Laziness
LazinessWhy are we so lazy?
Keratinization, absence of granular layer, and depositation of antibodies
and complement components in the stratum corneum. Most notable is the
hyperproliferation of keratinocytes in the epidermis. These keratinocytes
exhibit an increased mitotic rate and have ten times the turnover rate of
normal keratinocytes. There is also an infiltration of CD4+ T lymphocytes,
monocytes and neutrophils into the epidermis. Recently there has been much
debate over whether psoriasis is mediated by an autoimmune process.
The disease affects roughly two percent of the population in the
United States. It has the greatest prevalence among Scandinavians and
Northern Europeans, where it affects three percent of the population, and
the least prevalence among North American Indians, with just half a
percent being affected. Psoriasis seems to affect both males and females
equally. There are two types of the disease. Type I generally occurs
during adolescence, with an average age of onset of sixteen years for
females and twenty-two years for males. Type II affects people over sixty
years of age.
There are several immunological abnormalities associated with
psoriasis. Early psoriatic changes occur in advancing lesions before the
accumulation of inflammatory cells. These changes are mediated by
activated CD4+ T lymphocytes and can be detected before visible pathology
to the skin occurs. Activated T lymphocytes exhibiting an increase in
HLA-DR and IL-2R can be seen in close proximity to Langerhans cells in the
dermis before lesion formation. Since Langerhans cells are antigen
presenting cells, activation of the T cells may occur by the recognition
of an as-yet unidentified antigen in the context of MHC class II. These
activated T lymphocytes then migrate to the epidermis and activate
epidermal keratinocytes.
At this point, a cascade of events occurs and appears to become
cyclic after up-regulation of certain cytokines. This cyclic tendency is
probably responsible for the static nature of many psoriatic plaques. An
increase in ICAM-1 and ELAM-1 (endothelial leukocyte adhesion molecule) in
the vascular endothelium underlying the plaque recruits inflammatory cells
to the site of the lesion. Activated T cells produce increased IFN-gamma,
which in turn induces HLA-DR and ICAM-1 expression in keratinocytes. This
increase in ICAM-1 production causes increased retention of activated
T-lymphocytes in the epidermis, localizing them to the site of the lesion.
The IFN-gamma released by activated T-lymphocytes also causes an
up-regulation of keratinocytic cytokines, specifically IL-1, IL-6, IL-8
and TGF-alpha. TGF-alpha, IL-6, and IL-8 are all keratinocyte mitogens, so
their release stimulates the activation of surrounding keratinocytes,
inducing more ICAM-1 expression and causing increased retention of
activated T lymphocytes at the site of the lesion. IL-1 also serves to
increase ICAM-1 expression in keratinocytes. IL-8 (neutrophil activating
factor) mediates migration of monocytes, neutrophils, and CD4+ T-cells
from the vascular endothelium to the epidermis.
There are several indirect lines of evidence that implicate an
autoimmune role in the onset of psoriasis. There is...
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