Immunology - NOD like receptors and the Inflammasome

Armondo student on biology and medicine videos please make sure to subscribe join the forum and group for the latest videos please visit Facebook Armando hysteria in this video we're going to look at node like receptors as well as the inflammasome which are important complexes and receptors that help protect our body now just to differentiate we we have toll-like receptors which are also important receptors in initiating the immune response and protecting our body toll-like receptors are membrane bound receptors so they are bound to the plasma membrane but node like receptors which this video is going to

focus on are different node like receptors are silent cytosolic receptors so they're found within the cytoplasm of the cell and they also are the receptors involved in forming inflammable inflammasome x' which are protein complexes that just amplify the immune response as well as induce apoptosis so let's have a look at node like receptors found within the cell the human genome actually encodes for 23 node like receptor proteins broadly divided into two categories the first is that you have node like receptors with a pyrene domain so n lrp and then you have node like receptors with

a caspase recruitment domain so NLR c we are only going to talk about three node like receptors now as i mentioned none like receptors are cytosolic proteins and they're found within the cytoplasm as monomers and as monomers they are inactive so here we can find node like receptor p1 which means that it has a pyrene domain then we have node like receptor c4 which means that it has a caspase recruitment domain and then you have node like receptor p3 which means that has a pi domain so these know like receptors they have some common structural

features right so they contain leucine-rich repeat NAC HT as well as this one in particular has a pyrene domain because it has a P in it in this video we will actually emotionally focus on a node like receptor p3 because it is the best studied one out of all the node like receptors it also has a pyrene domain because it contains a P within it and a NAC CHT region and a leucine-rich repeat now node like receptor p3 are found as monomers in an inactive form like all other node like receptors now its inactive because

the leucine-rich repeat are blocked by some chaperone proteins but there are many things that can actually activate node like receptor p3 it's not fully understood how though regardless when it is activated node like receptor p3 will bind with other proteins known as adapter protein a SC made up of a pyrene domain and a card domain this process of binding to each other is known as all oligomerization so the pyrene domain of the adaptive protein will actually bind to the pyrene domain of the node like receptor p3 forming this type of structure so they're they're all

ago memorizing you can say now using its card domain a the adapter protein a SC brings protein monomers of pro caspase-1 into close proximity this structure now can be referred to as an inflammable or more correctly the node like receptor p3 inflammasome the node like receptor p3 inflammasome essentially initiates a caspase-1 self cleavage and the formation of the active hetero tetrameric caspase-1 so the inflammasome results in many active caspase-1 caspase-1 has many functions first of all the active caspase-1 can pre up propria proteolytically activate a number of proteins including pro interleukin 1 B and Pro

interleukin 18 and it will also induce their release which will be which will subsequently amplify the immune response under certain conditions activate activation of the inflammasome will lead to cell death the word is pyroptosis which comes from the Greek word for fire and for falling and this is referred to cell death but pyroptosis is is different from apoptosis pyroptosis is associated with a high inflammatory State and it frequently occurs upon infection with intracellular pathogens in Parab ptosis what happens is that water begins flooding the cell leading to the cell swelling and then membrane rupture at

the same time the cell will release all these inflammatory cytokines within it that were activated by caspase-1 right so it's important to know that pair up ptosis is different to apoptosis in this respect so what I drew here is a node like receptor p3 inflammasome that is made up of only two node like receptor p3 monomers right but it the inflammasome is actually made is forms a ring like structure made up of 7 node like receptors as well as the adaptor proteins now this inflammasome complex will result in the proteolytic cleavage of the pro caspase-1

leading to caspo 1az as indicated by this diagram so now that we know what this inflammasome does how does it get activated as I mentioned many things activate it but it's not really understood how exactly if this makes any sense so the node like receptor p3 in Flamel is actually formed in response to a diverse diverse amount of pathogen associated molecular patterns as well as danger associated molecular patterns and changes in the ion gradient across the cell so let's have a look at some of these examples up an e flux of potassium can actually activate

node like receptor p3 inflammable information potassium efflux is can be induced by bacterial toxins as well as by extracellular ATP which engages with the potassium channel causing potassium to go out of the cell potassium efflux pathogen associated molecular patents or genetic material of pathogens such as these DNA single-stranded RNA and double-stranded RNA can stimulate the activation of node like receptor p3 engulfed danger associated molecular patterns and pathogen associated molecular patterns this will form a phago lysosomal vessel and this vessel can rupture and the rupturing of the vessel can induce node like receptor p3 activation this

can be through the release of reactive oxygen species ro s the da MP dangerous ocean molecular patterns and pathogen associated molecular patterns itself as well as cathepsin be a component of the lysosome a channel formed by type 3 and type 4 bacterial secretion can insert pathogen or social molecular patterns as well as danger associated molecular patterns within the cell leading to node like receptor p3 activation and subsequent inflammatory formation also the transcription of pro-inflammatory cytokines can stimulate node like receptor p3 activation as well and so they're like agonists so the bottom line is that many

pathogen associated molecular patterns and danger associate molecular patterns activate node like receptors within the cytoplasm which will lead to the formation of inflammation and the inflammasome will amplify the immune response as well as lead to cell apoptosis so I hope you enjoyed this video thank you for watching bye