Host-microbe interactions

The host response functions in a protective capacity, preventing the local infection from progressing to a systemic, life-threatening infection.

MICROBIOLOGIC ASPECTS OF THE MICROBIAL-HOST INTERACTION:

In general, gram-negative facultative or anaerobic bacteria appear to represent the predominant microorganisms associated with disease. (Predominant bacterial species that have been implicated in the disease processes include Porphyromona sgingivalis, Actinobacillus actinomycetemcomitans, Treponemadenticola, Bacteroidesforsythus, Fusobacteriumnucleatum, Prevotellaintermedia, Campylobacter rectus, Peptostreptococcus micros and Eikenellacorrodens).
to function as a pathogen, a bacterium must:
Colonize the appropriate host tissue site (periodontium) and then cause destruction of the host tissues.
Has the ability to evade host defense mechanisms aimed at eliminating the bacterium from the periodontal environment.

Thus virulence properties can be broadly categorized into two groups:

Factors that enable a bacterial species to colonize and invade host tissues,
Factors that enable a bacterial species, directly or indirectly, to cause host tissue damage.

Bacterial Adherence in the Periodontal Environment:

The surfaces available for attachment include the tooth or root, tissues, and preexisting plaque mass.
Bacteria that initially colonize the periodontal environment most likely attach to the pellicle- or saliva coated tooth surface.

Host Tissue Invasion (microbial colonization and proliferation within the tissues):

Bacteria may enter host tissues through ulcerations in the epithelium of the gingival sulcus or pocket and have been observed in intercellular spaces of the gingival tissues.
Direct penetration of bacteria into host epithelial or connective tissue cells (as A. actinomycetemcomitans, P gingivalis, nucleatum and Treponemadenticola).


"bursts of disease activity" observed in periodontitis may be related to phases of bacterial invasion of the tissues."' An additional possibility is that bacteria in the tissues may enable persistence of that species in the periodontal pocket by providing a reservoir for recolonization.
Consistent with this hypothesis is the observation that mechanical debridement alone is insufficient, and that systemic antibiotics in combination with surgical therapy are required, to eliminate A. actinomycetemcomitans from lesions in patients with localized aggressive periodontitis.

Bacterial Evasion of Host Defense Mechanisms.

To survive in the periodontal environment, bacteria must neutralize or evade the host mechanisms involved in bacterial clearance and killing.
Periodontal bacteria neutralize or evade host defenses via numerous other mechanisms:

Host Defense Mechanism

Bacterial Property
Biologic Effect
Bacterial Species
Specific antibody
IgA and IgG degrading proteases
Degradation of specific antibody
P. gingivalis
P intermedia
P. melaninogenica
Capnocytophaga sp.
Polymorphonuclear
leukocytes
Leukotoxin
Heat-sensitive surface protein
Capsule
Inhibition of superoxide production
Inhibition of PNM function
Apoptosis (programmed cell death) of PMN
Inhibition of phagocytosis
Decreased bacterial killing
A. actinomycetemcomitons
F. nucleatum
P. gingivalis
P. gingivalis
T. denticola
Lymphocytes
Leukotoxin
Cytolethal distending toxin
Killing of mature B and T cells;
nonlethal suppression of activity
Impairment of function by
arresting of lymphocyte cell
A. actinomycetemcomitans
A. actinomycetemcomitans
Release of IL-8
Inhibition of IL-8 production by epithelial cells
Impairment of PMN response
to bacteria


P. gingivalis

Microbial Mechanisms of Host Tissue Damage:

Some bacterial products inhibit the growth or alter the metabolism of host tissue cells; these include
A number of metabolic by-products such as ammonia; volatile sulfur compounds; and fatty acids, peptides, and indole.
A variety of enzymes produced by periodontal microorganisms. These enzymes appear to be capable of degrading essentially all host tissue and intercellular matrix molecules (proteolytic enzymes).These soluble enzymes may digest extracellular host proteins and other molecules and thereby produce nutrients for bacterial growth.
Bacteria may indirectly cause tissue damage is by induction of host tissue proteinases such as elastase and matrix metalloproteinases.

