Molecular, Cellular and Structural Immunology 4

Innate Immunity is the first line of defense against infections.

Toll-like receptors are proteins that respond to the presence of pathogenic microbes by activating antimicrobial defense mechanisms in the cells in which they are expressed. The major pathway that they use is the NF-kB.

Toll-like receptors (TLRs) are specific for different components of microbes. TLR2 recognizes several bacterial lipoglycans, TLR3, 7 and 8 are specific for viral nucleic acids and TLR4 is specific for bacterial LPS. TLR5 is for flagellin and TLR9 is for the unmethylated CpG oligonucleotides.

TLRs can be present on the cell surface for extra-cellular microbe recognition or as endosomes. TLRs can activate the transcription factors for stimulation of genes encoding cytokines, enzymes and other proteins involved in the antimicrobial functions of activated phagocytes and other such cells. It also activates the nuclear factor kB which promotes the expression of various cytokines and endothelial adhesion molecules and interferon regulatory factors.

NOD like receptors are cytosolic receptors sensing DAMPs and PAMPs in the cytoplasm. They have a nucleotide oligomerization domain.

NLRP3 (NOD like receptor pyrin domain containing 3) senses the release of ATP, uric acid crystals, endogenous substances being deposited in excessive amounts. Along with an adaptor protein and inactive form of caspase 1 are recruited. This activates caspase 1, cleaving a precursor form of IL-1B. 

IL1 induces acute inflammation (inflammasome).

NOD2 is specific for bacterial peptides that have entered the cytosol, activating the NF-kB transcription factor but not signalling through the inflammasome.

RIG like receptors are cytosolic sensors of viral RNA that responds to viral nucleic acids by inducing the production of the antiviral type1 interferons. They can recognize both double and single stranded bacterial/viral RNA e.g. RIG1 recognizes RNA with 5' triphosphate moiety as this is not present in mammalian host cell cytoplasmic RNA.

RLRs initiate signalling events that lead to IRF3 and IRF7 activation to produce type 1 interferons. 

Innate immunity has 3 important functions-it is the initial response to microbes that prevents, controls or elimates infection…