| 00:09 | Yes. Yeah. Sure. Um. Mhm. Oh, |
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| 00:36 | folks. Um it's going to get . So we are um near the |
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| 00:44 | . 12344 more after the day, it 3.5. It's probably about |
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| 00:53 | I think we'll see. Um, , so another full week, next |
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| 00:58 | , um, last Tuesday and then closed, um come back and two |
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| 01:07 | sessions. And so, uh let's , the um, so we're |
|
| 01:13 | we're, we're a little ahead of . So we're gonna get into um |
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| 01:21 | today, not all of it, a little bit and then, uh |
|
| 01:25 | start this chapter 25. Uh All right, again, not all |
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| 01:33 | it, but, and I, I posted, uh, I posted |
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| 01:36 | video lecture for this, this Ok. Um, so, uh |
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| 01:43 | means, you know, we this may be half a, half |
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| 01:48 | class or something, I don't know the end. But point is we |
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| 01:52 | plenty of time, right? Um right. So, uh, |
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| 01:57 | that weekly quiz, I realized that set the due date for today instead |
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| 02:01 | Monday. So no big deal. you got today to finish it. |
|
| 02:07 | , um, but we'll be, be back on the regular Monday if |
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| 02:11 | don't screw it up again. Friday, the Monday schedule, |
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| 02:15 | weekly quiz eight. So we got more of those quizzes after today. |
|
| 02:21 | , smart work a couple more of yet to come. And, |
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| 02:26 | oh, I forgot to put in , um, well, exam |
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| 02:31 | Ok. I did post the distribution that on canvas. So the average |
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| 02:36 | like a 73 something. I So. Uh anyway, the highest |
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| 02:44 | average so far in these exams. but again, within the range and |
|
| 02:48 | to get, you know, within plus or minus. So we've pretty |
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| 02:53 | been hitting that. Um Anyway, we got one more to go, |
|
| 02:58 | ? Uh Exam four. So remember not comprehensive, it's just, you |
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| 03:02 | , 23 24 25 and 26. . So, uh what else we |
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| 03:09 | um any questions or anything, questions? OK. So, um |
|
| 03:18 | do a little bit of recap. right. So we are um in |
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| 03:25 | midst of uh the immune system, ? We started with innate immune |
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| 03:30 | what you're born with and physical chemical . Uh uh we started with the |
|
| 03:43 | immune system last time. And so remember the main thing there is stimulated |
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| 03:51 | antigen. OK. That's the biggest . OK. So remember that stimulating |
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| 03:58 | via antigen means it has to recognize detect it um bind to it and |
|
| 04:05 | create an effect. OK? And halves of that system, B cells |
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| 04:11 | T cells, humeral sub media rely on that. OK. They |
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| 04:16 | work on their own. And so a big part of this are other |
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| 04:22 | types we've talked about before. Um Your antigen presenting cells, |
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| 04:29 | Macrophages, genetic cells play a role as well. OK. Presenting antigen |
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| 04:36 | these cell types, particularly T right? Um B cells also have |
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| 04:41 | have involvement of T cells. To activate them. And we'll talk |
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| 04:46 | that today. So, um so again, innate immune system that immune |
|
| 04:53 | , you gotta deal with different pathogen , right? Intracellular ellar. So |
|
| 04:59 | how you have specialized cell types, killer cells can deal with infected cells |
|
| 05:04 | one way. Your um cytotoxic T we'll talk about can interact in another |
|
| 05:10 | . Uh But then you have to with extra cellular pas. And so |
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| 05:15 | got antibodies that can, that can with them by activating B cells. |
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| 05:19 | got neutrophils, macrophages, dendritic cells phagocytosis. So, um uh so |
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| 05:28 | know, kind of remember the the types involved in these things. |
|
| 05:32 | Uh And so, you know, , right? So what's an |
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| 05:38 | An antigen is basically anything that can the immune system that can be protein |
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| 05:43 | nature, carbohydrate fat. OK. The um the uh um pollen, |
|
| 05:52 | more things you get, you're allergic or may be allergic to, these |
|
| 05:56 | can activate your immune system. And so I remember the the uh |
|
| 06:00 | between antigen and epitope is really just , right? The antigen is the |
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| 06:05 | entity within that is where it actually and that's the epitope, right? |
|
| 06:11 | the EP is basically the binding part the antigen. OK. Uh then |
|
| 06:16 | into a little bit of a right? Um The, the uh |
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| 06:21 | the idiotype and isotype, OK. so isotype R, the uh A |
|
| 06:33 | uh M E E and A That's it A G MD E. |
|
| 06:43 | right. OK. So these are . OK? And so these are |
|
| 06:50 | by what this area looks like. region. So all A's have a |
|
| 06:55 | same constant region makeup. So do and GS et cetera, right? |
