IMMUNOLOGY OF

D E N TA L C A R I E S
 The connective tissue of the dental
pulp is normally protected from
exogenous substances in the oral
cavity by the overlying enamel or
cementum.

These dental hard tissues comprise a

rigid physical barrier against
pathogenic challenges and iatrogenic
injuries.

Once the integrity of this barrier is

breached, noxious elements of
external origin may gain entry to the
pulp tissue.
3 BASIC REACTIONS TEND TO
PROTECT THE PULP AGAINST CARIES

1. A decrease in the permeability of the dentin

2. The formation of new dentin
3. Inflammatory & immune reactions
NONSPECIFIC IMMUNE DEFENSE
A decrease in the permeability of the dentin

Unless the pulp is exposed directly to the oral environment, the mode of
antigenic entry to the pulp is quite unique among peripheral tissues.

The dentinal tubules solely provide the route of entry of foreign antigens.

Physiological properties of the dentin, such as permeability and fluid

movement are thus the decisive factors that determine the amount of
antigens that can be introduced to the pulp.

The initial pulpal response results in an increased outward flow of dentinal

fluid and macromolecules, which reduces diffusion of noxious stimuli
through the dentinal tubules and helps to clear them from dentin.
The most common defense reaction by dentin
is tubular sclerosis.

The dentinal tubules become partially or

completely filled with mineral deposits
consisting of apatite and whitlockite crystals.
Sclerosis might arise through a combination of
both acceleration of peritubular dentin
secretion and intratubular precipitation of
minerals released during the demineralization
process.

It results in decreased tubular permeability,

thereby reducing diffusion of bacterial products
or solubilized matrix component down the
tubules. Thus, shielding the pulp from irritation.
 The formation of new dentin

Pulp tissue responds to further dentin damage by laying down a

tertiary dentin matrix beneath the site of injury, which is secreted
by surviving odontoblasts in response to environmental stimuli,
leading to an increase in metabolic activities of the cells.
This is another mechanism for limiting the diffusion of toxic
substances to the pulp.
Along the border zone between primary and tertiary dentin, the walls of
dentinal tubules are thickened and the tubules are frequently occluded
with material resembling peritubular dentin.
Thus, the border zone appears to be considerably less permeable than
ordinary dentin and may serve as a barrier to the ingress of bacteria and
their products.
TERTIARY DENTIN

Reactionary dentin Reparative dentin

 Inflammatory Reaction
Caries confined to primary dentin
The progression of caries tends to be intermittent, with periods of
rapid destruction interchanged with periods where caries advances at
a slow pace. Sometimes it may be stopped temporarily or
permanently. The character of the caries lesion in these respects
influences the degree of pulpal inflammatory involvement.
The pulp tissue reacts to caries long before bacteria have penetrated
the pulp chamber.

Histopathological analyses of pulp tissues in teeth with carious lesions

indicate that
pulpal inflammation manifests itself beneath superficial caries before
the microorganisms in the carious process have made contact with
the pulpal tissue.
WHY?
During growth and cell death of microorganism in the caries
process, elements are liberated that may initiate pulpal responses by
different mechanisms, including:
1. Release of inflammatory mediators from pulpal cells,
including odontoblasts (PGs, Leukotrienes and
proinflammatory cytokines)
2. Penetration of bacterial components, which act as
antigens and evoke an immune response.
 The first cells to encounter the bacterial challenge are
the peripherally located odontoblasts and dendritic
cells.

Both are capable of activating a variety of effector cells

of innate and specific immunity.
 The initial caries-induced inflammatory infiltrate principally includes
mononuclear cell types including lymphocytes, macrophages and
plasma cells.
These mononuclear cell infiltrates can be seen either in clusters or
dispersed in the pulp tissue proper underneath the carious lesion.

During early dentinal caries, neutrophils will not normally infiltrate the
pulp but with caries progression and resultant pulpal suppuration,
there is a marked increase in neutrophil infiltration.
 In superficial caries, the number of Class II molecule-expressing cells is
increased, represented by an accumulation of dendritic cells and Class
II molecule-expressing macrophages, as well as an aggregation of
HLA-DR-positive cells in dental pulp.

