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【正文】 accid, erosions numerous and slow to heal。 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。ve T cells activation ? HIVspecific activated T cells primed for HIV infection by LC vector HIV Immunopathogenesis: Strategic Attack ? CD4+ Tcell ultimate target – Especially activated CD4 cells ? HIVspecific CD4 response impaired early ? Cytotoxic T lymphocyte response wanes over time ? Progressive CD4+ lymphopenia ? Tcell receptor repertoire crippled Significance of Recognizing Primary HIV Infection ? Reduce transmission during period of high titer viremia Early intervention could... ? lower viral set point ? prevent establishment of sanctuary sites for HIV ? allow the generation of an HIVspecific CD4 cell response Psoriasis ? Affects 12% of population ? Salmonpink, sharply demarcated plaques with micaceous scale ? Elbows, knees classic ? Also mon: scalp, trunk, genitals, nail involvement ? Other variants: guttate, pustular, erythrodermic ? Arthritis in 5% of psoriatic patients Psoriasis: Evidence of TCell Mediation ? Early cells in psoriatic lesions ? Cyclosporine, antiCD4 monoclonal Ab’s as treatment ? Blocking T cell:APC 2nd signal prevents psoriatic lesion ? Psoriasis altered in HIV infection ? Bone marrow transplant recipients ? Streptococcal superantigens can induce psoriasis Psoriasis: New Immunologic Approaches to Treatment ? TNF inhibition – Antibodies to TNF – Soluble TNF receptors ? Costimulatory blockade ? Adhesion molecule inhibition – LFA1 – CD2 ? IL2 activation blockade Cutaneous Immunology Summary Points ? The immune system protects us from foreign microinvasion. ? The skin has its own immune system. ? The skin immune system isn’t perfect and sometimes screws up. ? Inflammatory skin disorders are understandable. ? New, more specific, treatments emerging.
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