Overview of Adaptive and Innate Immunology in Skin Disease

The lecture reviews adaptive and innate immunology with an emphasis on skin disease and how immune mechanisms guide therapy. It explains the organization of the immune system into primary lymphoid organs (bone marrow and thymus) and secondary organs (lymph nodes and spleen), where B cells mature in the bone marrow and T cells mature in the thymus before being activated in peripheral tissues. The innate immune system is described as rapid and pattern-based, using complement, defensins, and pattern-recognition receptors such as Toll-like receptors, while the adaptive immune system is antigen-specific and generates memory. The talk emphasizes that innate immunity is required to trigger adaptive responses through danger signals and co-stimulation. T-cell development is covered in detail, including positive selection in the thymic cortex, negative selection in the medulla, and central tolerance mediated by AIRE; defects in this process are linked to autoimmune syndromes such as APECED, while FOXP3-related defects cause IPEX. T-cell activation requires two signals: antigen presentation through MHC and a co-stimulatory danger signal via CD80/86 binding CD28; without this second signal, T cells become anergic. The lecture also reviews antigen processing and presentation: MHC class I on all nucleated cells presents endogenous cytosolic peptides to CD8 T cells, while MHC class II on professional antigen-presenting cells presents extracellularly derived peptides to CD4 T cells. Finally, it notes that the cytokine environment determines CD4 T-cell differentiation into subsets such as Th1, Th2, Th17, and regulatory T cells, which is relevant to autoimmune and inflammatory skin diseases and biologic therapies.