Cells in the immune system like Macrophages and dendritic cells are the first line of defense in recognizing various kinds pathogens.These cells are developed several kind of receptors for recognizing different types of pathogen Associated Molecular patterns known as PAMPs.
There are different classes of these proteins, they recognize different types of PAMPs, Toll-like receptor (TLR) is composed of multiple leucine-rich repeats that are useful for recognizing various PAMPs.Each members of TLR family recognize different kinds of PAMPs,For example TLR5 recognizes flagellin,which is highly conserver constituent of the bacterial flagellum.
Bacterial genomes contain methylated CPG oligonucleotide motifs, which are recognized by TLR9, once the genome is degraded in the lysosome.
TLR6 and TLR2 are dimers,that recognize diacyllipopeptide.
TLR1 and TLR2 are dimers that recognize triacyllipopetide and TLR4 recognize lipopolysaccharide (LPS) a component of Gram Negative bacteria.
Like TLR9 TLR3 and TLR7 are located endocylic vesciles and recognize double stranded RNA and single stranded RNA respectively.
When any TLRs activated, it sends the signal to nucleus by activating transcription factors.
Some pathogens such as viruses exists and replicate in cytosol.there are at least two classes receptors that an detect pathogens in cytosol and signal their presence to the immune system.One class of such receptors are members of nuclear oligomerization domain family or NOD proteins.
For example NOD 2 protein, which is located in the cytosol, can detect bacterioproteoglycans of intracellular bacteria.When NOD2 protein recognizes its ligands the muramyl dipeptide, it sends the signal to nucleus to activate transcription.
Finally there is a class intracellular receptor protein that can contain a RNA helicase domain and two caspase recruitment domains, one member of this family RIG-I recognizes double stranded RNAs that are component of life cycle of many RNA virus,
This class of proteins also sends the signal to nucleus, but unlike TLRs it activates the production type 1 interferons. In all the toll like receptors, NOR proteins and RNA helicase domain family provide the innate immune system with the ability to detect both extra cellular and intracellular pathogens and to activate immune response
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