|
| 07:00 | that identifies the isotype within an Um You'll have different a antibodies that |
|
| 07:11 | different engines. OK? We call idiotype a idiotype. For example, |
|
| 07:17 | combined the X engine, this a the Y engine, they're different idio |
|
| 07:22 | and they differ of course on what's here. OK. That's where they |
|
| 07:28 | , right? So you change up variable region, you can bind different |
|
| 07:33 | . Uh And then finally, we with uh this diagram, the what's |
|
| 07:38 | result of this binding of body? . Multiple things can happen as this |
|
| 07:45 | shows you right? Clumping a glutin uh optimization coding the patent facilitating thy |
|
| 07:54 | neutralization, keeping it from attaching to surface, right? Um activating |
|
| 08:01 | right. And then this one which is about really dealing with large |
|
| 08:06 | . And so antibodies can be used bring cell types to the, to |
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| 08:12 | um to the pathogen. And then to, to slay a large pathogen |
|
| 08:20 | a collective effort, right? You're gonna have a single macrophage, uh |
|
| 08:25 | capable of ingesting this thing, It's too big. You have to |
|
| 08:28 | lots of cells and then they collectively chemicals toxins to kill it. |
|
| 08:34 | And the attraction there is having the on the pathogen and then that allows |
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| 08:41 | binding of various cell types, So remember the this right here that |
|
| 08:48 | part of the antibody, OK? is where it can bind? So |
|
| 08:53 | I think that any questions about any those. OK. So let's look |
|
| 08:59 | this question here. All right. gonna, we're gonna get into a |
|
| 09:02 | bit about functions, features of specific types. OK? Um And we |
|
| 09:12 | listed for the five here G AM D. OK. So I'm looking |
|
| 09:20 | the incorrect match. No. And you're looking at this, so I |
|
| 09:42 | through the chapter again myself, chapter . There's a lot of details of |
|
| 09:48 | in there. We're not going to into all that stuff. OK? |
|
| 09:51 | complicated, right? I suggest if find it interesting, take the immunology |
|
| 09:56 | . OK. And which we OK. Uh but we're not going |
|
| 10:00 | all those details. So don't worry that. It's kind of more surface |
|
| 10:08 | you will. OK. OK. count down here. OK. |
|
| 10:28 | this is a pretty easy one. , it's um IgG that doesn't match |
|
| 10:33 | . What looks like this was IG is what does that? Not IG |
|
| 10:44 | , not IgG. OK. So let's look at some of these various |
|
| 10:49 | here that so um IG A this the one that forms uh neutralizing |
|
| 10:58 | right? Uh COVID vaccine uh in these kinds of uh antibodies. |
|
| 11:05 | the um especially respiratory pathogens, respiratory are very often need to attach to |
|
| 11:16 | cells of your respiratory system, throat, et cetera. And uh |
|
| 11:22 | remember the mucosa, right? So have the mucosal surface which is a |
|
| 11:26 | barrier but then you have the mucus uh that it produces, that contains |
|
| 11:32 | can contain the antibody. OK. uh the percentages here you see are |
|
| 11:38 | the percentages in blood. OK. you can see that there's not a |
|
| 11:42 | of this circulating in the blood because in the mucosal secretion. So by |
|
| 11:47 | there, they combined the pathogen and the dimer function increases the binding sites |
|
| 11:54 | four, right. So by doing we can buy, it can bind |
|
| 12:00 | and then it keeps it from right. And so that's an important |
|
| 12:04 | for many respiratory pathogens is to be to stick to your mucosal membranes. |
|
| 12:10 | . Um Cold virus COVID uh Lots of different types. OK. |
|
| 12:19 | The IG MS, those are I call it the five headed |
|
| 12:25 | OK. Which actually makes it have 10 binding sites. OK. |
|
| 12:29 | , jump the gun IgG is OK. Um IgG. So it's |
|
| 12:35 | , at its highest in the 35%. It's, it's uh I |
|
| 12:39 | it a work course, antibody has different functions. Um It's the type |
|
| 12:44 | is produced in the highest levels, of in the, in the, |
|
| 12:48 | the secondary part of the um And uh you, you typically began |
|
| 12:55 | IgM antibodies first, then followed up IgG at much higher concentrations. |
|
| 13:02 | So they have a number of different . OK? Um And they're your |
|
| 13:07 | ones that do a lot of um that of immunity functions in terms |
|
| 13:13 | an antibody. OK. The uh . So you have two types D |
|
| 13:18 | E work on top of the They don't, they're not free floating |
|
| 13:24 | you will. OK. So uh cells, that's how they actually interact |
|
| 13:29 | engines through antibodies on their surface. . Um And so that's why they're |
|
| 13:35 | really low concentrations in the blood because a B cell mostly lives in your |
|
| 13:42 | system, not in your blood. so that's why, and that's where |
|
| 13:45 | gonna find IgD molecules. OK. And so basically binds engine in that |
|
| 13:53 | . And this thing, it can to various effects that we'll see. |
|
| 13:58 | . IgM, that's the five headed the pimer, right? Five of |
|
| 14:05 | stuck together. Now we have 10 sites in one unit. OK. |
|
| 14:11 | these are the first kind of antibodies produced, whether it's um vaccination |
|
| 14:17 | through uh initial vaccination or through the time you have an infection. |
|
| 14:22 | These typically are the ones that are in large amounts. OK. So |
|
| 14:27 | it does? So this is the clumping. OK. So they take |
|
| 14:33 | multiple units here, we can call one, you know, each, |
|
| 14:37 | infectious unit uh is, is then together by nine GM. And |
|
| 14:44 | so we're basically taking it from 10, uh how many that is |
|
| 14:49 | one infectious unit? So basically, take them all together much easier to |
|
| 14:53 | with. OK. Um So one the things that we don't get into |
|
| 14:59 | that your antibody producing cells go through , go through a learning curve |
|
| 15:06 | OK. The initial response to the antibodies you produce are not super |
|
| 15:14 | not the best. It, it better over time. OK? Upon |
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| 15:19 | exposure to the engine, the, B cell produces better binding antigens. |
|
| 15:24 | so a good immune response is equates really good binding between antibody and |
|
| 15:32 | OK. And so these IG MS form initially aren't super great at |
|
| 15:38 | OK. But what they, what make up for my lack of maybe |
|
| 15:43 | aspect is that they can do this comping thing, right. That's, |
|
| 15:48 | an important function to really um concentrate pathogens into one unit that can be |
