Manuscript accepted on :August 05, 2016
Published online on:
Aravindha Babu, L. Malathi, R. Karthick and S. Leena Sankari
Dept of Oral Pathology, Sree Balaji Dental College and Hospital, Bharath University, Pallikaranai, Chennai-600100.
Dental caries is the mostwidespread diseases in humans. In modern times, it has reachedepidemic proportions. Dental caries is a microbiologicinfectious disease of the teeth that endsin localized dissolution and destruction of the calcified structure of the teeth. Dental caries is a multifactorialdisease that is caused by thehost, agent, and environmental factors. The time factor is significantfor the initiation and progression of dental caries. A wide group of microorganisms is established from carious lesions. S.mutans, Lactobacillus acidophilus, and Actinomycesviscosus are the main pathogenic species involved in the inception and development of dentalcaries.
dental caries; streptococcus mutans; GlucosyltransferaseDownload this article as:
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Babu A, Malathi L, Karthick R, Sankari S. L. Immunology of Dental Caries. Biomed Pharmacol J 2016;9(2).
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Babu A, Malathi L, Karthick R, Sankari S. L. Immunology of Dental Caries. Biomed Pharmacol J 2016;9(2). Available from: http://biomedpharmajournal.org/?p=8090
Dental caries is an infectious microbiologic disease of theteeth that results in sectorial dissolution and destruction of the calcified tissue. Dental caries is one of the mostcommon diseases in humans. In modern times, it hasreached epidemic proportions. The prevalence of dentalcaries in developed countries varies highly and canreach over 90%. The rate of Caries has been increasing indeveloping countries with the increase in the popularityof highly refined sugars.1The human oral cavity is colonized by about 300 to 500 microorganism species. Most of them involve commensal and opportunistic bacteria. The relations between thehost (human organism) and bacteria commenced in theoral cavity are dynamic and subject to many conditions. They are representative of the virulent efficiency and properties of bacteria as well as defensive forces of the host.2
The development of dentalcaries requires the existence of cariogenic bacteria that arecapable of producing acid and a sugar present in the dietwhich favors the colonization of these bacteria to formacid.Dental caries appears to be a major public healthproblem which if left untreated can cause amplepain, discomfort, and treatment costs are very high. Dentalcaries results from the interaction within the host, thehosts diet, and the microflora on the tooth surface bounded by the time factor. A wide group of microorganisms aredetermined from carious lesions of which Streptococcusmutans (S. mutans), Lactobacillus acidophilus, andActinomyces viscosus are the main pathogenic speciesinvolved in the initiation and development of dentalcaries.1 Colonization by S. mutans occurs after tooth eruption,and if the fissures become colonized in their depths, thendecay may be unavoidable. However, if this colonization isdelayed until the fissure depths are occupied by otherbacteria, there is feasibility that decay will not occur orits occurrence will be greatly reduced.3
The Immune Response
The primary response
When an antigen is administered for the first time to an animal or human, there is a latent course of induction of3 to 10 days before antibodies appear in the blood. The antibody that is first obtained is entirely of the IgM type.The IgM antibody titer rises steadily during the next 2 to3 days, reaches a crest level, and then declines almost asfast as it developed. Meanwhile, if the antigenic stimulus was sufficient, the IgG antibody emerges in a few days. IgGreaches a peak in 7 to 10 days and then gradually falls overa period of weeks or months. A significant outcome of theprimary antigenic challenge is the education of the reticuloendothelialsystem of the body. Both B and T lymphocytesproduce what are known as memory cells or primed cells.These cells are culpable for the immunological memorythat is established after immunization.
