colven皮膚免疫(存儲版)
【正文】 Langerhans cells, dermal dendrocytes, dermal macrophages 2. Keratinocytes 3. Endothelial cells 4. Skinhoming Tcells 5. Draining regional lymph vessels and nodes The Skin Immune System Principles 1. Interface with environment 2. Unique nonimmune protection 3. Innate immune defenses 4. Specialized set of APCs 5. Skin homing memory Tcells 6. Antigen presentation in skin 7. Distinct response from other epithelia Cutaneous Immunology Overview I. Brief review of general immunology II. Skin immune system biology III. Skin immune system pathology Contact Dermatitis ? Erythematous, weepy, scaly, geometric plaques ? Irritant or allergeninduced ? Major cause of occupational illness ? Histology: Epidermal spongiosis Allergic Contact Dermatitis Pathogenesis Sensitization (Induction)1o exposure ? Contact allergen usually a hapten – LMW, links with endogenous protein ? Picked up by LC’s and presented to na239。Immune response amplified Cutaneous Lymphocyte Antigen (CLA) ? Specific skin homing marker on Tcells ? CLA+ lymphocytes are memory/effector cells (CD45RO +) ? Cell adhesion to endothelial cell – Eselectin is ligand ? With cutaneous inflammation, Eselectin upregulated, CLA+ cells selected ?? TCells ? Resident in epithelia。ve T cell (CD8+ or CD4+) with unique and specific Tcell receptor ? Add costimulatory second signal and a pinch of IL2 ? Stir.…Proliferate, differentiate! Adaptive Immunity To Activate a Lymphocyte… From, Janeway, CA, Immunobiology, 5th ed. Cytokines: More than Alphabet Soup ? Cell munication via released peptides ? High affinity receptors ? Low concentration, big effect ? Impact over short distances: Auto, juxta, paracrine ? Wide range of cellular effects ? Examples: Interleukins, TNF, interferons Cell Adhesion Molecules: Molecular Velcro ? Cell surface molecules with matching ligands on other cells ? Allow celltocell binding for munication and homing ? Expression of CAMs variable and under plex control ? Example: Intercellular adhesion molecule1 (ICAM1) on APC’s binding to lymphocyte functionassociated antigen1 (LFA1) on Tcells Effector TCells ? CD8+ cytotoxic T lymphocyte (CTL) –“The Hitman” – Kills on contact ? CD4+ helper T lymphocyte –“The Bureaucrat” – Directs other cells to do the dirty work Effector Tcells do not require costimulatory signal CD8+ Cytotoxic Tcell ? Directly cytotoxic to cells via binding to Ag:MHC I plex ? Cytosolic antigens (., viruses) ? Induces apoptosis ? Cytotoxicity is specific and directional ? Cytotoxins include: – Perforin, granzymes ? Also produces cytokines – IFN?, TNF CD4+ Helper TCells ? Binds to APCs via Ag:MHC II plex ? Then directs other effector cells (macrophages, B cells) to kill pathogens or neutralize toxins ? Uses cytokines as its “memos” Th1/Th2 Paradigm Th1 Th2 Th0 IL2 TNF IFN IL4 IL5 IL10 Cellmediated immunity Humoral immunity IL12 IL10 IL12, IFN IL4 CD4+ Helper TCells: Th1/Th2 Paradigm ? Th1 (type 1) – IL2, TNF, IFN? –Activate macrophages and CTL’s for intracellular pathogen killing and cytotoxicity – Facilitate cellmediated immunity
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