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1 California National Primate Research Center and Center for Comparative Medicine, University of California Davis, Davis, CA 95616, USA; and
2 Greer Laboratories Inc., 639 Nuway Circle, PO Box 800, Lenoir, NC 28645, USA
* corresponding author, fblu{at}greerlabs.com
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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KEY WORDS: oral mucosa • saliva • salivary glands • palatine tonsil • HIV/SIV
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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The factors listed above may result in a lowering of the concentration of infectious HIV-1 in saliva, making the oral cavity a rare site for HIV transmission. However, persistence of HIV/SIV infection results in susceptibility of the oral mucosa to opportunistic infections (Candida albicans, Herpes simplex virus, and cytomegalovirus). The mechanism by which HIV infects different cell types within the oral mucosa is not clear. The mucosal immunity in the female reproductive tract and the rectal mucosa has been intensively investigated for the development of a mucosal AIDS vaccine for the past 15 years (McGhee et al., 1992, 1994; Miller et al., 1993, 1996, 1997; Lu et al., 1998; Miller and Lu, 2003). Both routes are effective sites for HIV and SIV transmission (Miller et al., 1989, 1993, 1997; Mestecky et al., 1994a; Lu et al., 1998). However, HIV transmission through the intact oral mucosa has not been documented. Previous studies have shown that oral mucosal immunization with recombinant protein or plasmid DNA immunogen induced oral and systemic humoral and cellular immune responses (Etchart et al., 1997, 2001; Desvignes et al., 1998; Cui and Mumper, 2002; Lundholm et al., 2002). Thus, oral mucosa may provide a site for possible vaccination. This evidence leads to the suggestion that the oral mucosa possesses a protective type of immunity that may be superior to that of other mucosal sites.
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PHYSIOLOGY OF SALIVARY GLANDS AND CHARACTERISTICS OF SALIVA |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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-amylase, which is an enzyme for digesting starches; and (2) a mucus secretion that contains mucins for lubricating mucosal surfaces. The parotid glands produce only serous secretions, while the submandibular and sublingual glands secrete both the serous and mucus types. Finally, the minor salivary glands secrete predominantly mucus. Salivary glands are the most important source of secretory IgA (S-IgA) antibodies (Abs) in the upper respiratory and gastrointestinal (GI) tracts. However, it is not clear which salivary glands are the major source of S-IgA in whole saliva. IgA predominates in whole and parotid saliva, and whole saliva has been shown to contain higher levels of IgA, IgM, IgG than does parotid saliva in healthy humans (Crama-Bohbouth et al., 1984). This suggests that a portion of the Igs in whole saliva is derived from a source other than parotid salivary glands. However, measurement of the antigen-specific-activity Ab has shown that IgG-specific activity is significantly higher in the parotid saliva than in whole saliva of older individuals (Butler et al., 1990). In persons with AIDS, the anti-Candida albicans Ab levels are lower in parotid saliva as a result of a decrease in the rates of the Ab secretion (Coogan et al., 1994). It has been shown that the minor salivary glands produce from 30 to 35% of the IgA that enters the oral cavity, and that the S-IgA concentration in the minor salivary gland secretions is four times higher than that in parotid gland secretions (Crawford et al., 1975). The S-IgAs are synthesized by plasma cells associated with salivary glands. The IgA plasma cells in the salivary glands originate from IgA-committed B-cells migrating from Peyer’s patches (O’Sullivan et al., 2001; Lamm and Phillips-Quagliata, 2002; Zuercher et al., 2002b). There may also be some contribution from nasal-associated lymphoid tissue (NALT) (Jackson et al., 1981; Childers et al., 2002; Zuercher et al., 2002a; Yoshino et al., 2004). Saliva contains elements derived from the capillary bed beneath the oral mucosa, including that referred to as gingival crevicular fluid, which flows through the crevice between the gingiva and the tooth. The Ig composition of crevicular fluid is similar to that of plasma (Brandtzaeg et al., 1970; Grbic et al., 1995), but once mixed with salivary gland secretions, it becomes diluted. Maintenance of high levels of IgA in crevicular fluid may afford protection against periodontal attachment loss (Grbic et al., 1999). When bleeding in gingival crevices occurs, saliva also contains a transudate of plasma components. Evaluation of hemoglobin in saliva is an indicator of whether gingival bleeding has occurred (Piazza et al., 1994). Thus, saliva is a mixture of water, electrolytes, glycoproteins (immunoglobulins), enzymes, and other organic compounds. Salivary water and electrolyte concentrations are approximately equal to those of plasma. However, the total protein concentration in saliva is approximately one-tenth of that in plasma.
