Immunology | Inflammation: Toll Like Receptors and Interferons: Part 4

all right Eng so we've already gone over the compliment system right if you haven't seen that video or any of the other videos like phagocytosis or the entire inflammatory response click on the right icon and go to our immune playlist and watch those videos to catch up with us all right so now we're going to go over in this video we're going to talk about two things we're going to talk about toll likee receptors and then we're also going to discuss interferons okay interferons so first off what are toll like receptors toik receptors are going

to we're still in the anate immune system we're still talking about the non-specific ways that we deal with foreign Invaders or foreign pathogens so to like receptors we're going to talk about a lot of them over here they're these proteins that are present either on the cell membrane or in these vesicles inside of the cell that respond to form pathogens and en listen to these specific responses and we'll talk about those in great detail interferons are going to be anti they're going to be signaling nearby host cells to let them know that there is a

virus in the vicinity and to start making antiviral peptides and it can also release uh interference to tell other nearby cells like macras and neutro um sorry natural killer cells to start becoming activated and proliferating we'll talk about that in great detail though okay so first off let's focus on the interferon just like we did with the bacteria let's say by terrible chance this person was infected with the human herpes eight virus or maybe the rabdo uh rabies virus whatever they were infected by some type of viral particle right so let's say here's our virus

let's say it's a double stranded virus right this double stranded virus and let's just say it's uh DNA virus right let's say it actually gets inside of this healthy cell right here this healthy TI tissue cell and let's say it also infects this right here and let's say this cell is a maccrage so let's say it infects a maccrage and let's say over here it just infects a generalized tissue cell so two different tissue cells that it's infecting right so now what's going to be the result of this all right so watch this some viruses

depending upon what type of viruses they are we're not going to go into that in super detail we'll talk about that in micro they can cause a lot of different effects they can either get integrated into the host genome they can produce proteins we're not going to talk about that just know that whenever this virus is in this cell it will actually cause either maybe the death of the cell right or it could actually start producing so it could either do that through What's called the litic cycle or it can get integrated into the DNA

and go into the lysogenic cycle all we need to know is once this cell has been infected with the virus it might not be able to turn back from that point it might be done from that point on unless we can do something about it but usually this cell will be killed in response so now how does he protect this other cell from that same virus infecting him and same thing with this guy let's look here this virus will work inside here and cause the damage of this cell whenever this cell is damaged it will

secrete there's a specific Gene all right there's a transcription factor and that transcription factor is actually called IR uh irf and that irf transcription Factor will actually activate this Gene here and this Gene will produce an mRNA and then an mRNA will get translated into proteins and it'll produce interferons but interferons there's actually three subtypes alpha beta and gamma Alpha and beta are usually the ones that we're going to group together and Gamma is a different one right gamma is usually not secreted by generalized tissue cells usually by lymphocytes or certain types of immune system

cells these generalized tissue cells will secrete Alpha and beta interferons so how will that happen these Alpha and beta interferons let's say here's the alpha here's the beta interferons they'll be secreted out of this cell and then what can they do they can actually activate maybe some type of signaling mechanism maybe they activate this signaling mechanism M that signaling mechanism activates the genes of this nearby healthy cell this healthy cell then produces a specific molecule and this molecule is called protein kinas R protein kinase R and there could be other antiviral peptides this is just

one of them there can be other antiviral peptides what does protein kinas R do protein KY R can think about him as an anti vop peptide or like a scissors if this virus just so happens to try to penetrate this other cell whenever it tries to penetrate this other cell that protein KYR can lead to the destruction of that actual virus right so then what can happen he'll destroy the freck out of this virus and then release maybe the nucleotides all around here right so now this virus is no longer pathogenic it can no longer

cause damage to this tissue cell we've prevented that from happening so what happens protein cyas R does what acts on this viral particle and other antiviral peptides besides him and inhibits this virus from infecting that nearby healthy cell that's its design okay and again who does that Alpha and beta interferons and Alpha and beta interferons can actually be released by almost any cell so tons a lot of cells let's just put a lot of cells they can be produced by a ton of different types of cells beta a little bit more specific he can be

released by platelets also so beta can also be released by uh certain types of uh like the platelets right so you what was this transcription Factor right here called this was called irf now gamma interferance let's go to this maccrage again let's say this virus particle comes in here does the same thing infects this maccrage this maccrage is done he's fricked okay so now what if this maccrage is fricked and it's done can it actually do anything no it can alert nearby healthy cells though they there's a virus in the vicinity so same thing it

