SALIVA

&
Ig A SYSTEM

UNIVERSITI SAINS MALAYSIA

School of Dental Sciences
Dr. Erlina S M
 SALIVA
Is secreted by the three major salivary
glands and very numerous minor salivary
glands.
The major salivary gland are parotid,
submandibular, and sub lingual gland.
The minor salivary glands are lingual,
bucal, labial, palatine, glossopalatine
glands.
 Salivary Glands (overview)
Location:
Vestibule
Oral cavity proper
Size:
Major
Minor
Nature of secretion:
Mucous
Serous
mixed
 Major salivary glands:
Parotid:
location
duct: Stensons
secretion: serous (25% of
volume)
Submandibular:
location
duct: Whartons
secretion: mixed (serous)
(60-65%)
Sublingual:
location
duct: Bartholins
secretion: mixed (mucous)
(15%)
 Minor salivary glands:
labial: labial mucosa;
mucous and serous secretions
buccal: buccal mucosa;
mucous and serous secretions
palatal: posterior and lateral aspect of soft
palate; mucous secretions
lingual: tip and posterior aspect of tongue;
mucous and serous secretion
 Description of saliva:
odorless
colorless or cloudy
ropy or watery
bathes teeth and tissues
resting: unstimulated
active: stimulated (10 x resting rate)
 Flow of saliva:
continuous
sources of resting saliva
characteristics of flow:
amount: copious vs. scanty
viscosity (thickness; consistency):
ropy (more mucous)
watery (more serous)
 Factors affecting salivary flow:

increase flow: decrease flow:

sight/smell food fear/anxiety
mastication sleep
dental work fever
pain medications
after eating

Xerostomia: dry mouth and ongoing decrease of saliva.

Can result in mucositis, mouth infections, increase in caries
and tissue inflammation.
 General factors influencing the
secretion of Saliva

Increased secretion may be caused by the

following:
Taste
Smelll
Mechanichal stimulation of the oral mucosa
Mechanichal irritation of the gingiva
Mastication of the food
Chemical irritation of the oral mucosa
Distention or irritation of esophagus
Chronic irritation of oesophagus
Chemical irritation of the stomach
Pregnancy
 Flow Rate of Saliva
0.5
ml / min

0.4 unstimulated
0.3 stimulated
0.2
0.1
0.0
20-39 yr 40-59 yr > 60 yr
Age
 Composition of saliva:
99 % water, 1 % solids

organic solids: inorganic solids:

mucin (proteins) salts: bicarbonates,
enzymes (amylase) chlorides,
phosphates:
antibodies
(calcium,
blood clotting sodium,
factors potassium)
lipids phosphates are called
buffers
Composition of saliva

Organic constituents
Main organic constituents: urea, uric acid, free glucose, free
amino acid, lactate, fatty acid
Macromolecul in saliva: protein, amylase, peroxidase,
thiocyanate, lysozyme, lipid, Ig A, Ig M, Ig G.
Inorganic constituents
Ca, Mg, F, HCO3, K, Na, Cl, NH4.
Gases
CO2, N2, and O2
Water
Constituents derived from the oral cavity
Desquamated epithelial cells, Leukocytes PMN from crevicular
fluid, bacteria.
Modification of salivary composition by the ductal system
 pH of saliva varies:
normal levels are 6.0 to 7.9 (generally
around neutral)
falls slightly during sleep
rises during eating
falls after eating (significant in caries)
increase in salivary flow = increase in
buffers available = increase in pH
 General Function