The major characteristics of saliva are: (1) its large volume relative to the mass of the salivary glands; (2) its high potassium concentration; (3) its low osmolarity (hypotonic); (4) its commensal micro-organisms, such as Streptococcus mutans and Candida albicans; and (5) specialized organic materials, such as glycoproteins (immunoglobulins) and enzymes (-amylase, lysozyme, lingual lipase, and proteolytic enzymes released from micro-organisms).
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SALIVARY INNATE FACTORS AND SUSCEPTIBILITY TO HIV INFECTION |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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ORAL MUCOSA |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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, granulocyte-monocyte colony-stimulating factor (GM-CSF) (Yamamoto et al., 1994), TGF-ß, and their receptors (Vernier et al., 1996; Okada and Murakami, 1998; Sandros et al., 2000; Steele and Fidel, 2002; Schaller et al., 2004). Bacteria and Candida albicans often serve as stimuli for epithelial cells to produce cytokines and chemokines; for example, IL-1ß, exodus-2, P-selectin, GM-CSF, and TNF- are stimulated by C. albicans (Schaller et al., 2002; Steele and Fidel, 2002). Oral epithelial cells produce IL-8, considered to be a chemokine, which is stimulated by Viridans streptococci (Vernier et al., 1996). Following antigen priming in the oral mucosa of transgenic mice, 3 chemokine ligand genes—CCL12, CCL19, and CCL25 [thymusexpressed chemokine (TECK)]—were significantly up-regulated in oral tissues (Otten et al., 2003). The mucosa-associated epithelial chemokine, MEC (CCL28), which is expressed by epithelia in diverse mucosal tissues, including the oral cavity, is selectively chemotactic for IgA Ab-secreting cells (ASC) from both intestinal and non-intestinal lymphoid and effector tissues (Lazarus et al., 2003). Within the oral epithelium, APCs and T-cells are the predominant immune cells. Macrophages, fibroblasts, mast cells, and intra-epithelial lymphocytes in the buccal mucosa can also produce a broad range of cytokines, such as TNF-, IL-1ß, IL-6, and IL-10. Thus, oral epithelia are not merely mechanical barriers, but are also important elements of the innate immune system (Sandros et al., 2000). |
ORAL MUCOSAL BLOOD FLOW, LYMPHOCYTE TRANSMIGRATION, XEROSTOMIA, AND ORAL LESIONS DURING HIV/SIV INFECTION |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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The clinical stage of HIV infection at which oral mucosal immunity fails is, by definition, when opportunistic infection occurs (clinical progression to Stage IV of the disease, namely, AIDS). However, detailed knowledge on the etiology of this oral immune failure is lacking. Based upon hemoglobin levels in saliva, HIV-infected intravenous drug abusers and persons with AIDS-related complex have a high incidence of oral mucosal bleeding when compared with asymptomatic individuals (Piazza et al., 1994). The bleeding causes the release of systemic immune components into the oral cavity. This observation has led to the suggestion that the blood flow rate in oral mucosa, with the exception of the salivary glands, may be greatly increased as a result of the systemic route of HIV infection and/or local inflammation.
