1. Pulpal Pathogenesis Caroline G. Ayoub

2. Outline • Contents of the healthy pulp • Etiology of pulpal disease • Immunological shift from health to disease • Take home points

3. What’s in the pulp? • Cells of pulp: • Odontoblasts • Fibroblasts • PMNs • Lymphocytes • Macrophages • Dendritic Cells – pulp, PDL, PA lesion • Mast Cells (chronic inflamed pulp only) • Other: • Ground substance • Blood vessels • Nerves

4. Odontoblast • Dentin formation • Main source of TGF-b • Innate Immunity

5. Fibroblast • Most numerous cells of the pulp • Abundant in the cell-rich zone • Synthesize types I and III collagen • Have capacity to produce pro-inflammatory cytokines in response to PAMPs.

6. Immunocompetent Cells Dendritic Cells Lymphocytes Macrophages Primary function: Phagocytosis Antigen presentation via expression of Cl II MHC molecules on their surface • Peculiar dendritic morphology • High motility • Limited phagocytic activity • Expression of high amounts of Cl II MHC molecules • Potent capacity for antigen presentation to T lymphocytes • T lymphocytes: normal residents of human dental pulp • CD8+ outnumber CD4+ T lymphocytes in the dental pulp

7. Nerves PAIN A delta fibers C fibers Secondary dentin Dental pulp is among the most densely innervated tissues in the body

8. Etiology • Bacteria • Trauma • Orthodontic Tx

9. Health to Disease A schematic illustration of dental pulp responses to dental caries from Japanese Dental Science Review

10. How do pulp cells react to the insult? • Odontoblasts: Host defense activated • Fibroblasts: Inflammatory mediators produced • Macrophages: APC • Dendritic Cells: APC • Lymphocytes: T cells recognize MHC on APC

11. In other words…

12. What about the Nerves?

13. Neuropeptides • The largest class of neurotransmitters/neuromodulators • Possess multiple recognition sites for receptor binding • Cannot cross cell membranes: Target cells need to have receptors and binding sites • Examples include: • Substance P (SP) • Calcitonin Gene-Related Peptide (CGRP)

14. Substance P • In the central pulp, SP fibers traverse in close proximity to blood vessels. In the periphery, many SP fibers are directly associated with small blood vessels • SP fibers are also observed at the subodontoblast layer where they branch toward predentin, with some SP fibers penetrating into the dentin

15. CGRP • Branch extensively in the coronal pulp near the pulp horn tip and enter into dentin for up to 0.1 mm • Multiple studies have demonstrated that trigeminal afferent neurons expressing CGRP innervate dental pulp • The existence of high-affinity binding sites for CGRP has been reported in the dental pulp as well as other tissues in the body.

16. So… Two dynamic changes occur to afferent neurons during inflammation: 1st there is a sprouting of afferent fibers 2nd local increases in inflammatory mediators trigger neuropeptide release Neurogenic inflammation

17. Take Home Points • Innate Immunity • Adaptive Immunity • Neurogenic Inflammation