , consisting of
secretions from the parotid ,
sublingual, submandibular and
minor glands of oral cavity
Edgar WM. Saliva: its secretion, composition and functions. Br Dent J. 1992;172:305-312
MAJOR
SALIVARY
GLANDS
Parotid Sublingual
Submandibular
PAROTID GLAND
 Its superficial portion is located
subcutaneously lying in front of the
external ear and its deeper portion
lies behind the ramus of the
mandible , filling the retromandibular
fossae.
 The parotid is the largest of the
salivary gland .
The main excretory duct ,
STENSEN’S (parotid ) duct

SUBMANDIBULAR GLAND
Second largest salivary
gland
The submandibular gland
is on the medial aspect of
the body of the mandible in
the submandibular
triangle.
The main excretory duct is
WHARTON’S duct
opening into the floor of the
mouth close to the
frenulum of the tongue.
SUBLINGUAL
GLAND
Sublingual gland is the

smallest
It is almond shaped.
The main duct is
BARTHOLIN DUCT
opens with or near the
submandibular duct.
Secrets 5 % of the total
saliva
MINOR SALIVARY GLANDS
LABIAL AND BUCCAL

GLANDS
GLOSSOPALATINE
GLANDS
PALATINE GLANDS
LINGUAL GLANDS
VON EBNER’S GLANDS
TYPES OF SALIVARY
GLAND CELLS
SEROUS CELLS-
Synthesize ,store and secrete
proteins
Mucous cells- Synthesize ,
store and secrete mucous and
acid mucopolysaccharides.
Myoepithelial cells-have
contractile function and help to
expel secretions from the
lumen of terminal secretory
units and ducts
 Basic functional unit of salivary gland are cluster
of cells called an acini.
Terminal secretory unit
FORMATION
Composition :
water-99% or
more
•& 1% include:
Antibacterial
factors
•Salivary
antibodies
•Enzymes
•Salivary buffers & coagulation
factors
Antibacterial factors:
saliva contains numerous inorganic and organic factors
that influence bacteria and their products in the oral environment.
Inorganic factors :
bicarbonate
sodium
potassium
phosphates
calcium
ammonium
carbon dioxide
Organic
components:
• Lysozymes
• Lactoferrin
• myeloperoxidase
• lactoperoxidase
• agglutinins ( glycoprotein,
mucins, Fibronectin)
Lysozyme is a hydrolytic enzyme that cleaves the
linkage between structural components of the
glycopeptides muramic acid- containing region of
the cell wall of certain bacteria ,resulting in cell
lysis.
LACTOFERRIN
Lactoferrin links to free iron in the saliva causing bactericidal or

bacteriostatic effects on various microorganisms requiring iron for
their survival
Lactoferrin also provides fungicidal, antiviral, anti inflammatory,

and immunomodulatory functions
The lactoperoxidase- thiocyanate system
in saliva has been shown to be bactericidal to
some strains of Lactobacillus and Streptococcus
by preventing the accumulation of lysine and glutamic
acid, both of which are essential for bacterial growth.
Myeloperoxidase, an enzyme similar to
salivary peroxidase, is released byleukocytes and
is bactericidal for Actinobacillus but has added effect of
inhibiting the attachment of Actinomycetes strains
to hydroxyapatite .
Statherins inhibit the spontaneous precipitation
of calcium phosphate salts and the growth of
hydroxyapatite crystals on the tooth surface,

preventing the formation of salivary and dental
calculus.
The histatins, a family of histidine-rich
peptides have antimicrobial activity against
some strains of Streptococcus mutans and inhibit
hemoagglutination of the periopathogen
P. gingivallis.
Neutralize lipopolyscaccharides of G –ve
bacteria.
SALIVARY ANTIBODIES
•Important group of defensive substance

in saliva are immunoglobulins.
•Salivary immunoglobulin is
IgA.
•Small amount of IgM and
IgG.
•IgA inhibits bacterial
adherence.
ENZYMES
The major enzyme is parotid
amylase.
Binds to bacteria promotes adhesion lead
to either
surface immune exclusion or adhesion of
cariogenic
and periodontopathogenic bacteria.
Proteolytic enzymes in the saliva are generated by
both the host and oral bacteria. These enzymes
have been recognized as contributors to the
initiation and progression of periodontal disease.
⋆ To combat with these enzymes,
saliva contain antiproteases that
inhibit cysteine proteases such as
cathepsins and antileukoproteases
that inhibit elastase.
SALIVARY BUFFERS AND
COAGULATION FACTORS
The maintenance of physiologic