Secondary (Booster response)
The response to a booster dose varies in a number of waysfrom the primary response. The secondary response alsoinvolves the synthesis of IgM and IgG antibodies. Acollaboration between B and T cells is necessary to initiatea secondary response. There is an abrupt production of the IgMantibody and a much larger and more prolonged productionof the IgG antibody. This accelerated response is associatedto immunological memory. The immune response (primaryand secondary) and immunological memory are the bases ofvaccination and revaccination.1
Immunology of the Oral Cavity
Antigens and antibodies of the oral cavity
The application of natural immune responses to cariesproducing organism and the development of a vaccine involves the knowledge of the antigenic properties ofthe organism. The cell surfaces of S. mutans possess manyantigens. The cell wall enzyme glucosyltransferase (GTF),responsible for thesynthesis of insoluble extracellular mutans,has been largely studied as it has the serotype-specificpolysaccharide containing glucose, rhamnose, andoccasionally galactose and galactosamine. In addition, thecell wall contains lipoteichoic acid (LTA), a polymer ofglycerol and phosphate covalently linked to a glycolipid,which is found virtually in all Gram-positive organisms.This antigen may be accountable for some immunologicalcross-reactions between bacterial species.
Immunological micro environments in the mouth
The cervical regionand rootsurface plaques in older subjects are thus subjected to the influenceof SIgA, serum immunoglobulins, complement factorsand PMNLs from the gingival crevice. IgA, IgG, IgM,and the third component of complement can be detectedin plaque extracts, and in the free aqueous phase ofplaque (plaque fluid) separated from the solid phase by centrifugation.
Plaque in the fissures and more coronal parts of thesmooth surfaces of the teeth is probably influenced only bysalivary antibodies. PMNLs survive for a very short timein human saliva, although in monkeys their survival maybe more prolonged and in the gingival crevice they maypersist for long periods.
Antibodies or oral bacteria including S. mutans can bedetected in human serum and saliva. In order to see whereor not these antibodies might play a part in natural cariesimmunity, numerous comparisons of caries experience,and levels of immunoglobulin or specific antibody havebeen carried out, but consistency in the results of suchexperiments is not apparent. Various small-scale humantrials in adults have shown that it is feasible to increaselevels of salivary S-IgA antibodies to mutans streptococci,and in some cases to interfere with mutans streptococcalcolonization.4
The Relationship Between Caries and sIgA
IgA deficiency is a relatively common disease afflicting 1:1000 individuals which have been associated with dental caries. It was found that subjects with IgA deficiency fell into two groups in terms of oral antibody: ie., those with compensatory IgM antibodies against S. mutans in saliva and those without.
In Panhypo-or agammaglobulinemia
increased caries activity have been reported.It has been shown that human parotid sIgA antibodies against surface antigen I/II of S. mutans could block S. mutans adhesion to saliva-coated hydroxyapatite suggesting that there is a mechanism of protection available to the host against certain cariogenic bacteria.Serum antibodies, intragingival antibodies, complement, and granulocytes are constantly extravasating from the periodontal crevice and into the oral environment. These components may confer modest protection to the tooth in the cervical area, but they are not likely to be significance in coronal portions of the teeth.5
Caries Vaccines and its Role in Immunology of dental Caries
Bacteria passing through themouth into the stomach andintestine come in contact with specialized lymphatic tissuelocated in Peyer’s patches along with intestinal walls.Certain T (Thymus) and B (Bone marrow) cells in Peyer’spatches become sensitized to these microorganisms.These sensitized T and B cells migrate through lymphaticsto theblood stream and eventually settle in glandular tissuesincluding the salivary glands. These sensitized cellsproduce IgA that are secreted in the saliva, which arecapable of agglutination of oral bacteria, reduce adherenceand easy clearance.Immunization of dental caries should begin early in thesecond year of life.Both active and passive approaches have shown success in human clinical trials.Signals and growth of cariogenic streptococcus in dental biofilms.4