|
| 15:54 | with. Right. So that's an function initially later on, right. |
|
| 15:58 | get better, uh and, and switch to IgG types that have gone |
|
| 16:05 | the school, so to speak, become a better antibody. OK. |
|
| 16:10 | you know, there's molecular reasons why all happens. So it's a |
|
| 16:13 | that's when you can get very very quickly. But just kind of |
|
| 16:17 | that the initial antibodies you produce actually better. OK, in terms of |
|
| 16:22 | binding function and immune response. Um And so the IgEs like the |
|
| 16:33 | sit on top of the cell, types, typically mass cells, basal |
|
| 16:36 | , remedies are involved in the inflammatory . OK? These kinds of |
|
| 16:42 | uh synthesizing cytokines of different types, ? And so the um uh you |
|
| 16:50 | , those that have a allergic this is typically due to hyperactive cells |
|
| 16:56 | are binding these pollens or mold spores whatever your the allergen is to um |
|
| 17:02 | basically kind of an inflammatory response, ? And what's the outcome of |
|
| 17:06 | Well, watery eyes, um you know, typical um kind of |
|
| 17:12 | things. But, you know, from that, we do have a |
|
| 17:15 | in inflammation and uh immune response. . But again, E and D |
|
| 17:22 | on top of the cell. That's of how they do their thing. |
|
| 17:26 | ? Um Now, OK. So look at a little bit about BC |
|
| 17:30 | function. So as we get into , I'm gonna show you um a |
|
| 17:35 | of things and I gathered from other sources but uh not for the purpose |
|
| 17:40 | me actually testing you on it, just to kind of help you understand |
|
| 17:46 | this works. And it's really the between the, the tea dependent uh |
|
| 17:54 | by A B cell and the T response. OK. So you can |
|
| 17:59 | OK. What's that about? And , I have some additional things that |
|
| 18:04 | will help uh help you understand. . So uh anyway, so the |
|
| 18:10 | , so you have B CS or of cell you got in your body |
|
| 18:17 | are not all genetically identical. And so the um uh most of |
|
| 18:26 | your cells are except the games, ? Are genetically same DNA equivalent, |
|
| 18:31 | ? Gametes aren't but B cells too bezels have a segment in their genome |
|
| 18:36 | recombines. OK? And that ability you to form antibodies to I think |
|
| 18:46 | said like 10 of the 13 different which means you can respond to lots |
|
| 18:52 | different potential engines out there. If your B cells conform by recombining |
|
| 18:58 | genetic segment that makes antibodies, the sites, you can produce uh an |
|
| 19:04 | variety of antibodies with, with various sites that can allow you again to |
|
| 19:11 | respond to lots of things that are there. Ma many times things you |
|
| 19:15 | want to respond to that leads to responses. But um but nonetheless, |
|
| 19:19 | a good thing. OK? So how this happens is OK, you're |
|
| 19:26 | have a pool of selves, B in China. And this is just |
|
| 19:34 | simplified, obviously, very simplified, showing four different B cell pools |
|
| 19:39 | right? 1234, OK? You'll thousands of these. OK? And |
|
| 19:45 | uh upon initial exposure to an whether it's vaccination infection, OK. |
|
| 19:52 | that's shown by the red dots here the antigen. OK? So 11 |
|
| 19:59 | your one pool of your B cells recognize this. OK? This example |
|
| 20:05 | number four. OK. So they bind to the antibodies on top |
|
| 20:09 | the B cell. OK? And then is what we call the, |
|
| 20:16 | B cell pool. Number four recognizes um cognate antigen we call it, |
|
| 20:24 | , it's what this pool of B binds to. Is that one particular |
|
| 20:29 | type? OK. Uh The result that binding is to then increase the |
|
| 20:37 | of that, that specific pool of . OK. And so basically, |
|
| 20:45 | mitosis, right? So we're gonna that's clonal expansion, right? We |
|
| 20:50 | out this group because they're the ones responded to that and then they, |
|
| 20:55 | stimulates them to be to divide. ? And So you create this identical |
|
| 21:01 | of B cells never respond to that energy. OK. In the |
|
| 21:09 | to differentiate into two types memory cells plasma cells. The plasma cells are |
|
| 21:13 | actual ones that form antibodies. Memory cells don't. But what they |
|
| 21:20 | , they, they survive in your for decades. You have memory cells |
|
| 21:25 | your body that we, well, yet, you don't, but I |
|
| 21:29 | . They're like 40 years old. . And so uh that's what their |
|
| 21:34 | is to, they'll, they'll remember energy. OK. So at some |
|
| 21:40 | , you get another exposure to that engine, then these memory B cells |
|
| 21:46 | produce more memory cells and plasma OK? And so that's the nature |
|
| 21:55 | how your memory cells work. And so plasma cells live whereas these |
|
| 22:01 | memory cells live a long time. are maybe 60 days. OK? |
|
| 22:07 | plasma cells go away. OK? can produce more if you need to |
|
| 22:11 | exposure to antigen. But um but plasma cells don't hang around |
|
| 22:17 | A couple of months. OK. um now the thing is how, |
|
| 22:24 | we get this activation, right? so there's two different ways to activate |
|
| 22:30 | Visa. OK. And one is we call t independent. OK. |
|
| 22:39 | kind of in a nutshell to, activate a B cell, no matter |
|
| 22:43 | type of activation you have to cluster , what's called A B. Cr |
|
| 22:55 | BC R stands for B cell stands this B cell receptors. BC R |
|
| 23:02 | short. OK. So you can how this polysaccharide here is contacting multiple |
|
| 23:14 | . I'm sorry, antibodies on the and they're gonna cluster together and that's |
|
| 23:19 | activate. OK. And so that's for something like a polysaccharide, |
|
| 23:27 | Or a nucleic acid or a right? Because these are very repetitive |
|
| 23:35 | , right? Think of starch, ? Just glucose, string of |
|
| 23:39 | right? So uh all possessing the epitope binding site, right? So |
|
| 23:45 | antibodies can all collectively kind of cluster in that scenario. OK. And |
|
| 23:50 | will activate it. OK. And the t independent doesn't work that |
|
| 23:59 | OK. And so if we look here, here's a antigen and they |
|
| 24:04 | this kind of clustering together capping. ? And but by doing it, |
|
| 24:09 | you're activating this B cell, But if it's a protein antigen, |
|
| 24:18 | . Proteins vary right? Amino acid , it can vary. And so |
|
| 24:24 | it can't typically cluster lots of antibodies the surface to activate the B cell |
|
| 24:32 | . OK. You have to get involvement of A T cell. |
|
| 24:37 | So what happens is the B cell actually internalize antigen as well and then |
