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Immunity in the oral cavity

John Taylor, Newcastle University, UK

The oral cavity is a unique anatomical structure, characterised by the juxtaposition of soft and hard tissues and which is continuously subject to challenge by the external environment and foreign material. Diseases and disorders caused by oral microorganisms are very common and economically important, in particular dental caries (loss of tooth integrity caused by bacteria-derived organic acids) and periodontitis (‘gum disease’; chronic destructive inflammation of the supporting tissues of the teeth caused by anaerobic bacteria). Also, halitosis (oral malodour) is caused by sulphide- producing oral bacteria. Oral diseases secondary to systemic disease, e.g. oral candidiasis, due to acquired immunodeficiency are of increasing clinical importance. Also, a number of autoimmune diseases such as Sjögren’s syndrome and bullous pemphigoid have oral manifestations.

The mouth is well served by numerous major and minor salivary glands and the saliva they secrete is a key component of the host defence against infection in the mouth. Thus, patients with xerostomia (‘dry mouth’) have more dental plaque and increased risk of periodontitis and candidiasis. The saliva contains many molecular elements which restrict microbial growth: for example lysozyme cleaves bacterial cell walls, lactoferrin complexes iron ions which are an essential microbial nutrient, and histatins inhibit the growth of Candida albicans and Streptococcus mutans (the latter being an aetiological agent of dental caries). Whereas growth inhibitory elements of the saliva could be considered as components of innate immunity, salivary IgA is part of the adaptive immune response. This serves to aggregate oral bacteria such as S. mutansand prevent the formation of dental plaque, a biofilm on the exposed surface of teeth which comprises a thriving ecosystem for oral pathogens.

The tonsils are immune tissues located towards the back of the mouth; they comprise the palatine-, lingual- and tubal tonsils as well as the adenoids (pharyngeal tonsils) and are collections of lymphoid tissue immediately beneath the epithelium. Together the different tonisllar tissues form a ring of lymphoid tissue known as Waldeyer’s ring which serves to protect the opening to the pharynx. The tonsils are often a site of bacterial infection, likely because the clefts in which they appear are a site of collection of debris; this can lead to recurring chronic inflammation and tonsillar enlargement (tonsillitis).

The anatomy and microanatomy of the tissues which surround and support the teeth (the peridontium) is complex and susceptible to acute and chronic inflammation caused by plaque bacteria which accumulate in the space between the tooth and the gum (the gingival sulcus). Fortunately, the periodontium has a number of host defence elements including the gingival epithelium which prevents bacterial adhesion by constantly shedding keratinocytes into the oral cavity (‘cell turnover’) and protecting against invasion by having a substantial keratin component (unlike other tissues of the oral and gastrointestinal mucosa). The connective tissues of the periodontium are highly vascular, facilitating vascular leukocyte emigration in response to infection and the gingival sulcus is bathed with a serum exudate (gingival crevicular fluid, GCF). The latter carries all the key molecular (complement components, antibodies) and cellular (neutrophils and plasma cells) components of the immune response necessary to prevent tissue invasion by the sub-gingival plaque bacteria. The destructive, chronic inflammation that manifests clinically as peridontontis is caused by an excessive and inappropriate immune response to pathogenic plaque bacteria, coupled with a failure of the normal processes that limit inflammation and drive tissue repair.

Interest in oral immunology has heightened in recent years with the recognition that there are clinical associations between periodontitis and systemic diseases with inflammatory components (and in particular diabetes). Also, saliva which mixes with GCF in the oral cavity, is a rich and non-invasive source of disease biomarkers such as cytokines, tissue destructive enzymes and pathogenic microorganisms, as well as DNA for studies of genetic associations  and pharmacogenomics

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