| 00:05 | Mhm. Hey folks, welcome. can't have class outside today. Um |
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| 00:17 | uh this down a little bit. right. So today we are uh |
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| 00:26 | gonna get 24. We just start little bit last time. Um So |
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| 00:32 | get through most of that about the . OK? But not, we |
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| 00:38 | finish all of that. So we'll will carry over into next Tuesday. |
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| 00:43 | I did that a little late but uh the video for the um 25 |
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| 00:49 | is on next Tuesday is available. sorry about a little late on |
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| 00:54 | but it's available. You can look that beforehand. Um And so uh |
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| 01:01 | you haven't already, so our exam tomorrow. Ok? So if you |
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| 01:05 | last minute questions, you know, free to email or you can drop |
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| 01:11 | . Um Let's see. Uh So we get to on the horizon very |
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| 01:18 | is microbial diseases. So um the way to approach that stuff is really |
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| 01:28 | make a, I would say make cable for yourself. OK. And |
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| 01:32 | an example of that in the notes 26. Um You know, it's |
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| 01:37 | opinion is me that, that most , that chapter 26 because you have |
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| 01:43 | know a disease, disease, what it? What are some of the |
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| 01:47 | things about it so forth? Uh elaborate as we get closer, but |
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| 01:52 | to give you a, a heads on that, uh, and then |
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| 01:55 | to remember that exam four, although can call it a final exam, |
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| 02:01 | it's only going to be covering this . It's not comprehensive. OK. |
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| 02:08 | uh and you've got, I guess a month until that happens. |
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| 02:13 | uh lots of time yet. So what else um any questions about anything |
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| 02:21 | particular? OK. So let's just bit of a recap, right? |
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| 02:27 | kind of uh let's see. Um obviously, we're talking about our immune |
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| 02:35 | , right? We started with innate system, right? And all those |
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| 02:43 | , different cell types involved cytosis. uh what else? Uh complement |
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| 02:52 | um inflammatory response. Um Mhm I think that Interferon, I think |
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| 03:02 | touches all the bases there. uh so we consider that kind of |
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| 03:07 | and 2nd line defenses now in like third line, which is uh very |
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| 03:15 | . So number, first and foremost this right antigen, right, presence |
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| 03:21 | antigen. So gotta recognize it, it, recognize it bind to it |
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| 03:28 | in effect the curve, right? why we call the adaptive immune system |
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| 03:31 | for that reason. OK. And um I, I think I mentioned |
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| 03:36 | time that as we get into this goes into a lot of detail |
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| 03:42 | OK? On. And because it's complicated, it, it, |
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| 03:46 | it, it, it, it be nothing but detail and it's very |
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| 03:51 | system. OK? So I'm only you a, don't wanna say water |
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| 03:59 | , but you know, just kind the basics the to give me kind |
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| 04:02 | OK. This is how it operates know that there's other layers of |
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| 04:07 | And so we only talk about a types of tt cells, for |
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| 04:11 | there's many more than, than what telling you. Um So, you |
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| 04:16 | , but, but that's OK, don't need to get into the details |
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| 04:20 | everything. All right, you may it interesting. So if you |
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| 04:25 | you want to learn more and the course is um offered, I think |
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| 04:30 | the fall semester, I believe. So there you get all the details |
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| 04:36 | if, if you, if you that. Uh but it is |
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| 04:38 | it is a fascinating system. So it's a a cell type um B |
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| 04:45 | as we'll learn in, in a bit not super detailed, but these |
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| 04:51 | have segments of your genome that rearrange recombine because they produce um antibodies. |
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| 05:00 | . And so you have the ability recognize almost any kind of engine that |
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| 05:05 | not there. You can something like to the 14th, different types of |
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| 05:10 | they can make of different antibodies. so 10 to the 14th, that's |
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| 05:14 | big number, right? So you imagine all types of ans that are |
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| 05:18 | there, right? And, and just in terms of a microbe but |
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| 05:23 | and right, we eat and floors this and all can serve as a |
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| 05:28 | well. So anyway, um so briefly this um so the two |
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| 05:35 | right? And um so, so that kind of differentiation here, cellar |
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| 05:44 | . Um And with cytotoxic T cells pathogens, OK. Um But we |
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| 05:54 | have uh other T cell types that job dealing with other cell types, |
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| 06:01 | cells and micro that predict cells. that's another kind of part of the |
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| 06:05 | . OK. So, um so talk a little bit about, but |
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| 06:11 | we're gonna start with a question So about question about antibodies. That's |
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| 06:19 | we're gonna start. OK. So a look through these. OK. |
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| 06:24 | there's some terms you're gonna go through epitope. Uh OK. OK. |
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| 06:36 | Antibodies finding antibodies. So uh what reading this um the types of |
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| 06:46 | Um So in terms of chemical right, you can have protein |
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| 06:53 | you can have carbohydrate, you can fat lipid based antigens. OK? |
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| 06:59 | the all the biomolecules, you can of the basic types, those you |