|
| 24:44 | it to the surface using the MH molecules. OK. Like so |
|
| 24:49 | And then that can attract a T , we call a T helper actually |
|
| 24:54 | helper type two. And that's, then this binding, activate it So |
|
| 25:00 | get the release of cytokines. And among those will be types that |
|
| 25:07 | the B cell. OK. So I just want to show you kind |
|
| 25:12 | uh a couple of slides I OK. So activating a B cell |
|
| 25:17 | T cell help, right? So polysaccharides like coypus nucleic acids. So |
|
| 25:22 | have in common, very similar uh of repetitive structure which can cluster a |
|
| 25:30 | of antibodies on the surface of the cell. OK. And then activate |
|
| 25:35 | . But the thing is this isn't , a strong, a strong immune |
|
| 25:41 | . OK. So what I mean that is you don't get, you |
|
| 25:46 | plasma cells that produce antibodies, you get memory cells from that. |
|
| 25:51 | So there's a term called immunogenicity, means kind of like strength of response |
|
| 25:59 | you will and protein antigens by you be the strongest response. |
|
| 26:04 | Tight binding uh equates to uh the of A T cell to help activate |
|
| 26:09 | B cell. Uh Those kind of do lead to both plasma cell proliferation |
|
| 26:18 | memory cell. OK. Stronger immune with protein antigens. OK. Um |
|
| 26:26 | again, t independent, this is that has to happen. The antigen |
|
| 26:30 | big, you know, apply it's a big molecule and you can |
|
| 26:34 | multiple antibodies on the surface and cluster , activating the cell. But what |
|
| 26:38 | lose is the lack of memory cell . OK. So, conversely with |
|
| 26:48 | , proteins cannot crossing multiple B cell , right? So you see how |
|
| 26:54 | looks here, right? Red is protein engine. OK? So we |
|
| 26:59 | to get involvement of a B cell the process. OK. That was |
|
| 27:03 | active help activate it. OK? you produce a stronger response because you're |
|
| 27:08 | , activating both plasma cell production and cell production. OK. So that's |
|
| 27:14 | you know vaccines of course, are of the protein parts of viruses and |
|
| 27:21 | . Because for that reason, it a stronger response, not always because |
|
| 27:28 | the pneumonia vaccine, for example, made from the capsule which is which |
|
| 27:32 | polysaccharide. So sometimes you know, have to make compromises because it's a |
|
| 27:37 | part that's the most active in terms immune response. But when you |
|
| 27:42 | you try to construct these vaccines that proteins, they give the strongest responses |
|
| 27:47 | China. Um So again, these these pictures only for informational purposes kind |
|
| 27:55 | is any questions about that? Do depend? Do you independent? |
|
| 28:00 | So I mean, if I had , you know, put a number |
|
| 28:04 | both these, I would say probably most common is the t dependent mode |
|
| 28:09 | involving a T cell. OK. OK. So here again, |
|
| 28:18 | This is the T dependent dependent right? So the B cell acting |
|
| 28:23 | an engine presenting cell, right? antibodies on the surface that bind. |
|
| 28:30 | . But also internalizing. OK. showing that on its surface and involving |
|
| 28:38 | T helper cell um to activate it then the activation leads to using plasma |
|
| 28:46 | producing memory cells. OK. Um . So any questions about that? |
|
| 28:56 | . So as you again, when get into the book, it's gonna |
|
| 28:58 | you a lot of stuff there. kind of, you know, certainly |
|
| 29:02 | I read it, go ahead but of put the brakes on it a |
|
| 29:04 | bit and just kind of use these stuff as your guide as you go |
|
| 29:09 | it. OK. Um Right, look at this question here. So |
|
| 29:16 | the um diesel activation is, you , this is the crux of the |
|
| 29:24 | immunization response. Yeah. Sure. All right. Let's count down from |
|
| 30:16 | . Pretty sure it will be a dunk. Yep memory cells, of |
|
| 30:21 | . OK. So you build those , create those basically in the primary |
|
| 30:27 | and now they're kind of primed and to go upon a second exposure. |
|
| 30:32 | . So um the uh so when look at this and again, this |
|
| 30:40 | , remember the learning curve for cells make antibodies, right? So initially |
|
| 30:46 | initial exposure to antigen, whether through or through um vaccination, OK. |
|
| 30:52 | gonna produce uh B cells making IG you know, the PTA meric |
|
| 30:58 | right, not super strong binding, they have that ability to clump |
|
| 31:04 | right? Multiple pathogens. Uh But you produce uh more and better and |
|
| 31:12 | when they switched to IgG. And so there's a term called the |
|
| 31:18 | cells that's responded to the antigen. made IG MS those same B cells |
|
| 31:26 | what's called class switching. And that switching from M to G and |
|
| 31:31 | those GS are much better binding antibodies , produced in higher amounts as you |
|
| 31:39 | your red versus blue lines. And so um of course, you |
|
| 31:46 | a booster shot to kind of increase bank of um uh memory cells. |
|
| 31:53 | , and to that initial second they're really primed, ready to |
|
| 31:57 | You have a much quicker response. see the time frame is longer here |
|
| 32:02 | the initial primary response and shorter in secondary response. For that reason. |
|
| 32:08 | cells are ready to go. So um obviously, it's the basis |
|
| 32:14 | vaccination. Um OK. So uh questions about that? OK. All |
|
| 32:26 | . So let's look at T cell . OK. And so again, |
|
| 32:31 | , I'm only describing really kind of in the generic fashion, uh cytotoxic |
|
| 32:38 | cells, uh T helper cells uh two types. There's many, there's |
|
| 32:44 | than that. OK. That your goes into. Uh I'm just focusing |
|
| 32:48 | kind of the, the main so to speak, that produce |
|
| 32:53 | the, the, the main OK. Um The uh and they |
|
| 32:59 | , they also refer to II I the word learning curve. The book |
|
| 33:03 | the word naive naive B cells. are the ones that are kind of |
|
| 33:08 | the learning stage and so naive to , right? So going going from |
|
| 33:13 | to 1 level to the next, that learning curve of being a better |
|
| 33:18 | producer if you will. OK. so uh so the two class |
|
| 33:23 | So remember that distinction, right? your M ac class ones are on |
|
| 33:29 | body cells, right? Skin liver cells, et cetera. |
|
| 33:34 | Class twos are these macrophages, dendritic . B cells, very small |
|
| 33:40 | OK. So you have T cells interact different T cells interacting with each |
|
| 33:45 | , right? And that distinction is to the type of MH C |
|
