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00:00 it's okay. Mhm. Okay Welcome. Let's uh we've got um

00:32 we're heading towards the last couple of of course. So we've got this

00:36 . Next week and then we'll come On 2nd for the last class.

00:44 let's see. So we're gonna finish innate immune system. Start on

00:49 the immune system finish that on Um just a note. Let's

00:55 Uh so we're talking about expanding little on vaccines. Your your book,

00:59 24 has a section where it talks little bit about it. I kind

01:04 expanded a little bit. Um so see that if you, if you

01:08 to the notes um the uh until Monday um chapter 25. And so

01:17 one of those classes. So the lecture for that's already up is

01:21 So if you wanna take a look that before next Monday. Um Like

01:27 previous ones, just a bunch made lot of ethical questions surrounding, you

01:32 , discussion about different ah fixed within 25. So that will be next

01:38 . And then um Smart work again due. So that's number 23 which

01:42 finish up today is due sunday weekly again. Just forward going over this

01:49 . And um then uh let's So the Exams and Exams three will

01:55 available Wednesday. So you can you go and log into cars and look

02:00 it. Um certainly have any let me know the distribution for the

02:06 was Um exactly where it was as see here. So it was like

02:14 or so average uh the Um median 74. Yes. So uh yeah

02:24 we got one more exam obviously. that's gonna again not comprehensive was just

02:31 what the These chapters 23 through Okay so that's not until mid may

02:40 . So and I guess then the schedule will come out I guess that

02:47 be two weeks before. So at end of april so that last week

02:51 april so just be God for And uh so um any questions?

03:01 . Uh we have an official vehicle this. Sign up for example For

03:06 last exam it's gonna be it's gonna it's gonna be 14 days before so

03:11 14 days is from the 10th. when you can sign up. I

03:16 I think that's a Tuesday I the so May 10 someone looks like it's

03:34 be April 26, 26 is to . So um Okay questions. Okay

03:45 so on to so I just want start with a little bit of a

03:50 of a recap. Okay let's look this question first. We talked about

03:55 things last time then it will kind do a little wrap up of our

04:00 of where we're at right now. So as you're answering so remember

04:07 So we're in the native new So of course in this section is

04:10 about the infectious disease. Looking at microbial pathogens which we're getting to.

04:16 I haven't really got mixed in here there but we're focused now on how

04:21 body fights disease your innate immune Today we'll begin talking about the adaptive

04:27 system. And so um then next is when you kind of turn the

04:33 to the microbe the pathogen and how um can get through all these various

04:39 that we've been talking about. So and then we'll end up with looking

04:44 different types of infectious diseases. So talk more about that on Wednesday.

04:51 . Um so another thing so today looking at uh the last time we

04:58 at physical chemical barriers um the cells the innate immune system, different types

05:07 white blood cells. And then today going to focus a little more on

05:13 of the innate immune system like um inflammatory response of these kinds of

05:20 . Okay so uh put the clock here. Mhm mm hmm.

05:53 Okay so here let's see what we . Um Okay so modest sites can

06:05 to battlefield. No remember modern sites into macrophages dendritic cells. Okay they

06:12 that in the lymphatic system abstractions are things that will help out figure

06:17 So things like antibodies and complement or . Okay. Not to T.

06:23 . R. S total like I mean see molecules those are your

06:27 antigens. Alright so that's what you on your cells tissues you're not gonna

06:32 about passages. Um third line That was the third line is your

06:38 distributes system. Okay we'll talk about later today licensing is going to be

06:43 chemical barrier. First line defense. Natural killer cells are defense against um

06:52 sailor pathogens. So infected cells can can be potentially found out by natural

06:58 cells and they'll deal with them. so on this list none of these

07:04 true. Okay um Okay so again kind of went over this a little

07:12 so summary from last time. So uh naming system looking at 1st and

07:18 line defenses will go through the rest these today here and uh the of

07:26 you can't forget your own microbes, own micro motor that serves to keep

07:31 out. Um So the man's pants think those are the same thing.

07:37 basically structures on the periphery of pathogen can be detected through these total like

07:42 . These will be on various cells your immune system um scattered throughout your

07:48 . And so interaction with a structure the pathogen either examples here are uh

07:56 of the virus buying cities um the result and also remember that you have

08:04 internal tactically suffers inside the cell so can affect and then um certain patterns

08:13 do that be on the inside of cell and maybe one of one of

08:16 structures context when these internal receptors. united case whatever whichever one gets activated

08:24 cytokines produced. Right so you have put aside all kinds of different effects

08:27 so we're going to see the functions lots of different cited kinds and the

08:32 response. That's what that's what we're start out with first. Um So

08:36 whole host of different effects from attracting to the site of infection to activating

08:43 cell types etcetera. Okay. Uh basically I look at it as like

08:47 alarm his arm belt in the body off. So signaling potential infection.

08:54 and mobilizing your immune system. Then looked at some different cell types in

09:00 in the immune system, focused most on these in terms of function.