The transmigration of activated lymphocytes from blood to oral mucosal tissues requires that the lymphocytes express membrane receptor integrins such as L-selectin, CLA (cutaneous lymphocyte antigen), or 47 to bind vascular endothelial ligands such as GlyCAM-1 (glycosylation-dependent adhesion-molecule) or MAdCAM-1 (mucosal addressin cell adhesion molecule) (Viney et al., 1996; Kantele et al., 1999; Rott et al., 2000; Galkina et al., 2003). It is interesting that, when compared with oral immunization, systemic immunization induces ASCs with different homing receptor phenotypes: Systemic antigen exposure results in a higher incidence of specific ASCs that express L-selectin, whereas oral exposure results in a higher incidence of specific ASCs that express agr; 47 (Lamm and Phillips-Quagliata, 2002; Rott et al., 2000; Youngman et al., 2005). Once tethered, the lymphocytes then roll along the endothelial surface attached by integrins such as VLA-4 (very late antigen) to fibronectin and VCAM-1 (vascular cell adhesion molecule) expressed by blood vessels. In the second phase of lymphocyte trafficking, the beta 2-integrin LFA-1 (lymphocyte function-associated molecule) on the non-villous surfaces of lymphocytes becomes activated and adheres to ligands expressed on endothelium, ICAM-1 (CD54), a cell-surface protein with 5 Ig-like domains, and ICAM-2 (CD102), a molecule with 2 Ig-like domains. The ICAM-1 could be more important in the adhesion to inflamed tissues, whereas the ICAM-2 could predominantly mediate interactions of lymphocytes with non-activated endothelial cells (Lehmann et al., 2003). Finally, the binding of LFA-1-ICAM-1 to PECAM-I (platelet endothelial cell adhesion molecule) is involved in the diapedesis of lymphocytes between endothelial cells as they exit the vessel (Springer, 1990; Walker, 2004).
Xerostomia and Oral Lesions Associated with HIV/AIDS
Dryness of the mouth is frequently observed in HIV-positive individuals (Foltyn, 1993; Younai et al., 2001; Ohmit et al., 2003; Okunseri et al., 2003). In comparison with those with an undetectable viral load, individuals having a viral mRNA load of more than 100,000/mm3 copies are much more likely to report dry mouth (Younai et al., 2001). It has been shown that HIV+ persons have a significantly decreased salivary flow rate in the early stages of HIV infection (CD4+ > 200 cell/µL) (Lin et al., 2003). Similar results have suggested that xerostomia may be the initial presentation of HIV-1 infection (Ooi et al., 2005). Analysis of these data suggests that immunosuppressive drugs must be used cautiously in xerostomic individuals, and that screening for HIV is mandatory in the differential diagnosis of persons with xerostomia (Ooi et al., 2005). The prevalence of xerostomia and salivary gland hypofunction, associated with immunosuppression measured by CD4+ cell counts, is significantly higher in HIV-1-positive women when compared with a group of at-risk seronegative women (Navazesh et al., 2000). In addition, infection with HIV-1 may be associated with enlargement of the major salivary glands (Schiødt et al., 1989; Pinto and De Rossi, 2004). Furthermore, not only is the secretory function of salivary glands reduced in HIV+ individuals, but the composition of saliva is altered as well (Lin et al., 2003). The nature of salivary gland dysfunction in early HIV/SIV infection warrants further investigation.