| 33:51 | OK. Uh But then also they um have what's called a co |
|
| 33:58 | . OK. And it's the co that recognizes that the cell types. |
|
| 34:05 | C class. OK. So what mean by that is the CD eight |
|
| 34:12 | the class one. OK. You here, the four recognizes the class |
|
| 34:21 | . OK. So um so what the two C cell types of each |
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| 34:27 | ? Cytotoxic T cells recognize MH C which are gonna be cell your skin |
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| 34:34 | , liver cells, et cetera. a reason to recognize those is when |
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| 34:39 | infected, right? So you have virus infected liver cell, potentially a |
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| 34:44 | T cell may find it and be to deal with it. OK? |
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| 34:50 | A at helper cell of one type another recognizes these three cell types |
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| 34:58 | And we saw that with B the T helper cell helps activate |
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| 35:02 | And that's what they do. When interact with these three cell types, |
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| 35:06 | activates a macrophage, activates a dendritic activates a B cell. That's kind |
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| 35:11 | the role of those guys. So let's look at cytotoxic T cells |
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| 35:17 | . OK. And so again, with intracellular pathos, right? So |
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| 35:21 | how natural killer cells look for infected that have a different pattern of MH |
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| 35:30 | molecules on the surface like you lacking them typically. So that looks |
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| 35:35 | . So it deals with deals with from that aspect, the cytotoxic T |
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| 35:39 | a little different. It's through the of antigens being presented to them, |
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| 35:47 | ? Through these M ac class one on the surface. OK. So |
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| 35:53 | infected cell, the virus is going its cycle, right, copy genome |
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| 36:00 | proteins, some of these proteins can bound to MH C molecules and then |
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| 36:08 | to the body. And that's where cell can find it interact with |
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| 36:12 | And then it goes OK. this was, this is a virus |
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| 36:17 | cell, get rid of it, ? No, you don't want |
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| 36:20 | you don't want to be carrying those . So it it basically either either |
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| 36:27 | sticks these things called Kerins Perin right? Create holes in the surface |
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| 36:35 | little protein tunnels um and or induce . So cic T cells release, |
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| 36:43 | full of various chemicals they release and . If you recall is a |
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| 36:52 | all of your cells can go into those cells become damaged or just old |
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| 36:58 | don't function very well. You want get them out of the population, |
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| 37:02 | you tell them to go kill themselves . And that's what apoptosis is. |
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| 37:06 | them out of the population if you've been sunburned and you, your skin |
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| 37:12 | ridden and flakes off, That's basically . Your, your body is getting |
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| 37:17 | of those dead skin. They're killing skin cells because they've been mutated through |
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| 37:22 | , light exposure, right? get rid of them, right? |
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| 37:25 | , uh so it's a normal thing your cells to do, but sometimes |
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| 37:29 | in this way, they can be to do it when needed. |
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| 37:34 | Um OK. So your t helper of two types, right? The |
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| 37:41 | ones interact with macrophages, dendritic OK? And they uh you |
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| 37:49 | a number of functions, one of is to activate when you activate a |
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| 37:52 | or dendritic cells. So, you know, these little arms we |
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| 37:56 | here, right? These in more these means it's better at theo |
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| 38:04 | right? More arms out here you bind uh potential pathogen engulf it, |
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| 38:10 | it up, right? And so having more of these is makes it |
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| 38:16 | at doing that, right? So you activate it, basically creating more |
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| 38:20 | those arms, if you will OK. And this gives you a |
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| 38:25 | . This picture gives you an idea in the upper left corner, think |
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| 38:31 | one like a like a rose, rose bud that hasn't blooms, |
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| 38:36 | The flower petals become quite visible. similarly here, the these folds you |
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| 38:42 | here these activated cells that represents the of more of these pseudo pops, |
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| 38:49 | ? So it's better now, better to fatties, but it's all closed |
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| 38:54 | with no arms sticking out. That's something that's gonna f fo very |
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| 38:58 | So you got to activate it and , that's what this process does. |