hydrogen ion
concentration (pH) at the mucosal
epithelial cell
surface and the tooth surface is an
important
In saliva the most important salivary
function
buffer of salivary
is the buffers.
bicarbonate - carbonic acid
system.
Saliva also contains coagulation
factors (factors VIII,IX and X;
plasma thromboplastin
antecedent[PTA]; Hageman
factor) that hasten blood
coagulation and protect wounds
from bacterial invasion.
An active fribinolytic enzyme

may also be present.
LEUKOCYTES
•In addition to desquamated epithelial cel

the
saliva contains all forms of leukocytes of
which the
•principal
The number of PMNs varies
cells are PMNs. from person
person at different times of the day and is
increased
in gingivitis.
 PMNs reach the oral cavity by
migrating
through the lining of the gingival
 Living PMNs in saliva are sometimes
sulcus.
called
orogranulocytes, and their rate of
migration
into the oral cavity is termed the
ORGANULOCYTIC MIGRATORY RATE
Chronic Conditions Associated with Salivary Gland
Hypofunction in Adults:
Medication
- Antidepressants
- Antipsychotics
- Antihistamines
- Antiemetics
- Antiretroviral therapy (protease inhibitors)
- Decongestants
- Appetite suppressants
Diuretics
Irradiation
Chemotherapy
Iorgulescu G. Saliva between normal and pathological. Important factors in determining

systemic and oral health. J Med Life. 2009;2(3):303–7.
Medical conditions:
- Sjögren’s syndrome
- Viral infections (HIV, HCV)
- Uncontrolled diabetes
- Alzheimer’s disease
- Hypertension
- Depression
Iorgulescu G. Saliva between normal and pathological. Important factors in determining

systemic and oral health. J Med Life. 2009;2(3):303–7.
SJOGREN’S SYNDROME
Is a clinicopathologic entity characterized by

dry eyes(keratoconjunctivitis sica) and dry
mouth(xerostomia) resulted from immune-
mediated destruction of the lacrimal and salivary
glands.
Shafer A, Hine M, Levy B, Rajendran R, Sivapathasundharam B. Shafer's textbook of

oral pathology. 7th ed. Elsevier
Can be occur in –
1. Primary form- known as sica syndrome
2. Secondary form- associated with another autoimmune

disease( RA, SLE,POLYMYOSITIS,VASCULITIS)
The disease is probably initiated by loss of tolerance in

CD4+T-Cell population.

SJOGREN’S: ORAL MANIFESTATIONS
Dry, reddened, sticky mucosa

 Atrophy of tongue
 Saliva not expressible/ cloudy
 Enlargement of salivary glands - 2/3 cases of
primary SS - Uncommon in secondary
Dryness of the mouth - xerostomia Deep red
tongue Dental caries common

TREATMENT
Symptomatic treatment for dryness of eyes – by lubricating
agents such as 0.5% methylcellulose eye drops for 4-5 times
daily.
 Cyclosporine ocular drops
 Bromhexine 16 mg TDS has been found to increase the
lacrimal secretion.
 Artificial saliva and cyclosporin(2.5-5mg/kg), for
xerostomia.
Routine dental care
 Steam inhalation may help dryness of the respiratory tract.
Candidiasis -topical nystatin 3times/day for a week,
Systemic - ketoconazole 200-400mg/day or fluconazole 50-
100 mg/day or itraconazole -100mg/day for 2 weeks
Systemic steroids are effective in reducing parotid
swelling
hydroxychloroquine 200 mg daily is useful

