Microbial interaction with the host in periodontal diseases

Malik Hudieb, BDS, PhD

Department of Preventive Dentistry Faculty of Dentistry Jordan University of Science and Technology

Pathogenesis.. Definition
The development of a disease and the chain

of events that led to this disease.

includes the study of the relationship between:

the cause

the lesions

clinical signs.

Medical dictionary

Gingivitis and Periodontitis

Microbial interaction with the host

Periodontal diseases:

Healthy Gingiva

Gingivitis

Periodontitis

Bacterial Plaque

Host response

Immune system

Inflammation
Bacterial plaque.. Types of bacteria Immune response.. Inflammation Clinical signs

Plaque

Clinical signs

Microbial interaction with the host

Periodontal diseases: Bacterial Plaque Host tissues

Microbial interaction with the host

Periodontal diseases: Bacterial Plaque Host tissues

Host Response

Protective or Destructive?

Host Response

Clinically healthy gingiva

Oral Deposits
Acquired Pellicle Materia alba Dental Plaque Calculus

Copyright 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

DENTAL PLAQUE
Organized biofilm.. Adheres to teeth, prostheses, and hard surfaces Periodontal pockets
(Wilderer and Charaklis 1989)..

DENTAL PLAQUE
- Microorganisms: 70%.. - Organic components (influenced by the environment):
polysaccharide-protein matrix, by-products(enzymes..), food debris and desquamated cells.

- Inorganic components such as calcium and

phosphate.

Dental Plaque

ORGANIC COMPONENTS OF PLAQUE MATRIX polysaccharides - produced by bacteria glycoproteins - from saliva/ initially coats the clean tooth (Pellicle) lipids - membranes of bacterial and host cells

Dental Plaque
Initial bacterial colonization
(Dental pellicle) is predominantly gram-positive facultative spp, Actinomyces species and Streptococci.

Dental Plaque
Secondary colonization :
Gram-negative anaerobic spp. Prevotella intermedia, Capnocytophaga spp., fusobacterium nucleatum, P.gingivalis.

Dental Plaque
Maturation:

Plaque ..

MICROBIAL SPECIFICITY OF PERIODONTAL DISEASES

Nonspecific Plaque Hypothesis: Small amounts of plaque can be neutralized Large amounts of plaque produce disease.

MICROBIAL SPECIFICITY OF PERIODONTAL DISEASES

Modern version of specific theory: (Socransky 1979) 6-12 bacterial species are responsible for the majority of cases of destructive periodontitis Additional species are responsible for small number of other cases. Unified theory: (Theilade in 1986). All bacterial plaque may contribute due to its ability to colonize and evade host defenses and provoke inflammation and tissue damage.

Specific Plaque Hypothesis: Certain types of bacteria is pathogenic. These bacteria produce more substances that cause the destruction of periodontal tissues.

Microbiologic Aspects of the interaction

Virulence factors (enables bacteria to cause the disease): Bacterial adherence, colonization and survival in the periodontal region Host tissue invasion Evasion of host defense mechanisms
Socransky .. Subgingival flora..

Host tissue damage

Adherence, colonization and survival..

GCF washes the periodontal pocket Available surfaces: 1. Tooth and root (pellicle, saliva coated). 2. Tissues. 3. Preexisting plaque mass (coaggregation).

Adherence, colonization and survival..

Host tissue invasion

Ulcerations.. (NUG) Direct penetration..(A.a, P. gingivalis..)

Evasion of host defense mechanisms

Host defense mechanisms???

The immune system

Innate immune system immediate, non-specific response Adaptive immune system specific pathogens.. adaptive immune responses faster and stronger attacks at the second exposure..

Defense mechanisms.. (innate)

The intact barriers (junctional epithelium) The regular shedding of epithelial tissues Saliva (..) The gingival crevice fluid (..)

Immune cells: Neutrophils , Macrophages, Complements.. Washing effect..

Inflame to set fire. Inflammation is A dynamic response of

INFLAMMATION

vascularised tissue to injury. It is a protective response. It serves to bring defense & healing

mechanisms to the site of injury.

Inflammation
Injury
Chemical mediators

Leukocyte infiltration..

Increase blood flow (redness and warmth). Increase vascular permeability (swelling, pain & loss of function). Leukocytic Infiltration.

Mechanism of Inflammation
1. Vaso dilatation 2. Exudation - Edema 3. Emigration of cells

Adaptive immunity
Requires the recognition of specific antigens Antigen presentation Lag time between exposure and maximal response Cell-mediated components

4. Chemotaxis

Exposure leads to immunologic memory

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Chemical Mediators:
Chemical substances synthesised or released and mediate the changes in inflammation.

Microbiota of Disease
Gram-negative facultative or anaerobic bacteria. P. gingivalis, A.a, T. denticola, B. forsythus, F. nucleatum, P. intermedia, C. rectus, P. micros, E. corrodens.

Histamine by mast cells - vasodilatation. Prostaglandins Cause pain & fever. Bradykinin - Causes pain.

Bacterial Adherence
Actinomyces viscosus attaches through fimbriae to proline rich proteins on saliva coated tooth surfaces. P. gingivalis attaches to other bacteria, epithelial cells, and connective tissue fibrinogen and fibronectin.

