Histology of the Mucosa

Mucosal tissues consist of two sheets (Fig. 6.1). The superficial sheet represents a unilayered or, at the ocular surface, a multilayered arrangement of epithelial cells. They usually have a strong mechanical connection by intercellular adherence junctions (e.g. desmosomes and zonulae adherentes) and are sealed by an apical tight junction complex that prevents entrance of foreign materials including potential antigens. Impairment of the epithelial integrity is a major reason for a deregulation of mucosal immunity and is observed in dry eye disease and in allergic eye disease but is also caused by the surgical trauma during corneal transplantation.

The epithelium is separated by a thin basement membrane from the underlying loose connective tissue of the lamina propria. The lamina propria not only has mechanical properties for anchorage of the epithelium but is highly vascularized to serve for metabolic purposes and to provide migratory pathways for lym-phoid cells. Lymphoid cells can immigrate in a regulated fashion via specialized postcapillary high endothelial venules (HEV) or flat-lined vessels into the tissue and can leave from the tissue via afferent lymphatic vessels towards the regional lymph nodes and eventually into the blood circulation in order to recirculate (Fig. 6.1). The lamina propria is filled with a

Fig. 6.1 A, B. Structure and function of the mucosal immune system. MALT consists of a diffuse lymphoid tissue (A) and of an organized follicular tissue (B), shown here at different enlargements. Mucosal tissues in general are composed of two sheets, the luminal epithelium (e) with its basement membrane (bm) and an underlying lamina propria (Ip), which both contain lymphocytes. The lamina propria is composed of loose connective tissue with small blood vessels (b), afferent lymph vessels (l) and numerous cells including lymphoid cells [T-lymphocytes (black), B-lymphocytes (blue), plasma cells (p)]. Accessory cells occur like fibroblasts f), macrophages (mf),mast cells (mc) or dendritic cells (dc). Intraepithelial lymphocytes are mainly CD8+ suppressor/cy-

Fig. 6.1 A, B. Structure and function of the mucosal immune system. MALT consists of a diffuse lymphoid tissue (A) and of an organized follicular tissue (B), shown here at different enlargements. Mucosal tissues in general are composed of two sheets, the luminal epithelium (e) with its basement membrane (bm) and an underlying lamina propria (Ip), which both contain lymphocytes. The lamina propria is composed of loose connective tissue with small blood vessels (b), afferent lymph vessels (l) and numerous cells including lymphoid cells [T-lymphocytes (black), B-lymphocytes (blue), plasma cells (p)]. Accessory cells occur like fibroblasts f), macrophages (mf),mast cells (mc) or dendritic cells (dc). Intraepithelial lymphocytes are mainly CD8+ suppressor/cy-

totoxic T cells whereas in the lamina propria of the diffuse tissue (A) they occur in roughly equal numbers together with CD4+ T-helper cells. Follicular lymphoid tissue (B) is formed by accumulations of B-lymphocytes with parafollicular T-cell zones, vessels and an overlying specialized follicle-associated epithelium for antigen transport towards the follicle. Naïve lymphocytes enter follicular regions via blood vessels (b), come into contact with antigens, antigen-specific lymphocytes proliferate, differentiate and leave via lymphatics (l). They finally reach the blood circulation and may later emigrate to populate the same or other mucosal tissues as effector cells (T cells and plasma cells)

large number of different cell types and macro-molecules that serve the purpose of nutrition and protection as maintained, e.g. by im-munoglobulins and antibacterial peptides. The lamina propria also enables the communication of cells with each other and their extracellular matrix by different types of molecules. Cyto-kines, chemokines and adhesion molecules transfer (immunoregulatory) information, guide the migration by forming a gradient, act as traffic signals anchored to the extracellular matrix and cells or provide direct cell contacts.

Cells in the lamina propria consist of so-called fixed cells like fibroblasts that are responsible for the production and maintenance of the connective tissue itself and free cells (e.g.

lymphocytes, plasma cells, macrophages, DC, eosinophils or mast cells) that can migrate in and partially out of the tissue and mainly have protective tasks. Lymphoid cells occur in both mucosal layers: in the connective tissue as lamina propria lymphocytes (LPL) and plasma cells and inside mainly the basal layers of the epithelium as intraepithelial lymphocytes (IEL). Antigen presenting DC also occur in the epithelium and lamina propria. The other free cell types normally only occur inside the lamina propria.

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