**3.1 Role of host susceptibility in gingivitis**

Even though the development of gingivitis after plaque accumulation is a universal finding, the rate or speed of development and the degree of the clinical inflammatory response are variables between individuals, even under similar plaque accumulation conditions [9]. The studies recognizing the role of host contributing to the pathology of periodontal disease was a major breakthrough [10]. Various studies using the experimental gingivitis model showed 13% of all individuals representing a "resistant" group [9, 11, 12]. The factors modulating the appearance of gingival inflammation in response to plaque accumulation are mainly exacerbated gingival response to plaque, including metabolic factors such as puberty and pregnancy; genetic factors such as Down syndrome; nutritional factors such as vitamin C deficiency; the intake of drugs such as those leading to gingival enlargement; systemic diseases such as leukemia, immune deficiencies, and diabetes mellitus; and other conditions such as stress [9].

Gingivitis and periodontitis are the result of a coordinated action of clearly defined cellular players (proinflammatory and anti-inflammatory), which communicate with each other [13]. An inflammatory reaction can develop in two directions, either being destructive or regenerative depending on the bacterial antigen load and properties. If destructive, the innate immune reaction is followed by an adaptive or specific immune response, associated with the loss of tissue structure to create space for the immune process, and resolution of inflammation is associated with the regeneration of these structural hard and soft tissue components. It is therefore important to understand the cellular and molecular elements involved in the pathways from health to disease and from disease to repair and regeneration. The complex biological mechanisms occur in many phases from bacterial biofilm formation to periodontal regeneration and repair.

#### **3.2 Host cells in periodontal pathogenesis**

The inflammatory infiltrate of periodontal disease (gingivitis and periodontitis) is characterized by polymorphonuclear leukocytes (PMNs), macrophages, lymphocytes, plasma cells [6]. The periodontium consists of cellular elements (epithelial cells, the periodontal ligament and gingival fibroblasts, and osteoblasts and osteoclasts) and molecular elements (extracellular matrix components such as the various collagens and the noncollagenous proteins). The interactions between these components determine the nature of periodontal disease activity, whether gingivitis or periodontitis.

#### *3.2.1 Polymorphonuclear leukocytes (PMNs/neutrophils)*

PMNs are the first line of defense against bacteria, and proper PMN functionality is essential for protecting the integrity of the periodontium [14]. Neutrophils, present in clinically healthy gingival tissues, migrate through the intercellular spaces of the junctional epithelium into the sulcus [15, 16], in response to inflammatory chemotactic mediators such as IL-1, IL-8, or bacterial peptides (i.e., fMLP), and provide a "low-grade defense" against plaque bacteria [15, 17–19].

The proportion of neutrophils increases from 2% to 30% in modest inflammation causing vascular permeability which facilitates leukocyte emigration and increases the flow of GCF into the pocket [15]. At the molecular level, the interaction of adhesion molecules (e.g., ICAM-1) on endothelial and epithelial cells with β2 integrins on neutrophils facilitates neutrophil migration.

In the tissues, neutrophils phagocytose microorganisms and produce reactive oxygen species (ROS) to kill within the cells by the formation of neutrophil extracellular traps (NETs). NETs can be released by viable neutrophils and also following a form of programmed cell death called NETosis [20–24]. NETs are webs of complexed nuclear and mitochondrial chromatin/DNA and antimicrobial molecules such as histones and antimicrobial peptides (AMPs) [25, 26]. In established lesions, neutrophils release toxic superoxides, free oxygen radicals, and tissue degrading enzymes contributing to local inflammation and tissue damage [27].

#### *3.2.2 Macrophages*

Macrophages are mononuclear cells mainly participating in the early or innate defense against microorganisms and in specific immunity through their antigenpresenting function by releasing various cytokines. These cells present with varied phenotypes or subsets [28] and diverse functionality.

#### *3.2.3 Natural killer cells*

These killer cells are involved in the innate immune response by playing a vital role in host defenses against infected and malignant cells by producing cytokines such as TNF-α and interferon-g. These lymphocyte subgroup cells increase significantly from healthy human gingiva to diseased periodontal tissues [29, 30], in the immune response to plaque biofilm accumulation. Impaired lymphocyte function is also reported in various systemic conditions associated with periodontal diseases (e.g., Papillon-Lefèvre syndrome [31], Chédiak-Higashi syndrome [32], and smoking [33]).

#### *3.2.4 Lymphocytes*

Lymphocytes are one of the main types of immune cells with subsets T and B cells. When the innate or non-specific immunity is not able to cope with the

**15**

**Figure 1.**

*Immune responses in periodontal pathogenesis.*

*Pathogenesis of Gingivitis*

pathogenesis of periodontitis.