Bacterial host tissue invasion

Pathways: 1. Ulcerations in epith. of gingival sulcus or pocket. 2. Direct penetration into host epith. or connective tissue cells. Examples: A.a, P.gingivalis, F.nucleatum, T.denticola.

Bacterial host tissue invasion

Clinical significance?
A reservoir for recolonization. Resistance to mechanical debridement.

Bacterial Host Defense Evasion

Mechanisms: Bacterial adherence and tissue invasion. Production of neutralizing substances.
examples: immunoglobulin-degrading proteases, leukotoxin and cytolethal distending toxin (by A.a), apoptosis of lymphocytes (by T.forsythus,F.nucleatum), p.gingivalis inhibit the production of IL-8 by epithelial cells(evade PMNkilling).

Mechanisms of Host Tissue Damage

Direct degradation of host tissues. By: metabolic by products (ammonia, sulfur, fatty acids, peptides and indole) and proteolytic enzymes (trypsin-like degrading collagen, fibronectin,and immunoglobulins).

Mechanisms of Host Tissue Damage

Indirect: by release of biologic mediators from host tissue cells that lead to host tissue destruction. Examples: release of IL-1, TNF, PGs by monocytes,macrophages and PMNs on exposure to bacterial endotoxin. These stimulate bone resorption.

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Immunologic aspects of the interaction

Innate factors and the initiation of inflammation. Complement system Neutrophils (acute infl. response) Macrophages and lymphocytes (chronic infl. response).

Innate factors
Responsible for signs of vascular changes (erythema and edema). Complement derived anaphylatoxins lead to degranulation of mast cells. A cascade of events that result in production of inflammatory cytokines and chemotaxis of leukocytes into local tissues.

Neutrophils
First leukocytes to arrive at the site of inflammation. Dominant in JE and gingival crevice. Functions: transendothelial migration, chemotaxis, transepithelial migration, opsonization, phagocytosis and intraphagolysosomal killing. Disordersaggressive periodontitis. P.gingivalis impedes transepithelial migration.

Neutrophils
Opsonization: coating of particles (bacteria) with host proteins to facilitate phagocytosis. Examples: molecules derived from complement component, specific antibodies (mainly IgG).

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Neutrophils
Phagocytosis: ingestion of the bacterial cell. Bacterial cell killed by oxidative or nonoxidative (lysosomal) mechanisms.

Antibodies
Functions: facilitate host clearance of periodontal pathogens. Essential for opsonization and phagocytosis of A.a and P.gingivalis. Neutralize bacterial components important in colonization or host cell interactions.

Host mediators of destruction

Proteinases. Cytokines. Prostaglandins.

Proteinases
MMPs:degrade extracellular matrix molecules(collagen,gelatin,elastin). expressed by: neutrophils,fibroblasts,macrophages and epithelial cells secreted in inactive form. Activated by bacterial enzymes and host enzymes.

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Proteinases
Neutrophil serine proteinases: elastase and cathepsin G. Degrade elastin, collagen and fibronectin. Activate MMPs. -macrogobulins in plasma and GCF inhibit elastase and cathepsin G.

Cytokines
IL-1 and TNF main ones involved in tissue destruction. IL-1 and TNF are produced by activated macrophages or lymphocytes. Facilitate recruitment of leukocytes, induce PGE2 production by macrophages and fibroblasts. Stimulate bone resorption and induce tissuedegrading proteinases.

Prostaglandins
Are arachidonic acid (found in plasma membrane of cells) metabolites generated by cyclooxygenases. Produced by macrophages and fibroblasts stimulated by IL-1,TNF-, bacterial LPS. Induces MMPs and bone resorption. NSAID?

Microbiology and Immunology in health

Predominantly gram-positive facultative Microorganisms. Chronic infl. Cells (lymphocytes), neutrophils in JE and gingival sulcus. Intact epith., GCF. BALANCE

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In Gingivitis
Increase in proportions of gram-negative anaerobes. Infiltration of neutrophils and lymphocytes (mainly T-cells) Systemic conditions can affect host susceptibily (ex. Pregnancy)

In Chronic Periodontitis
Attachment loss and bone resorption. Amount of destruction consistent with the amount of local factors. Specific microorganisms:P.gingivalis, T.forsythus,T.denticola,P.intermedia, A.a,F.nucleatum,E.corroens,C. rectus. serum and GCF antibody specific to these M.os.

In Chronic Periodontitis
Factors affecting host response such as diabetes, smoking, stress, and HIV infection. Genetics: association between composite genotype(IL1 genes) and occurrence of periodontitis in Caucasians.

In Aggressive Periodontitis
Rapid progression of attachment and bone loss. Other features indicate a greater influence of host response in disease process. Primary etiologic role of A.a. 1. leukotoxin production enables it to lyse phagocytes. 2. Ability to invade tissues

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Aggressive Periodontitis
Problems in host response:
Dysfunctional neutrophils. Problems in chemotaxis. Elevated levels of proinflammatory cytokines. Elevated titers of IgG2 (mainly in LAP).

Necrotizing Periodontal Diseases

P. intermedia, F. nucleatum, Spirochetes Host factors: Immunosuppression, stress, malnutrition, smoking. NUP and HIV infection.

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