Introduction Prevention of caries Brief introduction about types of Immunity Causative factors of dental caries Virulance of S mutans Natural immune barriers Salivary secretion and its composition Natural barriers Innate immune responses of dental pulp to caries Acquisition of oral microbes Factors affecting oral microbial colonization Innate salivary factors found in oral cavity Adaptive immunity Secretary IgA Types of Immunization Routes of Immunization Conclusion

1. IMMUNOLOGY
OF
DENTAL CARIES
DR URVASHI SODVADIYA

2. Flow chart
 Introduction
 Prevention of caries
 Brief introduction about types of Immunity
 Causative factors of dental caries
Virulance of S mutans
 Natural immune barriers
Salivary secretion and its composition
Natural barriers
Innate immune responses of dental pulp to caries
 Acquisition of oral microbes
Factors affecting oral microbial colonization
 Innate salivary factors found in oral cavity
 Adaptive immunity
Secretary IgA
 Types of Immunization
 Routes of Immunization
 Conclusion

3. Introduction
Microorganisms
Host
Time
Substrate
Dental
caries

4. Prevention of Caries
Oral hygiene
Fluoride
application
Vaccine
Xylitol
Pit and fissure
sealants
Role of the
primary caregiver
in children
Lee Y. Diagnosis and prevention strategies for dental caries. Journal of lifestyle medicine. 2013 Sep;3(2):107.

5. Ecological Approaches to
Caries Prevention
Antimicrobial
Peptides
Probiotics
Quorum-
Sensing Targets
Natural
Products
Sugar Polyols
Philip N, Suneja B, Walsh LJ. Ecological approaches to dental caries prevention: paradigm shift or shibboleth?. Caries research. 2018;52(1-2):153-65.

6. TYPES
OF
IMMUNIT
Y
Immunity
Innate Adaptive

7. VIRULENCE OF S. MUTANS:
Ags associated with surface of S. mutans
Glucosyl-
transferases
(GTFS)
Adhesin
antigen I/II
(Ag I/II)
Glucan
binding
proteins
(GBP)

8. 2 functional
domains
Glucosyl-
transferases (GTF)
Sucrose-dependent cellular
adhesion
GTFB GTFC
Water insoluble
glucans
GTFD
Water soluble
glucans
Amino-terminal
Catalytic
domain
Carboxyl-
terminal

9. Glucan binding
protein (Gbps)
GbpA
Carboxyl
terminal
- Involved in cellular
adherence to tooth
surfaces
- Minimizes stress on
the bacterial population
Matsumoto-Nakano M, Fujita
K et al; 2007
GbpB GbpC
- Binds to soluble
glucan
Involved in dextran
induced aggregation
and is expressed only
under stress conditions
GbpD
Similar
characteristics
as GbpA

10. Protein antigen C
“sucrose-independent adhesion”
Association of Pac with
the virulence of S.
Mutans for infective
endocarditis(IE)
development.
Russell MW et al; 1992
Contribute to the
interactions of
S.mutans with
fibronectin, collagen
type I, and fibrinogen
Involves in platelet
aggregation

11. Natural immune barriers

12. Gland Salivary secretion
Submandibular Gland 65%
Parotid gland 23%
Sublingual Gland 4%
Minor salivary gland 8%
Composition: water, electrolytes, mucins, and proteins including enzymes
Liquid barrier: “Saliva”

13. Liquid barrier: “Saliva”
Protective barrier for enamel, mucosa and gingiva: (Van Nieuw
Amerongen, Bolscher, & Veerman, 2004)
• Flushing microbes and foodstuffs,
• Buffering acids
• Remineralizing the tooth
• Antimicrobial activity
• Permitting selective adhesion of commensal
microorganisms to maintain a symbiotic environment
in the dental biofilm
 Mucins,
 Salivary agglutinin
 Secretory IgA
 “Flow rate”
 Salivary statherin,
 Proline- rich proteins,
 Cystatins,
 Histatins
“Acquired Salivary
pellicle”
Mucin: major component
 Defensins (Tao et al; 2005),
 Calprotectin,
 Cathelicidins (LL- 37)
Menexes, & Kalfas, 2012,
 Histatins peroxidase
systems,
 Lysozyme,
 Lactoferrin
 sIgA
“Anticaries activity”
Hard tissue barrier: “Enamel”
Soft tissue barrier: “Mucosal epithelia”