|
| 39:01 | ? One of the things, you , it can also by throwing out |
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| 39:05 | of kinds of different types, you of course induce these other effects, |
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| 39:10 | activation information, et cetera. So remember cytokines is that catch all |
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| 39:16 | for a number of different molecules I bring about different immune responses. |
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| 39:23 | Um So then activating a B right? This was the th type |
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| 39:30 | , OK. B cells. And just saw that the tt dependent |
|
| 39:36 | OK. Um OK. Any So again, you know, when |
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| 39:43 | go to the book, you oh my God, this, this |
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| 39:45 | is going to way more detail than Knapp did, right? Don't worry |
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| 39:49 | it. OK. So I'll just to the level that I'm showing |
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| 39:53 | OK? Um OK. So let's book, doesn't talk about this. |
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| 39:59 | which I thought was kind of but I don't think it's not gonna |
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| 40:02 | a, it's not complicated. In , of course, I'm gonna show |
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| 40:06 | , I guarantee it's gonna be 100% close. Ok. So, |
|
| 40:11 | so reading from the top down you're go read it this way? |
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| 40:17 | So which of these represents vaccination? . A box, B box C |
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| 40:23 | or D box? Ok. Huh. Oh, that's why, |
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| 40:44 | know why they open the pool. haven't done that in a while, |
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| 40:51 | I've lost my mind completely. All right. Sorry about that. |
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| 41:13 | . Mhm. Oops. Not Yeah, they, yeah. |
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| 41:27 | Ok. Cut down from 20 most answered. Let me up a little |
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| 41:33 | 10, 9, I say Correct? Ok. That pretty |
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| 41:46 | Uh, over 99%. Yeah, gonna be c OK, let's look |
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| 41:55 | b the second one. Then we'll summarize this here. Open that |
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| 42:02 | Ok. Yeah. Ok. So baby, uh, getting his |
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| 42:12 | Ok. By the mother. Obviously , do, do continue. |
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| 42:46 | Get enough for 10. Yeah, right. So obviously as everybody clearly |
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| 43:02 | , um, so naturally artificially, , artificially acquired and it's gonna be |
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| 43:06 | a shot, right? So, , certainly vaccination fits that, |
|
| 43:12 | naturally acquired through getting, just getting infection, right? That's gonna |
|
| 43:17 | uh, naturally acquired active immunity would , you have an infection and you |
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| 43:23 | immune to it. Ok. So act of passive is is your body |
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| 43:27 | making the antibodies or are you being the antibodies on a platter? |
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| 43:33 | That's passive. So obviously a baby the mother's milk requires antibodies. Um |
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| 43:40 | is not doing anything. It's just them from fully formed from the |
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| 43:44 | right? Uh but it's natural, ? You know, getting mother's milk |
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| 43:48 | a natural thing, not artificially Uh Some of the vaccination is |
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| 43:53 | that's artificial acquisition, but active, in response to that vaccine in that |
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| 44:01 | , you're actively producing an immune And so artificially acquired passive immunity. |
|
| 44:07 | would that? What would that You can, you can get |
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| 44:12 | I think people that have a, have a, they were hospitalized with |
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| 44:16 | pretty bad viral infection, I believe get a shot of IG GB uh |
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| 44:22 | antibodies to that pathogen. And then course, is artificially acquired passive, |
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| 44:27 | being given to a shot, fully antibodies to the, to the |
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| 44:32 | So, um anyway, the, four different descriptions here. OK. |
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| 44:41 | Many questions about that. Clearly, everybody got these pretty much knows |
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| 44:45 | OK. Not hard to figure So let's do a little bit of |
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| 44:50 | a little bit about, not about , but let's do this question first |
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| 44:55 | wrap up this section. We'll talk little bit about vaccines. OK? |
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| 45:02 | me time to read that the OK. OK. Let's count down |
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| 45:56 | five. Um OK. Um All . B cells can directly kill, |
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| 46:09 | right, start from the top. A is true. I mean, |
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| 46:12 | , that's what the the two sides the system do, right? Um |
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| 46:17 | B cells can differentiate in antibody syrop cells and memory cells. Um C |
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| 46:24 | not consistent, right? So a clonal population would not produce antibodies to |
