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00:00 | it's okay. Mhm. Okay Welcome. Let's uh we've got um |
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00:32 | we're heading towards the last couple of of course. So we've got this |
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00:36 | . Next week and then we'll come On 2nd for the last class. |
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00:44 | let's see. So we're gonna finish innate immune system. Start on |
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00:49 | the immune system finish that on Um just a note. Let's |
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00:55 | Uh so we're talking about expanding little on vaccines. Your your book, |
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00:59 | 24 has a section where it talks little bit about it. I kind |
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01:04 | expanded a little bit. Um so see that if you, if you |
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01:08 | to the notes um the uh until Monday um chapter 25. And so |
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01:17 | one of those classes. So the lecture for that's already up is |
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01:21 | So if you wanna take a look that before next Monday. Um Like |
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01:27 | previous ones, just a bunch made lot of ethical questions surrounding, you |
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01:32 | , discussion about different ah fixed within 25. So that will be next |
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01:38 | . And then um Smart work again due. So that's number 23 which |
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01:42 | finish up today is due sunday weekly again. Just forward going over this |
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01:49 | . And um then uh let's So the Exams and Exams three will |
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01:55 | available Wednesday. So you can you go and log into cars and look |
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02:00 | it. Um certainly have any let me know the distribution for the |
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02:06 | was Um exactly where it was as see here. So it was like |
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02:14 | or so average uh the Um median 74. Yes. So uh yeah |
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02:24 | we got one more exam obviously. that's gonna again not comprehensive was just |
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02:31 | what the These chapters 23 through Okay so that's not until mid may |
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02:40 | . So and I guess then the schedule will come out I guess that |
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02:47 | be two weeks before. So at end of april so that last week |
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02:51 | april so just be God for And uh so um any questions? |
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03:01 | . Uh we have an official vehicle this. Sign up for example For |
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03:06 | last exam it's gonna be it's gonna it's gonna be 14 days before so |
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03:11 | 14 days is from the 10th. when you can sign up. I |
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03:16 | I think that's a Tuesday I the so May 10 someone looks like it's |
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03:34 | be April 26, 26 is to . So um Okay questions. Okay |
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03:45 | so on to so I just want start with a little bit of a |
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03:50 | of a recap. Okay let's look this question first. We talked about |
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03:55 | things last time then it will kind do a little wrap up of our |
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04:00 | of where we're at right now. So as you're answering so remember |
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04:07 | So we're in the native new So of course in this section is |
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04:10 | about the infectious disease. Looking at microbial pathogens which we're getting to. |
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04:16 | I haven't really got mixed in here there but we're focused now on how |
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04:21 | body fights disease your innate immune Today we'll begin talking about the adaptive |
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04:27 | system. And so um then next is when you kind of turn the |
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04:33 | to the microbe the pathogen and how um can get through all these various |
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04:39 | that we've been talking about. So and then we'll end up with looking |
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04:44 | different types of infectious diseases. So talk more about that on Wednesday. |
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04:51 | . Um so another thing so today looking at uh the last time we |
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04:58 | at physical chemical barriers um the cells the innate immune system, different types |
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05:07 | white blood cells. And then today going to focus a little more on |
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05:13 | of the innate immune system like um inflammatory response of these kinds of |
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05:20 | . Okay so uh put the clock here. Mhm mm hmm. |
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05:53 | Okay so here let's see what we . Um Okay so modest sites can |
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06:05 | to battlefield. No remember modern sites into macrophages dendritic cells. Okay they |
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06:12 | that in the lymphatic system abstractions are things that will help out figure |
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06:17 | So things like antibodies and complement or . Okay. Not to T. |
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06:23 | . R. S total like I mean see molecules those are your |
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06:27 | antigens. Alright so that's what you on your cells tissues you're not gonna |
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06:32 | about passages. Um third line That was the third line is your |
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06:38 | distributes system. Okay we'll talk about later today licensing is going to be |
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06:43 | chemical barrier. First line defense. Natural killer cells are defense against um |
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06:52 | sailor pathogens. So infected cells can can be potentially found out by natural |
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06:58 | cells and they'll deal with them. so on this list none of these |
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07:04 | true. Okay um Okay so again kind of went over this a little |
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07:12 | so summary from last time. So uh naming system looking at 1st and |
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07:18 | line defenses will go through the rest these today here and uh the of |
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07:26 | you can't forget your own microbes, own micro motor that serves to keep |
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07:31 | out. Um So the man's pants think those are the same thing. |
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07:37 | basically structures on the periphery of pathogen can be detected through these total like |
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07:42 | . These will be on various cells your immune system um scattered throughout your |
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07:48 | . And so interaction with a structure the pathogen either examples here are uh |
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07:56 | of the virus buying cities um the result and also remember that you have |
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08:04 | internal tactically suffers inside the cell so can affect and then um certain patterns |
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08:13 | do that be on the inside of cell and maybe one of one of |
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08:16 | structures context when these internal receptors. united case whatever whichever one gets activated |
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08:24 | cytokines produced. Right so you have put aside all kinds of different effects |
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08:27 | so we're going to see the functions lots of different cited kinds and the |
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08:32 | response. That's what that's what we're start out with first. Um So |
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08:36 | whole host of different effects from attracting to the site of infection to activating |
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08:43 | cell types etcetera. Okay. Uh basically I look at it as like |
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08:47 | alarm his arm belt in the body off. So signaling potential infection. |
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08:54 | and mobilizing your immune system. Then looked at some different cell types in |
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09:00 | in the immune system, focused most on these in terms of function. |
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09:07 | , you're granular sites Dr. Phil Party when your main infection fighters early |
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09:14 | these are fields are more about releasing . Not really think it's a toxic |
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09:18 | . You've said it feels more about with large pathogens. They too are |
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09:23 | of produces releases toxic and some things terrific. And then we'll than macrophages |
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09:31 | dendritic cells. Okay these are remember your innate and adaptive immune system can |
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09:38 | together in certain processes and it's macrophages dendritic cells are typically the ones that |
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09:45 | doing that working with the adaptive And so we saw that that function |
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09:50 | antigen presentation which I which I'll mention in a second. So um uh |
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09:57 | lymphatic system of course is important. where your B cells T cells |