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| 07:03 | , those typically make up the structures an antigen which and uh so as |
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| 07:11 | might imagine, you know, recognizing and embody a engine. It's gonna |
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| 07:17 | one major type of binding like binding is a big thing with an |
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| 07:21 | and embody um effects. OK. about how well is the painting and |
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| 07:28 | , that translates into a a let's it better function. OK. So |
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| 07:34 | binding peoples is a term called amino , right? How strong does the |
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| 07:41 | um induce the immune system? So it can be very strong or |
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| 07:48 | can be not so strong. And vary in terms of, of how |
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| 07:52 | can stimulate, how well they can the immune system. OK. So |
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| 07:58 | let me go ahead and turn this the and so it turns out that |
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| 08:05 | strongest effects come from protein antigens. . Um Carbohydrates less. So uh |
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| 08:12 | lipids even less. So OK. I'll elaborate a second on that. |
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| 08:20 | right. So number four, So uh let's see the um if |
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| 08:34 | antibodies have a bind epitope, that's true. So the antigen is a |
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| 08:40 | entity within the androgen. If there's actual binding in, in that area |
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| 08:44 | there, here's the epitope. That's . OK. So antibody types may |
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| 08:49 | pollen forms. That's actually true as . So I've been drawing antibodies like |
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| 08:55 | this generic form like that. They can some can form multiple types |
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| 09:04 | this, right? Like a dimer form or even in this um 2345 |
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| 09:13 | this form, OK. A So there are variations they're basically two |
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| 09:19 | , two variations, you see, some antibody types can do that. |
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| 09:25 | ? The two B sets. here and here. OK. Um |
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| 09:33 | Well, hold on. There's may a correction here. OK? Is |
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| 09:40 | , so this was very nonspecific to sites? Is that true or |
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| 09:45 | You argue that it might be more two. So yeah, this is |
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| 09:52 | binding. OK. But so too be bind here, right? If |
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| 09:59 | see that's where a cell may OK. So you could argue it |
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| 10:06 | be three, OK, three binding . Now, if it said agen |
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| 10:10 | sites getting specific right, then it would be, that would be |
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| 10:16 | . But just generic binding sites, can, there can be three binding |
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| 10:22 | , OK? Two agen and one that a cell combined to OK. |
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| 10:29 | I'll circle that temporarily see what else got immuno levels are the same as |
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| 10:33 | . Yes, that's just terminology So that means the same thing I |
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| 10:37 | is how we abbreviated immunologic. Uh Antibody classes can be identified by |
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| 10:43 | composition of their cost of because that's true as well. We'll talk |
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| 10:48 | that in a second. So as , I would say that's not completely |
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| 10:54 | . OK? As written. So , if it's specified, anybody has |
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| 11:00 | , that's mostly true. OK? of the Y shape here and it |
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| 11:04 | here and here. OK? Um even then, you know, you |
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| 11:09 | have a third one here though, ? If you're just saying binding sites |
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| 11:12 | not being specific, OK. And we can even expand that when we |
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| 11:17 | into these polymer forms right here and , right? Because that even adds |
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| 11:22 | binding sites, right? So let's let's get into specifics here about some |
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| 11:28 | these things. OK. Um All . Uh So it's all that action |
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| 11:34 | these sentences. So that's what they to. OK. And so what |
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| 11:39 | antigens? What you can imagine what might be, it's gonna be on |
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| 11:41 | periphery, right? Other virus bacterium protozoan. So remember, although we |
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| 11:47 | on bacteria and viruses, there are many other things can cause disease as |
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| 11:52 | , right? They can be ans uh proo types, even multicellular |
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| 11:57 | right? That uh occasionally affect So in any case, you're gonna |
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| 12:02 | things on the surface, you glycoprotein molecules, protein molecules out the |
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| 12:08 | of gram negative. Um So things the periphery, right? And so |
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| 12:13 | , the binding epitope versus antigen, ? So it's just a matter of |
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| 12:19 | , let's say, right, the is a larger entity within the engine |
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| 12:24 | an epitope that where the binding OK. And so this um |
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| 12:30 | right? So agen types, Chemical types, right? Protein, |
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| 12:37 | polys lipid, right, the protein peptide to these drugs and that relates |
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| 12:45 | to tight binding, right? So , OK. Um the binding sites |
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| 12:52 | sequences of amino acids, OK. because proteins in general, right, |
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| 12:58 | have a very specific shape, Per structure. They have lots of |
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| 13:05 | of even those amino acids, Humongous number of combinations, right? |
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| 13:12 | lot of variety, right? And what led to tight binding with an |
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| 13:17 | . Is that right? Um carbohydrates um uh even a acids and lipids |
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| 13:26 | less of that variation. OK. So, so proteins don't necessarily bind |
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| 13:33 | strong, right? So um proteins be the best, the best immunogenic |
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| 13:43 | , prompting the immune system, um the immune system. OK? Um |
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| 13:50 | I talk about or put in the , the proteins, carbs lipids. |