The highly motile dendritic cells, after obtaining protein fragments,

will move to regional lymph nodes and initiate a primary immune
response upon which there will be recruitment of antigen-specific T
cells.
RESPONSE TO DEEP CARIES
Once the caries lesion with its bacterial front has penetrated the
primary dentine and advanced to reparative dentin and/or to the pulp
tissue proper, a massive mobilization of the inflammatory response will
take place.

A most conspicuous feature is the aggregation of neutrophils.

Although short-lived in an acute inflammatory lesion, neutrophils

release tissue-destructive elements, including oxygen radicals,
lysosomal enzymes and excessive amounts of nitric oxide.

Collectively, this means that the microbial load on the pulp has
increased dramatically and the vital functions of the pulp at this stage
are clearly threatened.
 As caries progresses, the inflammatory reaction may become more
pronounced and acute in nature as microorganisms approach and
penetrate the pulp.

Once the carious lesion with its bacterial front has penetrated the
primary dentin and/or the pulp tissue proper, a massive mobilization
of the inflammatory response will take place.

In this phase, an increase of bacterial products, activation of the

complement system due to the development of a local immune
reaction, and the accumulation of arachidonic acid metabolism with
the destruction of cellular components would occur, which are
chemotactic for leukocytes.

They might provoke an increase of macrophages and neutrophils in

the advanced stage of immune reaction in the human dental pulp
 acute inflammation in the pulp is characterized by migration of
leukocytes.

Neutrophils may line up along the dentinal tubules originating

from the source of irritation.
Although short-lived in an acute inflammatory lesion, neutrophils
are important constituents of the body defense against foreign
agents such as bacteria and their products.

They have the ability to phagocytose the bacteria and release

excessive amounts of nitric oxide which is regarded as a central
component in innate immunity aimed at eliminating invading
microorganisms.
SPECIFIC IMMUNE DEFENSE

Products released from bacteria present in dental plaque and carious

dentin, including various enzymes, metabolic products and chemotactic
agents, not only nonspecifically stimulate the inflammatory defense of the
pulp, but also may act as antigens and interact with the immune system.

It has been demonstrated that inflamed pulps beneath carious lesions

often show various forms of lymphoid cells and plasma cells, inflammatory
cells related to the immune defense.

Chronically inflamed pulps of carious human teeth contain a substantial

number of plasma cells, which primarily produce IgG.

Furthermore, inflamed dental pulps contain increased amounts of

immunoglobulin, in particular Ig G, in contrast to normal pulps
 The dendritic cells in the odontoblastic region of the pulp are
strategically positioned as a primary immunosurveillance system.

These cells have been reported to be located along the impaired

odontoblast layer in rapidly progressing lesions with enamel
cavitation just reaching the dentin.

They play an important role in capturing the antigens by taking

up the antigenic material as it passes through the dentinal
tubules and transferring them to regional lymph nodes.
 In teeth with dentinal caries of various depths but without carious pulp
exposures, there is a marked localized accumulation of dendritic cells
at the pulpal region immediately subjacent to the pulpal end of the
carious dentinal tubules.

The accumulation in this position indicates that these cells are

responding actively to incoming carious bacterial antigens that have
permeated the dentinal tubules.

B- and T-lymphocytes were detected in the pulp tissues of carious

teeth that were clinically diagnosed as reversible or irreversible
pulpitis.

These cells increased in relation to the severity of clinical symptoms.

 T-lymphocytes showed an increase even in teeth with
shallow dentinal caries, while B lymphocytes and plasma
cells increased only in teeth with deep caries.

Therefore, it is assumed that during the carious process, B-

lymphocytes and plasma cells appear later than T-
lymphocytes at the site of carious injury.

T-lymphocyte-mediated immune responses may play a

central role in the initiation of pulpal specific immunity
following exposure to protein antigens. Signals provided by
T-lymphocytes are probably prerequisite for the activation of
other antigen-specific effector cells, such as B lymphocytes
 In the most advanced phase of carious lesion, the
humoral immune response is furthered by B-lineage cells
concomitant the destruction of pulp tissue by proteolytic
enzymes released from infiltrating neutrophils and
macrophages.

Antigen-antibody complex formation, in addition to

various products of inflammatory cascade, gives rise to a
non-specific response that, while designed to rid the
body of pathogens, effects destruction of parenchymal
tissue as well.