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Structure of the human uvula
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
1999 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, Vol. 119, no 6, 712-717 p.Article in journal (Refereed) Published
Abstract [en]

Eleven uvular biopsies were investigated for their morphology, the presence of mast cells and the distribution of hyaluronan and its major ligand CD44. Three microanatomical sites--surface epithelium, subepithelial area and area of glands--were examined. The oral side of the uvula was covered by a 15-20 cell thick layer of keratinized/parakeratinized surface epithelium, firmly anchored to the underlying connective tissue by connective tissue papillae. The width of the intercellular spaces in the epithelium increased toward the basal lamina, a location that exhibited intense hyaluronan and anti-CD44 staining. Most mast cells were located in the vicinity of blood vessels, at which sites there was high staining intensity of hyaluronan. Tissue mast cells could also be observed in the connective tissue septa enclosing the acini. Glands and muscle fibres became more sparse from the proximal part of the uvula to the distal end, while the amount of connective tissue increased. The localization and architecture of connective tissue elements and mast cells are consistent with the ability of the uvula to resist mechanical stresses and to develop oedema and fibrosis, respectively.

Place, publisher, year, edition, pages
1999. Vol. 119, no 6, 712-717 p.
National Category
URN: urn:nbn:se:umu:diva-68019DOI: 10.1080/00016489950180685PubMedID: 10587007OAI: diva2:615443
Available from: 2013-04-10 Created: 2013-04-10 Last updated: 2013-08-08Bibliographically approved
In thesis
1. Immune cells in human pharyngeal and palatine tonsils and in the uvula: tissue distribution, cellular composition and functional properties
Open this publication in new window or tab >>Immune cells in human pharyngeal and palatine tonsils and in the uvula: tissue distribution, cellular composition and functional properties
1999 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The adenoid (pharyngeal tonsil), the palatine tonsils and the uvula are strategically located at the entrance of the upper airodigestive tract. By virtue of their location they are incessantly exposed to inhaled and ingested antigens. Severe nasal obstruction, otitis media with effusion, recurrent tinsillitis and obstructive airways during sleep are conditions often due to diseases in these organs.

To advance our knowledge about the etiology and pathogenesis of these diseases, we have compared immune cell composition, cytokine expression and microbial colonisation in adenoids from children with hypertrophic obstructive adenoid (HOA) and chronically infected adenoid (CIA). Similarly, we compared immune cell composition in palatine tonsils from children with idiopathic tonsillar hypertrophy and recurrent tonsillitis. Finally, we wanted to characterise the human uvula from an immunological point of view, which had previously not been done. Its composition and distribution of immune cells, its cytokine profile, connective tissue elements and ultrastructure was studied.

When comparing adenoids from children with HOA and CIA, the most striking finding was their similarity. A cytokine profile that was independent of diagnosis but seemed characteristic for the adenoid emerged. T cell expression of IL-5 and TGF-β1 but not IL-4 suggested an ongoing humoral response driven by a "mucosal TH2" cell. αβ T cells also expressed TNF-α, IFN-γ and IL-2, indicating a concomitant cell mediated response. Cell mediated immune responses often reflect viral infection. In line with this, adenovirus DNA was found in 80% of the adenoid samples. Furthermore, IL-6, IL-8 and TNF-α expressed in the non-T cell fraction suggested that the tissue macrophages were activated. TNF-α, IFN-γ and TGF-β1 were expressed by γδ T cells. The following differences between HOA and CIA were however, noted: i) most intraepithelial lymphocytes were CD8+ γδ T cells in HOA, while CD8+ αβ T cells dominated intraepithelially in CIA; ii) the number of follicles was twice as high in CIA as in HOA; iii) there were signifacantly more granulocytes in the interfollicular area in CIA than in HOA; iv)IL-6 mRNA expressing γδ T cells were only found in HOA and v) there was a tendency of higher TNF-α mRNA levels in non-T cells of CIA compared to HOA. The following scenarios emerge: in CIA there appears to be an inadequate first line of defence, with a low frequency of intraepithelial γδ T cells and a high frequency of cytotoxic CD8+ αβ T cells eliminating infected epithelial cells. Togehter, these two conditions cause a "leaky" epithelium, allowing infiltration of microbes into the underlying tissue and subsequent recruitment of granulocytes and follicle formation initiated by activated macrophages. In HOA, activated intraepithelial γδ T cells appear to be involved in antimicrobial defence reactions and surveillance of the epithelium.

The difference in leukocyte profiles between tonsils from patients subjected to surgery due to idiopathic tonsillar hypertrophy or recurrent tonsillitis was limited to the surface epithelium. CD8+ γδ T cells utilising the unusual combination Vδ1/Vγ9 in their T cell receptor constituted the majority of intraepithelial lymphocytes in both groups. However, the frequency of these cells was significantly higher in recurrent tonsillitis. These results suggest that CD8+ Vδ1/Vγ9+ γδ T cells are characteristic of palatine tonsils and selectively expanded in recurrent tonsillitis. These γδ T cells may be involved in clearing infectious bacteria at the surface of the tonsil.

Tissue macrophages, αβ T cells, γδ T cells, mast cells and B cells constituted, in declining order, the immune cell populations in the uvula. No fillicle-like structures were present. Most T cells had a CD8+ CD28-TCR-αβ+ phenotype, suggesting a down-regulatory function. Production of the down-regulatory cytokine TGF-β was also noted. This is consistent with the hypothesis that the uvula contributes to the development of mucosal tolerance. Furthermore, the uvula seems to be protected from pathogens penetrating the internal milieu by a subepithelial barrier of γδ T cells and macrophages. TNF-α secreting immune cells were found at this location. TNF-α and TGF-β may cause tissue fibrosis, TNF-α indirectly by stimulating mast cells to release histamine. Tissue fibrosis in conjunction with water binding to hyaluronan present in the connective tissue is the most likely explanation for the observed enlargement of the uvula in patients with sleeping disorders.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 1999. 71 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 607
National Category
Immunology in the medical area
urn:nbn:se:umu:diva-79111 (URN)91-7191-629-6 (ISBN)
Public defence
1999-10-01, Sal D, Tandläkarhögskolan, Norrlands universitetssjukhus, Umeå, 10:00
Available from: 2013-08-08 Created: 2013-08-08 Last updated: 2013-08-08Bibliographically approved

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