The S. mutans present a set of virulence factors that enables them to adhere to and accumulate in the dental biofilm.Three main groups of Ags associated with the surface of these microorganisms participate in the process of adhesionand accumulation of S. mutans in the biofilm. These Ags are the main targets for thedevelopment of caries vaccine: theglucosyltransferases (Gtfs), antigen adhesin I/II (Ag I/II), and glucan-binding proteins (Gbp). One of the majorvirulence characteristics of S. mutans is precisely its ability to produce Gtfs, enzymes that synthesize intracellularpolysaccharides (ICP) and extracellular polysaccharides (ECP) from sucrose of the diet.6 Thus, the various antigenic components against which immune responses are produced are Adhesins, Glucosyltransferases, and Glucan-binding proteins. 7,8,9
Effective antigenic components have been obtained from S. mutansand S. sobrinus in the form of intact proteins and subunit vaccines.These single polypeptide chains are approximately 1600 residues inlength. S. mutans Ag I/II contain an alanine-rich tandem repeatingregion in the N-terminal third, and a proline-rich repeat region in the center of the molecule. These regions have been associated withthe adhesin activity of Ag I/II. Immunological approaches supportthe adhesin-related function of the AgI/II family of proteins and theirrepeating regions. Abundant in vitro and in vivo evidence indicates thatantibody with specificity for S. mutans AgI/II or S. sobrinus SpaA caninterfere with bacterial adherence and subsequent dental caries.Furthermore, numerous immunization approaches have shown thatactive immunization with intact antigen I/II or passive immunizationwith monoclonal or transgenic antibody to putative salivary-bindingdomain epitopes within this component can protect rodents, primates,or humans from dental caries caused by S. mutans.
mutans that have lost the ability to produceGTF are unable to produce disease in animal models. S. mutans hasbasically three forms of glucosyltransferases-GTF 1, GTF-S-1, GTF-Sand respective genes are GTF-B, GTF-C, and GTF-D. An antibodydirected to native GTF or sequences associated with its catalytic orglucan-binding function interfere with the synthetic activity of theenzyme and with in vitro plaque formation. Since GTFs from thetwo major cariogenic streptococcal species in humans, S. mutans andS. sobrinus, have very similar sequences in the functional domains,immunization with GTF protein or subunit vaccines from one speciescan induce a measure of protection for the other species.
Glucan-binding protein (GBP)
Various proteins with glucan-binding properties have beenidentified in S. mutans and S. sobrinus which are described elsewhere.S. mutans secretes, at least, three distinct proteins with glucan-binding activity: GbpA, GbpB, and GbpC. GbpA has a deduced sequence of563 amino acids. The molecular weight for the processed protein is 59.0 kDa. The expressed GbpB protein is 431 residues long and hasa calculated molecular weight of 41.3 kDa. The third S. mutans nonenzymaticglucan-binding protein, GpbC, is composed of 583 aminoacids. This protein has a calculated molecular weight of 63.5 kDa. Ofthe three S. mutans glucan-binding proteins, only GbpB has beenshown to induce a protective immune response to experimental dentalcaries. It can either be achieved through a subcutaneous injection ofGbpB in the salivary gland region or by mucosal application by the intra-nasal route.
Dextranase, an important enzyme produced by S. mutans, destroysdextran which is an important constituent of theearly dental plaque sothat the bacterium can easily invade dextran- rich early dental plaque.Dextranase, when used as an anitigen, can prevent colonization of theorganism in early dental plaque. 7,8,9
mutans andStreptococcus sobrinus are closely associated with dentalcaries. Fluoride treatment used abroad has successfully limitedcaries progression but was not sufÞ client to control thisinfectious disease even when used together with professionaltooth cleaning and dietary counseling in populations highlyexposed to this cariogenic microbiota.Along with established methodsof caries prevention, caries vaccines have the potential ofmaking a highly valuable contribution to disease control.Regardless of the mechanism by which immuneprotection against dental caries is achieved, further advancesto make immunization against caries practical will dependupon clinical trials aimed at establishing whether the findingsfrom animal experiments can be transferred to humans.
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