SALIVA: AN ORAL MICROBIAL MODULATING AGENT
AJEIGBE A. Yekeen 09/55EJ028 Department of Microbiology, University of Ilorin, Nigeria
• • • • • • • • • • • Introduction Salivary glands Components of the saliva General functions of saliva Immunoactivities of the saliva Inactivation of salivary defenses Factors affecting salivary flow and the effects of reduced salivary flow. Oral microbiota & general health Saliva and Dental Caries Summary References
• The oral cavity is the gateway of the body to the external world and represents one of the most biologically complex and significant sites in the body. • Saliva (also referred to as spit, spittle, drool or slobber) is a watery, sometimes frothy fluid found in the oral cavity. • The saliva possess a number of properties which makes it one of the most important bodily secretions.
Properties of saliva
• • • • Hypotonic; Dilute viscous solution; Contains both organic and inorganic compounds; Produced by the various secretory glands.
(Lamont and Jenkinson, 2010)
• Hundreds of minor salivary glands also secrete saliva and these accounts for the remaining 10% of saliva in the oral cavity.Salivary Glands
• Saliva is secreted by three (3) major salivary glands namely parotid. sub-mandibular and sub-lingual (Fig 1) and these secrete about 90% of the saliva in the mouth.
Fig 1: The location of salivary glands in the oral cavity Source: Britannica. 2003
Teeth & Submucosa
Protection against demineralization
.General functions of the saliva
Saliva action sites.
Major components of the salivary pellicle
The major components of the salivary pellicle can be grouped based on their functions into: Digestive components such as amylase Buffering components such as carbonic anhydrase Immunoactive components such as cystatins. histatins. Statherin and mucin glycoprotein 1 and 2. lysoozyme.
. peroxidase. S-IgA. lactoferrin.
• Description: The histatins are a family of cationic histidine-rich peptides (Amerongen and Veerman.
. 2010). They also kill Candida albicans (Lamont and Jenkinson. 1992). 1984) and inhibit hemoagglutination of the periopathogen.. Porphyromonas gingivallis (Murakami et al..Histatins
• Antimicrobial activity: Bactericidal and fungicidal • Histatins possess antimicrobial activity against some strains of Streptococcus mutans (Mackay et al.
Histatins bind to a Candida membrane receptor. • For example. 2010). and then the peptide is taken up by the cells.
. This result in arrest of the cell cycle and the cells lose ATP by efflux (Lamont and Jenkinson.Histatins
Immunoactivity: The bactericidal and fungicidal effects occur through the union of positively loaded histatins with the biological membranes resulting in the destruction of their architecture and altering their permeability.
Lactoferrin is considered to be a part of the innate immune system (Legrand et al. belonging to those proteins capable of binding and transferring iron (Fe3+) ions (Metz-Boutique et al. 1984)..
..e. 2005). and a member of a transferrin family i.Lactoferrin
• Description: Lactoferrin (formerly known as lactotransferrin) is a glycoprotein.
1995). Yersinia enterocolica. anti-inflammatory • Lactoferrin affects microorganisms which are iron dependent such as enteroinvasive E. Listeria monocytogenes. fungicidal.
. Marchetti et al. bactericidal. coli HB 101. Streptococcus pyogenes... 1995.. and Staphylococcus • Lactoferrin also reduces the entry of viruses such as Herpes simplex virus (Fujihara and Hayashi. and the human immunodeficiency virus (Harmsen et al.Lactoferrin
• Antimicrobial activity: Bacteriostatic. 1996). cytomegaloviruses (Andersen et al. 2001). Yersinia pseudotuberculosis. respectively. antiviral.
• Lactoferrin contribute to defense against the invasion of facultative intracellular bacteria into cells by binding both target cell membrane glycoaminoglycans and bacterial invasins. 2002. 1993). • Its main contribution to antiviral defense consists in its binding to cell membrane glycosaminoglycans (Edgar..
