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17. DEFENSE MECHANISMS OF THE GINGIVA

For a comprehensive reading on this topic, please refer to CHAPTER 16 - DEFENSE

MECHANISMS OF THE GINGIVA in Carranza’s Clinical Periodontology, 13th ed., 2018.

The gingival tissue is continuously subjected to challenge, influencing the host response
type. The epithelial surface, immune response, crevicular fluid, and saliva provide active
responses to maintain gingival health. This chapter describes important mechanisms of the
gingival response repertoire, including the role of sulcular fluid, junctional epithelium,
permeability, sulcular epithelia, sulcular fluid, saliva, and leukocytes.

1. The Sulcular Fluid

Sulcular fluid, or gingival crevicular fluid (GCF), contains an array of biologic
mediators, cells, and bacteria. The presence of GCF in humans is considered as a “transudate.”
However, other authors demonstrated that GCF is an inflammatory exudate rather than a
transudate (66, 111). In strictly normal gingiva, little or no fluid can be collected.
Potential markers from crevicular fluid are now used as diagnostic tools for the activity of
periodontal diseases and a return to homeostasis, with potential for the evaluation of systemic
markers.

Permeability of Junctional and Sulcular Epithelia

Substances that have been shown to penetrate the sulcular epithelium include albumin,
endotoxins, thymidine, histamine, phenytoin, and horseradish peroxidase (88, 87, 92, 45, 25, 105,
72). The intercellular movement of molecules and ions along intercellular spaces appears to be a
possible mechanism of penetration through an intact epithelium (104). Substances that take this
route do not traverse the cell membranes.

Amount
The amount of GCF collected on a paper strip can be studied in multiple ways. The
wetted area can be made more visible by staining with Ninhydrin; it is then measured
planimetrically on an enlarged photograph or with a magnifying glass or a microscope. An
electronic method has also been used (the Periotron® device). The wetness of the paper strip
affects the flow of an electric current and provides a digital readout. A comparison between the
Ninhydrin-staining method and the electronic method performed in vitro revealed no significant
differences between the two techniques (107). The amount of GCF collected is extremely small.

Composition
The components of GCF are characterized by individual proteins, metabolites, specific
antibodies, antigens, and enzymes of several specificities (66, 79, 96, 32, 86). The GCF also
contains cellular elements (25, 28, 113). Multiple research efforts have attempted to use GCF
components to detect or diagnose active disease or to predict which patients are at risk for
periodontal disease (Table 16.1). These compounds can be derived from the host or produced by
bacteria in the gingival crevice, but their source can be difficult to elucidate.
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a. Cellular Elements
Cellular elements found in GCF include bacteria, desquamated epitheial cells, and
leukocytes, which migrate through the sulcular epithelium (25, 28).
b. Electrolytes
Potassium, sodium, and calcium have been studied in the GCF. Most studies have
demonstrated a positive correlation of calcium and sodium concentrations with the
sodium/potassium ratio seen with inflammation (51, 52, 53).
c. Organic Compounds
Both carbohydrates and proteins have been investigated. Glucose hexosamine and
hexuronic acid are two compounds that are found in GCF (43). Glucose concentration in GCF is
three to four times greater than that in serum (43). The total protein content of GCF is much less
than that of serum (12, 14). No significant correlations have been found between the
concentration of proteins in GCF and the severity of gingivitis, pocket depth, or extent of bone
loss (8). The methodology used to analyze GCF components is as varied as the diversity of those
components.

Cellular and Humoral Activity in Gingival Crevicular Fluid

Analyzing GCF constituents in health and disease may be extremely useful as a result of
GCF’s simplicity and because GCF can be obtained with noninvasive methods.
The analysis of GCF has identified cellular and humoral responses in both healthy
individuals and those with periodontal disease (59). The cellular immune response includes the
appearance of cytokines in GCF, but there is no clear evidence of a relationship between cytokines
and disease. However, IL-1α and IL-1β are known to increase the binding of PMNs and
monocytes/macrophages to endothelial cells, to stimulate the production of prostaglandin E2 and
the release of lysosomal enzymes, and to stimulate bone resorption (62). Because the amount of
fluid recoverable from gingival crevices is small, only the use of very sensitive immunoassays
permits the analysis of the specificity of antibodies (24, 26, 27).

Clinical Significance
As an exudate, GCF is a biologic fluid that has potential in diagnostics and disease
management (66). The amount of GCF is greater when inflammation is present, and it is
sometimes proportional to the severity of inflammation (31, 98). A lot of different factors
influence the amount of GCF.
Circadian Periodicity: There is a gradual increase in the amount of GCF from 6 a.m. to
10 p.m. and a decrease thereafter (9).
Sex Hormones: Female sex hormones increase GCF flow, probably because they enhance
vascular permeability (62). Pregnancy, ovulation, and hormonal contraceptives all increase GCF
production (61, 63).
Mechanical Stimulation: Chewing and vigorous gingival brushing stimulate the flow of
GCF (11).
Smoking: Smoking produces an immediate transient but marked increase in GCF flow
but, in the long term, a decrease of salivary and GCF flow (73).
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Periodontal Therapy: There is an increase in GCF production during the healing period
after periodontal surgery (4).

