Pathway 14-1 Pulp Reaction to Caries

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Questions and Answers

What unique feature of the dental pulp distinguishes its response from other connective tissues?

Paucity of collateral circulation (correct)

Lack of neurovascular supply

Encasement in a flexible environment

Presence of collateral circulation

⭐️What cytokines do odontoblasts elaborate in response to TLR stimulation by pathogens?

Interferon-gamma and IL-6

Proinflammatory cytokines, chemokines, and antimicrobial peptides (correct)

TGF-b1 and FGF

IL-10 and TNF-beta

⭐️Which chemokine gene is NOT constitutively expressed by unstimulated odontoblasts?

CCL5 (correct)

CXCL12

CCl2

CCL26

⭐️How do TGF-b1 influence the expression of TLRs in odontoblasts?

It inhibits TLR2 and TLR4 expressions Signup and view all the answers

⭐️Which type of dendritic cell specializes in antigen presentation in the dental pulp?

CD11c positive dendritic cells Signup and view all the answers

What is the role of IgG, IgM, and IgA in relation to odontoblasts in carious lesions?

They are actively transported to the infection front by odontoblasts Signup and view all the answers

What is the consequence of hyperimmunization in animal studies involving dentin exposure?

Increase in pulp tissue destruction Signup and view all the answers

⭐️What happens to dendritic cells as they migrate from the central pulp?

They increase in size and become CD86 positive Signup and view all the answers

⭐️Which factor is NOT commonly produced by odontoblasts in response to caries?

TGF-b1 Signup and view all the answers

⭐️During the progression of a carious lesion, where do pulp dendritic cells migrate first?

Into the odontoblast layer Signup and view all the answers

⭐️What is the primary defense mechanism against caries before tertiary dentinogenesis occurs?

Decreased dentin permeability due to mineral crystal deposition Signup and view all the answers

⭐️Which growth factor is primarily associated with the signaling process for odontoblast differentiation?

Transforming growth factor- b 1 （TGF-b1） Signup and view all the answers

What characterizes reactionary dentin compared to other types of tertiary dentin?

It resembles physiologic dentin in morphology. Signup and view all the answers

What role does TGF- b 1 play during the carious dissolution of dentin?

It diffuses across intact dentin to stimulate odontoblasts. Signup and view all the answers

⭐️Which type of dentin is formed due to aggressive carious lesions affecting odontoblasts?

Fibrodentin Signup and view all the answers

Which of the following best describes the organization of reparative dentin?

Varied, ranging from organized to irregular structures Signup and view all the answers

What is the involvement of Toll-like receptors (TLRs) in odontoblasts in response to pathogens?

TLRs facilitate the detection of pathogen-associated molecular patterns. Signup and view all the answers

What best describes the mechanism by which dentin sclerosis protects against caries?

Reducing the size of dentin tubules to limit permeability Signup and view all the answers

What best describes the role of matrix proteins in dentinogenesis?

They can act directly or across intact dentin to stimulate dentin formation. Signup and view all the answers

What distinguishes tertiary dentin from primary and secondary dentin?

It shows a higher variability in morphology due to various stimuli. Signup and view all the answers

How does the immune response intensify as the depth of a carious lesion increases?

Counts of immune cells such as neutrophils and T cells increase. Signup and view all the answers

Which immune cells are primarily recruited to the site of a carious lesion as its progression continues?

Lymphocytes, macrophages, and plasma cells Signup and view all the answers

What happens to CD11c+ dendritic cells as caries progress in the dental pulp?

They aggregate in the pulp and extend into the odontoblast layer Signup and view all the answers

Which chemokine is notably produced by odontoblasts and is involved in the recruitment of immune cells in response to bacteria?

IL-8 (CXCL8) Signup and view all the answers

What characterizes the secretion of antibodies by odontoblasts in carious dentin?

IgG, IgM, and IgA are actively transported to the infection front. Signup and view all the answers

What role do odontoblasts play in the early inflammatory response to caries?

They initiate the innate immune response by detecting pathogens. Signup and view all the answers

⭐️Which statement correctly describes the Toll-like receptor (TLR) expression by odontoblasts?

TLR3, 5, and 9 expression increases in response to specific bacterial stimuli. Signup and view all the answers

⭐️What effect does TGF-β1 have on the expression of Toll-like receptors in odontoblasts?

It inhibits the expression of TLR2 and TLR4 when exposed to bacteria. Signup and view all the answers

What is the primary mechanism by which odontoblasts recognize pathogens?

Via pattern recognition receptors that detect PAMPs. Signup and view all the answers

Study Notes

### Dental Pulp Response to Dental Caries

The dental pulp, a dynamic tissue, responds to external stimuli, adapting to the unique challenges arising from its location within the tooth.
Dental caries is a common infectious disease that affects the dentin.
It can progress to the pulp causing necrosis and potential tooth loss.