14. SALIVA-MICROBE
INTERACTIONS
Interactions causing
Aggregation or
agglutination of bacteria
Interactions that foster
adhesion of bacteria to
surfaces
Interactions that
contribute to microbial
nutrition
Interactions that kill or
inhibit the growth
Of microorganisms

15. Innate Immune Responses of the Dental Pulp to
Caries
Hahn CL, Liewehr FR. Innate immune responses of the dental pulp to caries. Journal of endodontics. 2007 Jun 1;33(6):643-51.

16. Dentinal Fluid and the Deposition of Intratubular
Immunoglobulins
• Increased outward flow of dentinal fluid reduces diffusion of
noxious stimuli through the dentinal tubules
• Nonvital tooth >> vital tooth
Caries status Ig present
Normal pulp IgG (in the dentinal tubules near the predentin
area)
Beneath shallow caries IgG1, IgA1, and IgM, but not IgA2
(uninfected dentinal tubules)
deep caries IgG1, IgA1, IgA2, and IgM (uninfected
dentinal tubules with high intensity)
Hahn CL, Liewehr FR. Innate immune responses of the dental pulp to caries. Journal of endodontics. 2007 Jun 1;33(6):643-51.
Complement-mediated bacterial lysis in the initial pulpal response to caries
appears: limited

17. Odontoblas
t
𝛽-D-2, beta-defensin–2
TGF- 𝛽1, transforming growth factor- 𝛽1
Hahn CL, Liewehr FR. Innate immune responses of the dental pulp to caries. Journal of endodontics. 2007 Jun 1;33(6):643-51.

18. Hahn CL, Liewehr FR. Innate immune responses of the dental pulp to caries. Journal of endodontics. 2007 Jun 1;33(6):643-51.
Neuropeptides, Neurogenic Inflammation, and Caries
Calcitonin
gene-related
peptide
(CGRP)
Neurokinin
A (NKA)
Substance P
(SP)
End result
Transient increase of interstitial tissue pressure
and outward flow of dentinal fluid
T Cells in Innate Immunity in the Dental Pulp

19. ACQUISITION OF ORAL BACTERIA

20. FACTORS AFFECTING
ORAL MICROBIAL COLONIZATION
 Intraoral temperature :
 Maximum : 68.0°C
 Minimum: 15.4°C
 Localized inflammatory processes:
modulate oral tissue temperature
 Mean temperature of healthy
gingival sulci: 33.7 - 36.6°C
 Temperature within a diseased
periodontal pocket: several degrees
higher
Influence oral microbes
Temperature
 Resting plaque pH of caries-free
subjects: slightly alkaline (∼7.2)
 Resting plaque pH of subjects with
severe caries: 5.5
 Acid-sensitive bacteria
 Acid-tolerant bacteria
 Protection from low pH conditions
by producing buffer compounds
 Streptococcus salivarius: urea
Oxygen
 Dental plaque: not homogeneously
spread
 buccal and lingual surfaces of teeth
at or above the height of contour:
free of dental plaque
 Why plaque does not form to a great
extent on mucosal surfaces ???
Mechanical abrasive forces
Salivary flow rate
 Physical cleansing action of saliva
 Frequent swallowing combined
with continuous salivary flow:
 constantly replenishes the fluids
in the oral cavity
 promotes the dilution and
clearance of acid and bacterial
toxins from plaque into saliva
Age