It keeps the teeth healthy by providing

a lubricant, calcium and a buffer.
It also helps to maintain the health of
the gums, oral tissues (mucosa) and
throat.
It also plays a role in the control of
bacteria in the mouth.
 It helps to cleanse the mouth of
food and debris.
It provides minerals such as
calcium, fluoride, and
phosphorus.
It helps in swallowing and
digesting food.
 Lack of saliva will make the
mouth more prone to disease and
infection.
Lead to a burning feeling.
 Major salivary components
Histatins
Statherins
Lysozyme
Proline-rich proteins
Carbonic anhydrases
Amylases
Peroxidases
Lactoferrin
Mucin 2 (MG2)
sIgA
Mucin 1 (MG1)
1 10 100 1000 10000
Size (kDa)
 Multifunctionality
Amylases, Cystatins, Carbonic anhydrases,
Histatins, Mucins, Histatins
Peroxidases Anti- Buffering
Bacterial
Cystatins, Amylases,
Mucins Anti- Mucins, Lipase
Viral Digestion
Salivary
Families
Anti- Mineral-
Fungal ization Cystatins,
Histatins
Histatins, Proline
Lubricat-
Tissue ion &Visco- rich proteins,
Amylases, Coating elasticity Statherins
Cystatins, Mucins,
Proline-rich proteins, Statherins Mucins, Statherins
adapted from M.J. Levine, 1993
 Salivary Protein Functions
Oral Function Problem Protein Function
Acts as an airway Air-born Anti-bacterial
organisms systems
Dehydration Water-retaining
glycoproteins
Speech Need for Lubrication system
lubrication
Taste --- Gustin
Entry-point for food Food-born Anti-bacterial
mastication, organisms systems
swallowing Soft and hard Lubrication;
tissue abrasion mucins, statherin
 Salivary Protein Functions

Oral Function Problem Protein Function

Control of Colonization & Anti-bacterial
indigenous & infection systems
invading bacteria, Controlling Immunoglobulins,
fungi and viruses pathogens and histatins,
commensals glycoproteins,
Adhesion of lysozyme,
bacteria versus sialoperoxidase,
their detection lactoferrin
Adhesion-
modulating proteins
 Salivary Protein Functions

Oral Function Problem Protein Function

Digestion ___ Starch & fat

hydrolysis: amylase
and lingual lipase

Protection & repair Toxins, Mucin-rich

of soft tissues carcinogens, protective barrier
degradative film
proteases Protease inhibitors,
cystatins, tissue
growth factors
 Salivary Protein Functions

Oral Function Problem Protein Function

Protection & repair Enamel mineral Biologically

of hard tissues is potentially controlled protective
soluble; acid- & reparative
damaged enamel inorganic
requires environment,
remineralization stabilized by
statherin, acidic
proline-rich and
pellicle proteins
Pellicle formation _____ _____

Plaque acid Plaque pH Basic amino acids

 Antimicrobial Factors in Human
Saliva
Non-immunoglobulin Factors Origin
Lysozyme Salivary glands, crevicular fluid (PMNs)
Lactoferrin Salivary glands, crevicular fluid (PMNs)
Salivary peroxidase Salivary glands
SCN- Salivary glands, crevicular fluid
H2O2 Salivary glands, crevicular fluid
(PMNs),
bacterial and yeast cells
Myeloperoxidase Crevicular fluid (PMNs)
Cl- Salivary glands, crevicular fluid
Agglutinins, aggregating proteins Salivary glands
Histidine-rich polypeptides Salivary glands
Proline-rich proteins Salivary glands

Immunoglobulin Factors
Secretory IgA Salivary glands
IgA, IgG, IgM Crevicular fluid
 SECRETION Ig A in SALIVA
Saliva contains 19 mg per 100 ml of Ig A
Daily 100 mg of Ig A is secreted into the
mouth
In contrast, per 100 ml saliva are found 1,4
mg Ig G and 0,2 mg of Ig M
 Concentration of
immunoglobulins
Fluid Ig G Ig A Ig M IgG:Ig A
Serum 125 220 80 5.7
Whole saliva* 0 19.4 0.2 0.07
Parotid saliva** 1.4
4.0 0.04 0.009
Gingival Fluid
0.04 110 25 3.2
350
* : unstimullated
** : stimulated
: determined in periodontitis
 Ig A
are glycoprotein
are built of subunits containing
two identical light chains (L chains), each containing
about 200 amino acids
two identical heavy chains (H chains), which are at
least twice as long as L chains
The first 100 or so amino acids at the N-terminus
of both H and L chains vary greatly from
antibody to antibody the are termed the
variable (V) regions
 Ig A (heavy and light
chains) is produced by
plasma cells locally in the
salivary glands.
These plasma produces
also J chains.
So plasma cells in salivary
glands produce Ig
dimmers.
 J Chain
Joining Chain
 Dimeric
IgA

CH2 CH3 CH3 CH2

CH2 CH3 CH3 CH2

J Chain
 Secretory IgA consists of
at least two IgA
molecules covalently
linked by J chain and with
the secretory component.

