**2.1 Structure of the lacrimal gland**

The lacrimal gland is located on the upper lateral side of the orbit, beneath the conjunctiva (**Figure 14**). The lacrimal gland consists of several separate lobules formed by the tubuloacinar serous glands [7, 67]. The lacrimal gland is structurally similar to salivary glands. This gland was divided into lobules by irregular tight connective tissue. In the lobules, acinar cells and mucus tubules are located together. The acini have large lumens built with prismatic cells. Secretions produced in acinar and tubular structures are transmitted to the superior fornix

**23**

process [4, 7].

**Figure 13.**

**Figure 12.**

*(Dr. Alpaslan Gokcimen).*

through the small duct channels. Tears drain in the inner aspect of the eye and then nasal cavity with the nasolacrimal duct (**Figures 15** and **16**), [10, 67]. The myoepithelial cells located between the epithelial cells and the basal lamina help this

*(a) In the section stained with hematoxylin-eosin in the sublingual gland, the irregular tight connective tissue was divided into lobules. Interlobular ducts are observed. (b) The sublingual gland is a mixed gland consisting of mucous tubules and serous acini. Mucous tubules are predominant. (c) Serous acinus of the sublingual is* 

*observed. (d) The mucous tubule of the sublingual gland is seen (Dr. Alpaslan Gokcimen).*

*(a) In the parotid gland, which is a pure serous gland, the irregular tight connective tissue is divided into the lobules. Interlobular ducts are seen. (b) Serous acinus and intralobular ducts are observed in the parotid section* 

*Morphology of Salivary and Lacrimal Glands DOI: http://dx.doi.org/10.5772/intechopen.84380* *Morphology of Salivary and Lacrimal Glands DOI: http://dx.doi.org/10.5772/intechopen.84380*

#### **Figure 12.**

*Chronic Autoimmune Epithelitis - Sjogren's Syndrome and Other Autoimmune Diseases...*

Golgi complex together form secretory granules [4–10].

b.The submandibular gland as with the parotid gland has the irregular tight connective tissue that surrounds the organ and divides it into lobules (**Figure 11a**). The submandibular gland has both serous acinus and mucous tubules (the compound is a tubuloacinar gland), and the acinar cells were predominant. Hence, serous majority makes seromucous secretion. Acinus has the same structure as the parotid gland. The duct channels are also arranged in the same way as the parotid, and secretion is excreted in the oral cavity with "Wharton duct." The fat cells from connective tissue cells are located between the acinus and the mucous tubules. Myoepithelial cells are likewise located between the serous cells and the basement membrane and the basal membrane with mucous cells. A rich capillary system surrounds the organ. This system is accompanied by nerve vessels. Mucogenous granules are present in them because the mucous cells are pale. Since serous cells contain zymogen granules, they stained in dark color and have basophilic appearance. The ergastoplasm is dominant, and therefore, protein secretion is predominant to carbohydrate secretion [4–10].

c.The sublingual gland has the same structure as the other two major salivary glands. This gland is a mixed acinotubular. However mucous tubules are its predominant compound (**Figure 13a**–**d**). The duct channels of the gland, myoepithelial cells, and capillary and neural networks are as in the other two salivary glands, and salivary secretion reaches the oral cavity with a major sublingual duct. The fat cells are located between the functioning parenchyma [4–10].

The lacrimal gland is located on the upper lateral side of the orbit, beneath the conjunctiva (**Figure 14**). The lacrimal gland consists of several separate lobules formed by the tubuloacinar serous glands [7, 67]. The lacrimal gland is structurally similar to salivary glands. This gland was divided into lobules by irregular tight connective tissue. In the lobules, acinar cells and mucus tubules are located together. The acini have large lumens built with prismatic cells. Secretions produced in acinar and tubular structures are transmitted to the superior fornix

d.The properties of macroscopic salivary glands are given in **Table 2**.

