Biomedical Engineering Reference
In-Depth Information
ascend towards the epidermal surface, their shapes become increasingly flattened.
In so doing, they synthesize a sturdy, water-repellent keratin protein (keratiniza-
tion.) The structure of keratin becomes increasingly complex with each ascent.
Keratinization is initiated when columnar basal cells differentiate into polyhedral
cells to form an overlying spinous layer (5-10 cell layers thick). Further into
development, these cells become more squamous (with cytoplasm containing
keratohyaline granules), thereby forming the granular layer (1-3 cell layers.) Cells
in the granular layer undergo further transformation, losing their nucleus and
organelles (via cytoplasmic lysozymes), rendering them technically dead. These
dead cells make up the outermost, cornified layer (roughly 10-15 cell layers), and
have a turnover rate of about one month.
In areas such as palms and soles where the cornified layer is thick, an additional
layer (called clear layer or stratum lucidum) is found. Rich in protein-bound lipids,
the clear layer lies between the granular layer and cornified layer.
Depending on the density of disulfide bonds, keratin is classified as soft (as seen
in skin) or hard (as seen in hair and nails).
2
The net result of keratinization solidifies
cell-cell bonding, producing a barrier that prevents fluid loss and unwanted entry
of potentially noxious molecules and organisms.
Keratinocytes also produce several protective immunogenic molecules.
3
These
molecules include interleukins (IL-1, IL-6, IL-8), transforming growth factors
(TGF-
), platelet-derived growth factor (PDGF), fibroblast growth factor
(FGF), tumor necrosis growth factor (TNF-
α
, TGF-
β
α
), interferons (IFN-
α
, IFN-
β
), and
granulocyte-macrophage colony-stimulating factor (GM-CSF or G-CSF.)
Melanocytes, which are largely responsible for skin color, are found randomly
dispersed within the basal cell layer.
1
There, keratinocytes outnumber them by a
ratio of 10:1. However, repeated exposure to ultraviolet (UV) light increases their
population, which in turn, leads to an increased production of melanin (UV-
protective pigment.) Melanin is delivered via dendritic processes that insinuate
between adjacent keratinocytes, extending to the target keratinocyte. Once pig-
ments are delivered to keratinocyte cytoplasm, they are arranged in an umbrella-like
manner, such that the nucleus is shielded from harmful UV rays. Recent data
shows that UV light elicits melanization through the activation of the p53 pathway,
resulting in the synthesis of melanin stimulating hormone (MSH) by keratinocytes.
4
Interestingly, the p53 pathway also comes into play when constitutive pigmenta-
tion fails to prevent keratinocyte mutation (by UV light), thereby inducing
apoptosis of defective and potentially premalignant cells.
Langerhans cells (LCs), which are found mostly in the mid-epidermis, partici-
pate in cell-mediated immune responses.
5
Also known as epidermal dendritic
cells (DCs), this subclass of leukocytes make up about 2-4% of all epidermal
cells. Along with self- and non-self antigens, LCs are capable of capturing any
haptens that have potential to violate the epidermal surface, rendering them
appropriate for initial presentation to naïve T lymphocytes.
6
This phase, termed
sensitization, involves migration of antigen-containing LCs from the epidermis