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| 13:55 | ? Now, you can make um want specifics about this but you can |
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| 13:59 | certain molecules that aren't so immunogenic like lipids and pines by often adding something |
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| 14:08 | to it, adding another molecule to , oftentimes like you add another protein |
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| 14:13 | it and that combination that makes it immunogenic. OK? Because there are |
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| 14:20 | right? That the vaccines are all can take anything and they right. |
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| 14:26 | you won't even make that as strong you can into the binding to get |
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| 14:29 | good response. And so you can some molecules that aren't, so they |
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| 14:36 | a sugar more. So by adding the market and we have vaccines that |
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| 14:42 | polysaccharide types that uh counteract like a vaccine. Uh because the bacteria that |
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| 14:49 | pneumonia, the primary one has a caption. And so we produce antibody |
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| 14:55 | it, but we make it stronger adding other molecules to it to make |
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| 14:58 | better. So anyway, those are of things tricks, so to |
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| 15:02 | you can do to make something that's so immunogenic, more immunogenic. |
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| 15:08 | Um All right. So anybody OK. So there's what we call |
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| 15:17 | and variable, right? And so class is a uh G D |
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| 15:27 | and OK. And so uh we differentiate those and that's the next |
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| 15:34 | is about idiotype and isotype. That's we differentiate these things. OK. |
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| 15:39 | of course, anybody binding site. . Up here contains variable regions. |
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| 15:45 | the B cells that make these They will have RS of their viewing |
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| 15:51 | can rearrange and rec combine and express sequences, right? And so that's |
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| 15:59 | enables you to recognize a like an number of, right? Because we |
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| 16:05 | variables, variable regions here, That can um um be specific for |
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| 16:13 | particular antigen. OK. So then have regions that basically they're pretty much |
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| 16:18 | , they're the same in terms of sequence, right? And so here |
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| 16:24 | , binding site. So antigen binding and then here's where you can bind |
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| 16:28 | F C route. So remember that's option, for example, a macro |
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| 16:33 | have an F C uh um to the option process we call that. |
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| 16:41 | so, so now we'll get into um the different types. OK. |
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| 16:49 | do you distinguish uh an I G from an I G D and so |
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| 16:53 | ? Ok. And that uh is here. So you have what they |
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| 16:58 | ID types and isotopes? Ok. you have basically five isotopes, A |
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| 17:05 | D E, yeah, or five , right? The um isotype differ |
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| 17:14 | these regions. OK. So if have a pool of I G A |
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| 17:19 | , OK. You'll have some I A s that recognize one type of |
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| 17:26 | and others that recognize a different OK? But you know they're I |
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| 17:30 | A s because they're all similar in region. OK? Idiotype. All |
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| 17:37 | . So a idiotype, idiotype. one recognizes this engine, a |
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| 17:44 | Other one recognizes that engine. So course, you're gonna have I G |
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| 17:48 | s, you recognize many different types engines. OK? Um But all |
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| 17:53 | idiotype to each other. OK? we talk about isotype. That's how |
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| 17:59 | differentiate one from the other I G nine G G for example. |
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| 18:04 | But they'll differ in these constant OK? Um So any questions about |
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| 18:17 | time I type a type? Yeah. But the same field is |
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| 18:24 | of the All right. So you have, right? So for |
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| 18:33 | these I G A idiotype could have same a bic sides but they could |
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| 18:43 | , you can have each, each type in the amount of, may |
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| 18:47 | different in the very Yeah. Oh of those. Yeah. OK. |
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| 18:54 | you're saying in one antibody, can regions be different? No, they're |
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| 19:00 | be the same. Yeah. So will be the same for. |
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| 19:05 | So in one antibody that and that the same, the sites are the |
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| 19:13 | . OK. And so that's, see that that's actually important to have |
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| 19:21 | you active, start activating the cells make them. OK. Um Any |
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| 19:26 | questions? OK. So um all . So when you have antibody and |
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| 19:33 | body, what can result from Well, we know some of this |
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| 19:38 | , right? We know about the thing. But so agglutination, |
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| 19:44 | think of gluten is basically clumping OK? So in doing so you |
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| 19:50 | have you reduced the number of infectious . So think about concentrate. |
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| 19:58 | So here you have uh we have bacteria but by clumping them, you |
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| 20:10 | bring it down to 212. I'm , that's not a one, that's |
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| 20:17 | one. All right. So this one unit and that's two, |
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| 20:21 | So you reduce the number of infectious , you gotta deal with concentrate, |
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| 20:26 | pump them up, OK? Um that's due to this fact that you |
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| 20:30 | have these um antibodies have two binding binding sites, right? So you |
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| 20:38 | continue clump them together this way. . Oops we know about that |
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| 20:43 | All right. So remember that's the C region over here. That's binding |
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| 20:49 | the cell. Um neutralization. neutralizing antibodies. So that's uh |
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| 20:55 | the uh vaccines uh against code, what they produce are the antibodies, |