Polymeric IgA produced by plasma cells located in the

submucosa binds to the poly-Ig receptor on epithelial cells,
and the complex is transported to the luminal surface of the
mucosa. The poly-Ig receptor is enzymatically cleaved during
the transport process and becomes the secretory component of
secretory-IgA
 IgA is the second most abundant immunoglobulin in serum.
IgA is the most abundant immunoglobulin in external
secretions such as breast milk, saliva, tears, and mucus of
the bronchial, genitourinary and gastrointestinal tracts.
In serum IgA is primarily a monomer.
In secretions IgA (termed secretory IgA) is predominately a
dimer but higher multimers do exist.
Secretory IgA has an associated J chain and a polypeptide
chain called secretory component which is derived from the
receptor that is responsible for transporting polymeric IgA
across membranes.
 Secretory Component is synthesized by the
secretory epithelial cells of salivary acini.
The assembled sIg A is then transported into the
duct lumen and excreted into the mouth.
 Functions of Secretory Component
(SC):
1) To allow the transport of polymeric IgA
(pIgA-primarily dimeric IgA) through cells
(ductal epithelium) as Secretory-IgA (sIgA)

2) To protect the pIgA from proteases while

S-IgA is in the ductal cell and once the
SIgA enters the gastrointestinal tract (e.g.
oral cavity) or respiratory tract.
 Secretory Ig A in Saliva
Secretory Ig A has three sub components:
Ig A molecule (two of these are combined to
produce a dimer of Ig A)
J chains (polypedtides of about 15.000
daltons)
SC (secretory component), polypeptides
about 80.000 daltons
 Secretory IgA
Predominant Mucosal
Immunoglobulin

Secretory Component
Not made by the Plasma Cell. Allows
Transport onto mucosal surfaces & Protects
against Proteases
 Secretory IgA (S-IgA) has important
functions on mucosal surfaces:
1) To neutralize pathogenic factors on Mucosal
Surfaces (e.g., GTF and bacterial proteolytic
enzymes),
2) To help neutralize the toxic effects of endotoxins
3) To neutralize viruses on mucosal surfaces.
4) To retard penetration of antigens into mucosal
tissue (prevents a secondary stimulation of the
mucosal S-IgA system)
IgA

Lamina propria
 SC Lumen
D
u
c
SC
t
a
Secretory
Plasma l
Component
Cell (SC) is a
major part of C Dimeric
SC
the e Secretor
Polymeric Ig y IgA
l
Receptor (Trimers are
l
(PIR) also formed)
Origin of Secretory Component of
sIgA
Introductory to mucosal imunity
Mucosa represent a vast surface area
vulnerable to colonization and invasion
Total amount of sIgA exceeds circulating
IgG.
Antigens are separated from mucosal
immune tissue by epithelial barrier.
Antigens must be transported across the
epithelium.
Protection from microbial colonization
(adherence)
Prevention of environmental
sensitization
Focus of much vaccine work
May have regulatory influence on
systemic immunity
May block allergic sensitization
 This mucosal barrier and the other cells associated
with these epithelial cells can be loosely divided into
4 major anatomical areas:

Nasal, Respiratory, Gastrointestinal, and

Reproductive (Urogenital)

These anatomical areas together are called the:

Mucosal Associated Lymphoid Tissues
(MALT)
 Mucosal
NALT
BALT
***
#
GALT
*** #

RALT
***
The secondary lymphoid organs can be sub-
divided into the Systemic (***) and Mucosal
immune systems
 MALT

Differs fundamentally from Systemic immune

responses in that:
major isotype in mucosal secretions is secretory,
dimeric IgA

most of the antibody-producing cells and

effector T occur in the MALT
separate inductive and effector lymphoid sites
 References

Immunology of Oral Disease, Ivan M

Roitt & Thomas Lehner, Blackwell
Scientific Pub., WU290R741
Oral Bioscience, David B Ferguson,
Churchill Livingstone, WU102F352, 1999
Essentials of Oral Histology and
Embriology, James K Avery, Mosby
Co.,WU101A954,2000
THANK YOU