Drugs in Gingival Crevicular Fluid

Drugs that are excreted through the GCF may be used advantageously in periodontal
therapy. Tetracyclines are excreted through the GCF (7). Metronidazole is another antibiotic that
has been detected in human GCF (29).

2. Leukocytes in the Dentogingival Area

Leukocytes have been found in clinically healthy gingival sulci. The leukocytes found are
predominantly PMNs. They appear in small numbers extravascular in the connective tissue
adjacent to the apical portion of the sulcus; from there, they travel across the epithelium to the
gingival sulcus, where they are expelled (17, 41) (Figs. 16.3 and 16.4).
Leukocytes were reported in the gingival sulcus in nonmechanically irritated healthy
gingiva, thereby indicating that their migration may be independent of an increase in vascular
permeability. The majority of these cells are viable and have phagocytic and killing capacity (58,
84, 91). Therefore, leukocytes constitute a major protective mechanism against the extension of
plaque into the gingival sulcus.

3. Saliva

Saliva exerts a major influence on plaque by mechanically cleansing the exposed oral
surfaces, buffering acids produced by bacteria, and modulating bacterial activity with immune
mediators (78). Saliva is now considered a main biologic fluid for diagnosis of human health and
diseases. Systemic and local disease markers are available through saliva.

Antibacterial Factors
Saliva carries inorganic and organic factors that influence bacteria and their products in
the oral environment.
Lysozyme works on both Gram-negative and Gram-positive organisms (46); its targets
include Veillonella species and Actinobacillus actinomycetemcomitans.
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 (75, 93).
Myeloperoxidase, an enzyme that is similar to salivary peroxidase, is released by
leukocytes; it is bactericidal for Actinobacillus, 74 but it has the added effect of inhibiting the
attachment of Actinomyces strains to hydroxyapatite (74, 21).

Salivary Antibodies
As with GCF, saliva contains antibodies that are reactive with indigenous oral bacterial
species. Although immunoglobulins G (IgG) and M (IgM) are present, the preponderant
immunoglobulin found in saliva is immunoglobulin A (IgA), whereas IgG is more prevalent in
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GCF (106). Salivary antibodies appear to be synthesized locally, because they react with bacteria
that are indigenous to the mouth but not with organisms that are characteristic of the intestinal
tract (33, 35). IgA antibodies present in parotid saliva can inhibit the attachment of oral
Streptococcus species to epithelial cells (30, 1100.

Enzymes
The enzymes that are normally found in saliva are derived from the salivary glands,
bacteria, leukocytes, oral tissues, and ingested substances; the major enzyme is parotid amylase.
Certain salivary enzymes have been reported in increased concentrations in periodontal disease:
hyaluronidase and lipase (16), β-glucuronidase and chondroitin sulfatase (37), aspartate
aminotransferase and alkaline phosphatase (109), amino acid decarboxylases (37), catalase,
peroxidase, and collagenase (55).
Proteolytic enzymes in the saliva are generated by both the host and oral bacteria. These
enzymes have been recognized as contributors to the initiation and progression of periodontal
disease (45, 690. High-molecular-weight mucinous glycoproteins in saliva bind specifically to
many plaque-forming bacteria. The glycoprotein-bacteria interactions facilitate bacterial
accumulation on the exposed tooth surface (30, 33-35, 112).

Salivary Buffers and Coagulation Factors

The maintenance of physiologic hydrogen ion concentration (pH) at the mucosal
epithelial cell surface and tooth surface is an important function of salivary buffers. The primary
effect action of buffers has been investigated with relationship to dental caries. In saliva, the
most important buffer is the bicarbonate–carbonic acid system (68).
Saliva also contains coagulation factors (i.e., factors VIII, IX, and X; plasma
thromboplastin antecedent; and Hageman factor) that hasten blood coagulation and protect
wounds from bacterial invasion (60).

Leukocytes
In addition to desquamated epithelial cells, saliva contains all forms of leukocytes, of
which the principal cells are PMNs. The number of PMNs varies from person to person at
different times of the day, and it is increased in the presence of gingivitis. PMNs reach the oral
cavity by migrating through the lining of the gingival sulcus. There is a positive correlation
between rate of PMN migration and the severity of gingival inflammation, and it is therefore a
reliable index for the assessment of gingivitis (102).

Role in Periodontal Pathology

Saliva modulates plaque initiation, maturation, and metabolism. Salivary flow and
composition also influence calculus formation, periodontal disease, and caries. Increases of
inflammatory gingival conditions, dental caries, rapid tooth destruction, and cervical or cemental
caries are associated, at least partially, with decreased salivary gland secretion (xerostomia; Box
16.1). Xerostomia may result from sialolithiasis, sarcoidosis, Sjögren syndrome, Mikulicz
disease, irradiation, surgical removal of the salivary glands, and other factors.