**2.1 Structure of the lacrimal gland**

Prismatic-shaped epithelium is arranged on the basal lamina to form intralobular ducts. The basal cell membrane forms inward folds. A large number of mitochondria are located parallel to these basal invaginations. Basal invaginations are often seen in tissues and organs which allow water transport. The best example of this condition is the renal proximal and distal tubular epithelial cells and the striated duct in the salivary glands. Striated ducts have the ionic pump activity. These structures enable reabsorpsion of sodium and secretion of potassium and hydrogen ions, but reabsorption of sodium more than the potassium secretion. Thus, the secretion becomes hypotonic [7]. In this way, many substances which are reabsorbed from the apical are transported to the basal portion by active transport. The basal labyrinth is involved in transport of water and reabsorption of sodium from the saliva. Acinus and all excretory ducts are surrounded by a rich capillary network. The spherical-shaped nuclei of serous cells are in the middle of the cytoplasm. The organelles are welldeveloped granular endoplasmic reticulum and Golgi apparatus; the granular endoplasmic reticulum and ribosomes form ergastoplasm. Ergastoplasm is seen basophilic because it makes abundant protein synthesis. The ergastoplasm and

**22**

*(a) In the parotid gland, which is a pure serous gland, the irregular tight connective tissue is divided into the lobules. Interlobular ducts are seen. (b) Serous acinus and intralobular ducts are observed in the parotid section (Dr. Alpaslan Gokcimen).*

#### **Figure 13.**

*(a) In the section stained with hematoxylin-eosin in the sublingual gland, the irregular tight connective tissue was divided into lobules. Interlobular ducts are observed. (b) The sublingual gland is a mixed gland consisting of mucous tubules and serous acini. Mucous tubules are predominant. (c) Serous acinus of the sublingual is observed. (d) The mucous tubule of the sublingual gland is seen (Dr. Alpaslan Gokcimen).*

through the small duct channels. Tears drain in the inner aspect of the eye and then nasal cavity with the nasolacrimal duct (**Figures 15** and **16**), [10, 67]. The myoepithelial cells located between the epithelial cells and the basal lamina help this process [4, 7].


#### **Table 2.**

*Comparison of secretory content, structure and discharge channels of saliva glands.*

#### **Figure 14.**

*Sagittal view of the upper and lower eyelids. The glands of Krause (arrow) are located in the superior conjunctival fornix. The glands of Wolfring (arrowhead) are found at the nonmarginal border of the tarsal plate [67] (with permission by Dr. Bhupendra Patel).*

On the other hand, the lacrimal gland is made of several lobules separated by loose connective tissue. Each lobule consists of many acini, lined with columnar serous cells that produce a watery secretion. The central lumina of many units converge to form intralobular ducts, which unite to drain into 8–12 excretory ducts [11, 12].

#### **2.2 The saliva and tear composition**

Saliva is made up mostly of water (97–99.5%) originating from plasma of acinar cells [13]. The content of salivation has mucous, serous, or serous-mucous features. Mucous secretion is a thick form viscous fluid of highly glycosylated glycoproteins. Serous secretion is fluent and with clear consistency, forming thin, watery secretion containing proteins and glycoproteins. Seromucous form mixed secretin of intermediate thickness [14, 15]. Saliva is composed of a variety of electrolytes, including sodium, potassium, calcium, magnesium, bicarbonate, phosphates, immunoglobulins, proteins, enzymes, mucins, and nitrogenous products, such as urea and ammonia [16].

**25**

**Figure 16.**

*[67] (with permission by Dr. Bhupendra Patel).*

*Morphology of Salivary and Lacrimal Glands DOI: http://dx.doi.org/10.5772/intechopen.84380*

histatins have been isolated from human saliva.

*[67] (with permission by Dr. Bhupendra Patel).*

basic, and glycosylated [20].