Oral lesions—such as candidiasis, oral hairy leukoplakia, Kaposi’s sarcoma, aphthous ulcers, and herpes simplex viral infections—are most common in HIV-infected persons (Lü et al., 1994; Anil and Challacombe, 1997; Patton et al., 2002) and SAIDS retrovirus serotype-1 (SRV-1)-infected macaques (Schiødt et al., 1988). Oral candidiasis, particularly the pseudomembranous type, has been consistently reported as the most prevalent HIV-1-associated oral lesion in all ages (Gillespie and Marino, 1993; Espinoza et al., 2003; Pinto and De Rossi, 2004). Oral candidiasis is more common in HIV-1-infected children with higher caries experience, gingival inflammation, and plaque accumulation (Chen et al., 2003; Pinto and De Rossi, 2004). However, more than 50% of older persons with AIDS present one or more oral mucosal lesions, and denture use leads to a three-fold increase in the probability of mucosal lesions (Espinoza et al., 2003). Oral hairy leukoplakia and Kaposi’s sarcoma appear to be associated with male-to-male HIV-1 transmission risk behaviors (Patton et al., 2002). Sublingual ranula is considered another HIV/AIDS-associated lesion, especially in children (Chidzonga and Rusakaniko, 2004). Persons with oral candidiasis or multiple oral lesions have significantly lower numbers of CD4 lymphocyte counts and lower ratios of CD4/CD8 lymphocytes than those without any oral lesions (Glick et al., 1994; Chiang et al., 1998). Oral mucosal lesions are common in both young and elderly people, are more prevalent among those with advanced HIV diseases, and may appear in the early phase of HIV infection, suggesting the necessity for an improvement in the prevention, diagnosis, and treatment of these lesions.
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THE IMMUNE FUNCTION OF SALIVARY GLANDS AND POTENTIAL REGULATORY FACTORS FOR SALIVA FLOW |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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Studies of the human salivary gland show that IgA-plasma cells are present in HLA-DR+ epithelium that surrounds the duct (Thrane et al., 1992). Further, human salivary glands can produce IgA under in vitro culture conditions (Hurlimann and Zuber, 1968). Salivary gland output and composition of saliva have been reported to be altered as a result of HIV infection (Lin et al., 2003).
Anatomically, human salivary glands are surrounded by the lymphatic system, which is linked to the thoracic duct and blood. The human parotid gland is spatially covered by anterior auricular and intraglandular parotid lymph nodes and superficial lymph nodes, whereas the submandibular gland is surrounded by submandibular and submental lymph nodes. Salivary glands are surrounded by lymphoid tissues and process plasma cells, T-cells, and APCs. Salivary glands may serve as inductive and effector sites for eliciting immune responses in oral mucosa and systemic lymphoid tissues (Sankar et al., 2002; Tucker et al., 2004).
The parasympathetic nerve signals that induce copious saliva flow cause moderate dilation of the blood vessels. In addition, saliva flow itself directly dilates the blood vessels, and thus provides the increased nutrition that is needed by the secreting cells. Part of this additional vasodilator effect is caused by kallikrein secreted by the activated ductal cells of the parotid and the sublingual salivary glands (Ørstavik et al., 1982), which in turn acts as an enzyme to split one of the blood proteins, an 2-globulin, to form bradykinin, a strong vasodilator peptide, which results in increased blood flow to the secreting glands (Emmelin and Gjørstrup, 1973; Hibino et al., 1994). The major bradykinin B2 receptors are prominent in the perivascular smooth-muscle cells of the tunica media, which are within the small arterioles of salivary glands of both rats and humans (Figueroa et al., 2001). HIV infection results in dry mouth or changes the blood flow rate of the interlobular connective tissue, and this may be mediated by the kallikrein-kinin system. It is possible that HIV replication may affect vascular endothelial cells and cause the obstruction of the capillary bed that supplies blood to the salivary gland secreting cells. Consequently, it may cause a low salivary secretion rate, xerostomia, and an increased susceptibility to oral co-infections or lesions.
