Host response in Periodontal Disease  Endothelial cells

Wednesday, 27 September 2017

7:51 PM  Osteoblasts

Effect PAMPs on epithelial cells (pp262)

 Gingivitis
 Expresses TLR and other mediators
 Periodontitis
 Allow migration of leukocytes to the sulcus through the production of IL-8
 Inflammatory responses  Activates other cells (endothelial cells, neutrophils)
 Role of Immnune system in inflammation  Produce MMPs

 Tissue destruction, bone loss, tooth loss Effect Pamps on dendritic cells

Basic concepts: immunity and inflammation  Sentinels of the innate immune system

 Chapter 12, 209-226  Recognize antigens

 Chapter 15, 259  Produce cytokines that activates the T-cells

Effect Pamps on fibroblasts
Host defense Process
 Innate or non specific immunity  Role in homeostasis, pathogenesis and healing
 Adapative or specific immunity  Prodcue pro-inflammatory cytokines
Innate or non-specific immunity  Secretes proteinases
Effect Pamps on endotehlial cells
 Healthy and intact peithelial tissues
a. SEM: intact epithelial surface on gingival sulcus  Activation and increased adhesion of monocytes resulting in cytokine
production
 Immune cells Effect Pamps on osteoblasts
o Neutrophils
o Macrophage  Inhibits prod of a bone -protecting factor (OPG - soteoprotegerin)
o Mast cell  Inhibits osteoblast differentiation
o Natural killer cell  Inhbits mineralization
Effect of PAMPS on monocytes
o Peripheral dentritic cells (DC)
Complement system  Production of cytokines
o Series of 30 membrane associated cell receptors and plasma proteins  Proliferation and adhesion to endothelial cells
activated through a cascade of enzymatic reactions  Differentiation into osteoclasts
Effct on PAMPs on:
o C3
o Activation of Complement system  T-cells = activaiton and differentiation
 Recruitment of additional phagocytic cells to the site of  B-cells - Production of antibodies
infection
 Opsonization of Pathogens Etiology of periodntal disease
 Direct killing of pathogens  Dental plaque
Vascular and cellular response in acute inflammation
 Contributing factors;
Adaptive immunity o Local and systemci
Specific response of the body after encountering a pathogen Host response to bacteria
Cell mediated and humoral response
Prevents local infection from becoming systemic including the sacrifice of local Marked changes occur in the peridontium due to the body's inflammatory
tissues reaction to bacterial invasion of the junctional and the gingival connective
Lymphocytes tissue
o T cell The onset and severity of periodontal disease is due to the heightened
response ov the body to the pathogens
o B cell
Components for Innate Immunity for the Periodontium o Responsible for most of the breakdown of Periodontal tissue
Healthy and intact epithelial tissue Inflammatory mediators of peridontitis that contribute to tissue destruction (ch 13
Non keratinization of the sulcular epithelim pp238-240)
Shedding of degerated or infected and rapid repair of JE cells at base of sulcus Matrix metalloproteinases (MMP)
(+) of PMNs in the sulcus Cytokines
Antimicrobial substance in the GCF (IgG) Prostaglandins
Antibacterial and cleansing action of saliva
Flushing effect of the gingival crevicular fluid to was the gingival sulcus Proteinases
Antibacterial and cleansing action of saliva MMP's (matrix metalloproteinases)
a. Components of saliva: o Primary proteinases involved in perio tissue destruction; collagenase
Elastase
 Mucin- eliminates bacteria
 Lactoferrin - binds w/ iron, necessary for bacterial metab MMP's
 Peroxidase - toxic to bacteria Source: neutrophils, gingival fibroblasts, macrophages, JE cells, osteoblasts,
 Histatins - histidine - rich proteins, anti-fungal osteoclasts
 IgA - primary acquired immune component in saliva Overproduciton results in the breakdown of the CT, PDL fibers, and alveolar
bone of the periodontium
 Tongue that provides a natural cleansing effect on the gingiva Cytokines
 Presence on Pattern Recognition Receptors (PRR) on Macrophages and Solube proteins that act as messengers to transmit signals form one cell to
dendritic cells (pp259) another
o Recognize Pathogen - Associated Molecular Patterns (PAMPs) to o Interleukin -1 (IL-1); IL-6; Tumor Necorsis Factor TNF- a
signal an immune response Initiate tissue destruction and bone loss in chronic inflammatory disease (ex.
o Ex. of PRR: Toll-like Receptors (TLR) Peridontitis)
o Neutrophils, macrophages, B-cells, JE cells, gingival fibroblasts,
TLR osteoblasts
Major class of signlaing receptors
Importance: TNF a : stimulates osteoclast activity
a. Recognition of microbes by the innate immune system IL-1 : osteoclast proliferation - stimulates bone resorption
b. Bridging of the innate and acquired immune response IL-6 : differentiates monocytes to osteoclasts - inhibits bone formation