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10:02 | Dendritic cells kind of reside that's kind their environment. Um B cells and |
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10:09 | cells will activate the lymphatic tissue and can do there thing. Okay um |
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10:19 | we ended I think with fabio santos so remember the process there. So |
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10:23 | is the macrophages that we see the here of a pathogen to our total |
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10:31 | receptors. So it starts with binding ingestion forming food vacuole like you see |
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10:38 | and then fusing with the license zone digest it. And then remembering another |
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10:42 | here is this antigen presentation which let just flip to that real quick. |
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10:49 | . Which is shown here. So a macrophage just like we saw the |
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10:52 | slide and so congestion occurring here. um uh binding ingestion and then going |
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11:04 | the process of psychosis. But then fragments of that pattern can be shown |
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11:12 | the body. Okay so through MHC . Okay so there's a differentiation |
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11:18 | Class one. Class 2 Right. too macrophages B cells. Dendritic |
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11:24 | everything else then is a class one cells, your liver cells basically Most |
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11:30 | your body cells falling into the Class category. And so class two types |
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11:37 | interact with particular types of T cells help them cells um binding like that |
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11:44 | T helper cell recognize both the MHC as well as the antigen and then |
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11:50 | of course typical is released the site kinds again right you can activate |
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11:54 | So here's what an activated and inactivated activation looks like compared to activated one |
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12:01 | of like a that you're a flower almost. And so you see the |
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12:05 | of lots of membrane folds. So more of these folding wings |
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12:11 | Equate to a greater ability to Vegas ties. Right. So that's that's |
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12:15 | activation is about activating these things is just making it more fake acidic if |
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12:21 | will. Okay um so back once a second here, that's an option |
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12:30 | . That was the last thing. , that's the last time we talked |
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12:33 | . So here is um uh we think of it as enhanced figure |
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12:39 | Okay. Certain pathogen is gonna be of a better word, slippery. |
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12:44 | ? Not able to buy. And it's a binding part that you see |
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12:48 | is critical to initiating the whole figure effect. Okay, it's not able |
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12:53 | bind very well that this doesn't occur a very good. Great. And |
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12:58 | to enhance that. So something like capsule can produce this effect where the |
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13:03 | is not going very well or a capsule or some other structures that may |
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13:11 | it to not bind so well. so that can be worked around through |
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13:16 | production of antibodies that combined them into pathogen or complement combined to it basically |
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13:23 | it more sticky if you will. and so now that it's more easily |
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13:26 | and it can be sensitized. Okay that whole process is optimization. The |
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13:32 | is actually facilitating this. In this the antibodies other example would be a |
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13:39 | . Those Michaels are the option. okay. That doesn't allow for |
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13:44 | Okay. Um so that means so already. So so this is what |
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13:50 | gonna finish up today or these fourth . Okay, interference isn't really a |
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13:57 | but we'll see we've seen this before so many of these things over |
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14:02 | Any questions? Okay yeah. Um you'll see what awesome party you |
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14:14 | T. L. R. There were categorized under it would be |
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14:29 | . Uh They would just be classified an immune system defense. That alerts |
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14:34 | body to a potential infection. May followed under a process maybe or |
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14:45 | Um But you C. T. . R. As you think, |
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14:50 | it's like putting the fire on Uh you know. Okay so here's |
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15:00 | question if this is gonna relate to first thing we're going to talk about |
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15:03 | is the inflammatory response. So um what are you looking at this? |
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15:08 | inflammatory response? We're looking at the inflammatory response which has a which has |
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15:16 | finite period um a few days To a week or two where you start |
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15:25 | then finish it um chronic inflammations, continual processes that occur maybe even a |
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15:33 | temporarily, but then they come So kind of trigger these inflammations in |
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15:37 | body. Uh these kind of chronic um can can uh sometimes are autoimmune |
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15:47 | um over time they do take a on the body. And so uh |
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15:53 | know, many of these are kind uh gastrointestinal types of things where certain |
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16:00 | and things may flare up and cause , student, autoimmune uh aspect of |
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16:06 | condition. So um so chronic ones and of course a long time, |
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16:10 | , years. Okay. But we're focus on the acute inflammatory response which |
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16:16 | all gone through at one time or , or maybe going through it right |
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16:21 | if you have like a minor wound something, a splinter in your finger |
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16:23 | what have you is relatively mild. the thing about inflammatory response is a |
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16:31 | response is meant to be a local and to contain the infection in that |
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16:37 | area. Okay, that's the And so not allowed to spread. |
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16:42 | so it's about bringing all the relevant types to the site and then carrying |
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16:50 | the effect. Okay, and so there's gonna be a stepwise process to |
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16:54 | , right? So for this question basically ranking uh 112136, I guess |
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17:03 | with what we've given. And so as was answered the majority yes, |
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17:09 | going to be cytokine release is gonna first. So like with um you |
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17:15 | , instructions yourselves followed, or other of some sort. And so inflammatory |
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17:22 | is going to be very cytokines are to trigger this. And so with |
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17:27 | so we're talking essential in this process getting neutrophils. Two figures of ties |
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17:36 | infectious agent. Okay, so neutrophils the blood circulating blood, you gotta |
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17:40 | them out, right? And so a lot of this process is about |
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17:45 | the blood vessels more permeable more If you will to get the neutrophils |
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17:51 | and then they can do their So, again begins with cytokine |
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17:56 | then I probably would put this That's one I would say this is |
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18:03 | Okay, so, bad circulation is manipulating blood vessels. Okay? Um |
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18:08 | not everything's listed here, but what have, I would say it's like |
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18:12 | too. Um I would say three be this. So one of the |
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18:18 | is neutrophils, you know, your flows pretty quick. And so you |
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18:23 | to slow it down. There's ways slow it down and then kind of |
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18:27 | onto the neutrophils so that you can them down all right? And that's |
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18:31 | the sticking part is all about, ? And so once you get them |
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18:34 | stick to the blood vessel wall, they can squeeze out, and that's |
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18:38 | that would be for exit. And then the latter processes here, |
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18:44 | , swelling, I think we've come . Okay, repair them. We |
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18:48 | to occur. So it could be that's supposed to scam performs right? |