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| 21:01 | code the virus and the virus can't enter, can't bind to a |
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| 21:06 | , selling it in, right. neutralizing antibodies to it does have to |
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| 21:09 | a virus. It can be a . It could be because bacteria |
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| 21:13 | pathogens, adhere to your tissues. if you can coat them antibodies and |
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| 21:17 | then they can't do that. Uh also, you know, part of |
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| 21:22 | pathogen, the salt, if you , it's not just the cells themselves |
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| 21:27 | the virus or, or bacterium, it's also gonna be toxins. All |
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| 21:30 | . So they can secrete toxins and tend to be molo are specific, |
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| 21:35 | find the target cell and bind to target cell and then get in the |
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| 21:39 | . And so if you can prevent , you know, you antibodies can |
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| 21:43 | that effect on them as well. uh the tetanus tetanus uh vaccine works |
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| 21:51 | way. Um Compliment, you know that, right. So that's the |
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| 21:58 | where a couple of activation pathways is antibody. And then um this |
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| 22:04 | So this um I will only say whole term once uh antibody dependent cell |
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| 22:13 | cytotoxic, right? Mouthful, A DC C. So basically what |
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| 22:18 | is in a nutshell is use antibodies will uh buy into the engine and |
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| 22:27 | use those antibodies to get other immune cells together to overcome this pathogen. |
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| 22:36 | this is for your large pathogens. . Multicellular types very often. |
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| 22:43 | So we mentioned that we mentioned last eosinophils in that context, they helped |
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| 22:50 | , they collectively they kind of help bring down large pathogens and this is |
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| 22:55 | they do it. Ok. So involve antibody and so they'll have a |
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| 23:00 | to bind that end and then the end binds the antigens on the |
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| 23:05 | OK. So it allows you to together you coat this parasite with these |
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| 23:10 | and that allows you to have a of cells then buying into it. |
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| 23:14 | so collectively eosinophils, all right, release toxins, right? Could be |
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| 23:20 | macrophage as well. All right. so collect it all together, then |
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| 23:25 | the toxin can help fill the So it's a way to bring down |
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| 23:30 | types of um organisms like this that you. OK. So again, |
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| 23:36 | these are occur as a result of antibody binding. OK. And so |
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| 23:43 | let's look at this question here. . So we're gonna go into a |
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| 23:48 | bit about antibody uh functions if you . OK. How do you differentiate |
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| 23:55 | from the other? What's, what's about one versus the other, that |
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| 23:58 | of thing? OK. Um And they do some do have, they |
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| 24:05 | have differentiating functions, right, in of their role in this process. |
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| 25:14 | . OK. Let's see, and looks like it's not correctly match. |
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| 25:23 | . So uh let's go for the up. So I G D only |
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| 25:29 | and back to us another cell That's generally true. OK. So |
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| 25:34 | cells, b cells actually interact with through the antibodies on their surface and |
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| 25:41 | antibodies are I G D and also G M. OK. So that's |
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| 25:47 | . Um I G M yes, one of those forms that five headed |
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| 25:54 | , if you will five antibodies coming . OK. Um I G A |
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| 25:59 | true mucosal secretions. Uh And so incorrect because that's I G A that |
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| 26:07 | this does this dimer formation, not G G I G G pretty much |
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| 26:13 | as a in this monitor form. . So, um and here it |
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| 26:21 | . All right, this is I I G eight. OK. So |
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| 26:28 | percentages, you don't even memorize these but you know, it put you |
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| 26:31 | relative amounts in um blood, And so um 15% but it's most |
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| 26:40 | it's mostly found in, in your uh mucosal surfaces and secretions of your |
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| 26:48 | , right? Nasal passages, et cetera. OK. Um And |
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| 26:54 | for many pathogens and adherence to these surfaces is very important. The meningitis |
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| 27:02 | for one sticks around in your, your throat. And so if you |
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| 27:07 | are infected and it can produce I A, it will coat, |
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| 27:11 | It can coat the uh um pathogen prevent it from, from um |
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| 27:18 | And so, by forming a you increase the number of antigen binding |
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| 27:23 | to four. OK. So you bind up more. So these can |
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| 27:29 | the effect of neutralizing antibodies. And uh your I G G much higher |
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| 27:37 | and turned in the blood. Often you refer to I G G |
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| 27:42 | kind of a workhorse antibody. It a lot of different functions. |
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| 27:47 | It's, it's um one of the ones in your response to an infection |
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| 27:54 | to a vaccine. Uh the high level production of I G |
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| 27:59 | OK. So um again, various functions, optimization compliment neutralize, neutralizing |
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| 28:07 | . So and more, OK. so um your I G DS uh |
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| 28:15 | , so I G D and I E we'll talk about in a |
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| 28:20 | Both those are types of that sit top of a cell, right? |
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| 28:23 | that's kind of where they do their . OK. So I G D |
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| 28:27 | mentioned they sit on top of blood and so their quantity in and the |
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| 28:32 | is very low because because being on of a B cell B cells are |