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THE IMMUNE FUNCTION OF PALATINE TONSILS |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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TCR+ T-cells (Salles and Middleton, 2000). Thirty-five percent of the crypt epithelial cells are microfold or M cells (Gebert, 1997), which play an important role in the uptake of luminal antigens to initiate immune responses (Gebert, 1997). CD8+ T-cells and TCR+ T-cells in the lymphoid follicles of the tonsils increase significantly in human tonsillitis (Olofsson et al., 1998). Studies in normal children’s palatine tonsils have demonstrated that the density of dendritic cells is the highest in the extrafollicular T-cell areas, where CD4+ T-lymphocytes are especially abundant (Noble et al., 1996). Numerous macrophages can be found in all compartments (Gorfien et al., 2001). Both dendritic cells and macrophages capture, process, and present antigen to T-lymphocytes, which is a critical step in the early immune response (Gorfien et al., 2001). Functional analysis of ASCs has revealed that the number of S. pyogenes-specific IgA-ASCs increased in individuals with recurrent tonsillitis when compared with those with a tonsillar hypertrophy (Kerakawauchi et al., 1997). Intra-tonsillar vaccination with tetanus toxoid in humans induced IgG- and IgA-ASCs that are highly restricted to the immunized tonsils, while a few ASCs were disseminated through the blood stream and to distant organs (Quiding-Jarbrink et al., 1995). In vitro cultures of human tonsil tissues have been proposed as a model for the study of HIV-1 pathogenesis (Glushakova et al., 1995). Human palatine tonsils obtained from tonsillectomies were cultured ex vivo and infected with semen from HIV-positive donors. HIV infection was transferred into tonsillar lymphocytes, but the progression from virus binding to primary infection was dramatically reduced when the lymphocytes were protected by an intact mucosal surface (Maher et al., 2004, 2005). These results suggest that the intact oral mucosa plays an important role in limiting HIV oral primary infection. In palatine tonsils taken from individuals chronically infected with HIV-1, the infected cells were not found in the stratified squamous epithelium adjacent to the pharynx; instead, the infected lymphocytes were localized on the surface of the tonsillar crypt epithelium (Frankel et al., 1997). The interaction of T-cells and dendritic cells in the surface of tonsillar tissue under in vitro culture may support HIV-1 replication. HIV-1 replicates actively in the crypt epithelium of tonsils or adenoids taken from asymptomatic HIV-1-infected individuals (Frankel et al., 1996). Adult macaques exposed to cell-free simian immunodeficiency virus (SIV) through the oral route become infected and developed simian AIDS (Baba et al., 1996). Thus, Waldeyer’s ring, the palatine tonsils, and adenoids may serve as potential sites of entry for HIV-1 and SIV. |
HIV TARGETING OF IMMUNE CELLS IN THE ORAL MUCOSA |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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). Thus, oral mucosa is an effective site for the induction of S-IgA Abs. SIVmac239 mucosal infection results in a high infiltration of IgA-secreting plasma cells in the oral mucosa. Similar to the oral mucosa, SIV-infected macaques have an apparent high frequency of IgA-secreting cells (mean number: 596/106 mononuclear cells) and IgG-secreting cells (mean number: 231/106 mononuclear cells) in submandibular salivary glands, when compared with that of normal monkeys (35/106 mononuclear cells for IgG-secreting cells and 44/106 mononuclear cells for IgA-secreting cells). However, the difference was not statistically significant, due to the small sample size (Fig. 1B).
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-secreting cells were predominant when compared with IL-10-secreting cells in oral mucosa and submandibular salivary glands (Figs. 2A, 2B). A low frequency of IL-6-secreting cells and small numbers of IFN--secreting cells were present in both tissues. IL-2-secreting cells were undetectable (Figs. 2A, 2B). Again, the oral mucosa had at least a 10-fold-higher frequency of TNF--, IL-10-, IL-6-, and IFN--secreting cells when compared with the submandibular glands (Fig. 2).
