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THE IMMUNE SYSTEM
humoral immunity – antibodies neutralize toxins and viruses, and opsonize bacteria
cell-mediated immunity – fungi, parasites, certain intracellular bacteria (also involved in the killing of virus-infected cells)
specific defects in cell-mediated immunity lead to:
| • | CMC (chronic mucocutaneous candidiasis) |
| • | EDV (epidermodysplasia verruciformis) |
| • | diffuse cutaneous leishmania ??? |
see also Deep Fungi - Opportunistic Fungi
the cutaneous immune system
Innate Immunity:
| • | the translation of insults into cutaneous inflammation |
| • | the NF-κB pathway is a crucial element of innate immunity (see below) |
Acquired Immunity:
| • | the recruitment of memory T-lymphocytes that have clonally expanded in response to antigens encountered at the cutaneous interface with the environment |
nuclear factor-κB:
| • | NF-κB mediated inflammation in the skin appears to be a final common pathway for the translation of environmental insults into inflammation (i.e. the crucial element of “innate immunity”) |
| • | exists as a cytoplasmic complex in endothelial cells, keratinocytes, fibroblasts and other resident skin cells |
| • | the final step of several pathways involves phosphorylation of this cytoplasmic complex , which allows free NF-κB to migrate into the nucleus |
| • | once in the nucleus, NF-κB-mediated gene transcription induces the expression of E-selectin, cytokines etc… |
| • | NF-κB is a common final pathway in triggering innate immunity for: |
| • | epidermal injury --> releases IL-1 and TNF-α (see below) |
| • | UV radiation --> ligand independent activation of IL-1 and TNF-α receptors |
| • | microbial products --> via Toll receptors (directly) and via cytokines (indirectly) |
| • | interleukin-1 and TNF-α have been called “primary cytokines” |
| • | epidermal injury releases IL-1 and TNF-α from injured keratinocytes |
| • | after binding to their receptors, these cytokines activate several cellular signaling pathways, including the NF-κB pathway |
| • | ultraviolet radiation from sunlight induces ligand-independent clustering and activation of IL-1 and TNF receptors, leading to NF-κB mediated inflammation |
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| • | receptors that resemble the drosophila Toll protein |
| • | = a family of innate immune-cell surface receptors that signal through NF-κB |
| • | rather than binding cytokines, these receptors recognize conserved molecules derived from microbes |
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