### The Three Main Pulp Responses to Dental Caries:

Decreased Dentin Permeability: This occurs due to dentin sclerosis, a process of increased intratubular dentin deposition and mineral crystal precipitation within the dentin tubules.
Tertiary Dentin Formation: This involves formation of a new layer of dentin in response to the caries.
- Reactionary dentin: Formed by resident odontoblasts in response to mild stimuli. Morphologically similar to physiologic dentin.
- Reparative dentin: Formed when aggressive lesions cause odontoblast damage, requiring repopulation with differentiating progenitors. This can produce irregular dentin that is more permeable than physiologic dentin.
Inflammatory and Immune Reactions: The pulp activates its immune system to combat invading pathogens.
- This response intensifies as the carious lesion progresses.
- It involves a combination of humoral and cellular responses.
- The odontoblast plays a crucial role in initiating this response.

Dentin Sclerosis

Dentin sclerosis is the initial response to dental caries.
TGF-b1 appears to play a central role in the increased intratubular dentin deposition that occurs during dentin sclerosis.

Tertiary Dentin Formation

Tertiary dentin is formed over a longer period than sclerotic dentin.
The nature of the tertiary dentin formed is dependent on the severity of the lesion.
TGF-b1, TGF-b3, IGF-I, IGF-II, PDGF, BMP-2, and VEGF have all been shown to stimulate dentinogenesis in vitro.

Pulp Immune Response

In the carious lesion, the pulp immune reaction increases in intensity as the lesion progresses.
T lymphocytes, B-lineage cells, neutrophils, and macrophages are all involved.
Toll-like receptors (TLRs) play a key role in pathogen detection.
Odontoblasts are capable of expressing TLRs, which recognize pathogen-associated molecular patterns (PAMPs) and initiate a host defense.
Odontoblasts also play a role in the humoral immune response, producing antibodies that accumulate beneath the advancing lesion.
Dendritic cells are vital components of the adaptive immune response. They are responsible for antigen presentation and stimulation of T lymphocytes.

Pulp Exposure

Pulp exposure can occur in both primary and immature permanent teeth.
It can lead to a proliferative response called hyperplastic pulpitis.
This response is fueled by a rich blood supply, leading to the formation of a "pulp polyp."

Early Inflammatory Response to Caries

Odontoblasts, the most peripheral cells in the pulp, are the first to encounter foreign antigens and initiate the innate immune response.
Pattern Recognition Receptors (PRRs), like Toll-like receptors (TLRs), recognize pathogen associated molecular patterns (PAMPs) on invading organisms.
Odontoblasts express TLR3, 5, and 9 in response to lipoteichoic acid, and TLR2 and 4 in response to lipopolysaccharide.
TGF-β1 inhibits the expression of TLR2 and 4 by odontoblasts in response to bacteria.
TLR stimulation triggers the release of proinflammatory cytokines, chemokines, and antimicrobial peptides, leading to immune cell recruitment and direct bacterial killing.

Chemokine Expression and Immune Cell Recruitment

Unstimulated odontoblasts express chemokines (CCL2, CXCL12, CXCL14) that attract immature dendritic cells.
They also produce CCL26, an antagonist for CCR1, CCR2, and CCR5, chemokines produced by monocytes and dendritic cells.
Bacterial cell wall constituents upregulate chemokine and chemokine receptor gene expression in odontoblasts, further recruiting immune cells.
Stimulated odontoblasts release chemokines like IL-8 (CXCL8), which, in concert with growth factors from carious dentin, induce a focal increase in dendritic cell numbers.
The influx of immune effector cells includes lymphocytes, macrophages, and plasma cells.
This cellular infiltrate is accompanied by localized capillary sprouting and nerve fiber coaggregation.

Dendritic Cells and Antigen Presentation

The density of dendritic cells increases with caries progression.
Pulp dendritic cells are responsible for antigen presentation and stimulation of T lymphocytes.
They aggregate in the pulp and subodontoblastic regions then migrate into the odontoblast layer and eventually into the dentinal tubules.
Two distinct populations of dendritic cells exist:
- CD11c+ dendritic cells found at the pulp/dentin border and below pits and fissures
- F4/80+ dendritic cells concentrated in perivascular spaces in the subodontoblastic zone and inner pulp
CD11c+ dendritic cells express TLRs 2 and 4 and are CD205 positive.
F4/80+ dendritic cells have migratory ability and become CD86 positive.
Dendritic cells and macrophages contribute to odontoblast differentiation by secreting GM-CSF and osteopontin.

Humoral Immune Response and Antibody Transport

Odontoblasts play a role in the humoral immune response.
IgG, IgM, and IgA are localized in the cytoplasm and cell processes of odontoblasts in carious dentin, suggesting active antibody transport to the infection site.
In early lesions, antibodies accumulate in the odontoblast layer and with lesion progression can be seen in the dentinal tubules.
This leads to a focal concentration of antibodies beneath the advancing lesion.

Advanced Caries and Immunopathologic Destruction

In the most advanced caries, the humoral immune response contributes to pulp tissue destruction.
Hyperimmunization to antigens can increase pulp tissue destruction.
Odontoblasts produce innate antimicrobial molecules like human beta defensin-2 (HBD2).
IL-1, TNF-α, and bacterial LPS stimulate HBD2 production.

Pulp Exposure and Hyperplastic Pulpitis

Pulp exposure in primary and immature permanent teeth can lead to a proliferative response, known as hyperplastic pulpitis.
Exuberant inflammatory tissue proliferates through the exposure, forming a "pulp polyp."
This proliferative response is likely facilitated by a rich blood supply.
Conventional root canal therapy or therapeutic pulpotomy are indicated.

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