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| 28:37 | found in your own fat. that's for their entire concentration. |
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| 28:42 | Um But also you can find I M molecules on B cells as |
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| 28:49 | OK. Both types, right? um and here comes a and that's |
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| 28:57 | it works. So we'll talk about , that's the beginnings of how B |
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| 29:00 | becomes active through this process. Um G M. So these are typically |
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| 29:08 | first ones that are formed in first to vaccine or, or infection. |
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| 29:17 | And they form these five, these forms. And so again, like |
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| 29:23 | , you mentioned earlier, it reduces number of units, right? So |
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| 29:28 | we have 1234 by having these petro , you basically reduce it down to |
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| 29:39 | by concentrated. So uh it can dealt with. Um So uh I |
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| 29:47 | E is mentioned, they don't sit top of a B cell, they |
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| 29:50 | on top of baso fis mas these are involved in allergic responses um |
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| 29:56 | also inflammatory response. Um and so can uh the binding can initiate release |
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| 30:03 | uh cytokines from these cells. Sometimes overdo it, right? That's when |
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| 30:09 | bind some kind of allergen that you , that may give a hyper hyper |
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| 30:15 | . So that these are the effects most, I think most of us |
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| 30:19 | Houston that at some point we all allergic to something. All right. |
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| 30:24 | uh that's this is one of those to that, those effects the set |
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| 30:28 | they release dignity, inflammation, watery and all the symptoms. I'm sure |
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| 30:34 | familiar with which? Ok. Um . So those are the antibody |
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| 30:41 | OK. So producing like how, are these things produced? Ok. |
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| 30:47 | I I slightly switch the order of next three slides, I think it |
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| 30:53 | more sense actually. So we start the kind of the clonal selection |
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| 30:59 | OK. So as mentioned, you um lots of, I don't know |
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| 31:06 | quantity, but you have hundreds thousands pools of B cells, OK? |
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| 31:15 | are capable, like I said, forming an bodies 10 to 14 give |
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| 31:25 | take, right? In terms of of different engines that they could potentially |
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| 31:31 | . Remember? OK. And so what happens when and when first exposure |
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| 31:40 | whether infection vaccine um that an engine presumably will bind to one of these |
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| 31:53 | cell subpopulation. OK? It'll have antibody sitting on the surface that will |
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| 32:00 | and bind the antigen. OK? so very simple example, we we |
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| 32:05 | seeing 44 different types of B OK? So here comes the an |
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| 32:11 | red, little red dots, So which of these does it bind |
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| 32:15 | ? It binds to the antibodies on , this 1/4? OK. And |
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| 32:24 | that then that that is the clonal process because now we're gonna, we |
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| 32:30 | this one and now we're gonna make of it, right? So they |
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| 32:36 | , right? So now we're that's the tonal expansion selection, expansion |
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| 32:41 | , make more of it, And so they will all produce um |
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| 32:49 | to that specific antigen. OK. this this red thing antigen is, |
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| 32:56 | what it will produce. All produce same amount of bodies to that. |
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| 33:02 | . Um And so in the not just you can have two types |
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| 33:10 | plasma cells, which are the ones actually produce more antibodies. OK. |
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| 33:15 | memory cells, memory cells don't produce , but they uh retain the knowledge |
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| 33:22 | you will of that, right? if you see this again, |
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| 33:28 | these will then differentiate to as cells met more memory cells. So um |
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| 33:43 | the memory cells versus cells. So cells are and a lot of |
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| 33:50 | 60 days give or take OK. your memory cells have lifetimes of |
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| 34:00 | 10 years, 20 years, 30 , 40 years. OK. Long |
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| 34:05 | . OK. Um Their response, ability to recognize that androgen again, |
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| 34:15 | ? Can get less over time. . So that's one of the |
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| 34:21 | of course, of many why you antibody responds to older people, |
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| 34:26 | Maybe it's not as robust as somebody because their memory cells are kind of |
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| 34:30 | little bit, right? Um Some died off as well. Uh And |
|
| 34:35 | the reason that you periodically have to this. You know what that |
|
| 34:41 | you have to do this maybe every years or so to help you out |
|
| 34:47 | terms of your, your memory zones are kind of going down. What |
|
| 34:51 | you do? Go to the doctor you get OK, the food |
|
| 34:59 | So that brings up. So tetanus about every 10 years, you have |
|
| 35:04 | get a booster so that pumps up memory cell population, get a better |
|
| 35:12 | if you need, you can encounter and Andy. So anyway, so |
|
| 35:17 | uh so um now this is one of the process is, is this |
|
| 35:24 | uh binding the antigen and then making happen? OK. And the antibodies |
|
| 35:31 | on top of this are I G I G D primarily. OK. |
|
| 35:38 | I'm gonna mention some things that you're gonna need to know those is when |
|
| 35:44 | , they, they are called which these are but naive B |
|
| 35:51 | they're, they, they don't know , right? They're active but, |
|
| 35:55 | they, they're, they're new. ? And like I said, |
|
| 36:00 | these are things if you want to immunology course, you learn it, |
|
| 36:04 | your book goes into some of it well. But um there's kind of |
|
| 36:08 | learning curve in a way. So cells that are first. So for |
|
| 36:12 | , this group here, right, forms and expands the antibodies they produce |
|
| 36:20 | that these produce are I G M G M I G M mission, |
|
| 36:26 | form that 5 30. OK? um those aren't as specific, they |
|
| 36:34 | and but it's not as it will OK. So further tweaking of the |
|
| 36:43 | cells in this process and more binding the same engine actually makes them |
|
| 36:49 | OK? Pro antibodies that are that are better bind more tight, |
|
| 36:55 | response. OK? And they actually . So initially I G M and |
|
| 37:01 | switch to I G G, And those I G G S in |
