Immunology - Toll Like Receptors Overview

arando huran biology and Medicine videos please make sure to subscribe join the foring group for the latest videos please visit Facebook arando hura now in this video we will look at tall like receptors which are important receptors um in the innate immune system they're found in immune cells for example let's begin by drawing out a plasma membrane of an immune cell now it can be a maccrage for example so the plasma membrane the outer membrane is made up of phospholipid by layer here is the intracellular fluid within the cell and extracellular fluid outside the cell

here inside the cell we also have a double lipid membrane that makes up the nucleus here I'm only drawing one lipid membrane but the nucleus has two lipid membranes anyways within the nucleus is where we find our genetic material which is DNA DNA contains genes that we can read and essentially transcribe to make RNA and then proteins it is important to understand this concept because tolik receptors um initiate this process you can say okay so tolik receptors are also abbreviated tlr and they are plasma bound receptors so they are always found on the uh the

membrane in humans there is approximately 10 toac receptors they have recently found a 11th one in the human gene but I don't think it actually makes anything um yeah but in mice it does so as I mentioned uh tolik receptors help initiate and promote the immune response but how well tolik receptors essentially recognizes different foreign uh agents components structures or materials that don't normally belong to our body so let's have a look at the different uh things these toac receptors recognize and look at the different toac receptors themselves so tolik receptor one and tolik receptor

2 are found on the um outer membrane here and they will bind to each other to form a dimer when they recognize things such as peptidoglycans of bacteria lipoic acids of gr negative bacteria lipoproteins as well as zyon of fungi so all these different things will activate tolik receptor one and tolik receptor 2 that will cause uh tolik receptor 1 and two to form a dimer and what happens after this I'll talk about later but we'll just focus on what these different toac receptors recognize first toac receptor 2 can also form a Dio with tolac

receptor 6 when uh when they recognize a foreign component as well when they recognize these same foreign components such as ppog glycans and lipoproteins now tolik receptor 4 recognizes lipopolysaccharides of gr positive bacteria and when toac receptor 4 recognizes this it will form a dimer with another toac receptor 4 toac receptor 5 recognizes fella notice that toac receptor 5 does not form a dier now toac receptor 11 Gene as I mentioned is found in humans but don't think they actually they're actually functional in mice they recognize uropathogen europ pathogenic bacteria bacteria that Target the urinary

system as well as propin now propin is found in grass or wheat for example anyway then you have tolik receptor 10 which I not sure what it does or the function is not certain but it is found on the human plasma membrane nonetheless now you might be thinking what about tolik receptor 3 6 7 and toic receptor 9 which have skipped or missed well these remaining toic receptors are found within endosomes somehow these these remaining toic receptors are begin being expressed Within endosomes so the story is when viruses bacteria or fungi they contain their own

genetic material such as double stranded RNA and single stranded RNA and viruses as well as uh cpg DNA uh in bacteria for example now cpg DNA essentially is DNA that contains cytosine and guanine dinucleotides that are unmethylated but you don't have to know that much detail just know its DNA so these genetic materials can either enter this cell through endocytosis or they can be released by the pathogen when the pathogen uh is also endos sized either way the genetic material will be within the endosome now some tolik receptors are found within the endosome these toac

receptors don't need to form diers toac receptor 3 recognizes and are Act activated upon contact with double stranded RNA or viruses toac receptor 7 and toac receptor 8 are activated upon contact with single stranded RNA viruses toac receptor 9 recognizes and are activated upon contact with cpg DNA of bacteria and fungi for example okay now that we know the tolik receptors and what they recognize what happens next when well to put it into simple terms they become activated the activation of tolik receptors will initiate a Cascade of events that will essentially lead to the activation

of search and transcription factors the main transcription factors that are activated are AP1 irf and nfkb now we'll go through each of these transcription factors and what they do in this scenario but what you have to first understand is that this is a very simplistic diagram in reality tolik receptors activate different transcription factors but they will but they're all really connected in some way so let's look at AP1 AP1 stands for activated protein one and this will essentially enter the nucleus and transcribe and well stimulate or activate certain genes within the DNA to transcribe uh

a specific RNA now this specific RNA will be translated by ribosomes out in the endoplasmic reticulum this RNA will be translated to form proteins for cell signaling um AP1 will essentially lead to differentiation proliferation and even apoptosis then you have irf and nfkb that can also enter the nucleus irf stands for interferon regulator or factor that will activate certain genes in the DNA that will make a specific RNA now this specific RNA will be translated by the ribosomes into interferons now interferons are essentially protein molecules that are a defense mechanism um for immune cells or

other cells likewise and we'll talk about them a bit more later now nfkb stands for nuclear Factor Kappa B and this is probably the most famous transcription factor it's like associated with many types of diseases NF Capa B will activate or stimulate or activate genes in DNA that will transcribe for a specific RNA that will make essentially a cyto kindes so the specific RNA will be translated by ribosomes to make pro-inflammatory cyto kindes now these pro-inflammatory cyto sign as the name suggests everything to do with inflammation it will promote inflammation the main uh side inflammatory

cyto kind is tnf Alpha but also other cyto kindes proinflammatory cyto produced are pro Incan 1B and pro Incan 18 now Pro Incan 1B and pro incin 18 are actually in a inactive form because they they have a pro before them now these proteins they actually have to be uh activated and they are activated by special enzyme within the cytoplasm called caspace one so caspace one here is responsible for the proteolytic cleavage of pro Incan 1B and pro interlukin 18 and this will lead to the maturation and release of these two cyto kindes so what

do all these products do well in luuc 1B and Incan 18 when they're released they will essentially enhance the immune response substantially they will activate lymphoid and they're all they also have a chemotactic effect but they also have other functions that I won't really talk about but those are the main ones tnf Alpha main function is to enhance the immune response essentially tnf Alpha also induces apoptosis by binding onto receptors of other cells that are infected or whatever and these T of alpha will essentially cause that cell to commit suicide now now let's talk a

bit more about interferons so interferons are produced uh when there's a viral infection you see the cell will produce interferons and will secrete interferons this these interferons will then signal to other cells about that specific virus and tell the cells to up their defense so it's a very important communication um sort of molecule so I hope you enjoyed that video this video on an overview of toac receptors the next video we we'll look at the inflammosome and how it's related to this actual diagram but it is a separate video nonetheless hope you enjoyed it thank

you