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18:53 | Something like that usually proceeded by Uh If you're getting trying to get |
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18:59 | out of the blood, of things other than cells will follow when |
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19:04 | make blood vessels more permeable. So comes out and that's where the |
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19:09 | Any inflammation occurs from that. Um yeah, we're gonna go through |
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19:13 | So let's look at um here. , so these terms extra visitation |
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19:21 | Nation is another one. You'll hear relate to the manipulation of of the |
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19:27 | , even getting them out of the vessel into the nearby area where they're |
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19:32 | . So um so here's a basic , just like a kind of puncture |
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19:39 | , remember we call that would be subcutaneous rank is just like a with |
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19:44 | splinter uh puncturing the skin layers. Maybe there's a certain microbes contaminating on |
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19:53 | the tablets on this planet. And you're you'll have macrophages in the |
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19:58 | not necessarily plentiful, but there will betraying around. Remember you can have |
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20:04 | most fixed and wandering macrophages. These likely wandering around. Um And we'll |
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20:10 | pathogen, potentially microbes that are introduced again, release chemicals it's gonna |
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20:17 | They're fake with the ties. And then um then through the whole |
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20:22 | are binding that I can't release, know, they're beginning to um had |
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20:28 | chemo attractant chemicals to draw ourselves to site Um beginning the whole process of |
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20:36 | the inflammatory response. Okay, so nearby capillary and of course there's gonna |
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20:42 | lots of red blood cells, but there'll be a few more than a |
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20:46 | , but there's certainly lots of white cells to um here is gonna be |
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20:50 | nuclear fill you see here. And the process of no these different chemicals |
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20:58 | manipulate blood vessels. Okay, so is going to increase the diameter of |
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21:05 | capillary. Okay, so that two bring it closer to the surface, |
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21:09 | ? So that's when he typically implement area, will be kind of reddish |
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21:14 | warm to the touch because of that effect. Okay? Um so to |
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21:21 | in the blood, but so of this is just occurring. Obviously this |
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21:25 | is only occurring in the immediate vicinity of where this infection occurred. |
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21:31 | Um And so the so by opening the bug dust, so basically lesson |
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21:39 | resistance to flow through the capillaries in area. So but the wind will |
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21:46 | and we'll slow down so we can down the speed and it kind of |
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21:51 | up the wood block. Okay, that serves two purposes. 1 to |
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21:56 | more blood to the site because more needs more of these neutrophils and slowing |
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22:02 | down means it's easier to grab and these out. Okay, so those |
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22:08 | two purposes, we're kind of doing manipulations with the blood vessels. |
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22:12 | Um And so here would be. here, I'm gonna show you an |
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22:18 | of this. But here is how see. So this process of kind |
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22:22 | grabbing it is the is the externalization and then they're squeezing out. That's |
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22:28 | they called margin ation. Um And it will kind of they're very of |
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22:34 | , flexible these cells, there's no wall, so they can kind of |
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22:38 | like amorphous blobs if they need to to squeeze through. And so to |
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22:42 | this happen, and there's other chemicals come into play, interact with the |
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22:48 | making up the blood vessels. Because you have to loosen those connections |
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22:52 | the cells to enable stuff to come . Right? So that's a lot |
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22:57 | cytokines interacting here, doing various things uh manipulating blood flow to making |
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23:06 | loosening up connections to make these cells out. Um And of course, |
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23:11 | of chemicals involved in this. so then you see the exiting digital's |
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23:17 | exited and they can go on and the bulk of the figure psychosis |
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23:22 | Okay. But you're gonna have other involved because as the chemicals are released |
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23:27 | they affect other cells that continue to the whole bas oh, these basal |
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23:33 | factors that manipulate the blood vessels for from things like mass cells in the |
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23:40 | . I really think things like histamine basic skills can do contribute here as |
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23:45 | , history and brady Kainan or a of cytokines that um again promote this |
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23:55 | the permeability of the blood vessels is they're doing. Okay. Um This |
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24:00 | the brady kind has dual function. not only helps to kind of loosen |
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24:05 | junctions between the cells making up the vessel. That's what we call window |
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24:10 | cells are what make up the blood here, these guys right here. |
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24:15 | um so in addition to helping loosen the junctions between themselves, it also |
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24:20 | on prostaglandins which serve the effect. effect is to intensify the pain in |
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24:27 | area. Okay. Do you want be aware um you know that something's |
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24:31 | on there and it's a wound you want to take care of it. |
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24:35 | these are ways to kind of more . Something's going on there. |
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24:41 | And so um so T. F. Is another major side of |
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24:46 | . Uh This could even be released only by macrophages for example in the |
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24:52 | here but also by the damaged tissue can release these things. Okay. |
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24:58 | it's served a number of factors are one to cause a lot of other |
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25:06 | of cytokines. So things like c protein, these sort of activate complement |
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25:11 | example. I l one intra that for work and um bring about uh |
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25:20 | Vegas halitosis of cell types may be fever. So it can it can |
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25:26 | a number of different other exciting times released as a result of this tea |
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25:31 | after it stands for tumor necrosis Okay. Also things like Elected will |
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25:39 | about in a second. These are by the liver and they kind of |
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25:43 | kind of to work on the complement . Okay, so lots of different |
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25:47 | and chemical reactions have to be going in this process. Okay. But |
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25:52 | all about, you know, activating cell types and things. Okay. |
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25:56 | so let's look at this. Uh . Here we go. Yeah, |
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26:04 | it's basically the same kind of uh huh diagram I'm showing. But just |
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26:11 | of more emotion here. So you kind of see what's going on. |
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26:15 | here's our capillary uh Oh here comes wound or subcutaneous wound puncture wounds. |
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26:23 | . Microbes contaminating microbes on the I guess there comes some macrophages in |
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26:29 | area. Mhm. And the whole tl r center time release um |
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26:39 | And then it's followed by a different of kinds. Um And I think |
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26:46 | getting close up here mm hmm. we go. So again these are |
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26:52 | endothelial cells. This long thing right . Okay, now of course there |
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26:56 | molecules selecting that's called that served to of grab the neutral the neutrophils that's |
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27:03 | gonna go on. So you see so this process is made easier by |
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27:10 | down blood flow in the area as as increasing blood volume. So that |
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27:15 | to kind of help them grab onto cells because it kind of slowed down |