**Figure 15.**

Histatins, the human salivary proline-rich proteins (PRPs) and statherin proteins are found in three kinds of protein saliva [17]. Histatins are a family of related neutral and basic histidine-rich peptides which are secreted mainly from parotid saliva and, to a lesser extent, submandibular saliva [18, 19]. A total of 12 salivary

*Oblique view of the right orbit. Oblique view of the right orbit showing the main lacrimal gland divided into the orbital lobe (OL) and palpebral lobe by the lateral horn of the levator aponeurosis (LA). Note the excretory ducts coursing through the palpebral lobe and draining into the superior conjunctival fornix (arrow)* 

The human salivary proline-rich proteins (PRPs) are a heterogeneous group of proteins that comprise about 70% of the parotid proteins. They are characterized by a predominance of the amino acids proline, glycine, and glutamic acid/glutamine (a total of 80% of all amino acids). PRPs are classified into three groups: acidic,

*Lacrimal gland histopathology. H&E staining of a normal lacrimal gland. The gland is composed of lobules separated by loose connective tissue. The lobules are composed of multiple acini lined by columnar secretory cells*  *Morphology of Salivary and Lacrimal Glands DOI: http://dx.doi.org/10.5772/intechopen.84380*

#### **Figure 15.**

*Chronic Autoimmune Epithelitis - Sjogren's Syndrome and Other Autoimmune Diseases...*

**Name of the gland Secretory content Structural properties of gland The opening of the** 

connective tissue Parenchyma: Asinus (Compound alveolar gland)

Stroma: Irregular tight connective tissue and ve fat cells Parenchyma: Compound tubuloalveolar gland

Stroma: Irregular tight connective tissue and ve fat cells Parenchyma: Compound tubuloalveolar gland

Parotid Pure serous Zymogen granules Stroma: Irregular tight

Mainly serous mixed (serous and mucous) Zymogen and mucinogen granules

(serous and mucous) Zymogen and mucinogen granules

*Comparison of secretory content, structure and discharge channels of saliva glands.*

Glandula sublingualis Mainly mucous mixed

Glandula submandibularis

**Table 2.**

**Figure 14.**

**excretory channels into the** 

Intercalated channel Intralobular channel Interlobuler channel Excretory channel Stenon channel

Intercalated channel Intralobular channel Interlobuler channel Excretory channel Wharton channel

Intercalated channel Intralobular channel Interlobuler channel Excretory channel Major sublingual channel

**mouth**

On the other hand, the lacrimal gland is made of several lobules separated by loose connective tissue. Each lobule consists of many acini, lined with columnar serous cells that produce a watery secretion. The central lumina of many units converge to form

Saliva is made up mostly of water (97–99.5%) originating from plasma of acinar cells [13]. The content of salivation has mucous, serous, or serous-mucous features. Mucous secretion is a thick form viscous fluid of highly glycosylated glycoproteins. Serous secretion is fluent and with clear consistency, forming thin, watery secretion containing proteins and glycoproteins. Seromucous form mixed secretin of intermediate thickness [14, 15]. Saliva is composed of a variety of electrolytes, including sodium, potassium, calcium, magnesium, bicarbonate, phosphates, immunoglobulins, proteins, enzymes, mucins, and nitrogenous products, such as urea and

intralobular ducts, which unite to drain into 8–12 excretory ducts [11, 12].

*Sagittal view of the upper and lower eyelids. The glands of Krause (arrow) are located in the superior conjunctival fornix. The glands of Wolfring (arrowhead) are found at the nonmarginal border of the tarsal* 

**2.2 The saliva and tear composition**

*plate [67] (with permission by Dr. Bhupendra Patel).*

**24**

ammonia [16].

*Oblique view of the right orbit. Oblique view of the right orbit showing the main lacrimal gland divided into the orbital lobe (OL) and palpebral lobe by the lateral horn of the levator aponeurosis (LA). Note the excretory ducts coursing through the palpebral lobe and draining into the superior conjunctival fornix (arrow) [67] (with permission by Dr. Bhupendra Patel).*

Histatins, the human salivary proline-rich proteins (PRPs) and statherin proteins are found in three kinds of protein saliva [17]. Histatins are a family of related neutral and basic histidine-rich peptides which are secreted mainly from parotid saliva and, to a lesser extent, submandibular saliva [18, 19]. A total of 12 salivary histatins have been isolated from human saliva.