Immunoactivity: • Lactoferrin links to free iron in the saliva causing bactericidal or bacteriostatic effects on various microorganisms requiring iron for their survival (Kirkpatrick et al.. Amerongen and Veerman. Nikawa et al. which prevents pathogen adhesion to target cells. 1971). 1992.
Salivary lysozyme originates from both the salivary gland secretions and from gingival crevicular fluid (Lamont and Jenkinson. where it is present in high concentrations (Jolles. 1969). 2010).Lysozyme
Description: Lysozyme is a single chain polypeptide and is a basic protein found in most secretions.
. including saliva.
. (Sigma. • Gram negative bacteria are less susceptible due to the presence of an outer membrane and a lower proportion of peptidoglycan.Lysozyme
Antimicrobial activity: Bactericidal on gram positive bacteria.
Immunoactivity: The natural substrate for lysozyme is the peptidoglycan layer of bacterial cell walls (Holtje. 1975).
. lysozyme hydrolyzes/digests the cell walls of Gram-positive bacteria by breaking the β (1-4) bond between N-acetylmuramic acid and N-acetylglucosamine in peptidoglycan (Figure 4) and between N-acetyl-Dglucosamine residues in chitodextrin (Rupley. • Hence. 1996). Holler. 1964.
Description: Peroxidase in saliva is derived from the salivary glands and polymorphonuclear neutrophils (PMNs) (Tenovuo and Lagerlof. 1994).
• Antimicrobial activity: Bacteriostatic and bactericidal
a potent antibacterial substance which is produced by the aerobic metabolism of oral bacteria (Edgar. 1992. Tenovuo and Lagerlof. Humphrey and Williamson.Peroxidase
• Immunoactivity: Peroxidase or sialoperoxidase offers antimicrobial activity because it serves as a catalyst for the oxidation of the salivary thiocyanate ion (SCN−) by hydrogen peroxide into hypothiocyanate (OSCN−).
. Amerongen and Veerman). 2001. 1994.
• S-IgA is found at all mucosal sites. The secreted form of IgA is called secretory IgA (or S-IgA). This molecule is secreted as a complex with a linking chain by cells that are found close to the parotid gland. such as the gastrointestinal tract.Secretory Immunoglobulin A (S-IgA)
Description: The major immunoglobulin in the salivary secretions is immunoglobulin A (IgA). respiratory tract and urogenital tract.
. and it is also present in tears and breast milk (in addition to saliva).
The wavy line represents the secretory component. Source: Marcotte and Lavoie.Fig ?: Schematic representation of SIgA. 1998.
bacterial.Secretory Immunoglobulin A (S-IgA)
Antimicrobial activity: Secretory immunoglobulin A (IgA) is the largest immunologic component of saliva. • Bactericidal. bacteriostatic and antiviral
. and enzyme toxins. It can neutralize viruses.
Secretory Immunoglobulin A (S-IgA)
Immunoactivity: The immunoactivities of S-IgA is one of the most important in the saliva. They include: • Immune exclusion • Inhibition of bacterial adherence • Toxin neutralization • Viral immunity
1998).Secretory Immunoglobulin A (S-IgA)
Immune exclusion • One of the major functions of SIgA is to perform immune exclusion. which facilitates their removal from mucosal surfaces (Marcotte and Lavoie. This involves the binding of SIgA antibodies with antigens.
. which consists of limiting the penetration of antigenic materials through the mucosal epithelium.
. 1998). 2010). Glycans on S-IgA are also able to non-specifically trap bacteria (Lamont and Jenkinson.Secretory Immunoglobulin A (S-IgA)
Toxin Neutralization • SIgA can neutralize toxins by blocking their binding to cell receptors (Marcotte and Lavoie.
1998). Free in saliva. polymeric IgA effectively aggregates bacteria (Lamont and Jenkinson.
. thus limiting the potential for ionic and hydrophobic interactions between bacteria and host receptors (Marcotte and Lavoie. 2010).Secretory Immunoglobulin A (S-IgA)
Inhibition of bacterial adherence • The binding of SIgA to adhesins can reduce the negative surface charge and the hydrophobicity of bacteria.
