Biomedical Engineering Reference
In-Depth Information
into the dermis, where they subsequently enter the lymphatic spaces and travel
to draining lymph nodes. Here, where the audience of naïve T-cells is maxi-
mized, they transfer their antigenic information (in an HLA-DR-dependent
manner) that transforms the T-cells into ones with antigen-specific memory.
Upon re-exposure to antigen, memory T-cells enter the skin, where they release
mediators that amplify the immune response, thereby recruiting non-antigen-
specific lymphocytes and macrophages, resulting in a delayed hypersensitivity
reaction. It is important to realize, however, that skin-homing T-cells normally
traffic in and out of skin (on a regular basis) as part of the skin-associated
lymphoid tissue (SALT.) This trafficking is mediated by homing interactions
between lymphocyte subsets (expressing the skin-homing molecule CLA) and
dermal microvascular endothelial cells (expressing e-selectin.) Indeed, it has
recently been shown that at any given time, normal human skin harbors approxi-
mately 1
10
6
T-cells per cm
2
and an estimated 2 × 10
10
T-cells in the entire
skin surface, which is nearly twice the number of T-cells in the entire systemic
circulation.
7
Like melanocytes, Merkel cells are found in the basal cell layer.
8
Seldom visible
under a light microscope, these cells contain membrane-bound, cytoplasmic
neuroendocrine-type granules (identified by electron microscopy.) They occa-
sionally form synaptic junctions with peripheral nerve endings and, in lower
vertebrates, may participate in slow-adapting touch perception. However, their
function in human skin has not been elucidated and it remains possible that they are
vestigial.
×
4.2.2
Basement membrane
Directly beneath the undersurface of the epidermis lies the basement membrane
(BM). Composed mostly of collagen IV, the basement membrane physically
'separates' the epidermis from the dermis. Although seen as a single entity
under light microscopy, the BM is of heterogeneous composition when viewed
under an electron microscope (and is referred to as the basal lamina.) The basal
lamina is complex (in molecular structure) and may be subdivided into the
lamina densa (superficial, composed of collagen IV) and the lamina lucida
(deep, composed of laminin and other glycoproteins.) Epidermal-dermal an-
choring fibrils (made from collagen VII) physically connect the lamina densa to
the papillary dermis. Epidermal-dermal communication is permitted through
hemidesmosomes (anchoring plaques, contain collagen XVII - also called bul-
lous pemphigoid antigen.)
Compromise of these essential molecular elements may have devastating con-
sequences for dermal-epidermal integrity and homeostasis. Thus, any efforts to
regenerate authentic skin must look beyond simple structural integrity to ensure
that the essential molecular complexities are faithfully replicated.