09:07 , you're granular sites Dr. Phil Party when your main infection fighters early

09:14 these are fields are more about releasing . Not really think it's a toxic

09:18 . You've said it feels more about with large pathogens. They too are

09:23 of produces releases toxic and some things terrific. And then we'll than macrophages

09:31 dendritic cells. Okay these are remember your innate and adaptive immune system can

09:38 together in certain processes and it's macrophages dendritic cells are typically the ones that

09:45 doing that working with the adaptive And so we saw that that function

09:50 antigen presentation which I which I'll mention in a second. So um uh

09:57 lymphatic system of course is important. where your B cells T cells

10:02 Dendritic cells kind of reside that's kind their environment. Um B cells and

10:09 cells will activate the lymphatic tissue and can do there thing. Okay um

10:19 we ended I think with fabio santos so remember the process there. So

10:23 is the macrophages that we see the here of a pathogen to our total

10:31 receptors. So it starts with binding ingestion forming food vacuole like you see

10:38 and then fusing with the license zone digest it. And then remembering another

10:42 here is this antigen presentation which let just flip to that real quick.

10:49 . Which is shown here. So a macrophage just like we saw the

10:52 slide and so congestion occurring here. um uh binding ingestion and then going

11:04 the process of psychosis. But then fragments of that pattern can be shown

11:12 the body. Okay so through MHC . Okay so there's a differentiation

11:18 Class one. Class 2 Right. too macrophages B cells. Dendritic

11:24 everything else then is a class one cells, your liver cells basically Most

11:30 your body cells falling into the Class category. And so class two types

11:37 interact with particular types of T cells help them cells um binding like that

11:44 T helper cell recognize both the MHC as well as the antigen and then

11:50 of course typical is released the site kinds again right you can activate

11:54 So here's what an activated and inactivated activation looks like compared to activated one

12:01 of like a that you're a flower almost. And so you see the

12:05 of lots of membrane folds. So more of these folding wings

12:11 Equate to a greater ability to Vegas ties. Right. So that's that's

12:15 activation is about activating these things is just making it more fake acidic if

12:21 will. Okay um so back once a second here, that's an option

12:30 . That was the last thing. , that's the last time we talked

12:33 . So here is um uh we think of it as enhanced figure

12:39 Okay. Certain pathogen is gonna be of a better word, slippery.

12:44 ? Not able to buy. And it's a binding part that you see

12:48 is critical to initiating the whole figure effect. Okay, it's not able

12:53 bind very well that this doesn't occur a very good. Great. And

12:58 to enhance that. So something like capsule can produce this effect where the

13:03 is not going very well or a capsule or some other structures that may

13:11 it to not bind so well. so that can be worked around through

13:16 production of antibodies that combined them into pathogen or complement combined to it basically

13:23 it more sticky if you will. and so now that it's more easily

13:26 and it can be sensitized. Okay that whole process is optimization. The

13:32 is actually facilitating this. In this the antibodies other example would be a

13:39 . Those Michaels are the option. okay. That doesn't allow for

13:44 Okay. Um so that means so already. So so this is what

13:50 gonna finish up today or these fourth . Okay, interference isn't really a

13:57 but we'll see we've seen this before so many of these things over

14:02 Any questions? Okay yeah. Um you'll see what awesome party you

14:14 T. L. R. There were categorized under it would be

14:29 . Uh They would just be classified an immune system defense. That alerts

14:34 body to a potential infection. May followed under a process maybe or

14:45 Um But you C. T. . R. As you think,

14:50 it's like putting the fire on Uh you know. Okay so here's

15:00 question if this is gonna relate to first thing we're going to talk about

15:03 is the inflammatory response. So um what are you looking at this?

15:08 inflammatory response? We're looking at the inflammatory response which has a which has

15:16 finite period um a few days To a week or two where you start

15:25 then finish it um chronic inflammations, continual processes that occur maybe even a

15:33 temporarily, but then they come So kind of trigger these inflammations in

15:37 body. Uh these kind of chronic um can can uh sometimes are autoimmune

15:47 um over time they do take a on the body. And so uh

15:53 know, many of these are kind uh gastrointestinal types of things where certain

16:00 and things may flare up and cause , student, autoimmune uh aspect of

16:06 condition. So um so chronic ones and of course a long time,

16:10 , years. Okay. But we're focus on the acute inflammatory response which

16:16 all gone through at one time or , or maybe going through it right

16:21 if you have like a minor wound something, a splinter in your finger

16:23 what have you is relatively mild. the thing about inflammatory response is a

16:31 response is meant to be a local and to contain the infection in that

16:37 area. Okay, that's the And so not allowed to spread.

