Question

16. Where are Toll-like receptors (TLRs) located? What TLR would recognize a bacterium that possesses a flagellum? What result does TLR-bacterium binding produce and how would that trigger an innate immune response?

Answer 1

Toll-like receptors are located in sentinel cells such as mast cells, macrophages and dendritic cells because their function is to recognize to structural shapes or patterns called PAMPs (pathogen-associated molecular patterns) that are present in whole groups of pathogens, but not the host. These cells leave the bloodstream and take up residence in tissues throughout the body, where they are detectors of pathogens.

TLRs 1, 2, 4, 5, and 6 bind to components of microbial cell walls and membranes unique to pathogens. TLR-5 recognizes a structural component of bacterial flagella called flagellin.

Toll-like receptors can detect a broad range of human pathogens, after TLRs detect pathogen or damage-associated molecular patterns, they must convert these signals into messages inside a cell via signal transduction. TLR signaling involves a variety of protein kinases, including IRAKs (IL-1R-associated kinases) and MAPKs (mitogen-activated protein kinases). The final response of a cell to TLR stimulation involves activation of transcription factors that regulate specific patterns of gene expression, leading to an increased production of hundreds of proteins. Like the cytokines, which are secreted from the cell to recruit and activate other cells, thus initiating and orchestrating the adaptative and innate immune response.The innate response, initiated by mast cells and macrophages, provides immediate protection. However, it is relatively nonspecific in its mode of attack on pathogens, which results in damage to healthy tissue if the innate immune response lasts too long.