The human salivary proline-rich proteins (PRPs) are a heterogeneous group of proteins that comprise about 70% of the parotid proteins. They are characterized by a predominance of the amino acids proline, glycine, and glutamic acid/glutamine (a total of 80% of all amino acids). PRPs are classified into three groups: acidic, basic, and glycosylated [20].

#### **Figure 16.**

*Lacrimal gland histopathology. H&E staining of a normal lacrimal gland. The gland is composed of lobules separated by loose connective tissue. The lobules are composed of multiple acini lined by columnar secretory cells [67] (with permission by Dr. Bhupendra Patel).*

Statherin is a low-molecular-weight acidic protein consisting of 43 amino acids. It is secreted by the parotid, submandibular, and von Ebner's salivary glands but is not present in labial saliva [21, 22].

Mucins are proteins that give the typical viscoelastic character to all the mucosal secretions (**Table 3**) [23–25].

Cystatins contain various kinds of endogenous proteinase inhibitors to regulate their protein metabolism or to protect tissues from proteolytic attacks by bacteria or viruses. Cystatins are important in the inhibition of several viruses, presumably by blocking necessary cysteine proteinases [26, 27].

Amylase is an abundant salivary component. It is produced mainly in the pancreas and salivary glands [17].

Secretory immune globulin A (slgA) is a member of the adaptive immune response [28, 29]. IgA, which is a connective tissue cell and located in the stroma, is secreted into the saliva by plasma cells [7, 30, 31].

Lysozyme is called muramidase, for its antibacterial effect also. It is a widely distributed enzyme occurring in many human secretions (**Table 3**).

Extra-parotid glycoprotein (EP-GP), an acidic salivary glycoprotein, was originally isolated from submandibular and sublingual saliva and has been shown to have a strong affinity to hydroxyapatite. EP-GP can be localized only in the serous acinar cells of the submandibular glands and is absent in the parotid gland [32].

Kallikreins are a group of serine proteases that are found in glandular cells, neutrophils, and biological fluids. Glandular (tissue) kallikrein is found in a variety of tissues and biological fluids, including saliva [33].


**27**

*Morphology of Salivary and Lacrimal Glands DOI: http://dx.doi.org/10.5772/intechopen.84380*

β-adrenergic receptor stimulation [34].

these fluids [17].

secretion [34].

secretion.

tions are listed below:

**2.3 Function of saliva secretion**

electrolytes close to the plasma concentration [10].

digestion of carbohydrates [7, 30, 31, 39].

Haptocorrin is an acidic glycoprotein that is present as a minor component in blood and other body fluids. It binds cobalamin (vitamin B12) but should be distinguished from two other vitamin B12-binding proteins: the intrinsic factor and transcobalamin. In human salivary glands, haptocorrin has been localized only in mucous acinar cells and in intercalated duct cells where it can be released via

β-Microseminoprotein is present in various amounts in mucous secretions [17].

Tear fluid is a complex solution intended to sustain the surface of the eye [35]. The lacrimal gland secretes tear fluid consisted mainly of water and electrolytes, and human tears have been disclosed to be isotonic with plasma [36]. In the secretion of the lacrimal gland, lysozyme, which is the antibacterial enzyme, contains

Lysozyme is mainly present in saliva and tear fluid, and it plays an important

In addition to salivary secretions, statherin is also present in tear fluid and nasal and bronchial mucus. Statherin prevents excessive precipitation of calcium salts in

Haptocorrin at the highest concentrations have been detected in tears and nasal

Saliva is mainly secreted by the parotid gland, submandibular gland, and sublingual gland [16, 37, 38]. In addition, the mucosa of the mouth, the tongue, and the soft palate also contains large amounts of microscopic salivary glands and helps