Effect PAMPs on cells of the perio tissues (pp262) Prostaglandins

 Role in the establishment and modulation of host response Arachidonic acid metabolites
IL-1B, TNF - a, and LPS increases produciton of cyclooxygenases
 Epithelial cells Function:
 Dendritic ells o Platelet aggregation
 Macrophages o Vasodilation
 Fibroblasts o Vasoconstriciton
 o Chemotaxis Microscopic features
o Bone resorption (increases osteoblastic activity)  Increase nubmer of Macrophages -> more cytokines, PGE< MMP
sources  Gingival fibroblasts more PG and MMP -> more destruction of
o Macrophages collagen
o Fibroblasts  Lymphocytes and B cells dominate
 (+) small gingival pocket
Balance should exist to prevent loss of tissues
Chronic inflammatory response  Impaired blood flow
Repair and regeneration - > anti-inflammatory agent  Extravasation of erythrocyte in to CT and breakdwon to component
pigments
Stages of Gingivitis (Progress of Perio disease ) Chapter 21 pp 355  JE develop ridges/ rete pegs
Initial lesion Protrudes in Ct
Early lesion Clincial features
Established lesion  Increased probing depth
Advanced lesion
 Hemorrhage on BOP
Initial lesion (2-4 days):  Bluish hue on reddened gingiva
Subclinical gingivitis  Swollen shiny gingiva that may have pusand gingival exudate
Early bacterial accumulation phase  Loss of gingival stippling
o Mainly gram + m.o
Microscopic features Advanced Lesion (chronic inflammation)
o Bacterial cell products (PAMPs) Phase of periodontal breakdwon
Recognized by and binds to membrane receptors (TLRs) Only in susceptible persons
Microscopic features
o Start of acute inflammatory immune response
Within 24 hours: acute inflammation in the CT beneath the JE  Plasma cell dominates in CT
Within SE : inc dendritic cells  (+) neutrophils -> JE and gingival crevice
Microsciopic features  Epithelial cells proliferate into the CT (rete pegs)
a. Release of cytokines
 (+) of periodntal pocket
 IL-1 = production of PG  Contineud loss of collagen
IL-8 = cause diapedesis
b. Release of histamine and kinins by mast cells  Cytokines, PGE< MMPs destroy CT and alveolar bone

 Vascular changes For the peridontium to remain healthy, the bacterial infection must be controlled so as
o Increase intercellular gap formation and premeability not to trigger an exaggerated host immune response that causes most of the tissue
o Vasodilation destruction seen in periodontal disease
Release of lysosomes by PMNs
o Destroys both bacteria ang gingival tissue
Increased PMNs in the CT migrate to the SE
Exudation from GS
(+) extravascular proteins
Edema
Release of MMPs
Destruction of basement membrane, and CT of the gingiva
Loss of perivascular collagen - collagenase (enzyme that breaks)
Activation of the Complement system
Gingival tissue destruciton
If the immne response is effective in eliminating the pathogens in the early
phase of acue inflammation, lipoxins from the breakdown of arachidonic acid
are produced -> inflammation resolves and tissue starts to repair
o Lipoxins
Inhibits chemotaxis
inhbits secretion of pro-inflammatory mediators
Induces appostosis (cell death) of PMNs
Attracts macrophages to start removal of cell debris
Early Lesion (early gingiviitis
After 4-7 days of subgingival plaque accumulation
Bacteria and their penetrate the JE
May continue for 21 dyas or longers
Microscopic Features
o Processes that occurred in the initial Lesion will continue but will be
accentuated
o T lymph 75% infiltrate in CT below JE
o Neutrohils, macrophages, plasma cells and mast cells are still present
o Development of rete pgegs/ ridges
Macrophages and PMNs, JE produce more cytokines, Pge , MMPs -> attract
more immune cells
Loss of collagen fibers supporting the marginal gingiva
o Circular group
o Dentogingival gorup
Localized tissue/ collagen destrcuction *70%) around cellular infiltrates
Degeneration of fibroblasts
Inflammatory infiltrates occupy areas of collagen fiber destruction
o -> allows neutrophils to move from CT to sulcus
Clincial
o Lcoalized erythema that may not even be visible
o Slight swelling
o Minimal BOP
If the immune response is effective in eliminating the pathogens in the intial
and early phases of acute inflammation
 Inflammation resolves and tissue starts to repair
Established lesion (chronic gingivitis)
2-3 weeks after accumulation of plaque
Reversible after successful periodontal therapy
2 types: stable or progressive