could activate maybe some transcription Factor like irf right when the cell's damaged that can actually activate these specific genes and these genes will produce alpha beta and gamma interferons what can these alpha beta and gamma interferons do we already know what Alpha and beta does alpha and beta can come over here so let's say here it secretes out Alpha and beta interferons it can come over here and activate that prot protein kinase R Cascade and Destroy This virus preventing it from infecting nearby healthy host cells right what does this gamma do we haven't talked much

about the gamma so this gamma interferons right here so let's say here's our gamma interferons the gamma interferons they can be secreted and what they can do is let's say here's a maccrage let's say that there's a a maccrage nearby so here's another maccrage this maccrage will get this signal so it has receptors for the gamma interferon that gamma interferon binds onto these receptors and what does it do it tells the maccrage to start proliferating so then what starts happening this macro page starts undergoing proliferation and then on top of that he starts becoming bigger

and hungrier so then he's going to become bigger hungrier he's going to start proliferating and he's going to increase his expression of mhc1 and MHC 2 molecules so again what's the overall effect of gamma interferons gamma interferons will work they'll actually be secreted by macrofagos or lymphocytes or natural killer cells and what they'll do is they'll work on nearby macras tell them to proliferate get bigger hungrier and increase their expression of mhc1 and mhc2 molecules and it can also do something with t- cells but we're not going to talk about that there is one other

function of Alpha Beta besides activating protein kinas R if there is another cell in the vicinity like a natural killer cell and we'll talk about this one when we talk about uh specifically it is a part of our inate immune system but I'm going to talk to you about it whenever we get into adaptive I know it might seem confusing but I'll explain to you why it's not a part of our adaptive immune system but it can activate these these Alpha and beta ones can activate natural killer cells and if the natural killer cells are

activated what can they come and do let's actually just show you the mechanism here so let's say this natural killer cell it's been activated he's going to come over here to where this infected host cell is so again this host cell has been infected with the virus right right so this host cell has been infected with the virus if this host cell has been infected with the virus it actually has a nuclei right if you remember what do all nucleated cells have they have MH C1 molecules and they also have present on it some type

of self antigen right if if what happens if this actual cell has been infected with the virus sometimes what can happen in virus infected cells there can be kind of three things that happens they can produce what's called mic they can actually cause um maybe there might be an antibody attachment through IGG or maybe it might downregulate the class one molecules let's say that the class one molecules due to the cell being virus infected or cancerous gets downregulated then what happens that natural killer cell will notice that and if it notices that there's no class

one or class two molecules present there specifically class one it'll actually cause apoptosis of this cell and I'm just doing a quick brief overview because we're going to talk about him in more detail when we talk about the uh adaptive immunity even though he's a part of our Nate immune system but I just want to show you that he will actually kill these cells that in a nutshells are alpha beta and gamma interferons so again one more time what is the purpose of interferons if a virus is infected a maccrage or lympo ites or immune

cells and it's infected generalized tissue cells if it infects these generalized tissue cells they'll then activate a transcription Factor like irf which can then activate these genes to produce interferons Alpha Beta gamma Alpha and beta are usually secreted by many many different types of tissue cells beta can also be secreted by platelets though and what can they do they can act on nearby healthy cells that haven't been infected with the virus yet stimulate these cells to make anti peptides for an example protein kinas R protein kinas R will then destroy this virus as it tries

to infect this cell preventing this virus look at him he's inactive he's chopped to Pieces he's inactive now and if this virus is inactive he can no longer infect this host cell what else if this maccrage or other different types of lymphocytes have been infected with this virus it can activate their transcription factors for example irf is one activates the genes to make alpha beta and gamma interferons Alpha and beta can do the same thing they can signal this host cell nearby let them to node to make antiviral peptides and protect himself from that virus

but it can also secrete gamma and these gamma interferons can act on nearby macras and the last thing is that Alpha and beta interference can also act on natural killer cells activating the natural killer cells and again we'll talk about natural killer cells in more detail there three mechanisms of how they kill I'm not going to go into that right now natural killer cells will come over here and they'll be able to notice some type of virus infected cell or they can also not can notice cancer cells by either three mechanisms I'll talk about in

more detail whether they lack class one molecules whether they're IGG bound or whether they have a similar molecule to mhc1 which is called Mica and we'll talk about that but again what will it do it'll initiate apoptosis of this cell that in a nutshell is our interferons one more thing about interferons and we're going to go on to like receptors interferons we actually use these as a drugs you can use inter Fons to treat herpes you can use interferons to treat genital warts um and they even use interferons to treat um multiple sclerosis also it's