16:42 so it's about bringing all the relevant types to the site and then carrying

16:50 the effect. Okay, and so there's gonna be a stepwise process to

16:54 , right? So for this question basically ranking uh 112136, I guess

17:03 with what we've given. And so as was answered the majority yes,

17:09 going to be cytokine release is gonna first. So like with um you

17:15 , instructions yourselves followed, or other of some sort. And so inflammatory

17:22 is going to be very cytokines are to trigger this. And so with

17:27 so we're talking essential in this process getting neutrophils. Two figures of ties

17:36 infectious agent. Okay, so neutrophils the blood circulating blood, you gotta

17:40 them out, right? And so a lot of this process is about

17:45 the blood vessels more permeable more If you will to get the neutrophils

17:51 and then they can do their So, again begins with cytokine

17:56 then I probably would put this That's one I would say this is

18:03 Okay, so, bad circulation is manipulating blood vessels. Okay? Um

18:08 not everything's listed here, but what have, I would say it's like

18:12 too. Um I would say three be this. So one of the

18:18 is neutrophils, you know, your flows pretty quick. And so you

18:23 to slow it down. There's ways slow it down and then kind of

18:27 onto the neutrophils so that you can them down all right? And that's

18:31 the sticking part is all about, ? And so once you get them

18:34 stick to the blood vessel wall, they can squeeze out, and that's

18:38 that would be for exit. And then the latter processes here,

18:44 , swelling, I think we've come . Okay, repair them. We

18:48 to occur. So it could be that's supposed to scam performs right?

18:53 Something like that usually proceeded by Uh If you're getting trying to get

18:59 out of the blood, of things other than cells will follow when

19:04 make blood vessels more permeable. So comes out and that's where the

19:09 Any inflammation occurs from that. Um yeah, we're gonna go through

19:13 So let's look at um here. , so these terms extra visitation

19:21 Nation is another one. You'll hear relate to the manipulation of of the

19:27 , even getting them out of the vessel into the nearby area where they're

19:32 . So um so here's a basic , just like a kind of puncture

19:39 , remember we call that would be subcutaneous rank is just like a with

19:44 splinter uh puncturing the skin layers. Maybe there's a certain microbes contaminating on

19:53 the tablets on this planet. And you're you'll have macrophages in the

19:58 not necessarily plentiful, but there will betraying around. Remember you can have

20:04 most fixed and wandering macrophages. These likely wandering around. Um And we'll

20:10 pathogen, potentially microbes that are introduced again, release chemicals it's gonna

20:17 They're fake with the ties. And then um then through the whole

20:22 are binding that I can't release, know, they're beginning to um had

20:28 chemo attractant chemicals to draw ourselves to site Um beginning the whole process of

20:36 the inflammatory response. Okay, so nearby capillary and of course there's gonna

20:42 lots of red blood cells, but there'll be a few more than a

20:46 , but there's certainly lots of white cells to um here is gonna be

20:50 nuclear fill you see here. And the process of no these different chemicals

20:58 manipulate blood vessels. Okay, so is going to increase the diameter of

21:05 capillary. Okay, so that two bring it closer to the surface,

21:09 ? So that's when he typically implement area, will be kind of reddish

21:14 warm to the touch because of that effect. Okay? Um so to

21:21 in the blood, but so of this is just occurring. Obviously this

21:25 is only occurring in the immediate vicinity of where this infection occurred.

21:31 Um And so the so by opening the bug dust, so basically lesson

21:39 resistance to flow through the capillaries in area. So but the wind will

21:46 and we'll slow down so we can down the speed and it kind of

21:51 up the wood block. Okay, that serves two purposes. 1 to

21:56 more blood to the site because more needs more of these neutrophils and slowing

22:02 down means it's easier to grab and these out. Okay, so those

22:08 two purposes, we're kind of doing manipulations with the blood vessels.

22:12 Um And so here would be. here, I'm gonna show you an

22:18 of this. But here is how see. So this process of kind

22:22 grabbing it is the is the externalization and then they're squeezing out. That's

22:28 they called margin ation. Um And it will kind of they're very of

22:34 , flexible these cells, there's no wall, so they can kind of

22:38 like amorphous blobs if they need to to squeeze through. And so to

22:42 this happen, and there's other chemicals come into play, interact with the

22:48 making up the blood vessels. Because you have to loosen those connections

22:52 the cells to enable stuff to come . Right? So that's a lot

22:57 cytokines interacting here, doing various things uh manipulating blood flow to making

23:06 loosening up connections to make these cells out. Um And of course,

23:11 of chemicals involved in this. so then you see the exiting digital's

23:17 exited and they can go on and the bulk of the figure psychosis

23:22 Okay. But you're gonna have other involved because as the chemicals are released

23:27 they affect other cells that continue to the whole bas oh, these basal

23:33 factors that manipulate the blood vessels for from things like mass cells in the

23:40 . I really think things like histamine basic skills can do contribute here as

23:45 , history and brady Kainan or a of cytokines that um again promote this

23:55 the permeability of the blood vessels is they're doing. Okay. Um This

24:00 the brady kind has dual function. not only helps to kind of loosen

24:05 junctions between the cells making up the vessel. That's what we call window

24:10 cells are what make up the blood here, these guys right here.

24:15 um so in addition to helping loosen the junctions between themselves, it also

24:20 on prostaglandins which serve the effect. effect is to intensify the pain in

24:27 area. Okay. Do you want be aware um you know that something's

24:31 on there and it's a wound you want to take care of it.