|
| 37:06 | second, you know, two point , let's call it these, these |
|
| 37:11 | point oh version the I G produce , very, very tech, very |
|
| 37:16 | effect with those antibodies. OK. again, there's, there's obviously, |
|
| 37:22 | know, chemicals and other signals underlying this, we're getting into all |
|
| 37:27 | But, but that, that that is the case, they kind |
|
| 37:30 | get, they get better at what doing, so to speak. |
|
| 37:34 | Um Now, uh so the other of this is activation, right? |
|
| 37:41 | , well, activation part two, say so um there's what's called t |
|
| 37:49 | and T dependent. All right, gonna go over something real quick and |
|
| 37:53 | we're gonna come back, we'll come to this in a second. So |
|
| 37:57 | one, don't, don't need to this concept of the test, but |
|
| 38:01 | helps to at least go over So you kind of have an idea |
|
| 38:05 | what's going on here, in So here's a B cell and we |
|
| 38:10 | to these, so here's your right? So we call that BC |
|
| 38:17 | for B cell receptor. OK? so these will bind, it's whatever |
|
| 38:24 | angel is, right? Um Like and so part of the process, |
|
| 38:29 | it's one thing to bind, let's like this, right? Binds angel |
|
| 38:33 | that. OK? But you need get these together in this fashion like |
|
| 38:42 | OK, that produces, that's step that produces an active cell but not |
|
| 38:49 | there yet. OK. That's something something we call camping. OK? |
|
| 38:54 | because you have, you know, binding sites of an bodies that can |
|
| 38:59 | , right? They can come together this. OK? And so this |
|
| 39:04 | um so for like, let's say smaller, but for your average size |
|
| 39:13 | , OK. Molecular weigh over 1000 sure. But um they sometimes sometimes |
|
| 39:22 | may have issues kind of getting this form properly, the capping part. |
|
| 39:27 | then you involve a T cell, T helper cell, OK? To |
|
| 39:33 | of help the activation process out because is this, this is not always |
|
| 39:39 | . OK? And so that's for C from our B cells. Mh |
|
| 39:44 | two. All right. B macrophage, den cells, Mh C |
|
| 39:49 | . So they, so B cells also internalize energy. They can also |
|
| 39:54 | that and then show it. And so that's where A T |
|
| 40:00 | OK? And then that will, will then send out cytokines that will |
|
| 40:06 | that Visa. OK? I wanna that probably most of the activation of |
|
| 40:13 | cells occurs this way. OK. of a key helper cell. |
|
| 40:19 | And uh that's what we call He depended that way. OK? |
|
| 40:35 | I wanna say that's probably how most these cells get. OK. The |
|
| 40:40 | way is what's on the previous OK. Is this here? |
|
| 40:46 | So here you see this big, . Very often it's A P Saar |
|
| 40:54 | be these big. And so they the ability because of their size to |
|
| 41:00 | contact a number of antibodies here, ? Forming that cluster that and that |
|
| 41:07 | B cell receptor, right? So kind of why because they're so |
|
| 41:11 | they can do that. You don't the involvement of a T helper |
|
| 41:14 | OK? But again, these uh uh only produce mud state activate and |
|
| 41:23 | plasma cells, they only produce I MS antibodies which are OK. But |
|
| 41:28 | not the best. That's kind of polysaccharide don't give you as good I |
|
| 41:33 | by themselves. That's how we have time to fiddle with them in the |
|
| 41:37 | to make them be better at But you don't even know that part |
|
| 41:41 | it. But it, it goes to why some, some make better |
|
| 41:45 | and others. OK. So, so again, it's really about creating |
|
| 41:52 | , this thing here, right? , and, and, and a |
|
| 41:56 | of them. And so because with type of engines or like let's say |
|
| 42:01 | average normal engine, let's say size wise that you have to involve |
|
| 42:07 | help of A T cell. Again, I think this is the |
|
| 42:10 | common way, most are the things , you know, pretty much average |
|
| 42:18 | size. OK? So basically the style is gonna reiterate this. |
|
| 42:24 | So um so here's a B cell its antigens on antibodies. On top |
|
| 42:31 | , here comes antigen and some of gets internalized, some out here, |
|
| 42:36 | internalized. And then we get the the key dependent process and involvement of |
|
| 42:44 | T helper cell. It's att H T help cell type two. |
|
| 42:49 | And I I made that distinction because H one types interact with macrophages and |
|
| 42:57 | cells. OK? But these guys specific for B cells. OK? |
|
| 43:02 | so they form plasma cells and memory . There we go. OK. |
|
| 43:10 | uh Yeah, what else? What's the next one? OK. Any |
|
| 43:18 | , right? So T dependent T . OK. Um OK. The |
|
| 43:27 | question, let's look at this question . Get this thing up. So |
|
| 43:35 | is about um secondary canon butter response antigen, either through vaccine or |
|
| 43:45 | right? First exposure, secondary antibody is faster and stronger than the primary |
|
| 43:53 | due to what cell types. Let's count down here. So it |
|
| 44:58 | , yeah, of course, it's memory cells. OK. So um |
|
| 45:04 | now you created those in your primary and now they're primed and ready uh |
|
| 45:11 | upon second exposure. OK. So so if you look at the primary |
|
| 45:18 | , OK. So um we need activation uh formal attachment memory cells and |
|
| 45:27 | um initially forming lots of I G . OK, which are OK at |
|
| 45:34 | and they form the the panto right? But then uh then they |
|
| 45:39 | improving I G G in more quantities in a better, better antibi better |
|
| 45:46 | uh bigger immune response. OK. so uh of course, because of |
|
| 45:52 | um memory cells you now have they can quickly respond. OK. |
|
| 46:00 | , just exposure or your immunization. . So um all right. So |
|
| 46:10 | to our T cells here. So there's gonna be two kind of |
|
| 46:17 | going on. OK. OK. recognition of uh the MH C molecule |
|
| 46:24 | , right? So uh set of T cells recognize class one. |
|
| 46:31 | And um they do that through what's a co receptor. OK. Shown |
|
| 46:42 | one aspect, the other one is T cell receptor that recognizes the |
|
| 46:49 | OK. So there's 22 parts of . OK. And on both |
|
| 46:54 | So for the uh side to T , they have the what's called CD |
|
| 47:00 | , the T helper cells have a one called CD four. And that |
|
| 47:04 | them to recognize the M AC class . OK. But also a receptor |
|
| 47:10 | recognize the antigen, right? So two parts are the agen M AC |
|
| 47:16 | OK. Recognition. OK. And uh with cytotoxic T cells, of |
|
| 47:22 | , it's about getting rid of infected . OK. So um so T |
|
| 47:31 | self media community interaction with yourselves, infected cells or cells that are presenting |
|
| 47:40 | OK? And creating effects. And with an infected cell um as part |
|
| 47:46 | the virus infection, for example, um parts of the virus, you |
|
| 47:53 | , because of course the virus life , we know right genome enters and |
|
| 47:57 | producing viral proteins and then and then . And so in any part of |
|
| 48:02 | cycle, some of those ans can bound up by and see molecules. |
|
| 48:07 | I remember that hold your like skin , liver cells, kidney cells hold |
|
| 48:13 | body cells right aside from red blood have the MH C class one. |
|
| 48:18 | any of those cells that can get , potentially can be seen by these |
|
| 48:23 | T cells. So finding occurs and leads to typically the the apoptosis release |
|
| 48:31 | chemicals inducing get itself out of the . It's no good. OK? |
|
| 48:40 | they also can release toxins as well kill it. So uh but the |
|
| 48:45 | line is that and what they do recognizing the ans on the surface. |
|
| 48:52 | . Now again, like I said , we don't go into all the |
|
| 48:57 | of this, but we mentioned memory in the context of these cells. |
|
| 49:01 | cells also have memory as well. . So it it it's on |
|
| 49:06 | both sides here. B cells and cells have that memory component. |
|
| 49:12 | And so your key helper cells, types, these recognize. So the |
|
| 49:20 | two uh Mh CS and these are macrophages and dendritic cells and B |
|
| 49:26 | OK. We talked about B cells . And so they uh uh recognize |
|
| 49:34 | your key helper type um uh ones microphage cells. Uh I mean, |
|
| 49:44 | saw one of the effects was the of the macrophage, for example. |
|
| 49:47 | but they can release uh cause release other types of molecules that can complement |
|
| 49:53 | set for these kind of effects. And then with these cells that |
|