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27:19 | it kind of tumbling along the And then I grabbed kind of like |
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27:24 | of velcro grabbing it and um and we're gonna loosen up these junctions in |
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27:31 | . Okay. That's gonna be brady that will do that. Which I |
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27:35 | is gonna come into view here, . There we go. And so |
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27:38 | see it there and then listening up and now they can squeeze through. |
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27:45 | right. Uh There we go. . And so of course not only |
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27:51 | the neutrophils squeeze through, neutrophils squeeze , but so too will flu other |
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27:58 | in the in the blood as well we'll see here in a second. |
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28:02 | of course Nature Fields will be the figure, civic type in the |
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28:07 | And uh mass cells will be activated well by cytokines. Again, history |
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28:13 | another type of basil active factor working the blood vessels. Okay. Um |
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28:18 | now you see the fluid filling up the area. So you're gonna have |
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28:21 | combination of fluid that exits the blood along with the neutrophils. But also |
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28:29 | neutrophils are doing their thing and advertising gonna fill up with dead cells. |
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28:34 | of course the neutrophils don't live You know dying. So it's gonna |
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28:39 | a whole mess of dead cells and and stuff collectively. It can be |
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28:44 | called purpose. It's the work that use for it. So um uh |
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28:49 | of course the amount of swelling can greater or lesser depending on the severity |
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28:54 | the infection and so forth. But these are the basics of this acute |
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29:01 | response and the characteristic uh effects or of information, redness, the |
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29:09 | pain, swelling, multi function So again through these basic active factors |
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29:16 | are causing this. Um So let's back to here. Okay. Any |
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29:26 | about that inflammatory response? Yeah. So you pull out a splinter. |
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29:32 | so you have now you have a skin, would there be a signal |
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29:40 | stop you know released? Yeah. gonna be um when when a lot |
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29:46 | a lot of these cytokines are Yeah. It's gonna be a the |
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29:51 | that are produced depending upon how many are at the site being activated. |
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29:57 | is a function of what is the of infectious agents that are present to |
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30:03 | a certain number of certain magnitude of . Okay. Plus once they're released |
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30:09 | are going to have a chemical chemicals have a finite lifetime. Whether it |
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30:14 | dissipate diffuse go away. Um But also not shown here, you know |
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30:20 | the terms of the repair slash healing . You're gonna have to potentially have |
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30:25 | saying pulling out the splinter right, could have some bleeding occurring. So |
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30:29 | may involve clotting factors and these kind things. So yeah that's gonna be |
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30:35 | of the healing process to um so I think so could see something before |
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30:47 | can release the chemical factory. They release those chemicals without having to |
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30:52 | well it's it all begins with the like to A. T. |
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30:57 | R. On macrophages will trigger the of can release. So technically if |
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31:01 | just do that and don't pay closer then they can release chemicals. But |
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31:06 | think being a micro features that are of just programmed to them once they |
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31:10 | buying something like that to then ingest . So um will a macrophage always |
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31:16 | that? I'm assuming it will but can see maybe it won't and just |
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31:20 | binding may induce subject and release. I think because there are specific cell |
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31:24 | that's kind of what they do. was kind of a protocol is not |
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31:30 | . Yeah. Mm hmm. Okay. So we can assume that |
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31:35 | just it's not directly linked but it's a process. Yeah. This is |
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31:41 | inflammatory response is yeah, it's its kind of process. Right. |
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31:45 | Right. And macrophages can do that . It doesn't have to do this |
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31:50 | just because I'm showing an inflammatory These are things you have these things |
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31:55 | your lungs for example that are just know val being up whatever it may |
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31:58 | in terms of microbes in there and not even related to inflammatory response. |
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32:03 | so this is all microbes and the based on, yeah but what they |
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32:11 | because they're not gonna are they fake your own microbiota now because they're going |
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32:17 | be your your your own microbiota have cell surface markers that are gonna your |
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32:22 | gonna say okay those guys are okay so that's yeah. Right so that |
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32:27 | pages are gonna pay attention to that well so. Okay um Alright so |
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32:39 | . It's a compliment is a number 13 factors are soluble in the |
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32:46 | Okay and the um are in an state. Okay until they get |
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32:53 | All right and so it's it's um worry about having to memorize all the |
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33:01 | in this thing. There's no need but it doesn't involve a an initial |
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33:07 | which is basically these are cleavages so cleave the protein and it activates it |
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33:13 | so it's a succession of these one activated, then it activates the next |
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33:19 | it activates the next and so on so forth. That's what they call |
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33:22 | the cascade. Okay the complement And so um you know when you |
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33:28 | to which The reason I mentioned these c. 3 and c. |
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33:33 | These are kind of the ones when get to this point these are the |
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33:36 | that initiate really the main effects. so C. Three is the inactive |
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33:42 | C. Five is inactive and the forms of the Airbnb of each |
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33:47 | And so C five is activated by C. Three a component. And |
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33:52 | like I said it's when those two activated those are the ones to initiate |
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33:56 | three main effects and the three effects the same no matter how you activate |
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34:01 | complement. Okay. And so um first way which is the length of |
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34:08 | uh this is the first one that discovered. So they called the classical |
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34:12 | I guess for that reason. But you see the effects of optimization, |
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34:19 | , sis and inflammation. So those effects of activation are the same but |
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34:26 | it's activated. Okay so the only between the pathways is what's activating. |
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34:32 | and so fastballs antibody the antibody binding microbe that will activate C. One |
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34:39 | eventually gets down to three. And to at the point of that initiating |
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34:46 | effects. The alternate pathway is binding pathogen components like a surface proteins and |
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34:57 | that body itself will actively complement. and then the third is elected. |
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35:04 | . Selected is produced by the liver believe in response to to necrosis factor |
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35:11 | others kind of sight kinds but regardless elected will then bind to it's a |
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35:18 | binding no molecule. Okay. And will life is actually produced by lots |
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35:27 | things. Plant their plants in particular these but we produce them for the |
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35:33 | of binding carbohydrates on bacteria bacteria known course for having all kinds of carbohydrate |
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35:40 | markets in their service. Especially a negative with the old policy. Saccharine |
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35:45 | there. Real long chain sugars. . And so um very common in |