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Human Langerhans cells in the oral epithelium are more effective at stimulating allergenic T-cells in vitro than are Langerhans cells from skin (Hasséus et al., 2004). Further, it has been shown that CD36+ dendritic cells are physiologic components of the oral mucosa, and that HIV infection does not change in terms of numbers of CD36+ dendritic cells, but negatively affects the dendritic cell expression of HLA-DR, particularly in the area of hairy leukoplakia (Pimpinelli et al., 1991). Similarly, it has been reported that systemic infection of rhesus monkeys with either simian retrovirus-1 or SIV does not significantly change the numbers of Langerhans cells in the oral mucosal epithelium (Hämmerle et al., 1993). One study, by immunohistochemical analysis, showed that human oral biopsies at 2 days post-oral immunization with HIV-1 DNA induced increased numbers of granulocytes and T-cells, as well as expression of HLA-DR (Lundholm et al., 2002). The role of CD8+ and CD4+ T-cells in the oral mucosa has not been fully investigated. The above results suggest that the oral mucosa is capable of eliciting specific mucosal immune responses by boosting immunocompotent Langerhans cells and T-cells. Oral immunization can increase the numbers of T-cells and HLA-DR expression on Langerhans cells that play a major role in antigen presentation to naïve T-cells in local and distal tissues.
HIV-targeted Oral Mucosal Cells
The mechanism by which HIV infects cells, either mucosal epithelial cells or Langerhans cells in the oral mucosa, is not clear. Studies on biopsies of oral hairy leukoplakia lesions of HIV-infected persons have shown that oral mucosal Langerhans cells are the target of HIV infection (Chou et al., 2000). However, SIV may infect oral lymphoid tissue through the antigen-transporting crypt epithelium, rather than through Langerhans cells (Cohen et al., 2000). Recent evidence has shown that oral epithelial cells are infected by CXCR4-tropic HIV strains through a galactosylceramide receptor and the CXCR4 chemokine co-receptor (Liu et al., 2003). Another study showed the absence of CD4+ glycoprotein, Fc gamma receptors, and HLA class II antigen expression in oral epithelium, and a paucity of Langerhans cells expressing the V1 domain of CD4 (Hussain and Lehner, 1995). Further, transcytosis of HIV can occur from the mucosal to the submucosal surface and vice versa (Leigh et al., 1998). It is still not clear which cell types and receptors in the oral mucosa are first targeted by HIV/SIV. Nevertheless, HIV-induced alterations of oral epithelial cells, together with impairment of mucosal CD4+ T-cells and the lack of Th1-type cytokines in whole saliva of HIV chronic infected individuals (Leigh et al., 1998), may contribute to oral opportunistic infections.
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ORAL MUCOSAL IMMUNIZATION |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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ORAL MUCOSAL AB RESPONSES SPECIFIC TO HIV/SIV INFECTION |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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Saliva samples may be used for monitoring seroconversion after HIV infection and for the evaluation of vaccine-induced oral mucosal immune responses (Lü et al., 1993). Thus, whole saliva can be used as a diagnostic specimen and is a good alternative to blood samples in epidemiological studies of HIV prevalence in high-risk groups (van den Akker et al., 1992; Lü et al., 1994; Lu, 2000a,b). The diagnosis of HIV infection can be established within 10 minutes by a salivary rapid test system (Lü et al., 1993, 1994). The use of saliva samples rather than serum is advantageous, because it offers a means of preventing needle-stick injuries. In addition, collection of saliva samples is simple and does not need specially trained laboratory personnel. Furthermore, handling of saliva samples is safer than serum, because infectious virus in oral samples is rare. It has also been suggested that testing for HIV-1 Abs in saliva specimens is cost-effective and suitable for screening. Saliva samples should be particularly considered for population-based collections, in pediatrics, and when compliance in giving a blood specimen is low.
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CONCLUDING REMARKS |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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Received December 16, 2005; Accepted September 8, 2006
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REFERENCES |
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TOPABSTRACTINTRODUCTIONPHYSIOLOGY OF SALIVARY GLANDS...SALIVARY INNATE FACTORS AND...ORAL MUCOSAORAL MUCOSAL BLOOD FLOW,...THE IMMUNE FUNCTION OF...THE IMMUNE FUNCTION OF...HIV TARGETING OF IMMUNE...ORAL MUCOSAL IMMUNIZATIONORAL MUCOSAL AB RESPONSES...CONCLUDING REMARKSREFERENCES |
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