Different substances and factors in saliva have various functions. These func-

1.Digestion: Basically, saliva is composed of water (~99.5%); electrolytes such as potassium, sodium, bicarbonate, calcium, phosphorus, and chloride; and various enzymes, among other important elements. Enzymes include amylase, lipase, lysozyme, immunoglobulins, thiocyanate, and urea. Alpha-amylase enzyme breaks the glycosidic linkages of carbohydrates 1–4 and provides

2.Lubrication and protection: Since the intraoral food is the first fragmentation place, the sensitive and delicate oral mucosa should not be damaged. For this purpose, saliva secretion protects the oral mucosa, and saliva contains mucins, which allow it to coat and lubricate [31, 40, 41]. The most important feature of salivary secretion is that it lubricates and protects the very sensitive oral mucosa. The best lubricating components of saliva are mucins. Mucins also cause an antibacterial function by selectively modulating the adhesion of microorganisms to oral tissue surfaces [42, 43]. Chewing, speech, and swallowing all are provided by the lubricating effects of mucins [43]. Glycosylated basic PRPs (PRGs) function as masticatory lubricants and have also been shown to interact with several types of microorganisms such as *Fusobacterium nucleatum* [44]. The physiological functions of the mucins include cytoprotection, lubrication, protection against dehydration, and maintenance of viscoelasticity in secretions [44, 45]. The viscoelastic properties of mucins play a role in lubrication and are considered to be an important characteristic of mucins [25, 46]. The capacity of mucins to protect epithelial surfaces depends largely

**Table 3** shows the distribution of saliva and tear content [17].

role in the protection of the oral cavity and eyes from infection.

**Table 3.**

*Comparison of saliva and tear secretion [17].*

#### *Morphology of Salivary and Lacrimal Glands DOI: http://dx.doi.org/10.5772/intechopen.84380*

*Chronic Autoimmune Epithelitis - Sjogren's Syndrome and Other Autoimmune Diseases...*

not present in labial saliva [21, 22].

pancreas and salivary glands [17].

blocking necessary cysteine proteinases [26, 27].

secreted into the saliva by plasma cells [7, 30, 31].

of tissues and biological fluids, including saliva [33].

Kallikrein +

*Comparison of saliva and tear secretion [17].*

secretions (**Table 3**) [23–25].

Statherin is a low-molecular-weight acidic protein consisting of 43 amino acids. It is secreted by the parotid, submandibular, and von Ebner's salivary glands but is

Mucins are proteins that give the typical viscoelastic character to all the mucosal

Cystatins contain various kinds of endogenous proteinase inhibitors to regulate their protein metabolism or to protect tissues from proteolytic attacks by bacteria or viruses. Cystatins are important in the inhibition of several viruses, presumably by

Amylase is an abundant salivary component. It is produced mainly in the

Secretory immune globulin A (slgA) is a member of the adaptive immune response [28, 29]. IgA, which is a connective tissue cell and located in the stroma, is

Lysozyme is called muramidase, for its antibacterial effect also. It is a widely

**Saliva Tear fluid**

Extra-parotid glycoprotein (EP-GP), an acidic salivary glycoprotein, was originally isolated from submandibular and sublingual saliva and has been shown to have a strong affinity to hydroxyapatite. EP-GP can be localized only in the serous acinar cells of the submandibular glands and is absent in the parotid gland [32]. Kallikreins are a group of serine proteases that are found in glandular cells, neutrophils, and biological fluids. Glandular (tissue) kallikrein is found in a variety

distributed enzyme occurring in many human secretions (**Table 3**).

Mucins ++++ + Asidic PRPs ++++ − α-Amylase ++++ + Basic PRPs +++ − Basic PRG +++ − Secretory IgA +++ ++++ Cystatins ++ + Statherin ++ + IgG + + EP-GP + + VEGh + ++++ Histatins + − Lysozyme + ++++

Lactoferrin + ++++ Lactoperoxidase + + Haptocorrin + + β-Microseminoprotein + + IgM + + Albumin + + Zn-α2 Glycoprotein + +

**26**

**Table 3.**

Haptocorrin is an acidic glycoprotein that is present as a minor component in blood and other body fluids. It binds cobalamin (vitamin B12) but should be distinguished from two other vitamin B12-binding proteins: the intrinsic factor and transcobalamin. In human salivary glands, haptocorrin has been localized only in mucous acinar cells and in intercalated duct cells where it can be released via β-adrenergic receptor stimulation [34].