24:35 these are ways to kind of more . Something's going on there.

24:41 And so um so T. F. Is another major side of

24:46 . Uh This could even be released only by macrophages for example in the

24:52 here but also by the damaged tissue can release these things. Okay.

24:58 it's served a number of factors are one to cause a lot of other

25:06 of cytokines. So things like c protein, these sort of activate complement

25:11 example. I l one intra that for work and um bring about uh

25:20 Vegas halitosis of cell types may be fever. So it can it can

25:26 a number of different other exciting times released as a result of this tea

25:31 after it stands for tumor necrosis Okay. Also things like Elected will

25:39 about in a second. These are by the liver and they kind of

25:43 kind of to work on the complement . Okay, so lots of different

25:47 and chemical reactions have to be going in this process. Okay. But

25:52 all about, you know, activating cell types and things. Okay.

25:56 so let's look at this. Uh . Here we go. Yeah,

26:04 it's basically the same kind of uh huh diagram I'm showing. But just

26:11 of more emotion here. So you kind of see what's going on.

26:15 here's our capillary uh Oh here comes wound or subcutaneous wound puncture wounds.

26:23 . Microbes contaminating microbes on the I guess there comes some macrophages in

26:29 area. Mhm. And the whole tl r center time release um

26:39 And then it's followed by a different of kinds. Um And I think

26:46 getting close up here mm hmm. we go. So again these are

26:52 endothelial cells. This long thing right . Okay, now of course there

26:56 molecules selecting that's called that served to of grab the neutral the neutrophils that's

27:03 gonna go on. So you see so this process is made easier by

27:10 down blood flow in the area as as increasing blood volume. So that

27:15 to kind of help them grab onto cells because it kind of slowed down

27:19 it kind of tumbling along the And then I grabbed kind of like

27:24 of velcro grabbing it and um and we're gonna loosen up these junctions in

27:31 . Okay. That's gonna be brady that will do that. Which I

27:35 is gonna come into view here, . There we go. And so

27:38 see it there and then listening up and now they can squeeze through.

27:45 right. Uh There we go. . And so of course not only

27:51 the neutrophils squeeze through, neutrophils squeeze , but so too will flu other

27:58 in the in the blood as well we'll see here in a second.

28:02 of course Nature Fields will be the figure, civic type in the

28:07 And uh mass cells will be activated well by cytokines. Again, history

28:13 another type of basil active factor working the blood vessels. Okay. Um

28:18 now you see the fluid filling up the area. So you're gonna have

28:21 combination of fluid that exits the blood along with the neutrophils. But also

28:29 neutrophils are doing their thing and advertising gonna fill up with dead cells.

28:34 of course the neutrophils don't live You know dying. So it's gonna

28:39 a whole mess of dead cells and and stuff collectively. It can be

28:44 called purpose. It's the work that use for it. So um uh

28:49 of course the amount of swelling can greater or lesser depending on the severity

28:54 the infection and so forth. But these are the basics of this acute

29:01 response and the characteristic uh effects or of information, redness, the

29:09 pain, swelling, multi function So again through these basic active factors

29:16 are causing this. Um So let's back to here. Okay. Any

29:26 about that inflammatory response? Yeah. So you pull out a splinter.

29:32 so you have now you have a skin, would there be a signal

29:40 stop you know released? Yeah. gonna be um when when a lot

29:46 a lot of these cytokines are Yeah. It's gonna be a the

29:51 that are produced depending upon how many are at the site being activated.

29:57 is a function of what is the of infectious agents that are present to

30:03 a certain number of certain magnitude of . Okay. Plus once they're released

30:09 are going to have a chemical chemicals have a finite lifetime. Whether it

30:14 dissipate diffuse go away. Um But also not shown here, you know

30:20 the terms of the repair slash healing . You're gonna have to potentially have

30:25 saying pulling out the splinter right, could have some bleeding occurring. So

30:29 may involve clotting factors and these kind things. So yeah that's gonna be

30:35 of the healing process to um so I think so could see something before

30:47 can release the chemical factory. They release those chemicals without having to

30:52 well it's it all begins with the like to A. T.

30:57 R. On macrophages will trigger the of can release. So technically if

31:01 just do that and don't pay closer then they can release chemicals. But

31:06 think being a micro features that are of just programmed to them once they

31:10 buying something like that to then ingest . So um will a macrophage always

31:16 that? I'm assuming it will but can see maybe it won't and just

31:20 binding may induce subject and release. I think because there are specific cell

31:24 that's kind of what they do. was kind of a protocol is not

31:30 . Yeah. Mm hmm. Okay. So we can assume that

31:35 just it's not directly linked but it's a process. Yeah. This is

31:41 inflammatory response is yeah, it's its kind of process. Right.

31:45 Right. And macrophages can do that . It doesn't have to do this

31:50 just because I'm showing an inflammatory These are things you have these things

31:55 your lungs for example that are just know val being up whatever it may

31:58 in terms of microbes in there and not even related to inflammatory response.

