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Toll-like receptors as part of the innate immune response

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  1. Introduction.
  2. Discovery of toll-like receptors In humans.
  3. Expression of human toll-like receptors.
  4. Toll-like receptors in innate and adaptive immunity.
  5. Pathways.
  6. Syphilis.
  7. Bacterial infections.
  8. Candidal infections.
  9. Autoimmune diseases.
  10. Melanoma and mycosis fungoides.
  11. Ultraviolet light.
  12. Conclusion.

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. [...]

[...] Furthermore, the type of T-cell response (Th1 vs. Th2) appears to depend on the ligand. Yersinia pestis is a GN bacillus that causes plague, a disease that was epidemic in Europe and killed millions of people. It was called the ?Black Death.? It is transmitted by the bite of the rat flea Xenopsylla cheopis. Clinically, painful buboes form in the axillae or groin, although other skin lesions such as vesicles, plaques, petechiae, and purpura can be seen. One mechanism by which Yersinia gains entry into the host's APCs is through low calcium response protein an outer-membrane protein. [...]

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