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35:51 | is a short of manos among Um And that's what this election's bind |
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35:55 | write. The binding will activate And again as you see for all |
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36:03 | ways of activation the effects net effects gonna be sent optimization, psychoanalysis and |
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36:10 | . Okay and so um so this going to process here quickly. So |
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36:17 | . We already know that. Right the difference here is we're not looking |
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36:20 | antibodies as the opposition member complement. so competent with buying and then the |
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36:27 | figures that excel will have a receptor the compliment to be able to bind |
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36:34 | engulfing. Okay psychologists so this is a gram negatives are more susceptible because |
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36:41 | negatives had that outer membrane right? positive has a pepper pike and layer |
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36:47 | these things don't form very well in . So more so in and out |
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36:53 | the olympic by their which is what be surrounding gram negative. Okay and |
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36:58 | they activated complement brings together these other components. 789. Don't worry about |
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37:05 | . The numbers. But what they is they form this tunnel. All |
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37:09 | in the membrane so basically like a a hole into the cell contents leak |
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37:16 | . Okay But he and gram negatives more susceptible to this. The in |
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37:22 | of information uh we can trigger interact mast cells and causes the cytokines that |
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37:30 | be part of the inflammatory response. So again all three effects uh the |
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37:37 | no matter how it's actively. Uh And again inside a long process |
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37:43 | companies activated the sustaining kind of deactivates . Uh and um it's likely uh |
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37:51 | degraded. And so more company needs be produced in your body was producing |
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37:57 | again he's just floating around your There's like 20 of these, there's |
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38:00 | of in your blood in its active . And then when activated, more |
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38:05 | more these effects can occur. But guess so compliments not a cell but |
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38:11 | it's protein factors. Okay. Um questions. Yeah. Mike and ike |
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38:18 | things they cause license in Michael effect down here. Yeah. Right, |
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38:28 | these C9 C9 complement factors come together this to form a polymer, basically |
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38:37 | a straw. It's probably pumped inside thing. Yeah. So obviously this |
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38:44 | work against viruses. Yeah. I think it's that's I think it's |
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38:50 | student for um something we look at like this. Yeah. Right. |
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38:57 | . Oh yeah, I guess they penetrate a pepto black hand layer very |
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39:02 | to get to the inter membrane of positive, which is why gram negatives |
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39:06 | more susceptible to this. Mhm. Well they do that I guess when |
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39:15 | could have the optimization effect perhaps uh inflammation effect in response. Hello, |
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39:26 | are other options. So what's the of using policies? So, gross |
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39:33 | I don't know, it's just I know if there's an advantage disadvantage I |
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39:37 | optimization can potentially be more effective against Can be more effective against maybe more |
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39:49 | , optimization guessing. Um but it's just it's an arsenal of |
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39:57 | Yeah, auctions it's options. All . Right. Trying to deal with |
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40:02 | kinds of things to be thrown You write viruses, gram negative gram |
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40:06 | , Porta zones, big worms, know, you name it. So |
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40:11 | have to have lots of options for things. Right. Good for |
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40:15 | You know? Um Okay, so . We talked about this before in |
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40:22 | context of Chapter six on viruses. , so host resistance mechanisms. Right |
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40:30 | we'll mention that again but then we'll another interferon type that we didn't talk |
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40:34 | . But remember the type one which did talk about before. That's the |
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40:40 | . So, so remember that the Type one Year from now on will |
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40:51 | help the initial effect itself, but will help others surrounding it. |
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40:57 | so um the uh the viral infection the infection itself can induce expression of |
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41:06 | interferon um likely as the virus is to his replication cycle, borrowed proteins |
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41:14 | things can be can be uh detected uh you know, receptors or other |
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41:20 | in the cell and that acts as activator too to promote expression of |
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41:29 | And so um so then this affected will release interference. It will diffuse |
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41:35 | into the surrounding tissues he sells with receptor for interfering will bind to |
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41:43 | take it in and then it acts a transcription activator to express these different |
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41:51 | proteins which you can either degrade viral as it infects or otherwise block expression |
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41:59 | viral genes. Okay so uh so type one this antiviral. Okay. |
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42:06 | uh only the cells that have not been infected uh well will be |
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42:13 | Okay. This guy here is likely to succumb to the infection but this |
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42:18 | in any other neighboring cells to be . So um The type one interferon |
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42:27 | was discovered 40 years ago and was of the first um biotechnology products that |
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42:36 | mass produced using comment D. A. Technology etcetera. Um But |
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42:43 | didn't turn out to be the wonder that was hoped to be still effective |
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42:50 | people still do in impossible. viral infection are given can be given |
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42:58 | injections and and it can work but not a type of drug suited for |
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43:04 | in a pill form or something like on the shelf that you can buy |
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43:07 | the counter and it doesn't have a long lifetime shelf life is not |
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43:11 | Um but it's it's it doesn't work at high doses either. So and |
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43:18 | toxicity level combined with the instability. for something that's not a good over |
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43:25 | counter products like an aspirin or something that so but it does have like |
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43:30 | said it does it is given treatment a viral infection and so it works |
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43:35 | better in individuals. Giving him a and kind of you know controlling those |
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43:40 | kind of thing. Uh and uh with acute viral infections. It's not |
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43:46 | that's good for long chronic type long effects but for immediate type of |
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43:52 | Yeah it can be quite effective. The type two is one that says |
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43:59 | of these that activates cell types so activates your different specific cell types. |
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44:05 | , neutrophils. Okay and again so here by increasing the self antigens on |
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44:11 | surface. Okay that will um so that the self antigens on these famous |
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44:19 | types can allow them to present antigen the body. So if they produce |
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44:24 | of them then potentially they can it our ability to to to show engine |
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44:28 | the body. And so that again a it's good for us because it |
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44:34 | you know enhance the ability to to um if there's an infection that it |
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44:39 | more readily show that too uh immune cells in your body. Okay which |
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44:44 | what you want to kind of enhance ability right to you know, head |
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44:49 | the infection before it gets too Okay hopefully Um uh Any questions about |
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44:57 | ? Yeah. To those are little read subtext that also find effect to |
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45:05 | that I don't know I don't know . Good question. I didn't I |