32:03 so this is all microbes and the based on, yeah but what they

32:11 because they're not gonna are they fake your own microbiota now because they're going

32:17 be your your your own microbiota have cell surface markers that are gonna your

32:22 gonna say okay those guys are okay so that's yeah. Right so that

32:27 pages are gonna pay attention to that well so. Okay um Alright so

32:39 . It's a compliment is a number 13 factors are soluble in the

32:46 Okay and the um are in an state. Okay until they get

32:53 All right and so it's it's um worry about having to memorize all the

33:01 in this thing. There's no need but it doesn't involve a an initial

33:07 which is basically these are cleavages so cleave the protein and it activates it

33:13 so it's a succession of these one activated, then it activates the next

33:19 it activates the next and so on so forth. That's what they call

33:22 the cascade. Okay the complement And so um you know when you

33:28 to which The reason I mentioned these c. 3 and c.

33:33 These are kind of the ones when get to this point these are the

33:36 that initiate really the main effects. so C. Three is the inactive

33:42 C. Five is inactive and the forms of the Airbnb of each

33:47 And so C five is activated by C. Three a component. And

33:52 like I said it's when those two activated those are the ones to initiate

33:56 three main effects and the three effects the same no matter how you activate

34:01 complement. Okay. And so um first way which is the length of

34:08 uh this is the first one that discovered. So they called the classical

34:12 I guess for that reason. But you see the effects of optimization,

34:19 , sis and inflammation. So those effects of activation are the same but

34:26 it's activated. Okay so the only between the pathways is what's activating.

34:32 and so fastballs antibody the antibody binding microbe that will activate C. One

34:39 eventually gets down to three. And to at the point of that initiating

34:46 effects. The alternate pathway is binding pathogen components like a surface proteins and

34:57 that body itself will actively complement. and then the third is elected.

35:04 . Selected is produced by the liver believe in response to to necrosis factor

35:11 others kind of sight kinds but regardless elected will then bind to it's a

35:18 binding no molecule. Okay. And will life is actually produced by lots

35:27 things. Plant their plants in particular these but we produce them for the

35:33 of binding carbohydrates on bacteria bacteria known course for having all kinds of carbohydrate

35:40 markets in their service. Especially a negative with the old policy. Saccharine

35:45 there. Real long chain sugars. . And so um very common in

35:51 is a short of manos among Um And that's what this election's bind

35:55 write. The binding will activate And again as you see for all

36:03 ways of activation the effects net effects gonna be sent optimization, psychoanalysis and

36:10 . Okay and so um so this going to process here quickly. So

36:17 . We already know that. Right the difference here is we're not looking

36:20 antibodies as the opposition member complement. so competent with buying and then the

36:27 figures that excel will have a receptor the compliment to be able to bind

36:34 engulfing. Okay psychologists so this is a gram negatives are more susceptible because

36:41 negatives had that outer membrane right? positive has a pepper pike and layer

36:47 these things don't form very well in . So more so in and out

36:53 the olympic by their which is what be surrounding gram negative. Okay and

36:58 they activated complement brings together these other components. 789. Don't worry about

37:05 . The numbers. But what they is they form this tunnel. All

37:09 in the membrane so basically like a a hole into the cell contents leak

37:16 . Okay But he and gram negatives more susceptible to this. The in

37:22 of information uh we can trigger interact mast cells and causes the cytokines that

37:30 be part of the inflammatory response. So again all three effects uh the

37:37 no matter how it's actively. Uh And again inside a long process

37:43 companies activated the sustaining kind of deactivates . Uh and um it's likely uh

37:51 degraded. And so more company needs be produced in your body was producing

37:57 again he's just floating around your There's like 20 of these, there's

38:00 of in your blood in its active . And then when activated, more

38:05 more these effects can occur. But guess so compliments not a cell but

38:11 it's protein factors. Okay. Um questions. Yeah. Mike and ike

38:18 things they cause license in Michael effect down here. Yeah. Right,

38:28 these C9 C9 complement factors come together this to form a polymer, basically

38:37 a straw. It's probably pumped inside thing. Yeah. So obviously this

38:44 work against viruses. Yeah. I think it's that's I think it's

38:50 student for um something we look at like this. Yeah. Right.

38:57 . Oh yeah, I guess they penetrate a pepto black hand layer very

39:02 to get to the inter membrane of positive, which is why gram negatives

39:06 more susceptible to this. Mhm. Well they do that I guess when

39:15 could have the optimization effect perhaps uh inflammation effect in response. Hello,

39:26 are other options. So what's the of using policies? So, gross

39:33 I don't know, it's just I know if there's an advantage disadvantage I

39:37 optimization can potentially be more effective against Can be more effective against maybe more

39:49 , optimization guessing. Um but it's just it's an arsenal of

39:57 Yeah, auctions it's options. All . Right. Trying to deal with

40:02 kinds of things to be thrown You write viruses, gram negative gram

40:06 , Porta zones, big worms, know, you name it. So

40:11 have to have lots of options for things. Right. Good for

40:15 You know? Um Okay, so . We talked about this before in

40:22 context of Chapter six on viruses. , so host resistance mechanisms. Right

40:30 we'll mention that again but then we'll another interferon type that we didn't talk

40:34 . But remember the type one which did talk about before. That's the

40:40 . So, so remember that the Type one Year from now on will

40:51 help the initial effect itself, but will help others surrounding it.