β-Microseminoprotein is present in various amounts in mucous secretions [17]. **Table 3** shows the distribution of saliva and tear content [17].

Tear fluid is a complex solution intended to sustain the surface of the eye [35]. The lacrimal gland secretes tear fluid consisted mainly of water and electrolytes, and human tears have been disclosed to be isotonic with plasma [36]. In the secretion of the lacrimal gland, lysozyme, which is the antibacterial enzyme, contains electrolytes close to the plasma concentration [10].

Lysozyme is mainly present in saliva and tear fluid, and it plays an important role in the protection of the oral cavity and eyes from infection.

In addition to salivary secretions, statherin is also present in tear fluid and nasal and bronchial mucus. Statherin prevents excessive precipitation of calcium salts in these fluids [17].

Haptocorrin at the highest concentrations have been detected in tears and nasal secretion [34].

## **2.3 Function of saliva secretion**

Saliva is mainly secreted by the parotid gland, submandibular gland, and sublingual gland [16, 37, 38]. In addition, the mucosa of the mouth, the tongue, and the soft palate also contains large amounts of microscopic salivary glands and helps secretion.

Different substances and factors in saliva have various functions. These functions are listed below:


on their high content of oligosaccharides and their ability to form a gel layer together with other salivary proteins [47]. Kallikreins have been implicated in the regulation of local blood flow in salivary glands [48].


**29**

*Morphology of Salivary and Lacrimal Glands DOI: http://dx.doi.org/10.5772/intechopen.84380*

sensation [22].

**2.4 Function of tear secretion**

inflammation [59]. The PRPs are thought to serve as a defense mechanism against dietary tannins by forming precipitates, which reduce harmful effects of tannins [60]. Statherin adsorbed onto hydroxyapatite can promote adherence of a few oral bacteria, such as *P. gingivalis* and *Actinomyces viscosus* [61]. Mucins promote the clearance of various bacteria by masking their surface adhesins, a factor which inhibits bacterial colonization [17, 62]. Salivary immunoglobulin A (slgA) associated response can be induced by local stimulation of mucosal membranes and secretory glands with antigens. Secretions of glands that are anatomically remote from the site of immunization, such as mammary, salivary, and lacrimal glands, can contain slgA antibodies to antigens encountered through the respiratory or gastrointestinal tracts. Following this pathway, IgA-producing cells are induced by the common mucosal immune response, consisting of lymphoid tissues concentrated in special structures, such as the Peyer's patches [17]. The protective role of slgA has been demonstrated in several experimental systems. Salivary immunoglobulin A can neutralize antigens (from viruses, toxins, and enzymes [63]. The enzymatic activity of lysozyme is able to cleave β-(l-4)-glycosidic bonds between muramic acid and N-acetylglucosamine residues in the peptidoglycan of the bacterial cell wall [64–66]. Haptocorrin play a role in the defense against microorganisms [17]. Beta-microseminoprotein has a protective function for the mucins by acting as a physiological inhibitor of endogenous mucindegrading enzymes from leucocytes or by acting as an antibacterial agent [17].

7.Taste and digestion: Saliva plays an active role in the sense of taste. We get the sense of taste with "gemma gustativa" known as taste buds. With microvilli of these taste buds, it is possible to bathe with saliva secretion continuously and thus to recognize different tastes. The saliva also forms a medium for the suspended food materials so that the environment for the stimulation of the taste buds is formed [16, 30, 40, 41]. PRPs are involved in the bitter taste