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45:10 | seen anything about that. Uh Like not gonna say it's your fault but |
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45:17 | just don't know. So like can just apply that type one and call |
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45:22 | a day or considerate possibility? You in terms of? Okay I guess |
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45:27 | missing I understood you. Are you that? Does this Apply the type |
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45:34 | ? Uh Yeah I don't it shouldn't don't don't let that cloud your You |
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45:40 | that was better than the other. do that because certainly they both have |
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45:44 | functions. 1 1 is an antiviral so that's certainly something you want. |
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45:50 | other one is not an antiviral it's a activated function constitutional functions. |
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45:58 | one of them is just a immune . The other one is an antiviral |
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46:02 | . Uh Well yeah it's all it's immune response because the virus is |
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46:06 | Right so um both immune responses but different functions within the immune immune system |
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46:17 | . So what's the purpose of trying to activate you make those guys more |
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46:23 | acidic that makes them more able to just and get rid of potential pathogen |
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46:30 | the type of was just locked down to his death basically. I don't |
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46:35 | if I don't get that. I there's just two different functions. One |
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46:38 | antiviral itself, they get infected with virus can produce the interferon. Um |
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46:44 | that's how it's produced by a virus cell produces the type of line. |
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46:49 | Um just two different functions for two uh huh. Parts of the innate |
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46:56 | system defense. Um Alright so fever think that's the last of our innate |
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47:04 | system functions before we go into that system. So uh fever of course |
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47:12 | adjusting the hypothalamus. So um so course you know that you're body's set |
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47:22 | right? So um you maintain your at a certain temperature right? So |
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|
47:27 | us it's 37 C plus or minus a degree. Okay. And some |
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47:33 | us have slightly lower core body temps looks slightly higher, some somewhere in |
|
|
47:39 | . Um But it's uh fear is about putting a temporary increase in your |
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47:47 | point. And by doing that you create effects that can be detrimental to |
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47:53 | infection infectious agent. Okay. And uh the chemicals that can the newspaper |
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48:00 | call pira jin's pyro fire generate gen , generate heat, fire. So |
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|
48:08 | and endogenous. So exogenous pyrotechnics um those that are occurring infectious agents, |
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|
48:15 | , bacteria. He's funny, it be uh Michaels Michaels on their surface |
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48:22 | It can be certain types that they . Um But once in the body |
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48:27 | the body they can induce indoctrinates, bones. Okay. And so interleukin |
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|
48:34 | mentioned before is one of those. so it can uh directly act on |
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|
48:38 | hypothalamus. So analogy is if it's outside, you're gonna get to your |
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|
48:45 | , turn the heat on and so can warm up, right? So |
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|
48:49 | know that you come in the you're shivering cold, you turn the |
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|
48:54 | up. Are you gonna be immediately ? No, you're gonna be you're |
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|
48:59 | still have the chills until you get that temperature, right? Because the |
|
|
49:02 | doesn't heat to your temp instantaneously. ? So um it takes time for |
|
|
49:08 | house to warm up, right, you will catch up that tempo and |
|
|
49:13 | better right now. Cool. You just right receiver, let's just go |
|
|
49:18 | the example here. So here is regular set point again, plus or |
|
|
49:23 | half a degree. And then uh increasing the temperature set point, |
|
|
49:30 | As what happens in a fever, are new set points, maybe something |
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49:33 | 38-40 somewhere in there. And so body is gonna feel cold because you're |
|
|
49:38 | there yet. You haven't cut off , that new set point. But |
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|
49:42 | you do, you don't feel but you don't feel great because your |
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|
49:46 | is not meant to uh it is meant to operate Optimally at 38, |
|
|
49:53 | , 40°. Okay, so even though at temperature now, you cut |
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|
49:57 | you don't feel great, as we know. Okay, so, uh |
|
|
50:02 | once you catch up. But realistically kind of let it go through, |
|
|
50:06 | oscillate between hot and cold because you're fighting the infection. And so maybe |
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|
50:13 | jin's will kind of go up and down a little bit, then maybe |
|
|
50:16 | back up and down a little So that kind of reflects a slight |
|
|
50:20 | and increase in fall in your in set point. And so you alternate |
|
|
50:25 | between being hot and cold. And so um once you have I |
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50:33 | that fever we call breaking the right? You get back to your |
|
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50:37 | set point and you're gonna feel warm course until you get down to that |
|
|
50:42 | than temperature. So what does all this do? What does the body |
|
|
50:47 | do? Okay, Well it's about the growth of the pathogen. |
|
|
50:53 | so uh pathogens, you grow pathogens the lab grown at 37°, right? |
|
|
51:01 | um if you elevate temp that will their growth rate. Okay, so |
|
|
51:08 | all about really buying time. That buying time concept works both ways |
|
|
51:15 | can work for us and against Okay, so from this perspective, |
|
|
51:22 | body temp buys us time. It's for our immune system to catch |
|
|
51:27 | Okay. The other side of that a pathogen that's hiding itself from the |
|
|
51:34 | system. Right? When we talk phase variation, right? You can |
|
|
51:38 | their formulary antigens now, the immune can't see it. That buys it |
|
|
51:43 | . And buying it buying time as can grow during that interval before it's |
|
|
51:47 | out. Right? So buying time the thing that works can work for |
|
|
51:51 | against us. Okay. So um in terms of increasing uh the adaptive |
|
|
51:57 | response to t cell activity. the T cells as well, we'll |
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52:03 | certain types of really instrumental in controlling whole that that government response. |
|
|
52:09 | And so if you increase their you're going to mobilize your adaptive immune |
|
|
52:13 | . That's right. And so you , fever is is kind of a |
|
|
52:17 | for like all hands on deck. get everybody involved. And so uh |
|
|
52:23 | turns out is also an important factor terms of growth to the microbe, |
|
|
52:29 | pathogen. So, iron of course lots of functions particularly for micro we |
|
|
52:35 | know in terms of uh the whole system and iron as a component in |
|
|
52:40 | respiratory enzymes of microbes. For of course the hemoglobin is probably one |
|
|
52:46 | the number one iron users uh to oxygen. We of course have lots |
|
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52:51 | enzymes that use iron. So important us as well. So we try |
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|
52:55 | hold on. So we have chemicals produce that enable us to hold on |
|
|
53:00 | our for example. Okay so but to actually have chemicals that can grab |
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|
53:07 | the iron. So it's like we're fighting for it in some cases. |
|
|
53:12 | but certainly iron. So the combination high temp and trying to keep iron |
|
|
53:17 | from them will lower limit their And so um again all about buying |
|
|
53:24 | so we can our adaptive immune system catch up and the adaptive immune system |
|
|
53:28 | some time to work. Um So beaver. And if we have to |
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|
53:35 | any questions, yeah, We've heard 40°. Um But that again is the |
|
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53:46 | of pathogens and you don't even need have um um Yeah I'm not |
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53:53 | I guess it goes above 40. not good because there is a limit |
|
|
53:57 | don't want to go too high either that can be detrimental obviously. And |
|
|
54:00 | that can be a combination of the of pathogen, particularly if it's infecting |
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|
54:06 | If it's a central nervous system, like meningitis can be in a in |
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|
54:12 | area where it's very close to his . So that that may be a |
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|
54:15 | why he gets so high potentially there the proximity and throwing out these pirate |
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|
54:21 | . That combination can be one that trigger a very high attempt which you |
|
|
54:27 | want that at that point, you to that's that's obviously dangerous. So |
|
|
54:31 | now there's certain kind of depends on pathogen type and where the effects on |
|
|
54:34 | body that kind of. Alright, let's wrap this section up for the |
|
|
54:41 | , we were just talking about all um So we'll talk really about um |
|
|
54:58 | into a little bit of the adaptive system. Chapter 25. Just kind |
|
|
55:01 | overview and then just a little bit antibody um structure. Okay, structure |
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55:09 | function and then we'll finish up the on Wednesday. Okay. Yeah. |
|
|
55:57 | right, so um let's see what got. So anybody can help facilitate |
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|
