Innate immunity constitutes the first line of defense and is fundamental for the recognition and the initiation of an inflammatory response against microorganism. Maintenance of homeostasis is a primary function of the innate immune system and it is achieved through immune surveillance by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and nucleotide-binding domain leucine-rich repeat containing receptors (NLRs). The PRR’s are predominantly expressed by cells of the myeloid lineage. TLRs and NLRs are distributed throughout the gastrointestinal mucosa mostly being expressed in the epithelium and in lamina propria cells. The gastrointestinal mucosa surfaces are in constant interaction with a wide variety of commensal
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There are several things that can arm the innate immune system. Microbial pathogens and stress factors pose a threat to the host and both can initiate the inflammatory cascade. The innate system has several mechanisms to counter the invasion by theses harmful agents. This include anatomical barrios such as skin and mucus membranes that prevent spreading throughout the body, oposination and removal of the invading factor by PRR’s. PRR’s are expressed in macrophages, dendrite cells and epithelial cells and are the frontline of defense against infections. PRRs activate intracellular signals that collaborate for activation of host defense. Currently, four different classes of PRRs have been identified, including TLR, RIG-I-like RNA helicases (RLH), C-type lectin receptors (CLR) and NLR. These germline-encoded PRRs are capable of recognizing highly conserved, pathogen-associated molecular patterns (PAMPs), such as lippopolysaccharide (LPS), release of danger signals, such as Adenosine-5 '-triphosphate (ATP), or danger-associated molecular patterns (DAMPs) induced by either pathogens or sterile inflammatory insults. PRRs can be subdivided into two major classes based on their subcellular localization. TLR’s and CLR are embedded in the cellular membrane and survey the extracellular milieu & endosomal compartments for PAMP’s. DNA sensors, NLR’s and RLR’s are cytoplasm immersed particles and survey the …show more content…
The first signal is implemented by microbial molecules and cytokines that that bind to TLR receptor and induces the up-regulation the transcription of nuclear factor κB, which will synthesis NLRP3, pro-IL-1β and pro-IL-18. Common priming signals for immune cells of the body and human RPE cells are LPS, tumor necrosis factor-α (TNF-α), nitric oxide, and IL-1α. Once the NLRP3 is activated, it recruits ASC and mediates the proximity-induced procaspase-1 autoactivation. The assembled NLRP3 inflammasome then turns itself into a cytokine processing platform by cleaving pro-IL-1β and pro-IL-18 into mature cytokines and releasing them into extracellular space for downstream
There are several things that can arm the innate immune system. Microbial pathogens and stress factors pose a threat to the host and both can initiate the inflammatory cascade. The innate system has several mechanisms to counter the invasion by theses harmful agents. This include anatomical barrios such as skin and mucus membranes that prevent spreading throughout the body, oposination and removal of the invading factor by PRR’s. PRR’s are expressed in macrophages, dendrite cells and epithelial cells and are the frontline of defense against infections. PRRs activate intracellular signals that collaborate for activation of host defense. Currently, four different classes of PRRs have been identified, including TLR, RIG-I-like RNA helicases (RLH), C-type lectin receptors (CLR) and NLR. These germline-encoded PRRs are capable of recognizing highly conserved, pathogen-associated molecular patterns (PAMPs), such as lippopolysaccharide (LPS), release of danger signals, such as Adenosine-5 '-triphosphate (ATP), or danger-associated molecular patterns (DAMPs) induced by either pathogens or sterile inflammatory insults. PRRs can be subdivided into two major classes based on their subcellular localization. TLR’s and CLR are embedded in the cellular membrane and survey the extracellular milieu & endosomal compartments for PAMP’s. DNA sensors, NLR’s and RLR’s are cytoplasm immersed particles and survey the …show more content…
The first signal is implemented by microbial molecules and cytokines that that bind to TLR receptor and induces the up-regulation the transcription of nuclear factor κB, which will synthesis NLRP3, pro-IL-1β and pro-IL-18. Common priming signals for immune cells of the body and human RPE cells are LPS, tumor necrosis factor-α (TNF-α), nitric oxide, and IL-1α. Once the NLRP3 is activated, it recruits ASC and mediates the proximity-induced procaspase-1 autoactivation. The assembled NLRP3 inflammasome then turns itself into a cytokine processing platform by cleaving pro-IL-1β and pro-IL-18 into mature cytokines and releasing them into extracellular space for downstream