Bullous Diseases Pathophysiology
The basement membrane zone (dermal-epidermal junction) is continuous along the basal epidermal cells and consists of four compartments: the basal cell plasma membrane, the lamina lucida, the lamina densa, and the sublamina densa.
The basal cell plasma membrane contains hemidesmosomes which are located at regular intervals along the dermal surface of the plasma membrane of the basal keratinocytes. These anchor the epidermis, through connecting (anchoring) filaments to the lamina densa and ultimately to the underlying dermis. The hemidesmosomes also provide a site of attachment for the basal intermediate filaments, keratins 5 and 14. The hemidesmosomes consist of at least four protein components. Bullous pemphigoid antigen 1 (230 kD) and plectin are intracellular components. Bullous pemphigoid antigen 2 (180 kD, type XVII collagen) and alpha 6 beta 4 integrin are transmembrane components.
The lamina lucida lies beneath the plasma membrane and separates the hemidesmosomes from the lamina densa. It is an electron lucent region that contains the anchoring filaments laminins 5, 6, and 7. These originate in the hemidesmosomes of the plasma membrane and insert into the lamina densa, thus connecting the basal keratinocyte plasma membrane to the lamina densa.
The lamina densa lies beneath the lamina lucida. It is composed predominantly of type IV collagen. However, laminin, nidogen/entactin, and heparin sulfate proteoglycans are also found in this region.
The sublamina densa zone is located beneath the lamina densa. It contains anchoring fibrils, anchoring plaques, collagen fibers, and elastic fibers. Anchoring plaques are composed of type IV collagen and laminin. They are distributed randomly in the papillary dermis below the lamina densa and are connected by anchoring fibrils. Anchoring fibrils are composed of type VII collagen (290 kD). In addition to connecting anchoring plaques, these bind to laminin 5 in the lamina lucida and to type IV collagen in the lamina densa and in anchoring plaques. Anchoring fibrils thus act to connect all of these structures, ultimately anchoring the epidermis and its underlying basement membrane zone to the papillary dermis.