56:02 | psychosis. That's correct. That's the process. Um Remember the complex that's |
|
|
56:09 | by activated compliments factors. Uh different of one protects against. That's the |
|
|
56:17 | one compliment is not to sell its factors. So it's going to be |
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|
56:23 | . Okay, um so let's see questions. So here's the different |
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|
56:31 | We went through an innate immune Um My questions. So let's go |
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|
56:39 | adaptive immune system. So um the specialized lymphocytes or T cells and B |
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|
56:51 | and antibiotics. So let's look at very basic question here. Okay, |
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|
57:00 | system. Cell type most likely to with these extra sailor bacterial pathogens is |
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|
57:06 | So um like we saw some cell of the innate immune system. There |
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|
57:15 | also a differentiation in the exact immune in terms of pathogen types and how |
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57:23 | deal with them. Okay, so data being system is broken down that |
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|
57:29 | in terms of this. This side with one type. This side goes |
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57:33 | the other type because they can come kind of two types, so to |
|
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57:40 | . Make sure this is extra Yes, correct. Okay. |
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|
58:16 | So we have listed here the types would deal with extra sailor would be |
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|
58:22 | that we have listed are those that these. Okay, there's antibodies okay |
|
|
58:33 | anybody's are Y shaped proteins, various . And so what we have on |
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|
58:40 | list here the thing that produces those plants with B cells. Okay so |
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|
58:46 | toxic T cells will learn not today next time they deal with infected cells |
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|
58:52 | to natural killer cells but in a way baseball fields are more destructive produced |
|
|
58:58 | they don't really um directly kill things interference, antiviral. So interstellar |
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|
59:08 | Um So as mentioned the uh but doesn't mean system into dealing with 1/2 |
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|
59:18 | with exercise of pathogens. One with of passes. So human immunity and |
|
|
59:24 | mediated immunity. So cell mediated immunity the realm of various T cells. |
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|
59:31 | the hero community B cells. And the the specific types so B cells |
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|
59:39 | developing the plasma cells. This is form that produces um antibodies. Ok |
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|
59:45 | have memory cells. So vaccination um to infectious agents will first exposure to |
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|
59:56 | agents. First exposure to vaccine will production of both of these B cell |
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60:02 | . Okay uh plasma cells of course antibodies produce and secrete antibodies and then |
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|
60:11 | they will bind to exercise or So antibodies cannot work go inside of |
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|
60:15 | cell and buying a virus based. they worked on the outside of the |
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|
60:20 | . Um the social media community you t cell types. There's various t |
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60:29 | types and as you go through this I really kind of just narrow it |
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|
60:34 | and because there are many different types T cells of what I'm gonna be |
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60:38 | about. Okay. Um just to it kind of not so complicated. |
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60:43 | right because immunology is a very complex . Very interesting but unless very |
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|
60:50 | Okay uh do recommend if this is interest that we do offer immunology of |
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|
60:55 | I think every other semester here. And you can really get down into |
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60:59 | the details because it can be a complicated subject. Um It involves not |
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61:04 | not only do many B cells have but so too the T cells. |
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|
61:09 | so and there's also a learning curve these cells. It turns out that |
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61:14 | produced upon first exposure get better at they do. Okay so that's for |
|
|
61:20 | sides both T cells and B cells way. So it's a very can |
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|
61:25 | very complex but nonetheless obviously interesting Um So I'm just kind of giving |
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61:31 | don't see a watered down version but not the more complex version. Um |
|
|
61:37 | so T types. So you're sort toxic T cells are those that can |
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|
61:43 | out infected cells. Um You have t cells called t. Helper cells |
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|
61:49 | these um interact with cell types to them typically. Okay. To t |
|
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61:57 | type ones. Well 1st of all cells interact with MHC molecules. Okay |
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|
62:03 | different the differentiation of um functions between two types are based on the types |
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|
62:09 | MHC molecules that recognize. So start toxic t cells recognize MHC one. |
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62:14 | they're gonna interact with basically your body , skin cells, liver cells |
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|
62:20 | Okay because you're making your body cells what have these types of molecules. |
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62:25 | any of your body cells that potentially infected can be found out by side |
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62:31 | the toxic t cells and these will those cells. Get rid of. |
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62:34 | don't want them. Okay she helped one and two interact with MHC type |
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62:40 | molecules. And as you find on , dendritic cells and B cells. |
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62:46 | Actually then th-1 cells interact with This stands for antigen presenting cells this |
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62:53 | with with dendritic cells and um uh Okay. Release of cytokines activate |
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63:01 | That kind of thing. T. interact with B cells. So even |
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63:06 | cells that can be activated. Okay certain T helper cells help activate |
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63:12 | Okay so the division of labor among different t cell types interacting with different |
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63:18 | types. Okay causing different effects. . Um and so as I mentioned |
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63:24 | about buying this buying time idea. um so your definition system relies on |
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63:32 | detection. So it's all about Right? It's predicated on uh the |
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63:38 | of anti do. Okay and so about detection, recognition and binding. |
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63:48 | . And then that binding affects a sort of output whether it's release of |
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63:55 | by that lymphocytic cell protective antibodies. happened? So it's a kind of |
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64:02 | four step process. And that's the the time element because that those things |
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64:07 | occur like that. Okay. That's adaptive immune system the slower right takes |
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64:12 | to to to do these steps. . But nonetheless once it does kick |
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64:16 | it's very effective. Okay so um talking about binding recognition and binding. |
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64:25 | that's all about binding of in this looking at antibodies. Right, so |
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64:33 | structure has that y shape to Okay, I want to talk about |
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64:38 | of those in a second. So an example of bacterial cell and uh |
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64:44 | is buying. So energy. So can be literally almost anything. |
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64:50 | when you think about um for a that's potential pathogen in your body, |
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64:55 | is your music themselves? Gonna Let me see what's on the |
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64:59 | Right, so a an LPS layer a gram negative uh capsule perhaps of |
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65:06 | pathogen, a pepper like can uh types of molecules sticking on the |
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65:14 | Right? Glycoprotein? Like lipids, have you? Okay so all these |
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65:18 | potential antigens. Okay and so so kind of two viewpoints here in terms |
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65:24 | the binding. Okay so we have to an energy. Right? But |
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65:31 | Epic Tope is within the engine. the episode is actually where the actual |
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65:37 | occurs as we see here. All . So the gray area here's the |
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65:43 | . The red is the actual spot it binds. That's what we call |
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65:47 | episode. Epic Tope smaller binding occurs of the larger. Okay okay. |
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65:56 | . And so and it can also you don't have to be a bacterial |
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66:00 | . It can be a virus can a protozoan and it can be what |