40:57 so um the uh the viral infection the infection itself can induce expression of

41:06 interferon um likely as the virus is to his replication cycle, borrowed proteins

41:14 things can be can be uh detected uh you know, receptors or other

41:20 in the cell and that acts as activator too to promote expression of

41:29 And so um so then this affected will release interference. It will diffuse

41:35 into the surrounding tissues he sells with receptor for interfering will bind to

41:43 take it in and then it acts a transcription activator to express these different

41:51 proteins which you can either degrade viral as it infects or otherwise block expression

41:59 viral genes. Okay so uh so type one this antiviral. Okay.

42:06 uh only the cells that have not been infected uh well will be

42:13 Okay. This guy here is likely to succumb to the infection but this

42:18 in any other neighboring cells to be . So um The type one interferon

42:27 was discovered 40 years ago and was of the first um biotechnology products that

42:36 mass produced using comment D. A. Technology etcetera. Um But

42:43 didn't turn out to be the wonder that was hoped to be still effective

42:50 people still do in impossible. viral infection are given can be given

42:58 injections and and it can work but not a type of drug suited for

43:04 in a pill form or something like on the shelf that you can buy

43:07 the counter and it doesn't have a long lifetime shelf life is not

43:11 Um but it's it's it doesn't work at high doses either. So and

43:18 toxicity level combined with the instability. for something that's not a good over

43:25 counter products like an aspirin or something that so but it does have like

43:30 said it does it is given treatment a viral infection and so it works

43:35 better in individuals. Giving him a and kind of you know controlling those

43:40 kind of thing. Uh and uh with acute viral infections. It's not

43:46 that's good for long chronic type long effects but for immediate type of

43:52 Yeah it can be quite effective. The type two is one that says

43:59 of these that activates cell types so activates your different specific cell types.

44:05 , neutrophils. Okay and again so here by increasing the self antigens on

44:11 surface. Okay that will um so that the self antigens on these famous

44:19 types can allow them to present antigen the body. So if they produce

44:24 of them then potentially they can it our ability to to to show engine

44:28 the body. And so that again a it's good for us because it

44:34 you know enhance the ability to to um if there's an infection that it

44:39 more readily show that too uh immune cells in your body. Okay which

44:44 what you want to kind of enhance ability right to you know, head

44:49 the infection before it gets too Okay hopefully Um uh Any questions about

44:57 ? Yeah. To those are little read subtext that also find effect to

45:05 that I don't know I don't know . Good question. I didn't I

45:10 seen anything about that. Uh Like not gonna say it's your fault but

45:17 just don't know. So like can just apply that type one and call

45:22 a day or considerate possibility? You in terms of? Okay I guess

45:27 missing I understood you. Are you that? Does this Apply the type

45:34 ? Uh Yeah I don't it shouldn't don't don't let that cloud your You

45:40 that was better than the other. do that because certainly they both have

45:44 functions. 1 1 is an antiviral so that's certainly something you want.

45:50 other one is not an antiviral it's a activated function constitutional functions.

45:58 one of them is just a immune . The other one is an antiviral

46:02 . Uh Well yeah it's all it's immune response because the virus is

46:06 Right so um both immune responses but different functions within the immune immune system

46:17 . So what's the purpose of trying to activate you make those guys more

46:23 acidic that makes them more able to just and get rid of potential pathogen

46:30 the type of was just locked down to his death basically. I don't

46:35 if I don't get that. I there's just two different functions. One

46:38 antiviral itself, they get infected with virus can produce the interferon. Um

46:44 that's how it's produced by a virus cell produces the type of line.

46:49 Um just two different functions for two uh huh. Parts of the innate

46:56 system defense. Um Alright so fever think that's the last of our innate

47:04 system functions before we go into that system. So uh fever of course

47:12 adjusting the hypothalamus. So um so course you know that you're body's set

47:22 right? So um you maintain your at a certain temperature right? So

47:27 us it's 37 C plus or minus a degree. Okay. And some

47:33 us have slightly lower core body temps looks slightly higher, some somewhere in

47:39 . Um But it's uh fear is about putting a temporary increase in your

47:47 point. And by doing that you create effects that can be detrimental to

47:53 infection infectious agent. Okay. And uh the chemicals that can the newspaper

48:00 call pira jin's pyro fire generate gen , generate heat, fire. So

48:08 and endogenous. So exogenous pyrotechnics um those that are occurring infectious agents,

