Immunology of

Dental Caries

TETIANA HANIASTUTI

 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
A decrease in the permeability of
the dentin

The formation of new dentin

Inflammatory & immune reactions

A decrease in the permeability of the dentin

The dentinal tubules 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.

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:

Release of inflammatory
mediators from pulpal
cells,
including odontoblasts
(PGs, Leukotrienes and
proinflammatory
cytokines)

Penetration of bacterial
components, which act as
antigens and evoke an
immune response.

 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 antigenspecific T cells.

Inflammatory Reaction: 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.

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.

As caries progresses, the inflammatory reaction may become more

pronounced and acute in nature as microorganisms approach and
penetrate the 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.

But, neutrophils release tissue-destructive elements,

including oxygen radicals, lysosomal enzymes and
excessive amounts of nitric oxide which damage the
tissue.

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.

 T- and B-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 Tlymphocytes 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