Stephen J Challacombe Durdana Rahman Mukesh Mistry and Julian R Naglik

1. Introduction 37

2. Host Factors Predisposing to Oral Candidiasis 38

3. Classification of Oral Candida Infections 38

4. General Considerations of Oral Mucosal Immunity to Candida 41

5. Humoral Immunity against Oral Candidiasis 43

5.1. Saps and Oral Humoral Immunity 43

5.2. Host Immune Responses to Saps 45

5.3. Functional Aspects of Serum and Salivary Antibodies to Candida 46

5.4. Oral Immunity to Candida in HIV Infection 47

5.5. Serum Antibodies—Responses to Oral Candida Infection in Humans 47

5.6. Salivary IgA Subclass Antibodies to Candida 48

6. Innate Factors against Oral Candidiasis 48

6.1. Epithelial Cell Factors, Toll-like Receptors, etc 48

6.2. Cytokines 49

6.3. Salivary Histatins 50

6.4. Defensins 51

6.5. Other Soluble Factors 51

7. Conclusions 51

References 52

genic. The oral mucosa is protected by both The health of the oral cavity is dependent innate and specific immune factors, and the on the integrity of the mucosa, which nor- epithelium itself is capable of responding to mally prevents the penetration of microor- microbial challenge. The nature of the ganisms as well as macromolecules in the epithelial cell responses and the action of

Department of Oral Medicine and Pathology, Guys, Kings and St Thomas Dental Institute, Kings College London, UK.

the cytokines that they produce has been the subject of much recent investigation. The oral mucosa is covered by a mucin layer some 30 |im thick, but the superficial epithelial cells are constantly being desquamated so that attachment and reattachment of potentially pathogenic organisms such as Candida is a constant process. The oral mucous membranes are therefore protected by a series of both non-specific innate factors, which include the physical factors, i.e., mucin and the cornification of the epithelial cell layer and thickness of the epithelium as well as the lipid-rich layers within the epithelium that inhibit penetration of macromole-cules, and humoral factors derived from both secretions, tissue fluids, and epithelial cells within the cells.

From a specific immunity perspective, the oral mucosa is protected (or damaged) by the secretory (mucosal) immune system and the systemic immune system. Antibodies in the saliva may be stimulated locally or centrally and serum antibodies can reach the mucosal surface via tissue fluids and crevicular fluid. Epithelial cells may respond to cellular immunity, which could also be induced at local or distant sites.

Understanding the mechanisms of protection against oral candidiasis is a particular challenge since not only is there a complexity of host defensive factors, but also several different forms of oral candidi-asis, some of which are superficial and some penetrative, and the yeast itself produces both yeast and hyphal forms in different circumstances. Candida organisms are found as commensals in approximately 40% of the population (Arendorf and Walker, 1980) and the organism has a predilection for certain epithelial sites and particularly the dor-sum of the tongue. In superficial Candida infections it might be expected that humoral immunity, especially secretory IgA might play a predominant role. In other forms of Candida infection where penetration of the epithelial cells takes place, cell-mediated immunity (CMI) may be expected to be operative in addition to humoral immunity. Both immune cells and Candida organisms themselves in hyphal or yeast form may induce an epithelial cytokine response, which may play a further role in protection or damage.

This review will concentrate on humoral factors, both innate and specific, in relation to protection of the oral cavity against can-didiasis.

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