Secretory Immunoglobulin A (S-IgA)
Viral Immunity • SIgA plays an important role in viral immunity because of its presence at the site of initial contact between virions and host cells.
Mucin-glycoprotein 1 and 2 (MG 1 & 2)
• Description: Mucins are present at all surfaces within the human body that are exposed to the environment.
. They are the basis of salivary function (Lamont and Jenkinson. 2010).
Mucin-glycoprotein 1 and 2 (MG 1 & 2)
• Antimicrobial activity: Bacteriostatic and bactericidal.
• MG2 is however very important for agglutination of saliva. 31
. 2008). protecting the cell membrane from physical or biological damage (Lamont and Jenkinson. 2008). and MG1 is the main gel-forming mucin in saliva (Lamont and Jenkinson. • The non-gel forming mucins provide a relatively close coating of epithelial cells.Mucin-glycoprotein 1 and 2 (MG 1 & 2)
Immunoactivity: Mucin has high viscosity when it is hydrated and gel-like. • The viscosity and elastic properties of saliva are attributed to the gel-forming mucins.
.Fig : Depiction of mechanisms of bacterial agglutination by salivary mucins Source: Lamont and Jenkinson.
Inactivation of Salivary Defenses
This adaptation could be a factor that allows Streptococcus mutans to be effective as a cariogenic agent.
. Haemophilus and Neisseria species produce proteases that specifically cleave S-IgA1. disrupting functions such as complexing and clumping (Tachezy et al. • Other bacteria produce glycan hydrolysases that cleave sugar chains from mucins. 1996).Inactivation of Salivary Defenses
• Some Streptococcus. both in binding bacteria and in lubrication (Lamont and Jenkinson.. This causes changes in mucin properties making them much less efficient. 2010).
.Factors affecting salivary flow and the effects of reduced salivary flow.
• Certain drugs and therapies such as radiation therapy have been known to affect salivary flow. leading to a range of oral and dental disorders. It also causes difficulty in speech. • Emotional states such as anxiety.Factors affecting salivary flow and the effects of reduced salivary flow.
. stress and fear also affect salivary flow as evidenced by the “dry mouth” phenomenon. Xerostomia disrupts the normal homeostasis of the oral cavity. 2007). • Xerostomia refers to dryness of the mouth caused by hyposalivation. taste and eating (Brosky.
. This number will probably turn out to be closer to 1000 in the future. and various intracellular viruses. when all taxa and phyla have been recorded (Patricia et al. • The organisms present in the oral cavity are a mixture of commensals and pathogens. several species of protozoa (which graze on the bacteria for food). • It is also home to at least 30 species of fungi (mainly of the genus Candida).Oral microbiota & general health
• The human oral cavity is home to about 700 identified species of bacteria. 2008).
Porphyromonas. or root dentin (root caries) Inflammation and either rapid (aggressive. Haemophilus. other Candida species. Prevotella
Redness and swelling (inflammation) of the gingival tissues Actinomyces. Candida tropicalis. Tannerella. Lactobacillus. Actinomyces (root caries)
Decay (loss) of tooth enamel (dental caries) or dentin (dentinal caries). either generalized or localized) or slower (chronic) destruction of the tissues supporting the tooth
Streptococcus. Fusobacterium. Prevotella Redness and inflammation of the pharynx. Fusobacterium. 2010.
Reddening and inflammation of the oral mucosa
.Table 1: Important Oral Diseases. Group A Streptococcus. Coxsackie A virus Candida albicans. Treponema. their manifestations and microorganisms implicated
Source: Lamont and Jenkinson. Neisseria. (gums) Bacteroides.
Saliva and Dental Caries
.Fig 8: Factors affecting dental caries Source: Saliva and Dental Caries.
these researches have shown saliva as an important first line of defense. Yet. the role of the saliva as an microbial modulator in the mouth is not fully appreciated yet.
Despite a lot of research into the antimicrobial properties of saliva.