Toll-like Receptors and their Function - Toll-like receptors (TLRs) are immune receptors expressed on various immune cells and non-immune cells. - TLRs recognize molecules shared by pathogens and initiate immune responses. - TLR activation leads to signal transduction and the activation of downstream proteins. - Bacterial factors may be phagocytosed and digested, while viral factors may induce cell death. - TLRs play a role in the link between innate and adaptive immunity.

Toll-like Receptor Superfamily - TLRs are a type of pattern recognition receptor (PRR). - TLRs recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). - TLRs belong to the interleukin-1 receptor/toll-like receptor superfamily. - TLRs have Toll-interleukin receptor (TIR) domains. - TLRs can be classified into three subgroups based on their TIR domains.

Toll-like Receptors in Different Organisms - TLRs are present in vertebrates, invertebrates, bacteria, and plants. - TLRs are conserved components of the immune system. - TLRs have been identified in the mammalian nervous system. - Different mammalian species have varying numbers of TLRs. - Some TLRs found in humans are not present in all mammals, and vice versa. - Toll signalling is involved in the immune response of fruit flies. - Fruit flies have innate immune responses and lack adaptive immunity. - The toll pathway in fruit flies is similar to mammalian TLR signalling. - The toll pathway is activated by different stimuli, such as bacteria and fungi. - Drosophila have multiple toll family and spz family genes involved in immune response.

Toll-like Receptors and their Characteristics - TLR2 is also known as CD282. - TLR2 is a toll-like receptor. - TLR2 recognizes specific molecules and initiates immune responses. - TLR2 plays a role in host defense against pathogens. - TLR2 has been extensively studied in the context of immune responses. - Human cells do not express TLR11, but mice cells do. - Mouse-specific TLR11 recognizes uropathogenic E.coli and Toxoplasma gondii. - TLR11 recognizes flagellin from Salmonella. - Normal mice do not get infected by oral Salmonella Typhi due to TLR11 recognition. - TLR11 deficient knockout mice are efficiently infected and can act as a disease model of human typhoid fever.

Toll-like Receptors and their Medical Relevance - Toll-like receptors recognize molecules associated with threats. - Pathogen-associated molecules are difficult to change through mutation and are evolutionarily conserved. - TLR ligands are present in most pathogens and may be present in pathogen-derived vaccines. - Commercially available vaccines have been assessed for their TLR ligand capacity to activate immune cells. - Ligands recognised by TLRs include lipopolysaccharides, flagellin, viral RNA, and CpG islands in DNA. - Toll-like receptors can also bind to host molecules. - Endogenous ligands include fibrinogen, heat shock proteins, HMGB1, extracellular matrix components, and self DNA. - Endogenous ligands are produced as a result of non-physiological cell death. - Under inflammatory and autoimmune conditions, self DNA can form a complex with endogenous proteins and gain access to endosomal TLRs. - Endogenous ligands may participate in autoimmune diseases. - TLRs function as dimers, with some forming heterodimers. - Co-receptors may be required for full ligand sensitivity, such as MD-2 for TLR4's recognition of LPS. - Endosomal TLRs recognize nucleic acids and activate inflammatory cytokines and type I interferons. - Adapter proteins and kinases mediate TLR signaling. - MyD88-dependent and TRIF-dependent pathways are the two distinct signaling pathways of TLRs. - Imiquimod and resiquimod are TLR7 agonists used in dermatology and cancer immunotherapy. - TLR ligands are being tested as vaccine adjuvants. - TLR4 is important for the long-term side effects of opioids. - TLR4 activation leads to the release of inflammatory modulators and is involved in opioid tolerance. - Morphine-induced TLR4 activation attenuates pain suppression by opioids and enhances the development of opioid tolerance.