Gingival crevicular fluid
It is an Inflammatory exudate that flows into the oral cavity from the
gingival crevice.(Delima AJ, Dyke TEV 2003)
Historical Background
In the late 1950s and early 1960s a series of groundbreaking studies
by Brill and co-workers (Brill and Krasse, 1958; Brill and Bjorn, 1959) laid
the foundation for understanding the physiology of GCF formation and
its composition.
Andrew J.Delima , Thomas E. Van Dyke.Origin and function of the cellular components in
gingival crevice fluid. Periodontology 2000, Vol. 31, 2003, 55–76.
Composition:
- It is described as an admixture of molecules originating from the

blood, host tissues and subgingival plaque, including: electrolytes,
small organic molecules, proteins, cytokines, specific antibodies,
bacterial antigens, and enzymes of both host and bacterial origin.
(Andrew J. & Van Dyke 2003)
Main components of GCF are:
Cellular elements
Electrolytes
Organic compounds
Metabolic and bacterial products
 Enzymes & enzyme inhibitor
Cellular elements found in GCF include bacteria, desquamated
epithelial cells, and leukocytes (PMNs, lymphocytes,
monocytes/macrophages), which migrate through the sulcular
epithelium.(Egelberg J 1963)
In the sulcus, the differential leucocyte counts-

95- 97% Neutrophils
1 - 2% Lymphocytes
2 - 3% Monocytes (Attstrom 1970, Skougaard 1994).
Electrolytes - Potassium, sodium, and calcium have been studied in
GCF. Most studies have shown a positive correlation of calcium and
sodium concentrations.
Sodium concentration: First quantitative study on the absolute
concentration of sodium and potassium in gingival fluid was
performed by Matsue (1967), who used filter paper for his collections.
Most studies seem to agree that the crevicular fluid contains a
significantly higher amount of sodium than serum. Some of the
reports also indicate that the sodium concentration tends to increase in
cases of more severe inflammation.
Lipids:
GCF contains many classes of phospholipids as well as neutral
lipids. Serum seems to be the most probable source, although
salivary, bacterial and tissue sources cannot be excluded.
Metabolic and bacterial products identified in GCF include
lactic acid, hydroxyproline, endotoxins, cytotoxic substances,
hydrogen sulfide, and antibacterial factors, prostaglandin, urea.
⋆Anti bacterial factors:
⋆ Flow of crevicular fluid is able to remove various kinds
of particles, including bacteria from gingival pockets.
⋆ A peroxidase – mediated antimicrobial system has also

been show in human crevicular fluid (Anttonen and
Tenovuo, 1981).
Enzyme and Enzyme inhibitors
• Acid Phosphatase
•Alkaline phosphatase
•Pyrophosphatase
•β-glycoronidase
•Lysozyme
•Hyaluronidase
•Proteolytic enzymes: 1 carboxyendopeptidase – Cathepsin D
• 3 serine endopeptidase – Neutrophil elastase
Cathepsin G
Plasminogen activitor
1 metalloendopeptidase - Collagenase
•Serum proteinase inhibitor
•Lactic dehydrogenase
Role of gcf in defense
 Preliminary evidence also indicates the presence of interferon-α in

GCF, which may have a protective role in periodontal disease because
of its ability to inhibit the bone resorption activity of IL-1β.
 Because the amount of fluid recoverable from gingival crevices is

small, only the use of very sensitive immunoassays permits the
analysis of the specificity of antibodies.
A study comparing antibodies in different crevices with serum
antibodies directed at specific micro-organisms did not provide
any conclusive evidence about the significance of the antibody
presence in GCF in periodontal disease.
Even though the role of antibodies in the gingival defense

mechanisms is difficult to ascertain, the consensus is that in a
patient with periodontal disease,
(1) a reduction in antibody response is detrimental, and
(2) an antibody response plays a protective role.
In 1952, Waerhaug , while investigating the physiological properties of
the gingival pocket, administered India ink into healthy gingival sulci of
young experimental dogs.
After 1hr, he observed increased fluid transudation and emigration of

leukocytes and within the next 48 hr this ‘transudate fluid’ had
eliminated most of the ink particles from the sulci.
Brill & Krasse 1958, also working with an experimental canine model,
injected fluorescein dye intravenously into the animals’ hind legs and
discovered that it could penetrate into the epithelial lining of the gingival
sulcus.
Fluorescein could also be collected on strips of filter paper introduced into

the sulcus in over 90% of the animals, as quickly as one and a half minutes
after administration.
However, no dye was detected on other intraoral locations, such as the