Well-characterized interactions involve the release of interleukin-1 (IL-1), tumor necrosis factor (TNF), and prostaglandins from monocytes, macrophages, and PMNs exposed to bacterial endotoxin (lipopolysaccharide). These host-derived mediators have the potential to stimulate bone resorption and activate or inhibit other host immune cells.
Important aspects of host defense processes:
Inflammatory processes:
Host responses may either result in
a rapid resolution of the lesion (e.g. a staphylococcal abscess which heals)
No lesion at all develops in the affected tissue (e.g. smallpox infection in a successfully vaccinated host).
An ineffective response may result in a chronic lesion that does not resolve (e.g. tuberculosis)
A lesion in which the host responses contribute significantly to tissue destruction (e.g. rheumatoid arthritis or asthma).

In the classical description of inflammation, tissue is presented that appears macroscopically:
Redness and heat which due to vasodilatation and increased blood flow.
Swelling is a result of increased vascular permeability and leakage of plasma proteins that create an osmotic potential that draws fluid into the inflamed tissues. Related to the vascular changes there is an accumulation of inflammatory cells infiltrating the lesion.
Pain is rarely experienced in aggressive and chronic periodontal disease, but could theoretically occur due to stimulation of afferent nerves by chemical mediators of inflammation in necrotizing periodontal disease.
Possible loss of function in specific sites.


Leukocyte in dentogingival region:
Leukocytes (predominantly PMNs) are present in sulci even when histologic sections of adjacent tissue are free of inflammatory infiltrate.
Leukocytes are attracted by different plaque bacteria
The majority of these cells is viable and has been found to have phagocytic and killing capacity; therefore they constitute a major protective mechanism against the extension of plaque into the gingival sulcus.
Leukocytes are also found in saliva. The main port of entry of leukocytes into the oral cavity is the gingival sulcus.
The number of PMNs varies from person to person at different times of the day and is increased in gingivitis.
PMNs reach the oral cavity by migrating through the lining of the gingival sulcus.
Living PMNs in saliva are sometimes referred to as orogranulocytes, and their rate of migration into the oral cavity is termed the orogranulocytic migratory rate.
Some investigators think that the rate of migration is correlated with the severity of gingival inflammation and is therefore a reliable index for assessing gingivitis.

Saliva:

Secretions are protective in nature because they maintain the oral tissues in a physiologic state.
Saliva exerts a major influence on plaque by mechanically cleansing the exposed oral surfaces, by buffering acids produced by bacteria, and by controlling bacterial activity.
Saliva contains numerous inorganic and organic factors :
Inorganic factors include ions and gases, bicarbonate, sodium, potassium, phosphates, calcium, fluorides, ammonium, and carbon dioxide.
Organic factors include lysozyme, lactoferrin, myeloperoxidase, lactoperoxidase, and agglutinins such as glycoproteins, mucins, ß2-macroglobulins, fibronectins, and antibodies.
Lysozymeis a hydrolytic enzyme that cleaves the linkage between structural components of the glycopeptidemuramic acid-containing region of the cell wall of certain bacteria in vitro. Lysozyme works on both gram negative and gram-positive organisms.
The lactoperoxidase-thiocyanate system in saliva has been shown to be bactericidal to some strains of Lactobacillus and Streptococcus by preventing the accumulation of lysine and glutamic acid, both of which are essential for bacterial growth.
Myeloperoxidase, an enzyme similar to salivary peroxidase, is released by leukocytes and is bactericidal for Actinobacillus" but has the added effect of inhibiting the attachment of Actinomyces strains to hydroxyapatite.

Salivary Buffers and Coagulation Factors

The maintenance of physiologic hydrogen ion concentration (pH) at the mucosal epithelial cell surface and the tooth surface is an important function of salivary buffers
In saliva the most important salivary buffer is the bicarbonate-carbonic acid system.
Saliva also contains coagulation factors (factors VIII, IX, and X; plasma thromboplastin antecedent [PTA]; and the Hageman factor) that hasten blood coagulation and protect wounds from bacterial invasion. The presence of an active fibrinolytic enzyme has also been suggested.


Leukocytes
Saliva contains all forms of leukocytes (PMNs).

Role in Periodontal Pathology

Saliva exerts a major influence on plaque initiation, maturation, and metabolism.
Salivary flow and composition also influence calculus formation, periodontal disease, and caries.

Proteinases (proteases):

Periodontal disease results in tissue degradation, and thus proteases, derived both from the host and from bacteria, are central to the disease processes. Proteinases (collagenase, elastase-like and trypsin-like, as well as serine and cysteine proteinases) cleave proteins by hydrolyzing peptide bonds and may be classified into two major classes, endopeptidases and exopeptidases, depending on the location of activity of the enzyme on its substrate.