Immunology of the tonsils

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Abstract

The tonsils are lymphoepithelial structures that provide a protective immunological ring at the openings of both digestive and respiratory tracts. Here, as discussed by Marta Perry and Anthony Whyte, the unique nature of the various human tonsils reveals that they are capable of a variety of complex immunological functions.

Section snippets

Tonsillar crypts

Crypts are narrow epithelial diverticula, which considerably increase the available surface area for direct antigenic stimulation. In an average adult PT the estimated epithelial surface area of the crypts is 295 cm2, in addition to the 45 cm2 of epithelium covering the oropharyngeal surface[2]. Thus, crypts are functionally important features, varying in arrangement from the monocryptic units of the LT to the polycryptic, sometimes branching crypts of the NT and PT. In healthy tonsils the

Tonsillar epithelium

The pharyngeal surfaces of the NT and the TT are covered mainly with a ciliated respiratory epithelium, whereas those of the PT and LT are protected by stratified squamous nonkeratinized or parakeratinized epithelium, respectively. These epithelial layers are avascular and only a very few nonepithelial cells are found here. The surface epithelia are underlined by a band of thick connective tissue containing many vessels, nerves and lymphatics.

By contrast, the epithelia lining the crypts are not

Lymphoepithelium

There are three main components of the lymphoepithelium: (1) the epithelial cells, which are altered in shape and cellular contents but which represent a scaffold held together by desmosomes; (2) the infiltrating, motile nonepithelial cells; and (3) the intraepithelial vasculature (Fig. 3).

Stöhr was the first to suggest that lymphocytes migrated from the tonsillar parenchyma into the crypt epithelium of the PT (Ref. [4]). The mesh of the epithelial cells was graphically compared with a sponge

Evolution and ontogeny

In the human embryo there are six pairs of branchial arches, which develop on the lateral aspect of the head. Between these arches are successive endodermal grooves that form the pharyngeal pouches. This region, containing the primordia of lymphoepithelial organs, represents the most dynamic part of every embryo. In lower vertebrates, there is no tonsil but the thymus is present in all pharyngeal pouches. In man, however, the thymic anlagen reduce to only the third pouches[2]and aggregations of

Secretory immunoglobulins

IgG, IgA and IgM are detectable in the secretory material from the pharynx and in pharyngeal roof tissue homogenates as early as week five of gestation. Since levels of these immunoglobulins increase with fetal age, it has been proposed that the fetal tonsil (NT) reacts to autoantigens that are produced as a result of cell death during morphogenesis[30].

The mucosa of the pharynx has a complex secretory immune system. B cells, which can express J-chain, are stimulated by antigen initially in

Tonsillar leukocytes

Leukocytes, predominantly lymphocytes, are found in all the compartments of the tonsils, including the lymphoepithelium (where they are called intraepithelial leukocytes; IELs), the closely-associated mantle zone, the interfollicular regions, and the follicles. Populations of γδ T cells, with a natural killer (NK)-cell-like function due to the perforin complex, occur only in low numbers in tonsils, particularly in the lymphoepithelium. The number of IELs in patients with recurrent tonsillitis

Adhesion molecules and trafficking

Specialized trafficking HEV structures (Fig. 4) are found in both interfollicular and lymphoepithelial areas[47]. As may be expected from specimens usually removed for recurrent tonsillitis, a wide number of adhesion molecules have been reported in tonsillar tissue. The VCAM-1–VLA-4 interaction may be particularly important in the migration of IELs (Ref. [48]). Although P-selectin is expressed on tonsillar HEVs (Fig. 5), its ligand, P-selectin glycoprotein ligand 1 (PSGL-1), is substantially

Immunopathology

In the past, just as today, the anatomical position of the palatine tonsils made them accessible for study in health and disease, and a popular target for surgical intervention. As early as 3000 bc the procedure known as tonsillectomy was performed by the Greeks, who gave prominent consideration to diseases of the tonsils and palate[58]. In the last 100 years the most important indications for removal of the tonsils included hypertrophy, which interfered with respiration, and chronically

Experimental models

Although inbred strains of mice and rats are readily obtainable, they are not suitable as models for functional studies of the Waldeyer's ring. They have a very different pharyngeal anatomy to humans and lack both PT and NT, but they do possess bilateral aggregates of nasopharyngeal lymphoid tissue[77]. The rabbit has a monocryptic PT (Ref. [10]) and the shrew (Suncus murinus) has a microscopic PT equivalent, consisting of a single lymphoid follicle[78]. By contrast, tissues equivalent to

Conclusion

We have focused mostly on the PT and the NT because these are readily available at adenotonsillectomy and have therefore been studied in some detail. There is, by comparison, very little published work on the human LT and virtually none on the TT. Pharyngitis is a common presentation of lingual tonsillitis, and it may be that chronic inflammation of the LT is frequent in adults. One study suggests that the LT is immunologically more active than both PT and NT during middle-age[85]. Because of

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