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| 46:33 | different. That would be one right? So that engine comes |
|
| 46:38 | stimulates one pool of B cells and those all respond by producing antibodies to |
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| 46:46 | that one antigen. OK. So wouldn't be this, OK. Um |
|
| 46:53 | would be correct if it said to single isotope, epitope, not |
|
| 46:59 | Um But DD is true because T hydrox T cells, they can um |
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| 47:07 | an infected cell, right? But cells, B cells themselves don't really |
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| 47:12 | that. They can have antibodies, ? So, B cells can produce |
|
| 47:17 | cell types can produce antibodies that have effect, but a B cell cell |
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| 47:21 | really kill anything. OK. Um questions about that time. All |
|
| 47:30 | So again, so this wraps up 20 chapter 24 we're gonna talk a |
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| 47:36 | bit about uh vaccines and we talked this already, the uh response, |
|
| 47:44 | secondary response. And so of vaccination is based on that obviously. |
|
| 47:50 | so, um and I think we at this before as well. So |
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| 47:54 | immunity of course, is based on , having enough of the population vaccinated |
|
| 48:01 | protect those that are not vaccinated. so uh this table here, read |
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| 48:06 | , read it as kind of a a reproductive value maybe for the particular |
|
| 48:13 | , right? And so this value really how, how transmissible, how |
|
| 48:22 | it is. OK. So what means is, let's say a person |
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| 48:25 | mumps um can transmit or infect 4 7 other people in the area in |
|
| 48:33 | vicinity. Uh One with measles 12 18 and much higher transmissibility. |
|
| 48:42 | And so um obviously, if it's ability to be more contagious, |
|
| 48:49 | That number rises more contagious, then gotta have more people vaccinated. So |
|
| 48:55 | , threshold is 70 75% or above be able to protect people that aren't |
|
| 49:04 | . Uh But it goes up as disease has become more contagious. |
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| 49:10 | Because it spreads faster and more people infected per person that's sick that you |
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| 49:14 | to up the levels of vaccination in because remember, the vaccinated people act |
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| 49:20 | sinks to absorb the the infecting keeping the others protected that aren't |
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| 49:26 | So it's a very, very contagious . You better up the number of |
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| 49:30 | that are vaccinated to maintain that herd . OK. So, vaccines, |
|
| 49:37 | your book kind of puts it into categories. Um uh live uh itinerary |
|
| 49:46 | . OK? Um Killed, sorry, killed vaccines. A base |
|
| 49:53 | , killed vaccines or killed organisms. . The vaccine um subunit which are |
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| 50:00 | , parts of the uh infectious Um and then um the acid, |
|
| 50:08 | . Um I kind of expand a bit on that, but we'll look |
|
| 50:12 | the, the, the major groups . OK. And so you'll see |
|
| 50:15 | there's a, there's variability in terms immune response with some vaccines as well |
|
| 50:23 | the breadth of immunity. So the vaccines stimulate both humeral and cellular immunity |
|
| 50:35 | all of it. OK? And see differences. And so the first |
|
| 50:42 | , these live attenuated vaccines. So remember we talked about this way |
|
| 50:47 | in day one, right? Attenuated to um make it non virulent. |
|
| 50:54 | ? But still able to replicate. . That's what a liter vaccine can |
|
| 51:00 | . OK? And so this is what you're producing in that process. |
|
| 51:08 | . So the key here is a competent. OK. So we can |
|
| 51:15 | the cell, not period a viral cycle, but infect it. |
|
| 51:20 | And that cell can show antigen to body, right? And so |
|
| 51:27 | in two ways, the antigens out , right can stimulate antibodies. B |
|
| 51:35 | production, right? But then they infect a cell and then show |
|
| 51:41 | And that's how T cells get So you're now you're activating the whole |
|
| 51:46 | immune system. That's why these um to be the best ones in many |
|
| 51:52 | . OK. But the because basically like a, a, an uh |
|
| 51:59 | infection. OK? Uh But you want to give that vaccine to, |
|
| 52:05 | why you have to have different Um You wouldn't want to give it |
|
| 52:10 | an immunocompromised person. Maybe somebody is chemo, let's say, or otherwise |
|
| 52:17 | . Um Because you know, they could, it could become |
|
| 52:22 | the live alternative organism could become active an immunocompromised patient. OK. So |
|
| 52:28 | tend not to give these types to , you have alternatives for them. |
|
| 52:32 | ? But again, it gives you strongest kind of uh immune response. |
|
| 52:37 | . Uh And so examples of that , and you have to memorize the |
|
| 52:42 | . OK. But you know the measles mumps virus um vaccine. I'm |
|
| 52:48 | . Um we were all vaccinated with kids. I'm sure um the shingles |
|
| 52:55 | I think is that way flu. . So number of ones you may |
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| 53:00 | taken are in that category. Now, for the heat killed or |
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| 53:07 | killed, they call it in It could be through chemicals through, |
|
| 53:12 | temperature goodness, chemicals, temperature. you can see different examples here. |
|
| 53:19 | metal ions, freezing, heating, cetera radiation. OK. So basically |
|
| 53:26 | , your um in activating the So it cannot replicate, right? |
|
| 53:31 | it won't replicate in a cell. it's a viral type, it won't |
|
| 53:35 | a cell. So that means it's only going to going to activate your |
|
| 53:40 | cells, your humor. OK? it's acting as a extracellular pathogen, |
|
| 53:47 | ? It's not able to infect if a viral vaccine. It stays |
|
| 53:51 | And so that's where your antibodies come . So it's only gonna really stimulate |
|
| 53:56 | um B cells. OK. Um tend uh not to also, they |
|
| 54:05 | produce some memory cells but not as as, as other types. That's |
|
| 54:09 | you have to get booster shots more more frequently. So booster shots basically |
|