| 49:59 | we talked about that before macro basically more of the super posit, |
|
| 50:05 | And then um T helper type two activate B cells. OK. So |
|
| 50:13 | the um and it's the HIV virus actually infects um the these types of |
|
| 50:24 | helper cells because they have the CD , except that's what the HIV virus |
|
| 50:29 | and gets in. So you can if you're uh basically infecting those T |
|
| 50:35 | types that you're really gonna um severely your immune system because now you don't |
|
| 50:42 | your affecting production of antibodies by B as a result. So, uh |
|
| 50:48 | um so any questions about T OK. So let's um this is |
|
| 50:58 | thing, a book, a book really talk about it, but |
|
| 51:02 | you're gonna, it's not that difficult I think you're gonna, you're gonna |
|
| 51:06 | these couple of questions here. So a way to um categorize and |
|
| 51:14 | I guess you're immune system, You adapt of immune, there's different |
|
| 51:20 | , a couple of ways you can this, right? In terms of |
|
| 51:24 | stimulating it and how you respond. . So basically you have four |
|
| 51:32 | OK. So just read, so from the um top down, |
|
| 51:36 | So go this way. OK. what would vaccination be ABC or |
|
| 51:44 | like I said, I don't think gonna be very difficult for any of |
|
| 51:48 | , but it's worth mentioning because you certainly, I would, I assume |
|
| 51:52 | hear these terms. Let's count down . Forget this one. Then another |
|
| 52:35 | . OK? 21. OK. um let's go to the next question |
|
| 52:42 | quick and see what we get All right, next question. There |
|
| 52:49 | go. Yeah, this is about baby acquiring antibodies or getting antibodies having |
|
| 53:23 | . 36, you clearly you have concept, no doubt. So c |
|
| 53:36 | the first one that everybody answered. it's all about um the source, |
|
| 53:42 | ? First is the source artificial. basically is the shot or you're applying |
|
| 53:46 | through the environment basically transmitted to you infection. Um or um then it's |
|
| 53:55 | through mother's milk, right? How acquires uh yeah, antibodies. Um |
|
| 54:04 | then it's a question of, are doing the work to make the antibodies |
|
| 54:07 | are you just basically handing them off you being, are you receiving the |
|
| 54:12 | from the source? OK. That's act of passive. So certainly vaccination |
|
| 54:17 | artificial or part acquisition. But it's it is uh you're actively, your |
|
| 54:24 | is actively producing antibodies in response to antigen you're being given, um, |
|
| 54:30 | naturally acquired uh passive that of is baby. Right. Something on |
|
| 54:35 | mother formed and bodies being given to baby doesn't have to do anything to |
|
| 54:41 | them, it's getting them already So it's passive. Ok. |
|
| 54:45 | artificially acquired um, massive immunity. would that be on the 50 |
|
| 54:56 | You can actually get to a certain , doctor. Yeah, it is |
|
| 55:02 | . Yeah, exactly. Right. . So you can get, it's |
|
| 55:06 | uncommon to get, I think out I G G because you get out |
|
| 55:12 | a lot of G um the uh , if you're getting preformed antibodies and |
|
| 55:18 | do anything, it's passive and it's a shot, right? So, |
|
| 55:22 | acquired active immunity. That would be so that's where we talk about that |
|
| 55:28 | naturally acquired actives, immediate, what's one? Naturally acquire activity? I'm |
|
| 55:39 | , that requires activity. Yeah, . That you, you get sick |
|
| 55:45 | you, you produce antibodies, you COVID and you produce antibodies and you're |
|
| 55:49 | it or whatever, right? So infected. OK. So, uh |
|
| 55:53 | is explained on this slide. So, um so let's, let's |
|
| 56:03 | look at one question here to kind wrap up this part. So we'll |
|
| 56:09 | a little bit about vaccines before we . Um So it basically B |
|
| 56:16 | T cells, right? You not . Yeah, it's come down |
|
| 57:47 | Uh and there is a false So, if you need to change |
|
| 57:51 | answer, if you picked e pick else. All right, let's count |
|
| 57:59 | here. Yeah. If you pick you're correct. All right. So |
|
| 58:10 | is clonal single clonal antibodies to one , right? The clone, they |
|
| 58:19 | the same type of epitope slash Ok. So, you know, |
|
| 58:26 | T cells can directly kill infected Of course. Right. B cells |
|
| 58:31 | really don't, I mean, they antibodies but they don't really kill |
|
| 58:35 | So they produce antibodies that then it have an effect in some way. |
|
| 58:40 | . So um all right, any about. So we'll talk a little |
|
| 58:46 | about vaccines. OK? And uh one, you know, there's a |
|
| 58:53 | table, there's a few tables in . I'm not gonna ask you what |
|
| 58:57 | of virus is produced against polio. not gonna ask you those kind of |
|
| 59:02 | , right? So you have to the tables of OK. This is |
|
| 59:06 | polio virus vaccine is and blah, , blah. So don't worry about |
|
| 59:09 | . OK. It's more about what the types of vaccines, how do |
|
| 59:15 | , how do they differ and what's unique about it. OK. So |
|
| 59:21 | went through the whole uh fast to , primary secondary response, right? |
|
| 59:26 | obviously that's what a vaccine is doing you're exposing yourself and getting a |
|
| 59:33 | you're exposing your body to this engine you'll go through the process, you |
|
| 59:38 | to produce antibodies to that. And so of course, with the |
|
| 59:42 | , you try to produce a vaccine will produce a strong immune response, |
|
| 59:48 | know, and, and, and one probably first is to, to |
|
| 59:54 | sure it's safe. OK. And , um of course, that involves |
|
| 59:59 | of testing. Now, um one uh to mention here. So, |
|
| 60:05 | we also talk about, I talk , um I think we talk about |
|
| 60:13 | in the next section regardless. So immunity is all about um having an |
|
| 60:21 | population. OK. OK. Um will always be members in society that |
|
| 60:33 | right or wrong won't be vaccinated. Sometimes you just can't, it's, |
|
| 60:38 | , it's detrimental to their health, know, because they have some kind |
|
| 60:40 | condition or for other reasons. You can't expect 100 100% compliance on |
|
| 60:48 | in, in, in the So, so it's gonna be populations |
|
| 60:52 | won't, that will be vaccinated. how do you help them out? |
|
| 60:55 | do you help them? Now, most of the population most is like |
|
| 61:00 | is, that's kind of what the is about here. These are |
|
| 61:04 | OK. The that's the thing that's the percentage of the population that |
|
| 61:11 | be vaccinated for there to be help these other people who aren't vaccinated to |
|
| 61:16 | them from the effects of the So, in effect, the vaccinated |
|
| 61:21 | in the population are the syncs to the infectious agent keeping them away from |
|
| 61:29 | who are susceptible. Ok. So you have more people that are |
|
| 61:33 | right? So this is a, this is a, um, let's |
|
| 61:39 | this is an unvaccinated person. All . And this is uh un |
|
| 61:49 | let's call it un waxed, And then vaccinated people, triangles, |
|
| 61:56 | ? You have more vaccinated people, you are basically, there's an infectious |
|
| 62:04 | from the population, you have more people surrounding these unvaccinated types. Then |
|
| 62:10 | the important the vaccine is that's what keep the population healthy. OK? |
|
| 62:15 | spread. OK? But if most those triangles are red being unvaccinated, |
|
| 62:22 | you know there's not, there's not have much help. So there's a |
|
| 62:25 | for this, OK? And it to really to this value. So |
|
| 62:29 | of R zero as kind of a multiplication or a reproduction value for the |
|
| 62:35 | the infectious agent. OK. So 4 to 7, what that means |
|
| 62:41 | for each person with mumps, it'll transmitted to four or seven other |
|
| 62:48 | You go down here to measles, ? Or pertussis, right? One |
|
| 62:56 | thing 12 to 17, 12 to people, right? It's more |
|
| 63:02 | right? More contagious, right? you have these values that are high |
|
| 63:07 | O, more contagious, more OK? Um And so for that |
|
| 63:14 | , the threshold goes up, You need to have more people vaccinated |
|
| 63:19 | it's more easily transmissible. So more people need to be there to be |
|
| 63:24 | to absorb this. Ok. And think uh COVID is COVID is actually |
|
| 63:29 | here in this, in this range with mumps that four or five |
|
| 63:38 | So, but that's not uncommon. pertussis measles, uh these are as |
|
| 63:45 | disease which is just not as transmissible pertussis or measles. So through the |