48:15 , bacteria. He's funny, it be uh Michaels Michaels on their surface

48:22 It can be certain types that they . Um But once in the body

48:27 the body they can induce indoctrinates, bones. Okay. And so interleukin

48:34 mentioned before is one of those. so it can uh directly act on

48:38 hypothalamus. So analogy is if it's outside, you're gonna get to your

48:45 , turn the heat on and so can warm up, right? So

48:49 know that you come in the you're shivering cold, you turn the

48:54 up. Are you gonna be immediately ? No, you're gonna be you're

48:59 still have the chills until you get that temperature, right? Because the

49:02 doesn't heat to your temp instantaneously. ? So um it takes time for

49:08 house to warm up, right, you will catch up that tempo and

49:13 better right now. Cool. You just right receiver, let's just go

49:18 the example here. So here is regular set point again, plus or

49:23 half a degree. And then uh increasing the temperature set point,

49:30 As what happens in a fever, are new set points, maybe something

49:33 38-40 somewhere in there. And so body is gonna feel cold because you're

49:38 there yet. You haven't cut off , that new set point. But

49:42 you do, you don't feel but you don't feel great because your

49:46 is not meant to uh it is meant to operate Optimally at 38,

49:53 , 40°. Okay, so even though at temperature now, you cut

49:57 you don't feel great, as we know. Okay, so, uh

50:02 once you catch up. But realistically kind of let it go through,

50:06 oscillate between hot and cold because you're fighting the infection. And so maybe

50:13 jin's will kind of go up and down a little bit, then maybe

50:16 back up and down a little So that kind of reflects a slight

50:20 and increase in fall in your in set point. And so you alternate

50:25 between being hot and cold. And so um once you have I

50:33 that fever we call breaking the right? You get back to your

50:37 set point and you're gonna feel warm course until you get down to that

50:42 than temperature. So what does all this do? What does the body

50:47 do? Okay, Well it's about the growth of the pathogen.

50:53 so uh pathogens, you grow pathogens the lab grown at 37°, right?

51:01 um if you elevate temp that will their growth rate. Okay, so

51:08 all about really buying time. That buying time concept works both ways

51:15 can work for us and against Okay, so from this perspective,

51:22 body temp buys us time. It's for our immune system to catch

51:27 Okay. The other side of that a pathogen that's hiding itself from the

51:34 system. Right? When we talk phase variation, right? You can

51:38 their formulary antigens now, the immune can't see it. That buys it

51:43 . And buying it buying time as can grow during that interval before it's

51:47 out. Right? So buying time the thing that works can work for

51:51 against us. Okay. So um in terms of increasing uh the adaptive

51:57 response to t cell activity. the T cells as well, we'll

52:03 certain types of really instrumental in controlling whole that that government response.

52:09 And so if you increase their you're going to mobilize your adaptive immune

52:13 . That's right. And so you , fever is is kind of a

52:17 for like all hands on deck. get everybody involved. And so uh

52:23 turns out is also an important factor terms of growth to the microbe,

52:29 pathogen. So, iron of course lots of functions particularly for micro we

52:35 know in terms of uh the whole system and iron as a component in

52:40 respiratory enzymes of microbes. For of course the hemoglobin is probably one

52:46 the number one iron users uh to oxygen. We of course have lots

52:51 enzymes that use iron. So important us as well. So we try

52:55 hold on. So we have chemicals produce that enable us to hold on

53:00 our for example. Okay so but to actually have chemicals that can grab

53:07 the iron. So it's like we're fighting for it in some cases.

53:12 but certainly iron. So the combination high temp and trying to keep iron

53:17 from them will lower limit their And so um again all about buying

53:24 so we can our adaptive immune system catch up and the adaptive immune system

53:28 some time to work. Um So beaver. And if we have to

53:35 any questions, yeah, We've heard 40°. Um But that again is the

53:46 of pathogens and you don't even need have um um Yeah I'm not

53:53 I guess it goes above 40. not good because there is a limit

53:57 don't want to go too high either that can be detrimental obviously. And

54:00 that can be a combination of the of pathogen, particularly if it's infecting

54:06 If it's a central nervous system, like meningitis can be in a in

54:12 area where it's very close to his . So that that may be a

54:15 why he gets so high potentially there the proximity and throwing out these pirate

54:21 . That combination can be one that trigger a very high attempt which you

54:27 want that at that point, you to that's that's obviously dangerous. So

54:31 now there's certain kind of depends on pathogen type and where the effects on

54:34 body that kind of. Alright, let's wrap this section up for the

54:41 , we were just talking about all um So we'll talk really about um

54:58 into a little bit of the adaptive system. Chapter 25. Just kind

55:01 overview and then just a little bit antibody um structure. Okay, structure

55:09 function and then we'll finish up the on Wednesday. Okay. Yeah.

