
Innate Immunity The innate immune system depends on features like extracellular and intracellular pattern recognition receptors (PRR) that recognize general molecular patterns. Different types of PRR have been described, identifying microbe-, pathogen-, and danger-associated molecular patterns (abbreviated asMAMP, PAMP, and DAMP, respectively). PRR enhance ligation and phagocytosis of microbes or have signaling ability allowing activation of the cell. Ligation of extracellular toll-like receptors (TLR) by bacterial ligands like lipopolysaccharide (LPS) (binds to TLR4), peptidoglycan (PGN) (TLR2), and flagellin (TLR5) results in MyD88-dependent production of inflammatory cytokines like interleukin (IL)-1b, IL-6, IL-8, and partly TNF-a. The expression of TLRs is vast as they are found on the cell membranes of innate immune cells (dendritic cell (DC), macrophages, natural killer cells), cells of the adaptive immunity (T and B lymphocytes), and nonimmune cells (epithelial and endothelial cells, fibroblasts). A complex network of specialized DC subsets is involved on the one hand in inducing acute inflammatory responses upon invasion by pathogens and on the other hand in inducing tolerance to harmless dietary and inhaled antigens and commensal microbiota (Banchereau et al. 2000). Since DCs control many T-cell responses, they have been useful tools to beneficially manipulate the T-cell responses to recognize specific antigens (mostly viral or tumor antigens) in vitro or in vivo. Direct isolation of DCs from peripheral blood mononuclear cells results in extremely low yields (0.1 %). However large amounts of DCs can be generated from peripheral blood mononuclear cells (PBMC), bone marrow cells, or monocytes cultured in vitro in the presence of GM-CSF and IL-4. Complete activation and differentiation of T cells in contact with antigen-presenting DCs are determined by expression levels of co-stimulatory molecules like CD80 and CD86 and the production of cytokines (TNF-a, IL-10, IL-12) and other soluble factors (e.g., retinoic acid).
Life Science
Life Science
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