|
| 63:50 | is gonna be the most common motor and not surprisingly, uh those that |
|
| 63:55 | very contagious are, are those OK. So, um all |
|
| 64:02 | So what about vaccination then? Well, um different approaches. |
|
| 64:11 | Uh You know, because of, know what we know with the technology |
|
| 64:15 | have nowadays, we come to DNA and otherwise we have a lot more |
|
| 64:20 | available. OK. So in terms what you try to do with the |
|
| 64:25 | is um make it very immunogenic, ? If there's a strong immune |
|
| 64:31 | make it safe, right? Um also um best ones, the best |
|
| 64:41 | stimulate the entire death immune system. remember you got two components, |
|
| 64:46 | T cells and B cells. All . And you want the best |
|
| 64:53 | get all of those activated. OK. And the ones that do |
|
| 65:02 | the best are ones that tend to um one is really this group right |
|
| 65:08 | . We'll talk about first live attenuated . OK. So we talk about |
|
| 65:15 | vaccines from way back, right? are basically to attenuate means to limited |
|
| 65:22 | inactivate it, right. Don't make disease causing, right? But keep |
|
| 65:27 | alive. Ok. So a liver vaccine I E virus as an |
|
| 65:35 | um that virus has the ability to them. They infect the cell and |
|
| 65:42 | , but it's not causing disease. . So it's basically acting like it |
|
| 65:48 | would minus the disease part. And what stimulates B cells and key |
|
| 65:53 | So it's basically limiting a natural And in doing so at the |
|
| 66:01 | the entire adaptive immune system. And one that's a long lasting strong |
|
| 66:07 | OK. Um And so the uh so a number of vaccines are like |
|
| 66:16 | measles mumps vaccine. And again, don't need to the list here. |
|
| 66:23 | But these are things you likely have, have certainly have received. |
|
| 66:27 | . So a flu virus as well in this category or the flu |
|
| 66:32 | excuse me. So, um and the uh ways to affect this are |
|
| 66:39 | basically, you know, for a , you pretty much know what are |
|
| 66:45 | genes involved and causing the various right? So, knock those |
|
| 66:49 | OK. And um and but the beauty of this is the fact |
|
| 66:53 | they can still replicate and that's what boosts the immune system, right? |
|
| 66:58 | strong response. OK. And so activating, kill vaccines. Now, |
|
| 67:04 | live vaccines, could somebody come down full disease? I don't know, |
|
| 67:13 | certainly you could have some effects for . I'm sure we've had vaccines like |
|
| 67:17 | and you, you felt some effects us, OK? Um Little a |
|
| 67:24 | would be inactivated to kill the OK. And so that, that |
|
| 67:29 | have the ability to replicate that. um it's more working on B cells |
|
| 67:36 | antibody production. OK? Which is fine. OK. But it's just |
|
| 67:42 | as robust, let's say as a vaccine. OK? And there's |
|
| 67:47 | many ways to, to um to the virus, chemically radiation and see |
|
| 67:54 | examples there. OK? Of the the the thing is to make |
|
| 67:59 | it retains how you activate it, sure it retains its ability to stimulate |
|
| 68:03 | immune system, right? Keep those intact, right? So, um |
|
| 68:11 | those in that category are things like um been coughed, is it |
|
| 68:18 | So I think you're having allergic aren't you? You're having allergic |
|
| 68:23 | aren't you that your, your mass ? Yeah, your ma cells |
|
| 68:29 | are kicking in. Um I feel you. Yeah. Um OK. |
|
| 68:36 | if you really wanna get safe, ? Don't even deal with the whole |
|
| 68:42 | , whether you inactivate it or whatever the parts, use the parts of |
|
| 68:48 | . Um Then obviously there's the parts cannot, cannot replicate and, and |
|
| 68:54 | infection, but you can produce a response. Certainly. So subunit vaccines |
|
| 68:58 | be a different subcategories. OK. so the bottom line is you're, |
|
| 69:03 | taking parts of this microbe, Whatever they may be, you presumably |
|
| 69:09 | what the parts are gonna produce in response, right? This is of |
|
| 69:12 | , where animal studies come in to of gauge this as well. And |
|
| 69:16 | one simple way is really just to up the microbe, right? And |
|
| 69:20 | fractionate it centrifuge. You take the that, you know, is, |
|
| 69:25 | the engines that produce the response, ? And then that's your shot |
|
| 69:30 | Right. That's what, that's what's your vaccine. OK? You can |
|
| 69:34 | more sophisticated, all right, this somewhat of a crude process. You |
|
| 69:38 | , you might um um surmise, then we get more sophisticated, of |
|
| 69:44 | , by taking the gene for the . And then cloning that using the |
|
| 69:52 | cloning technology, put it into a cell and then make it express that |
|
| 69:58 | for you. OK? And um this process compared to this, I |
|
| 70:07 | just see in terms of economics and and things is gonna be um I |
|
| 70:12 | it will be more efficient to do because you can get, you can |
|
| 70:15 | cells, you know, you can lots of cells, bacterial cells grow |
|
| 70:18 | , you grow lots of them, them express it from a might, |
|
| 70:22 | might come in from uh just the standpoint efficiency. That's gonna be much |
|
| 70:27 | . OK? And so, um , that's, that would be your |
|
| 70:31 | , the uh and so uh DNA , you can use um um cells |
|
| 70:39 | your own cells, right? get that gene into your own |
|
| 70:44 | OK? And make them right, , you and representing cells, |
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| 70:49 | Macrophages and, and the like they uh absorb that um DNA express the |
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| 70:55 | and put it on the surface right MH C molecule that will uh that |
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| 71:01 | um activate your immune system. And that's what um the COVID vaccines |
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| 71:07 | all about. They are in that . Uh One of them, it's |
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| 71:10 | group, the other group is actually this, the, the Pfizer one |
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| 71:15 | a type like that. Uh it's the R N A vaccine to |
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| 71:19 | uh more specific, not DNA but common vector vaccine. That's the uh |
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| 71:24 | and J one was that type. so basically, you're using a um |
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| 71:30 | the virus that's replicate. OK? then you take out the part of |
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| 71:35 | genes that are available and you put , put in the um gene for |
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| 71:39 | engine. So it expresses, expresses on the outside here. So these |
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| 71:45 | the, whatever the particular engine is cloned in it, it expresses them |
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| 71:49 | the surface here. OK? And um the virus like particles, these |
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| 71:57 | kind of like a shell almost, ? So if you separate uh proteins |
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| 72:03 | a particle engines in there with so, so they'll be sitting here |
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| 72:11 | on the surface here and then that's your body can find and respond to |
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| 72:17 | . OK? Um H PB is virus like that or vaccine like |
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| 72:21 | And so again, toxoids, These are um um basically taking like |
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| 72:27 | tetanus toxin. So like the diphtheria due to a toxin as well and |
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| 72:32 | others and the toxin itself, you and then that becomes the shot, |
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| 72:39 | the vaccine, the inactivated toxin. , so a tetanus shot is, |
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| 72:43 | just that OK. Um So the yeah, that's uh more time. |
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| 72:52 | , uh, we'll pick this up finish this on Tuesday folks. So |
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| 72:56 | a good one and we'll see you |
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