colven皮膚免疫(文件)
【正文】 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 – Inhibit Th2 cell proliferation CD4+ Helper TCells: Th1/Th2 Paradigm ? Th2 (type 2) – IL4, 5, 10 – Activate B cells and antibody production to neutralize extracellular pathogens amp。 Langerhans Cells: To Lump or Split Dermal dendrocytes ? No Birbeck granules ? Factor XIIIa + ? CD1a, ATPase ? Blood vesselassoc. Langerhans cells ? Birbeck granules ? Factor XIIIa ? CD1a, ATPase + ? Epidermal Keratinocytes As Immune Cells Old view: Keratinocytes... ? Are passive barrier cells ? Are passive victims of immune attack Keratinocytes As Immune Cells Newer view: Keratinocytes... ? Produce cytokines – ., IL1, TNF?, Chemokines ? Respond to cytokines – ., IFN, IL1 ? Upregulate ICAM1 ? Present antigen ...Particularly when stimulated Endothelial Cells amp。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。 Nikolsky sign + ? Histology: Suprabasal epidermal split ? IF: Interkeratinocyte IgG Epidermal Targets of Autoantibody Attack Pemphigus vulgaris ? Desmoglein 3 (130 kD) ? Target: Desmosome – Keratinocyte cohesion Bullous pemphigoid ? BP Ag 1 (230 kD): Intrabasal keratinocyte ? BP Ag 2 (180 kD): Transmembrane ? Target: Hemidesmosome – Dermalepidermal junction adhesion Autoantibodies in Pemphigus are Pathogenic: Evidence ? PV patients’ sera in skin culture evokes histologic changes of PV ? Passive transfer of pemphigus IgG to neonatal mice causes disease ? Transient PV in neonates of affected mothers The Cause of Autoimmunity as of September 13, 2022 Health Disease Something Happens Primary HIV Infection ? Initial exposure to HIV leading to productive infection ? 1040% of cases asymptomatic ? Associated with significant viremia ? Transmission risk high ? Ends with HIV seroconversion Dendritic Cells: Targets of HIV Infection ? Langerhans cells (LCs) express CCR5 and CD4 ? LCs prime target cell in epithelial transmission of HIV ? HIV entry and productive infection can occur within LCs ? LCs selective for Mtropic HIV strains Dendritic Cells as HIV Vectors ? LCs can also trap and transport HIV without productive infection ? LCs present HIV antigen to na239。Presence and function in human skin controversial The Skin Immune System Components 1. APCs: 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 non
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