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66:04 | can be appalling. All right all things are antigens that can produce an |
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66:09 | . Okay um Now in terms of structure of antibodies. Right so again |
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66:15 | kind of wide shape but there's actually subjects here. Um We call heavy |
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66:21 | light change. You can guess what is. Right. So that's based |
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66:25 | size and heavy chains, bigger. chain smaller. Of course you have |
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66:31 | sulfide linkages holding it together. Uh you have different binding sites. Okay |
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66:39 | the classes. So I G. for immunoglobulin. I am a Okay |
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66:49 | now you know you have what are engine and binding sites you have two |
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66:53 | those minimum per antibody we'll see that um antibody types can actually come together |
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67:03 | form polymers. Ok so I G for example can can put two of |
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67:08 | together to form something that looks like it's. Okay so it actually has |
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67:20 | 121234 per molecule if you will per er Okay, it forms a dime |
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67:30 | Um IgM can form a Pentagram That makes 10 binding sites. So |
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67:35 | can happen with those two types of . Okay, um now the there's |
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67:42 | another binding site which is down Okay, so of course antigen binds |
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67:49 | these two sites. Okay, you there? Okay, at the |
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67:55 | but this site down here can be to a particular cell type. |
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67:59 | You have to have the receptor. we talked about optimization. Right? |
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68:03 | is how it happens this side buys pathogen. This side binds to the |
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68:10 | or neutrophils. Right? And brings the optimization process. Okay, um |
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68:19 | , uh in terms of the more , so more technology really. So |
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68:25 | I G uh so we have two molecules and one high G G. |
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68:31 | , so how can you, at molecular level distinguished these I G G |
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68:38 | from I G A s. How can you determine if an idea |
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68:42 | an idea? A right was all criminalizing sequence of various regions here. |
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68:48 | , so you have what are called types? Okay. Which differ in |
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68:54 | heavy chains? Okay, so an G A will be the same in |
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69:01 | um uh constant regions. Right, , idiot types. So I G |
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69:05 | media types. Okay, will be , similar the same in these heavy |
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69:15 | regions. Right? Um But they differ in the Andean binding sites. |
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69:21 | can be the same but they can you produce you can't just ig antibody |
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69:25 | the same engine, they'll all be same. Right? Same heavy region |
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69:29 | managing body sides. But they can be I. G. S. |
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69:33 | different antibiotics sites. Okay. Excuse . But the constant the but what |
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69:41 | them all together as being IJ is the same in this area here. |
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69:46 | course I G differs in that All right. So there is a |
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69:50 | type. Okay so you have a D E. M. Aisa |
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69:55 | Okay. And so um so that's differentiates these classes. So the Intertype |
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70:01 | within the class. Okay. And the ice A type are the different |
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70:06 | . Okay. Um The main question that. Okay so um video types |
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70:16 | an ice type. So ice you can have multiple media types. |
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70:21 | . That differ in antibiotic sites. . Um So if you look at |
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70:28 | , what happens when you have antigen fighting? What are the consequences of |
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70:34 | ? Right. So here's one we illumination clumping basically what this is clumping |
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70:43 | . So um but basically what you're is because anybody's have two binding sites |
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70:50 | can clump together multiple what they're calling units? Right, infectious unit could |
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70:56 | a microbe. Of course. And uh what you're doing is you're |
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71:02 | the number of effects just you So here you see 123 pathogens on |
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71:08 | own maybe three separate microbes. But clumping or illumination reaction with antibodies basically |
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71:16 | them into one unit. So easier the body to deal with. |
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71:20 | That's why your I. G. . Alright. That can form that |
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71:26 | inform the my pen is not working . Can form the dime. Er |
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71:32 | , you can have four binding sites diamond. Uh Gm can have |
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71:37 | So that can really clump together a of units in the ones that's why |
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71:40 | very effective in that function. observation. We already know about |
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71:46 | Right neutralization. So that's what the vaccine produces neutralizing antibodies. Okay. |
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71:55 | so what that does is basically coats pathogen. Okay. And prevent it |
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72:00 | adherence adherence to cast into your tissues very often a virulence factor. They |
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72:08 | be able to do that. Obviously can you can see that the virus |
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72:11 | need to do that because step one recognize host. Buy into it and |
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72:15 | entry into it. Right? So you're if you're blocking that through the |
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72:19 | neutralizing uh antibodies then you effectively are reducing the capacity of the virus that |
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72:27 | infection or or battery but also remember toxins produced many patterns produce toxin tetanus |
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72:35 | botulinum toxin etcetera. These are dealt also by antibodies that bind because the |
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72:42 | needs to also bind to a target . Get inside and cause damage. |
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72:47 | if you can not allow it to by putting everybody's on it, then |
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72:51 | effectively neutralized the toxin. Okay, of complement. Already talked about |
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72:57 | Right? So that that's the effect antibody binding. And then this we |
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73:01 | about as well early last time. the in the in the context of |
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73:07 | function of fields, right center field deal with large pathogens, multicellular types |
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73:15 | this. So something like this to bring this down. It takes a |
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73:19 | effort. Right well, 11 cell this is likely not going to be |
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73:23 | a lot of damage. She brings lots of immune system cell types to |
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73:28 | it down. That's what this antibody cell mediated toxicity. Way too many |
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73:35 | . Um 80 cc uh so we antibodies introduced to the passenger binds two |
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73:45 | . And then remember the fC portion to a cell continue receptors. So |
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73:51 | can have those can be found on macrophage on fields. And so it's |
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73:57 | way to kind of bring them together the large pathogen here. And then |
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74:04 | response by the cells is to release of different types of different types of |
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74:08 | chemicals to kill the pathogen. But point here is using hand buying to |
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74:13 | all these cells together right on top the pathogen because it's so big, |
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74:18 | gotta get to bring all these cells and their toxins to kill it. |
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74:23 | again, all effects of potential effects antibodies find it. Okay. |
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74:31 | you need questions biography, just like , visible. How? Oh |
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74:41 | they're not. They're not, they're , but they're not that big. |
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74:44 | parasite. Yeah. The large parasite could be it could be visible to |
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74:50 | it up. Yeah. At first could be okay, all different than |
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74:59 | . Okay, so it's like strategy . Okay. Yeah. Thanks |
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75:09 | See you on |
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