Immunology of tonsils and adenoids: everything the ENT surgeon needs to know

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Abstract

The lymphoid tissue of Waldeyer’s ring, and particularly the nasopharyngeal tonsil (adenoids), appears to be functionally comparable to nasal-associated lymphoid tissue in rodents. Antigen-stimulated lymphoid follicles give rise to: (a) clonal B-cell expansion; (b) B-cell receptor affinity maturation; (c) positive selection of B cells according to receptor affinity for antigen; (d) differentiation to B memory cells and plasma cells; and (e) variable induction of the joining (J)-chain gene. B-cell differentiation is also important to promote downstream isotype switching of the immunoglobulin (Ig) heavy chain constant genes. For tonsillar B cells, this process gives mainly rise to IgG and IgA plasma cells, partially associated with J-chain expression. Because the J chain is a key peptide in the polymer structure of secretory IgA, tonsils and adenoids may provide B cells for mucosal effector sites. Thus, several observations suggest that these lymphoid organs generate polymeric IgA (pIgA)-expressing B cells that migrate to the upper airway mucosa, lacrimal glands and salivary glands. Accordingly, the nasal route of vaccination induces secretory IgA-dependent regional mucosal immunity and will also enhance systemic immunity. Although the pIgA-producing capacity of tonsillar B cells is considerably decreased in children with recurrent tonsillitis, a conservative attitude towards adenotonsillectomy appears immunologically desirable, particularly in the young age group.

Introduction

The nasopharyngeal tonsil (adenoids) and palatine and lingual tonsils constitute the major part of Waldeyer’s ring, with the tubal tonsils and latteral pharyngeal bands as a less prominent components [1], [2]. These lymphoepithelial elements appear to be functionally comparable to the nasopharynx-associated lymphoid tissue (NALT) in rodents, which is an organized lymphoid structure present on both sides of the nasopharyngeal duct dorsal to the cartilaginous soft palate [3], [4]. All parts of Waldeyer’s ring are indeed strategically located to perform regional immune functions because these structures are exposed to both airborne and alimentary antigens. However, although tonsils and adenoids apparently play an important immune-inductive role as components of mucosa-associated lymphoid tissue (MALT), these structures also show similarities with lymph nodes and may in addition participate as effector organs of local systemic-type as well as mucosal-type of adaptive immunity.

Tonsils and adenoids contain four specialized lymphoid compartments participating in the immune functions of these organs [5], [6], namely the reticular crypt epithelium, the extrafollicular area, the mantle zones of lymphoid follicles and the follicular germinal centres (GCs). Primary follicles are present in human tonsils as early as at 16 weeks of gestation [5], which is similar to Peyer’s patches of gut-associated lymphoid tissue (GALT) but different from rodent NALT, whose organogenesis begins at birth [4]. Nevertheless, the formation of tonsillar GCs that reflects B-cell activation induced by exogenous antigens, does not take place until shortly after birth, and terminal differentiation of effector B cells to extrafollicular plasma cells can first be seen approximately 2 weeks postnatally [5].

The GCs characteristically arise in T cell-dependent B-cell responses and are associated with: (a) clonal expansion of B cells; (b) somatic hypermutation in B-cell immunoglobulin (Ig) variable (Ig V)-region genes; (c) positive selection of B cells that are able to receive antigen-specific signals by high affinity; (d) subsequent differentiation to B memory cells and plasma cells of various isotypes; and (e) induction of the J-chain gene in a variable subset of B cells. This gene encodes a 15 kDa peptide, the J chain, which is a crucial structural part of polymeric immunoglobulins (pIgs)—that is, dimers and larger polymers of IgA (collectively called pIgA) and pentameric IgM [7]. Without the incorporation of J chain, pIgs cannot bind to the transmembrane epithelial secretory component (SC), which acts as the pIg receptor (pIgR); this interaction is a central step in the formation and selective external transport of secretory IgA (sIgA) and secretory IgM (sIgM) antibodies.

This review deals with the immunological function of tonsils and adenoids and discusses accumulating evidence for a putative role of these structures in secretory immunity of the upper respiratory tract and associated glands. Results are indeed convincing to support the notion that pIgA precursor cells disseminate from Waldeyer’s ring to regional mucosal effector sites such as the nasal mucosa and lacrimal and salivary glands [6], [7], [8], [9]. Let me add that the ambitious title of this review was given to me by the congress organizers.

Section snippets

Germinal centres as B cell-inductive lymphoid compartments

Primary follicles of secondary lymphoid organs such as the tonsils and adenoids, consist mainly of recirculating B cells with a naive phenotype positive for surface IgD and IgM (sIgD+sIgM+)—both isotypes exhibiting the same specificity for antigen. These lymphocytes pass into the spaces of the network formed by follicular dendritic cells (FDCs). It is still unclear why both sIgD and sIgM need to be expressed to render B cells antigen-reactive [10]. Likewise, the nature and origin of FDCs are

J chain-expressing potential of tonsillar B cells

The tonsillar GC reaction normally generates a variable number of intrafollicular Ig-producing immunocytes (plasmablasts and plasma cells) predominated by cytoplasmic expression of IgG (55–72%) or IgA (30–18%). Both these GC immunocyte classes, and also those producing IgM and IgD, often show concurrent expression of J chain (13–80%), both in normal palatine tonsils and adenoids from children [19], [20]. Thus, the J chain-expressing capacity of IgA immunocytes in these organs is better than

Evidence for dissemination of tonsillar B cells to regional secretory effector sites

The finding that nasal and bronchial mucosae, as well as salivary and lacrimal glands, contain an IgA1 and IgD immunocyte distribution similar to that of tonsils and adenoids, supports the notion that these regional secretory effector sites are seeded mainly by B-cell blasts generated in GCs of Waldeyer’s ring [6], [7], [8], [9]. A possible minor contribution from bronchus-associated lymphoid tissue remains uncertain, because organized follicles apparently do not exist in the normal human lung

Effect of adenotonsillectomy on regional immunity

The observations discussed above provide quite convincing evidence for the theory that Waldeyer’s ring functions immunologically as NALT in humans and supply secretory effector sites of the upper aerodigestive region with antigen-stimulated pIgA precursor cells. To further support this notion, it is important to evaluate the effect of adenotonsillectomy on the regional SIgA levels. The pioneer report by Ogra [34] showed that combined tonsillectomy and adenoidectomy in children reduced the level

Acknowledgements

The author’s studies are supported by the Norwegian Cancer Society, the Research Council of Norway, and the Anders Jahre’s Foundation. Hege Eliassen and Erik Kulø Hagen are gratefully acknowledged for secretarial assistance.

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