Tear secretion is extremely important for the health of the cornea and conjunctiva. Lacrimal secretions allow the creation of human tear film, made of the lipid, aqueous, and mucous layers. Tears, conjunctiva, and corneal epithelium are kept moist and remove foreign bodies. The tear film lubricates the surface of the eye, functions as a barrier against foreign body and microbial invasion, and supplies the avascular cornea with nutrients and oxygen [7, 67]. The tear covering the corneal surface in the form of a film layer is not homogeneous. Tear is mixture secretion and included the lacrimal glands, goblet cells, and eyelid tarsal gland secretions. The tear film layer includes proteins such as albumin and lactoferrin, enzymes such as lysozyme, lipids, metabolites, and electrolytes. The gland produces many proteins and aqueous fluid to add volume to the tear film. Furthermore, the lacrimal gland also secretes several bactericidal and fungicidal agents, akin to the salivary glands [11, 12]. Different isoforms of zinc α2-glycoprotein are present as a minor component in several body fluids, for example, serum, sweat, tears, and saliva [17].

"As a conclusion, the relation between the structure and function of exocrine glands is similar to other tissues. They produce normal secretions functionally as long as they maintain their normal shape and proper division of functions of individual cells. Saliva and tear secretion are necessary for survival, and these secretions are a barrier between environmental factors and internal organs. Tears *Chronic Autoimmune Epithelitis - Sjogren's Syndrome and Other Autoimmune Diseases...*

the regulation of local blood flow in salivary glands [48].

in the calcium homeostasis of saliva [50, 51].

hydroxyapatite crystal growth [56].

on their high content of oligosaccharides and their ability to form a gel layer together with other salivary proteins [47]. Kallikreins have been implicated in

3.Buffering action and clearance: Bicarbonates, phosphates, and urea act to modulate pH and the buffering capacity of saliva. Saliva plays an active role in the sense of taste. We get the sense of taste with "gemma gustativa" known as taste buds. With microvilli of these taste buds, it is possible to bathe with saliva secretion continuously and thus to recognize different tastes. The saliva also forms a medium for the suspended food materials so that the environment for the stimulation of the taste buds is formed [30, 40, 41]. The acini of serous glands first produce an isotonic fluid; and when the secretion product reaches the ductus striata, it is absorbed back into the sodium and secreted into the secretory potassium and bicarbonate, resulting in salivary isotonic-hypertonic; and due to the high concentration of bicarbonate ions, it buffers the contents of the oral cavity [7, 49]. Statherin, together with the acidic PRPs, plays a role

4.Mucins play a role in mucosal surface coating, creating a chemical barrier, as a component of saliva decides on its viscosity, and are a part of the immune system and are important in the adherence of the microbial flora [52].

together as an antisolubility factor and modulate demineralization and remineralization [16]. The acidic PRPs bind Ca++ with a strength that indicates that they are important in pellicle formation and in maintaining supersaturation of ionic calcium in relation to phosphate ions in saliva [53]. Therefore, the acidic PRPs may be of biological significance in maintaining the calcium homeostasis of saliva and in preventing the formation of salivary stones [54]. Acidic PRPs inhibit apatitic crystal growth, suggesting that, when adsorbed on the tooth surface, they block specific mineral growth sites [55]. Statherin bound to the enamel surface can inhibit crystal growth of hydroxyapatite [17]. Cystatins have been reported to bind to hydroxyapatite [17] and therefore may play a role in acquired pellicle formation. Cystatins have been shown to inhibit

5.Maintenance of tooth integrity: Calcium, phosphate, and proteins work

6.Antibacterial activity: Immunoglobulins, proteins, and enzymes provide antibacterial action [16]. With intraoral secretion flow, the mucosa of the mouth remains moist, and also food residues and microorganisms are sent into the lumen of the digestive tract. Saliva makes this function with proteins and peptides that will neutralize all kinds of microorganisms. Therefore, in-house flora and hygiene are formed in this way [30, 40, 41]. Macromolecule proteins and mucins serve to cleanse, aggregate, and/or attach oral microorganisms and contribute to dental plaque metabolism. Especially in dental caries, systemic microorganisms are effective, and saliva secretion reduces the risk of systemic infection [30, 40, 41]. Histatins possess antimicrobial properties against a few strains of *Streptococcus mutans* [29] and inhibit hemagglutination of the periopathogen *Porphyromonas gingivalis* [57, 58] and neutralize the endotoxic lipopolysaccharides located in the outer membranes of Gram-negative bacteria, which may be an important part of the host's defense system [59]. Histatins are potent inhibitors of the growth and germination of *Candida albicans* [17]. Another biological role of histatins in the oral cavity is the inhibition of the release of histamine from mast cells, suggesting that they play a role in oral