| 54:15 | the production of more memory cells and differentiate into plasma cells. So and |
|
| 54:21 | all, you know, I know , you have to have a booster |
|
| 54:24 | every 10 years or so. Um , other ones uh maybe not as |
|
| 54:29 | but uh boosters to keep that memory cell population up. OK. Um |
|
| 54:37 | in the vaccine. So um these are gonna be comprise parts, fragments |
|
| 54:46 | the pieces of the pathogen that produce immune response, right? So, |
|
| 54:53 | basically, OK? Um And there's ways to do that. OK. |
|
| 54:59 | One of them is to just simply it up if you will. And |
|
| 55:04 | this is what becomes the vaccine. ? It's right here, right? |
|
| 55:12 | You could take the gene that produces antigen, OK? Clone it, |
|
| 55:19 | ? And as you see here and put it into a vector, |
|
| 55:24 | And then let that bacteria, for , express it. You need to |
|
| 55:28 | a lots of vaccine that way. . That's gonna be a more economical |
|
| 55:33 | than doing this. OK? Um literally to do the fractionation, you |
|
| 55:40 | have to grow up lots of your . OK? And then just digest |
|
| 55:45 | . OK. Here using gene you can really control how much you |
|
| 55:52 | . Lots of cells express, you a lot more quantity. Um So |
|
| 55:56 | it's, it's better. Um the DNA RN A and DNA vaccines, |
|
| 56:04 | . COVID vaccine, right? R an RN A vaccine basically injecting RN |
|
| 56:09 | and that's am RN A message and message contains a sequence for the spike |
|
| 56:15 | I think in COVID. OK. it goes into a cell that cell |
|
| 56:20 | transcribes or doesn't transcribe translates right? then the um engine goes to the |
|
| 56:27 | , it can show it to the . OK. Stimulating your immune system |
|
| 56:32 | become a vector vaccine that is taking , a whole virus for example and |
|
| 56:42 | his genome. OK? And such you take out the factors to make |
|
| 56:51 | non virulent. OK. But able express the particular viral proteins, |
|
| 56:59 | That produce the immune response. And with something like that, this can |
|
| 57:03 | the cell but not but not cause to it. But enable the transcription |
|
| 57:11 | of the viral antigen that can then be shown to the body and stimulate |
|
| 57:18 | immune system. OK. So um the the other, the J and |
|
| 57:26 | uh COVID vaccine was was of that . OK. Um what we call |
|
| 57:32 | like particles. So these are think these as like a hollow shell if |
|
| 57:38 | will the P PV P PV the vaccine for human papilloma virus |
|
| 57:44 | causes a cervical cancer uh is made something like that. And so the |
|
| 57:51 | covering here is the captured the P virus. Um So that is, |
|
| 57:58 | it's empty inside, it's hollow. it's the capsule, that's the actual |
|
| 58:02 | seat in your body. Immune system to that capsule, the captured the |
|
| 58:08 | . OK. Um The uh remember uh we focus a lot on |
|
| 58:17 | whole organisms or the virus or, or bacterium and the engines it |
|
| 58:22 | I remember toxins also are produced produced by many of these and you |
|
| 58:26 | have vaccines to toxins. So Tus shot is a Toxoid counteracts the |
|
| 58:33 | of the toxin. OK. Um . So other types here um the |
|
| 58:44 | nucleic acid vaccine, we talked about , but we're gonna, I'm gonna |
|
| 58:47 | for the next time. We'll talk the little more detail about this. |
|
| 58:51 | uh I remembering vesicles, some of aren't as common but you see |
|
| 58:56 | the men Meningococcal uh vaccine. This , this is a capsule. |
|
| 59:03 | Uh Or this one here contains a uh antigens shown there. And so |
|
| 59:09 | we look at um polysaccharide vaccines, is of that type. So like |
|
| 59:15 | pneumonia vaccine um uh is is of , the, the capsule is the |
|
| 59:22 | that activates the immune system. So sugars don't generally produce a strong |
|
| 59:28 | . OK. And So that's why call it intermediate affinity antibodies. So |
|
| 59:34 | don't bind strongly. So you get response but not super strong. |
|
| 59:40 | You can boost that up by adding protein to it. That's what conjugated |
|
| 59:47 | do. OK. And so uh will then allow you to involve T |
|
| 59:53 | uh into the, into the right? So you can activate humeral |
|
| 59:58 | uh CME immunity. OK? Which typically stronger. OK. The very |
|
| 60:03 | add protein to, to the, the vaccine. If it's of |
|
| 60:08 | of a chemical nature, that's sugar fat, for example, adding a |
|
| 60:13 | to it will make it strong. . Um The I think, |
|
| 60:20 | let's do this real quick. And I'm gonna go into more details on |
|
| 60:25 | the COVID vaccine next time and, the new COVID vaccine that's out. |
|
| 60:29 | But here is uh so again, , in this case DNA, the |
|
| 60:35 | example, we have a plasmid, . And the plasma would have the |
|
| 60:41 | as part of the vector and injecting muscle right here. They have this |
|
| 60:47 | of dramatic called a gene gun. . Um Basically injecting a solution to |
|
| 60:55 | and the plasmid contains the gene for antigen and inject it into muscle |
|
| 61:01 | Muscle cells are multinucleate. OK? so you get a lot of production |
|
| 61:10 | um uh as as the plastic gets , right, transcription translation in that |
|
| 61:16 | cell and a lot of production of OK, that then your body's immune |
|
| 61:22 | can't respond to, right. um the, the RN A vaccines |
|
| 61:28 | course, are MRN A, as mentioned earlier and you can get a |
|
| 61:31 | good um response because you actuated both and sailor immunity. OK. Um |
|
| 61:39 | , the engines, the engines themselves , are synthesized. They make them |
|
| 61:44 | around in the, in the body and that stimulates B cells and then |
|
| 61:50 | cells can take it and show it the, to the T cells. |
|
| 61:53 | that's how you get both, both of that activated. OK. Um |
|
| 61:59 | so the common vector vaccines, very common. Uh One here is |
|
| 62:04 | adenovirus. Uh uh it's a DNA that has been uh manipulated to not |
|
| 62:13 | it infectious. OK? Or rather make it virulent. OK? It |
|
| 62:17 | still infect but not, not go its viral cycle. OK? But |
|
| 62:23 | you fiddle with the genome and you in the, the uh gene for |
|
| 62:27 | antigen. So as the virus infects cell, then that antigen is produced |
|
| 62:34 | inside the cell and can stimulate the response by showing it to the |
|
| 62:41 | OK. Um So that's what the , like I said, the, |
|
| 62:46 | , the, the J and J was of that type. Um And |
|
| 62:50 | others are in that kind of same . Um Any questions. So you |
|
| 62:56 | off the Erie. Uh we'll, any questions, we'll finish up um |
|
| 63:04 | and then go into uh, chapter . Thanks |
|
