Principal immunoglobulin Humoral element in secretory immune system Has a neutralizing component to prevent attachment and adherence of oral

bacteria SIgA adheres selectively to M cells in intestinal Peyers patches, thus mediating the transepithelial transport of the Ab molecule from the intestinal lumen to underlying gutassociated organized lymphoid tissue

IgA functions at three anatomical levels in relation to mucosal epithelium: 1) luminal SIgA Ab prevents adhesion and entry of Ag into the epithelium; 2) IgA Ab in the lamina propria binds and excretes Ag to the lumen; and 3) IgA Ab in transit through the epithelium can inhibit virus production or neutralize proinflammatory Ags . An additional property of IgA is its inability to trigger the release of inflammatory mediators through receptors specific for its Fc domain

At Birth, IgA not detectable 4-6 wks levels rapidly rise IgA1 dominates, by 20 wks IgA2 increases to adult levels. Early childhood: lysozyme and salivary peroxidase are at adult levels MUC5B dominates over MUC7 from 1mo-1yr Antimicrobial peptides:

Beta-defensin-3 Cathelicidin LL37 Alpha-defensins 1,2,3 HNP1-3 were greater in cavity free children

Sterile at Birth S. mitis and S. oralis very early (within 24 hours) S. Sanguis by 9 months of age S. mutans and S. sobrinus 18-24 months window of infectivity

Sucrose-independent attachment (Ag I/II) Sucrose-dependent reaction (glucosyltransferase) Bacterial metabolic activities with lactic acid production

Increase resistance of teeth (e.g., fluoride, sealants) Improve diet Alter microflora mutant strains mechanical (remove niche) antimicrobial/antibiotic alter salivary components - specific and nonspecific

GALT: gut associated lymphoreticular tissue Others: BALT - bronchial NALT - nasal DALT - ductal SALT - salivary

 Inhibition of adherence of microorganisms on epithelial surfaces (or teeth, i.e., AgI/II) Neutralization of toxins or enzymes (e.g., GTF) Viral neutralization (e.g., polio virus) Antigen trapping and antigen exclusion Interaction of S-IgA with non-specific defense mechanisms (e.g., mucins, lactoferrin, lysozyme,lactoperoxidase)

Immunologic Means to Obtain Caries Immunity 1. Natural Immunity 2. Active immunity Local immunization Systemic immunization Oral/Mucosal Immunization 3. Passive Immunization

Natural Immunity to Dental Caries Maternal Protection Ontogeny of Mucosal Immunity Natural Caries Immunity

Unique Aspects of Infancy Teeth are erupting Oral cavity is being colonized Breast feeding is discontinued Immune system is developing

Obstacles Encountered in Demonstrating Caries Protective Role of IgA Dental caries is a chronic, slow process Dental caries may not be active when antibody activity is assessed Absorbance of antibodies by oral micro-organisms Determination of local antibodies in the microbial environment Cross reacting antigens between cariogenic and noncariogenic organisms

Why dont some individuals respond to the obvious challenge? Do individuals with caries and decreased antibodies have the ability to respond? Can the response in non-responsive individuals be induced?

Identification of virulence antigens of S. mutans Lack of understanding of the mechanism of immune protection Mechanisms involved in the induction and regulation of protective immunity Possibility of immunopathological complications to immunization Approval to test candidate vaccine in young population