21. INNATE SALIVARY FACTORS FOUND IN
ORAL CAVITY
• CATIONIC ANTIMICROBIAL
PEPTIDES
• ADHESIVE PROTEINS WITH
BACTERIAL AGGLUTINATION
• METAL ION CHELATOR
• PROTEASE INHIBITORS
• ENZYMES ACTING AGAINST
BACTERIAL CELL WALLS
Examples
 Α- and β-defensins,
 Cathelicidin (LL-37),
 Histatins 1 and 3,
 Adrenomedullin,
 Statherin,
 C-C motif chemokine 28,
 Azurocidin.
Examples
 Mucin-7
 Salivary agglutinin
 Surfactant protein A
 β2 microglobulin
 Proline Rich Proteins
 Fibronectin
Examples
 Lactoferrin:
 found in all major mucosal
secretions
 binds with iron (Fe3+) in
association with bicarbonate
Examples
 Cystatins:
 express salivary proteins that
are contributed by the
submandibular and
sublingual salivary glands
 Action: inhibition of
bacterial cysteine proteases
 Secretory leukocyte
protease inhibitor
 Skin-derived
antileukoproteinase
Examples
 Lysozyme
 hydrolyses the β(1-4)
glycosidic bond between N-
acetylmuramic acid and N-
acetylglucosamine residues in
the peptidoglycan of the cell
wall of gram-positive bacteria
 Peptidoglycan recognition
proteins 3 and 4

22. Adaptive
Immunity

23. Secretary IgA
Single most important humoral mediator : SIgA
S-IgA deficiency: S-IgM
Lower concentration of S-IgA: higher risk for caries

24. Types of Secretary IgA
S-Iga1 S-Iga2
Primarily against protein antigens Against polysaccharides
Predominant in plasma Predominant in saliva (35-50%)
How S-IgA2 is different from S-IgA1??

25. Secretary IgA: Mechanism of action
Block microbial
adhesins
Neutralize the action
of microbial enzymes
or toxins
Factors affecting salivary level of S-IgA
Genetic
Age
Salivary flow rate
Cigarette smoking
Pregnancy
Stress

26. Defense Mechanisms
of
Secretory Antibodies
sIgA
Subtypes
sIgA1 (60%)  antibodies to S. mutans
sIgA2  Lipoteichoic acid from S.
pyogenes
 Lipopolysaccharides (LPS)
from Porphyromonas
gingivalis (previously Bacteroid
es gingivalis), Bacteroides
fragilis, and Escherichia coli

27. Summary
Micro-organisms can be cleared from the oral cavity by antibody-
mediated aggregation while still in the salivary phase, prior to
colonization.
Antibody could also block the receptors necessary for colonization (e.g.,
adhesins) or accumulation (e.g., glucan-binding domains of GBPs and
GTF), or inactivate GTF.
In addition, the antimicrobial activity of salivary IgA antibody may be
enhanced or redirected by synergism with innate components of immunity,
such as mucin or lactoferrin

28. Bilateral injections (total volume, 0.2 ml) of a suspension of antigen (5 x 10" S.
Mutans/ml) into the region of the submandibular glands
Michalek SM, McGhee JR, Navia JM, Narkates AJ. Effective immunity to dental caries: protection of malnourished rats by local injection of Streptococcus mutans.
Infection and immunity. 1976 Mar 1;13(3):782-9.

29. Comparison of salivary immunoglobulin A levels in children delivered by cesarean
section with those delivered via vaginal delivery
Subramaniam P, Dwivedi S, Babu KG. Comparison of salivary immunoglobulin A levels in children delivered by cesarean section with those delivered via vaginal
delivery. Saudi Journal of Oral Sciences. 2016 Jul 1;3(2):85.

30. Immunization
Passive
topical
application of
antibodies
- Does not provoke a
stimulation of the host immune
system
- Less effective than the
active
- Repeated applications are
required
Active
application of
microbial
antigens
- Inducing the immune system
- More effective
- “Immunization in oral
cavity”
Types of
Immunization

31. Routes of
Immunization
i. Oral
ii. Intranasal
iii. Tonsillar
iv. Rectal
v. Systemic
vi. Active gingiva-salivary
route
Hahn CL, Liewehr FR. Innate immune responses of the dental pulp to caries. Journal of endodontics. 2007 Jun 1;33(6):643-51.

32. Conclusion
The oral immunology has its own importance, with highly sophisticated
and complementary host defense mechanisms. The variable components
of innate and acquired host defense plays a key role with much emphasis
given to the saliva.

33. Thank You!