Biomedical Engineering Reference
In-Depth Information
molecules such as lipopolysaccharide, bacterial lipoproteins, l agellin, yeast
mannans and DNA containing unmethylated CpG motifs. Activation via TLRs
results in increased production of pro-inl ammatory cytokines and prostanoid,
induction and release of chemoattractants, and activation of the JNK and NF-κB
signaling pathways. h ese compounds are seen as key links between innate and
adaptive immune systems, regulating the expression of numerous genes involved
in the initiation of the inl ammatory response including adhesion receptors,
chemokines and cytokines involved in leukocyte trai cking. Keratinocytes are
important and ot en under-appreciated participants in cutaneous immunity. h ey
produce large quantities of IL-1α, TNF, β-defensins and cathelicidins in response
to a variety of stimuli, including kinetic and thermal trauma, and UV radiation.
Keratinocytes also produce chemokines and immunoregulatory cytokines that
promote recruitment of leukocytes and modulate their functions, providing a link
between innate and adaptive immunity in skin. Ultimately, skin-resident dendritic
cells take up antigen, enter the local lymphatic channels and travel to the draining
lymph node(s) where they present antigen to T cells to promote adaptive immune
responses.
Adaptive Immune Surveillance
h e adaptive immune system enhances responses to specii c pathogens and
provides a means for maintaining memory of past encounters. Creating this
response requires the interaction of antigen-presenting cells with T or B cells
bearing cognate receptors for those antigens and the direction of those cells to
their required sites of function. h is process operates at three levels, which we
have termed primary, secondary and tertiary immune surveillance (Kupper
and Fuhlbrigge 2004). For skin, primary immune surveillance involves the
mechanisms for bringing antigens, antigen presenting cells (APC), and naïve T
cells together in the specialized microenvironment of the skin-draining lymph
nodes. Secondary immune surveillance involves the production and distribution
of antigen-specii c ef ector T cells back to the skin. Tertiary immune surveillance
relates to the production of 'central' memory T cells that circulate through lymph
nodes draining non-skin tissues and ef ector memory T cells directed to tissues
other than the skin.
Primary Immune Surveillance
Epidermal Langerhans cells (LC) and dermal dendritic cells (dDC) are professional
APCs that, when activated, develop the capacity to present antigens ei ciently and
to drive the maturation of naïve T cells to a memory/ef ector phenotype. APCs
become activated at sites of injury or pathogen invasion in the skin through innate
mechanisms, including PRRs such as TLRs and exposure to pro-inl ammatory
cytokines, rapidly engulf antigen and emigrate through the af erent lymphatics