one of the ways that you can try to be able because they believe multiple sclerosis is actually a um some type of autoimmune disease right so you can actually use interferons to be able to like prevent flareups or the progression of these diseases but they're not going to cure it so herpes genital WS mult sceris can't be cured you can control their symptoms in the progression by giving them interferons uh usually for example you can give uh the drug called aycl which is you know used to treat herpes all right so again that's basically all

these interferons are designed to do now let's get into these toll like receptors all right so let's continue down here so we already talked about interferons right we talked about Alpha we talked about beta we talked about Gamma interferance now let's go ahead and dig right into those toll like receptors so we have a ton of different to like receptors there's actually a total of 11 we're only going to talk about some of them being like we're not going to talk about 10 because they don't necessarily know the function of to like receptor 10 yet

we're not going to spend a ton of time on this because it's kind of General all right so let's go ahead and go through a couple of these all right so the first one we're going to start over here there's two toll like receptors that dimerize here this blue one here it could let's just say that this is toll like receptor one it's dimerizing right here next to toll likee receptor two all right so we have to like receptor one and we have to like receptor 2 these to like receptors they respond to specific types

of pathogens I told you that right like what types of pathogens any type of pathogens that have what's called GPI anchoring proteins so usually parasites in other words so usually these are parasites of some form it also loves to response to different types of lipoproteins so even certain lipoproteins it likes to respond to okay so there's a lot of that it can responds to the to the GPI anchoring proteins on parasites or it can respond to lipo proteins and it can stimulate these toll likee receptors to like one to like receptor one and to like

receptor 2 to dimerize and it'll trigger an intracellular Cascade Event the next one's right next to this right here so again we have the black one right there and that's let's just say that's toll like receptor two again it can dimerize with another one adjacent to it which is called toik receptor 6 toic receptor 2 and toic receptor 6 they respond to generally they love to respond to fungi so they can respond to fungi there's a specific molecule in fungi called zosin zosin is from the fungi and can actually activate these receptors as well as

lipoic acid which is on gram positive bacteria so lipo toic acid which is on gram positive bacteria okay then it can again it can stimulate these guys they'll dimerize and then it can send an INT intracellular Cascade right so again these guys are sending a Cascade Event these guys are sending some type of cascade and then we're going to go into the next one this next one here is going to be two of the same and this is going to be the dimerization of toll like receptor 4 so to like receptor 4 will dimerize right

so you got to like receptor 4 to like receptor 4 will respond to specifically the lipopolysaccharides on gram negative bacteria so they love to respond to the lipopolysaccharides on gram negative bacteria and again whenever that happens it can stimulate the toic receptor 4 to diarize and send a Cascade Event down here next one this next one's right here is going to be toll like receptor five and receptor 5 is going to be uh he going to be Sim similar molecules right so it'll be a homo dimer and these two molecules will dimerize together but what

will they respond to they respond to a specific protein on specific types of microorganisms like like felin so responds to felin like you know eoli eoli has the actual felin so the fella molecules it loves to respond to that and so whenever there's any type of felin it can stimulate the toll like receptors and that can actually cause them to dimerize and then send a interesting say their Cascade what is the next one the next one is going to be tolik receptor this is going to be toik receptor 11 toic receptor 11 and again this

is a homodimer it will respond to certain types of molecules right so these are usually um it's usually bacteria that are very very pathogenic within the urogenital system okay so it's usually designed to be bacteria uh that damage the euro genital system so it's pathogenic bacteria that that are affecting the urogenital system right so that can stimulate to like receptor 11 and that can send intercellular Cascades right so these are the to like receptors that are present on the actual cell membrane now let's talk about some of the toic receptors that are inside of this

vesicle or this endosome inside of the actual cell in other words there can be actually these these actual to like whenever you have a phagocytosis let's say this macras phagocytosis is some type of foreign molecule right or some type of foreign virus so we have we have a couple of these across the surface so let's say this one right here and blue is toll like receptor three let's say this one in purple right here is toll like receptor seven let's get these out of the way we'll talk about these in a second let's say this

one here is toll like receptor eight and let's move this red one over here and that's going to be called toll like receptor 9 so again this one over here that we're going to draw in red is to like receptor nine so we have a couple more that we got to talk about all right so what is one is this one again to like receptor nine all right so to like receptor 3 let's say that if fagos let's say we phagocytose this maccrage phagocytose is some type of substance right because this is a macras that

