Mucosal immunity

Cell image

The mucosal immune system comprises both specific responses, controlled through lymphocyte activity, and non-specific defence, which has both cellular and soluble components. However, exactly how T lymphocytes traffic to and maintain defence of the mucosa and how salivary antimicrobial proteins fit into the defence strategy are poorly understood.

T lymphocytes

The mucosal immune system has developed to protect epithelial surfaces from micro-organisms and one of the most important components of this defence is provided by T lymphocytes, which are present in both the epithelium and underlying connective tissue. These lymphocytes play an important role in immune surveillance, particularly in defence against intra-cellular pathogens, malignant transformation and graft rejection. T lymphocytes also play a key role in the pathogenesis of a number of immune mediated inflammatory disorders and in the oral cavity these include lichen planus, erythema multiforme and Crohn´s disease.

Triple staining of oral squamous cell carcinoma
Triple staining of oral squamous cell carcinoma lines showing nuclei (blue), the adhesion molecule E-cadherin (green) and the F-actin cytosleleton (red). (Acknowledgement is given to Nadia Al-Hazmi)

αeβ7 integrin

αeβ7 plays an important role in mucosal immunity by binding lymphocytes within the epithelium. In the gut the ligand for aeb7 is E-cadherin, but this group was the first to show there is an alternative, but as yet unidentified, ligand within the oral mucosa. Work is ongoing to identify that ligand and define the role of aeb7 in regulating epithelial-lymphocyte interactions in oral immune responses.

Section of submandibular salivary gland
Immunohistochemical demonstration of PLUNC expression in a section of submandibular salivary gland

A new family of defence proteins

PLUNCs are a family of novel proteins, which were discovered and sequenced in Sheffield by Bingle C and Bingle L. These proteins have structural similarity to lipopolysaccharide binding protein and so are thought to be important components of innate immunity. Recently PLUNCs have been shown to be present in saliva and uniquely that different PLUNCs are expressed in different salivary glands. Their contribution to maintenance of oral health is currently being investigated.

Key publications

Brown D, Furness J, Speight PM, Thomas GJ, Li J, Thornhill MH, Farthing PM. Mechanisms of binding of CLA-positive and aeb7 –positive lymphocytes to oral and skin keratinocytes. Immunology 1999; 98: 9-15.

Walton LJ, Thornhill MH, Macey MG, Farthing PM. Cutaneous lymphocyte-associated (CLA) and αeβ7 are expressed by mononuclear cells in skin and oral lichen planus. J Oral Pathol Med 1997; 26:402-7

Bingle L et al. SPLUNC1 (PLUNC) is expressed in glandular tissues of the respiratory tract and in cancers with a glandular phenotype. J Pathol 2005; 205: 491-497.

Bingle CD, et al. Phylogenetic and evolutionary analysis of the PLUNC gene family. Prot Sci 2004; 13: 422-430.