There are two major arms of the immune system: innate immune response, and acquired, or adaptive, immune response. Phagocytic cells recognize pathogens that bind to specific receptor recognition molecules or through complement fixation, and then activate pathways to contain infection. Essential components of the innate immune response include neutrophils, eosinophils, natural killer cells, natural killer T cells, mast cells, cytokines, complement, and antimicrobial peptides. In the latter, T lymphocytes recognize foreign antigens presented on major compatibility complexes I and II on the cell surface of antigen-presenting cells (APCs). Lymphocytes that recognize foreign antigens then clonally expand to provide an antigen- specific immune response. More recently, another key component of the innate immune response has been discovered, the Toll-like receptors (TLRs). These receptors allow the innate immune system to tailor its response depending on the stimulatory antigen and which TLR is activated. TLRs allow the innate immune system to control activation of the adaptive response, thus helping to bridge the gap between innate and adaptive immunity. The TLRs play an important role in many skin diseases.
[...] Toll-Like Receptors in Innate And Adaptive Immunity The TLRs have a key role in host defense by linking innate and adaptive immune responses. Activation of TLRs mediates the release of antimicrobial pep peptides and chemokines that recruit phagocytic cells to the site of infection. The TLRs influence the adaptive immune response through a variety of mechanisms. TLR ligands upregulate surface expression of the major histocompatibility complex inducing maturation of dendritic cells from phagocytic cells to potent APCs. Activation of TLRs by microbial products initiates the expression of co-stimulatory molecules on both T cells and APCs. [...]
[...] It is currently under development for the treatment of cancer both as monotherapy and in combination therapy, as well as an adjuvant for vaccines. It acts through TLR9 receptors present on B cells and plasmacytoid dendritic cells to stimulate B-cell proliferation, and natural killer cell activity. It is currently in trials as treatment for non–small-cell lung cancer and may likely be useful in the treatment of other cancers, as well. The TLRs may also be involved in the pathogenesis and treatment of other malignancies. [...]
[...] TLR4 plays a role in mounting an immune response against C. albicans. Anti-CD14 and anti-TLR4 antibodies (but not anti-TLR2 antibodies) have been shown to block mannan- induced cytokine production. However, when zymosan, was used as the ligand, anti-TLR2 antibodies blocked cytokine production. Thus, TLR4 is likely activated by mannan, and TLR2 is likely activated by other fungal cell components, such as glucan. It is likely that these TLRs work differently to foster an immune response against C. albicans; activation of TLR4 leads to neutrophil cytokines. [...]
[...] Conclusion A key component of the innate immune response has been discovered, the Toll- Like receptors (TLRs). These receptors allow the innate immune system to tailor its response depending on the stimulatory antigen and which TLR is activated, thus helping to bridge the gap between innate and adaptive immunity. There are now 11 (and perhaps up to 13) known human pathogen recognition receptors (TLR1 to TLR11), which allow cytokine synthesis in response to various classes of microbial products and common pathogens. [...]
[...] The DCs are a component of innate immunity. They are APCs that, upon taking up and processing foreign antigen, migrate to the lymph nodes, where they present the antigen in the context of MHC, and, with co-stimulatory molecules, activate naive T cells. Flagellin is a conserved protein monomer that makes up the flagellar filament in the periplasmic space beneath the outer membrane. It is an important ligand recognized by TLRs. Upon stimulation with bacterial flagellin, TLR5 expressing human monocyte–derived DCs induced maturation and chemokine production. [...]
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