we're talking about and other types of immune system cells if this phagocytose is some type of Mo like some type of virus specifically a virus that's consisting of double stranded RNA double stranded RNA viruses all right so that can stimulate that guy toic receptor 9 he responds to a specific type of DNA that can be methylated or unmethylated but it's usually cytosine with a guanine residue nearby and it's called C PG DNA it's called cpg DNA then okay so cpg DNA can actually stimulate this guy now right then tolik receptor 7 he responds to singl

stranded RNA so viruses that are consisting of single stranded RNA and then to like receptor 8 responds to double stranded he responds to double stranded RNA now we've mentioned so many different types of toll like receptors right so again let's do a real quick recap of all of them to receptor one and two respond to lipoproteins GPI anchoring proteins on parasites right to receptor 2 and six respond to fungi like the zosin and the lipoic acid on Grand positive bacteria toic receptor 4 responds to the lipolysaccharide on gram negative bacteria toic receptor 5 responds to

the felin like un certain types of bacteria like a coli that have fella and toic receptor 11 responds to specific types of pathogenic bacteria within the urogenital tract right to like receptor 3 responds to viruses consisting of double stranded RNA toic receptor 9 actually is activated by certain types of cpg DNA within bacteria and then toic receptor 7 responds to single stranded RNA and toic receptor 8 responds to double stranded RNA all of these effects Works in in these actual these all these intracellular Cascades events right so here's all those intracellular Cascades and it's going

to come from these guys too from toic receptor 3 toic receptor 9 toic receptor 7 and eight and what do all of these guys do they all come in here and activate the actual genes there is three genes I'll mention them I'll mention the transcription factors that you can have to activate each gene we don't need to know this specifically but it does help there is AP1 transcription Factor there's another one over here which is called I RF and we talked about that one so we should already know what this one does and then there's

one more which is actually going to be called nuclear Factor Kappa beta three of these transcription factors they all work on different types of genes for example if works on AP1 it'll synthesize specific types of uh protein signaling molecules right so it can s activate protein signaling molecules if it works on irf which which one does it actually cause the secretion of interferons we already know this one right Alpha Beta gamma interferons and if it works through nuclear Factor Kappa beta what is that one going to do it's going to stimulate the production of cyto

specific types of cyto kindes usually these cyto kindes can be tumor necrotic Factor Alpha interlan One uh technically beta and interlukin 18 okay now technically interlukin One beta interlukin 18 technically aren't in the active form they have to be acted on by cast bases to activate them but we don't really care about that again what's the overall effect though what was the overall effect of all of this we're producing protein signaling molecules to Signal chemot taxis we're secreting interferons to protect this cell from viruses and other cell from viruses right we're secreting tumor necrotic Factor

Alpha to initiate maybe some type of lucyisanerd proteins right tons of different effects interlukin One beta right let me actually fix that you can't even see the one there this should be interlukin one beta and again it will be activated two of these will be acted on by cast bases and these two can act as specific types of inter lucans to activate other different types of cells like interlukin 18 can activate natural killer cells right so a lot of different mechanisms here that are all designed for what to enhance the inflammatory response that's all we're

trying to do here that's why there's so many different mechanisms occurring here right because the whole design here is to enhance the inflammatory response to clean the area out from foreign debris certain types of pathogens and start start the repair process so now guys what have we done in this video we've talked about specifically we' talked about interferons right which ones did we talk about we talked about alpha beta and gamma and what their effects are we already know those and then we talked about toll like receptors very very many of them right so we

talked about one two three four five six seven eight nine different types of toll likee receptors in this right but dimerized because obviously there is one two three four five 6 7 8 nine we skip 10 and then we do 11 so technically there's 11 types of Toc receptors we only covered technically 10 all right because they don't really know what 10 does to like receptor 10 and again what was the whole purpose of this to enhance the inflammatory response through protein signaling chemotaxis interferons to protect from viruses and activate the macres or in natural

killer cells also and then enhance the inflammatory response through very very many ways right we're going to follow in this next video that you want to click up in the right corner the icon cuz we're going to go into the next inflammatory response and finish this entire process here and we're going to follow these antigen presenting cells all right and we're going to follow these free antigens that the neutrophils are exocytosing into the lymph node and we're going to talk about t- cells and B cells and so many different types of things all right guys