Immune system Toll-like receptors

Bacterial products also directly activate AMs via the receptors of the innate immune system (TOLL like receptors TLR). This activation induces the expression of mediators (e.g., TNF-a and IL-12). 

Endotoxicity results from the interaction of a bacterial cell envelope component (e.g., LPS or PG with a cell surface receptor constituting part of the nonspecific immune system, (i.e., a toll-like receptor on white blood cells). This results in the production of cytokines [e.g., interleukin 1 (IL-1) or tumor necrosis factor (TNF)] as part of an intracellular enzyme cascade which can cause severe tissue injury. Bioassays or immunoassays can be used to detect such reactions respectively. As noted above the most widely used bioassay is the LAL assay. A lysate of amoebo-cytes of the horseshoe crab (Limulus) contains an enzymatic clotting cascade which is activated by extremely low levels of LPS (nanogram levels or lower). There are variants of this assay that can detect PG, but they are not as widely used. As noted above, other bioassays employ cultured cell lines that respond to LPS or PG, respectively. Unfortunately bioassays are highly amenable to false positives (from the presence of cross-reactive substances) or false negatives from inhibition (by contaminants present in the sample) [10]. A detailed discussion of these assays is beyond the scope of this chapter and has been reviewed elsewhere [1]. 

Ozinsky, A., Underhill, D.M., Fontenot, J.D., Hajjar, A.M., Smith, K.D., Wilson, C.B., Schroeder, L., Aderem, A. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between Toll-like receptors. Proc Natl Acad Sci... 

Yoshimura, A., Lien, E., Ingalls, R.R., Tuomanen, E., Dziarski, R., Golenbock, D. Cutting edge recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol 163 (1999) 1-5. 

LPS), monophosphoryl lipid A, and CpG DNA. These substances contain pathogen-associated molecular patterns (PAMPs) that are recognized by and stimulate cells of the immune system. Many of these substances, for example, LPS, have been discovered to act as ligands for Toll-like receptors (TLR). These receptors are expressed on APC, recognize highly conserved motifs on bacteria and viruses, and mediate APC activation. Vaccine developers are now focusing... 

Pattern recognition receptors. These are proteins expressed by cells of the immune system that identify molecules associated with microbial pathogens or cellular stress. They include the so-called Toll-like receptors. 

One of the best understood pathways to induce innate immune activation is the family of Toll-like receptors (TLRs). TLRs detect highly conserved components of pathogens that are not present in our own cells. The TLRs appear to have evolved as a warning system to detect infections, and in some cases they can be triggered by synthetic nucleic acid therapeutics or accidentally by self molecules.34... 

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