**28**

inflammation [59]. The PRPs are thought to serve as a defense mechanism against dietary tannins by forming precipitates, which reduce harmful effects of tannins [60]. Statherin adsorbed onto hydroxyapatite can promote adherence of a few oral bacteria, such as *P. gingivalis* and *Actinomyces viscosus* [61]. Mucins promote the clearance of various bacteria by masking their surface adhesins, a factor which inhibits bacterial colonization [17, 62]. Salivary immunoglobulin A (slgA) associated response can be induced by local stimulation of mucosal membranes and secretory glands with antigens. Secretions of glands that are anatomically remote from the site of immunization, such as mammary, salivary, and lacrimal glands, can contain slgA antibodies to antigens encountered through the respiratory or gastrointestinal tracts. Following this pathway, IgA-producing cells are induced by the common mucosal immune response, consisting of lymphoid tissues concentrated in special structures, such as the Peyer's patches [17]. The protective role of slgA has been demonstrated in several experimental systems. Salivary immunoglobulin A can neutralize antigens (from viruses, toxins, and enzymes [63]. The enzymatic activity of lysozyme is able to cleave β-(l-4)-glycosidic bonds between muramic acid and N-acetylglucosamine residues in the peptidoglycan of the bacterial cell wall [64–66]. Haptocorrin play a role in the defense against microorganisms [17]. Beta-microseminoprotein has a protective function for the mucins by acting as a physiological inhibitor of endogenous mucindegrading enzymes from leucocytes or by acting as an antibacterial agent [17].

7.Taste and digestion: Saliva plays an active role in the sense of taste. We get the sense of taste with "gemma gustativa" known as taste buds. With microvilli of these taste buds, it is possible to bathe with saliva secretion continuously and thus to recognize different tastes. The saliva also forms a medium for the suspended food materials so that the environment for the stimulation of the taste buds is formed [16, 30, 40, 41]. PRPs are involved in the bitter taste sensation [22].

## **2.4 Function of tear secretion**

Tear secretion is extremely important for the health of the cornea and conjunctiva. Lacrimal secretions allow the creation of human tear film, made of the lipid, aqueous, and mucous layers. Tears, conjunctiva, and corneal epithelium are kept moist and remove foreign bodies. The tear film lubricates the surface of the eye, functions as a barrier against foreign body and microbial invasion, and supplies the avascular cornea with nutrients and oxygen [7, 67]. The tear covering the corneal surface in the form of a film layer is not homogeneous. Tear is mixture secretion and included the lacrimal glands, goblet cells, and eyelid tarsal gland secretions. The tear film layer includes proteins such as albumin and lactoferrin, enzymes such as lysozyme, lipids, metabolites, and electrolytes. The gland produces many proteins and aqueous fluid to add volume to the tear film. Furthermore, the lacrimal gland also secretes several bactericidal and fungicidal agents, akin to the salivary glands [11, 12]. Different isoforms of zinc α2-glycoprotein are present as a minor component in several body fluids, for example, serum, sweat, tears, and saliva [17].

"As a conclusion, the relation between the structure and function of exocrine glands is similar to other tissues. They produce normal secretions functionally as long as they maintain their normal shape and proper division of functions of individual cells. Saliva and tear secretion are necessary for survival, and these secretions are a barrier between environmental factors and internal organs. Tears and saliva are often the first line of defense, part of immune system, and element of transmission of information. These secretions constitute an important and even indispensable part of the body's functionality."