**4.1 Innate immunity**

*DOI: http://dx.doi.org/10.5772/intechopen.91614*

**4. Immune responses in periodontal pathogenesis**

elements of tissue repair and regeneration [38] as shown in **Figure 1**.

bacterial challenge, it activates the adaptive immune system by a group of cells, the T cells that have specific ability to present the bacterial antigens to the immunecompetent cells. T lymphocytes mainly contributes to periodontal pathogenesis by direct involvement in periodontal bone resorption [34, 35]. B cells, the second major lymphocyte subset, give rise to plasma cells that produce specific antibodies when triggered by the antigen and other regulatory cells. The number of B cells increases from health to gingivitis to periodontitis [6, 36], and its major role is in the

The immune systems are essential for the maintenance of periodontal health and are mainly categorized as innate immune system and the adaptive immune system (**Figure 1**). It is now widely studied that immune responses are complex biologic networks in which pathogen recognition, innate immunity, and adaptive immunity are integrated and mutually dependent [37]. They are also integrated with other systems, including the nervous system, hematopoiesis, and homeostasis as well as

The term "innate immunity" refers to the elements of the immune response that are determined by inherited factors, that have limited specificity, and do not change or improve during an immune response or as a result of previous exposure to a pathogen. Innate immune mechanisms include a number of relatively non-specific mechanisms, including the barrier effect of an intact epithelium, saliva, and GCF (**Figure 1**). The keratinized epithelium of the sulcular and gingival epithelial tissues provides protection for the underlying periodontal tissue in addition to acting as a barrier against bacteria and their products [15, 39]. Saliva, secreted from three major salivary glands, plays an important role in preventing the attachment of bacteria to the dentition and the oral mucosal surfaces. These components include molecules that non-specifically inhibit the formation of the plaque biofilm by inhibiting adherence to oral surfaces and promoting agglutination (e.g., mucins), those that inhibit specific virulence factors (e.g., histatins that neutralize lipopolysaccharide (LPS)) and those that inhibit bacterial cell growth (e.g., lactoferrin) and

#### *Pathogenesis of Gingivitis DOI: http://dx.doi.org/10.5772/intechopen.91614*

*Oral Diseases*

**3.2 Host cells in periodontal pathogenesis**

*3.2.1 Polymorphonuclear leukocytes (PMNs/neutrophils)*

integrins on neutrophils facilitates neutrophil migration.

phenotypes or subsets [28] and diverse functionality.

The inflammatory infiltrate of periodontal disease (gingivitis and periodontitis) is characterized by polymorphonuclear leukocytes (PMNs), macrophages, lymphocytes, plasma cells [6]. The periodontium consists of cellular elements (epithelial cells, the periodontal ligament and gingival fibroblasts, and osteoblasts and osteoclasts) and molecular elements (extracellular matrix components such as the various collagens and the noncollagenous proteins). The interactions between these components determine the nature of periodontal disease activity, whether gingivitis or periodontitis.

PMNs are the first line of defense against bacteria, and proper PMN functionality is essential for protecting the integrity of the periodontium [14]. Neutrophils, present in clinically healthy gingival tissues, migrate through the intercellular spaces of the junctional epithelium into the sulcus [15, 16], in response to inflammatory chemotactic mediators such as IL-1, IL-8, or bacterial peptides (i.e., fMLP),

The proportion of neutrophils increases from 2% to 30% in modest inflammation causing vascular permeability which facilitates leukocyte emigration and increases the flow of GCF into the pocket [15]. At the molecular level, the interaction of adhesion molecules (e.g., ICAM-1) on endothelial and epithelial cells with β2

In the tissues, neutrophils phagocytose microorganisms and produce reactive oxygen species (ROS) to kill within the cells by the formation of neutrophil extracellular traps (NETs). NETs can be released by viable neutrophils and also following a form of programmed cell death called NETosis [20–24]. NETs are webs of complexed nuclear and mitochondrial chromatin/DNA and antimicrobial molecules such as histones and antimicrobial peptides (AMPs) [25, 26]. In established lesions, neutrophils release toxic superoxides, free oxygen radicals, and tissue degrading

Macrophages are mononuclear cells mainly participating in the early or innate defense against microorganisms and in specific immunity through their antigenpresenting function by releasing various cytokines. These cells present with varied

These killer cells are involved in the innate immune response by playing a vital role in host defenses against infected and malignant cells by producing cytokines such as TNF-α and interferon-g. These lymphocyte subgroup cells increase significantly from healthy human gingiva to diseased periodontal tissues [29, 30], in the immune response to plaque biofilm accumulation. Impaired lymphocyte function is also reported in various systemic conditions associated with periodontal diseases (e.g., Papillon-Lefèvre syndrome [31], Chédiak-Higashi syndrome [32], and smoking [33]).

Lymphocytes are one of the main types of immune cells with subsets T and B cells. When the innate or non-specific immunity is not able to cope with the

and provide a "low-grade defense" against plaque bacteria [15, 17–19].

enzymes contributing to local inflammation and tissue damage [27].

**14**

*3.2.2 Macrophages*

*3.2.3 Natural killer cells*

*3.2.4 Lymphocytes*

bacterial challenge, it activates the adaptive immune system by a group of cells, the T cells that have specific ability to present the bacterial antigens to the immunecompetent cells. T lymphocytes mainly contributes to periodontal pathogenesis by direct involvement in periodontal bone resorption [34, 35]. B cells, the second major lymphocyte subset, give rise to plasma cells that produce specific antibodies when triggered by the antigen and other regulatory cells. The number of B cells increases from health to gingivitis to periodontitis [6, 36], and its major role is in the pathogenesis of periodontitis.