teeth, tongue, palate, and oral mucosa, and even extra-oral mucous
membranes sites provided negative results.
These findings suggested that the epithelium lining of the gingival sulcus
was permeable to small molecular weight compounds and that the
passage of tissue fluid into the sulcus acts as a possible defense
mechanism that may play an important role in the homeostasis of the
crevicular environment.(Krasse B 1996)
Collection of gcf
The collection methods include the use of-
absorbing paper strips
twisted threads placed around and into the sulcus
Micropipettes
intracrevicular washings
Collection of crevicular fluid by
means of capillary tubing.
Capillary tubing of known
diameter is placed at the entrance
of the crevice and the fluid
migrates up the tube by capillary
action.
Collection of crevicular fluid

by means of filter
paper strips.
Illustration of the positioning of papers for the filter paper
strip method of collection: (a) Intracrevicular method; (b)
Extracrevicular method ‘superficial’ [Löe & Holm-Pederson ],
(c) Extracrevicular method ‘deep’ [Brill].
Electronic device for measuring the
amount of fluid collected on filter paper.
(periotron)
CONCLUSION
The oral cavity is loaded with aerobes and anaerobes which are
normal commensals of the oral cavity.
These commensal organism becomes pathogenic if the host defense

is compromised.Hence an effective defense mechanism is necessary
within the oral cavity to safeguard from these attacks.

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ORAL CAVITY DEFENSE

This space is bordered in the

ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION

The oral mucosa is continuous with the skin

Posteriorily : mucosa of the pharynx

ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION A

 LUBRICATION: oral cavity moist and thus prevent the mucosa

 SENSORY: sensitive to touch, pressure, pain and temperature

ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION

ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION

ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION

ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION

they secrete interleukin-8 (IL- 8) and other chemokines and

natural antimicrobial peptides in response to bacterial plaque.

increased proliferation, by alteration of cell signaling events,

ORBANS ORAL HISTOLOGY AND EMBRYOLOGY 13TH EDITION

Saliva is a clean, tasteless,

 Its superficial portion is located

subcutaneously lying in front of the

external ear and its deeper portion

lies behind the ramus of the

mandible , filling the retromandibular

 The parotid is the largest of the

The main excretory duct ,

STENSEN’S (parotid ) duct

Sublingual gland is the

LABIAL AND BUCCAL

Terminal secretory unit

glycopeptides muramic acid- containing region of

the cell wall of certain bacteria ,resulting in cell

Lactoferrin links to free iron in the saliva causing bactericidal or

Lactoferrin also provides fungicidal, antiviral, anti inflammatory,

salivary peroxidase, is released byleukocytes and

is bactericidal for Actinobacillus but has added effect of

inhibiting the attachment of Actinomycetes strains

of calcium phosphate salts and the growth of

hydroxyapatite crystals on the tooth surface,

•Important group of defensive substance

The maintenance of physiologic

An active fribinolytic enzyme

•In addition to desquamated epithelial cel

Iorgulescu G. Saliva between normal and pathological. Important factors in determining

Iorgulescu G. Saliva between normal and pathological. Important factors in determining

Is a clinicopathologic entity characterized by

Shafer A, Hine M, Levy B, Rajendran R, Sivapathasundharam B. Shafer's textbook of

2. Secondary form- associated with another autoimmune

The disease is probably initiated by loss of tolerance in

Shafer A, Hine M, Levy B, Rajendran R, Sivapathasundharam B. Shafer's textbook of

Dry, reddened, sticky mucosa

Shafer A, Hine M, Levy B, Rajendran R, Sivapathasundharam B. Shafer's textbook of

Shafer A, Hine M, Levy B, Rajendran R, Sivapathasundharam B. Shafer's textbook of

- It is described as an admixture of molecules originating from the

In the sulcus, the differential leucocyte counts-

⋆ A peroxidase – mediated antimicrobial system has also

 Preliminary evidence also indicates the presence of interferon-α in

 Because the amount of fluid recoverable from gingival crevices is

Even though the role of antibodies in the gingival defense

After 1hr, he observed increased fluid transudation and emigration of

Fluorescein could also be collected on strips of filter paper introduced into

However, no dye was detected on other intraoral locations, such as the

Collection of crevicular fluid

These commensal organism becomes pathogenic if the host defense

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