55:57 right, so um let's see what got. So anybody can help facilitate

56:02 psychosis. That's correct. That's the process. Um Remember the complex that's

56:09 by activated compliments factors. Uh different of one protects against. That's the

56:17 one compliment is not to sell its factors. So it's going to be

56:23 . Okay, um so let's see questions. So here's the different

56:31 We went through an innate immune Um My questions. So let's go

56:39 adaptive immune system. So um the specialized lymphocytes or T cells and B

56:51 and antibiotics. So let's look at very basic question here. Okay,

57:00 system. Cell type most likely to with these extra sailor bacterial pathogens is

57:06 So um like we saw some cell of the innate immune system. There

57:15 also a differentiation in the exact immune in terms of pathogen types and how

57:23 deal with them. Okay, so data being system is broken down that

57:29 in terms of this. This side with one type. This side goes

57:33 the other type because they can come kind of two types, so to

57:40 . Make sure this is extra Yes, correct. Okay.

58:16 So we have listed here the types would deal with extra sailor would be

58:22 that we have listed are those that these. Okay, there's antibodies okay

58:33 anybody's are Y shaped proteins, various . And so what we have on

58:40 list here the thing that produces those plants with B cells. Okay so

58:46 toxic T cells will learn not today next time they deal with infected cells

58:52 to natural killer cells but in a way baseball fields are more destructive produced

58:58 they don't really um directly kill things interference, antiviral. So interstellar

59:08 Um So as mentioned the uh but doesn't mean system into dealing with 1/2

59:18 with exercise of pathogens. One with of passes. So human immunity and

59:24 mediated immunity. So cell mediated immunity the realm of various T cells.

59:31 the hero community B cells. And the the specific types so B cells

59:39 developing the plasma cells. This is form that produces um antibodies. Ok

59:45 have memory cells. So vaccination um to infectious agents will first exposure to

59:56 agents. First exposure to vaccine will production of both of these B cell

60:02 . Okay uh plasma cells of course antibodies produce and secrete antibodies and then

60:11 they will bind to exercise or So antibodies cannot work go inside of

60:15 cell and buying a virus based. they worked on the outside of the

60:20 . Um the social media community you t cell types. There's various t

60:29 types and as you go through this I really kind of just narrow it

60:34 and because there are many different types T cells of what I'm gonna be

60:38 about. Okay. Um just to it kind of not so complicated.

60:43 right because immunology is a very complex . Very interesting but unless very

60:50 Okay uh do recommend if this is interest that we do offer immunology of

60:55 I think every other semester here. And you can really get down into

60:59 the details because it can be a complicated subject. Um It involves not

61:04 not only do many B cells have but so too the T cells.

61:09 so and there's also a learning curve these cells. It turns out that

61:14 produced upon first exposure get better at they do. Okay so that's for

61:20 sides both T cells and B cells way. So it's a very can

61:25 very complex but nonetheless obviously interesting Um So I'm just kind of giving

61:31 don't see a watered down version but not the more complex version. Um

61:37 so T types. So you're sort toxic T cells are those that can

61:43 out infected cells. Um You have t cells called t. Helper cells

61:49 these um interact with cell types to them typically. Okay. To t

61:57 type ones. Well 1st of all cells interact with MHC molecules. Okay

62:03 different the differentiation of um functions between two types are based on the types

62:09 MHC molecules that recognize. So start toxic t cells recognize MHC one.

62:14 they're gonna interact with basically your body , skin cells, liver cells

62:20 Okay because you're making your body cells what have these types of molecules.

62:25 any of your body cells that potentially infected can be found out by side

62:31 the toxic t cells and these will those cells. Get rid of.

62:34 don't want them. Okay she helped one and two interact with MHC type

62:40 molecules. And as you find on , dendritic cells and B cells.

62:46 Actually then th-1 cells interact with This stands for antigen presenting cells this

62:53 with with dendritic cells and um uh Okay. Release of cytokines activate

63:01 That kind of thing. T. interact with B cells. So even

63:06 cells that can be activated. Okay certain T helper cells help activate

63:12 Okay so the division of labor among different t cell types interacting with different

63:18 types. Okay causing different effects. . Um and so as I mentioned

63:24 about buying this buying time idea. um so your definition system relies on

63:32 detection. So it's all about Right? It's predicated on uh the

63:38 of anti do. Okay and so about detection, recognition and binding.

63:48 . And then that binding affects a sort of output whether it's release of

63:55 by that lymphocytic cell protective antibodies. happened? So it's a kind of

64:02 four step process. And that's the the time element because that those things

64:07 occur like that. Okay. That's adaptive immune system the slower right takes

64:12 to to to do these steps. . But nonetheless once it does kick

64:16 it's very effective. Okay so um talking about binding recognition and binding.

64:25 that's all about binding of in this looking at antibodies. Right, so

64:33 structure has that y shape to Okay, I want to talk about

64:38 of those in a second. So an example of bacterial cell and uh

64:44 is buying. So energy. So can be literally almost anything.

64:50 when you think about um for a that's potential pathogen in your body,

64:55 is your music themselves? Gonna Let me see what's on the

64:59 Right, so a an LPS layer a gram negative uh capsule perhaps of

65:06 pathogen, a pepper like can uh types of molecules sticking on the

65:14 Right? Glycoprotein? Like lipids, have you? Okay so all these

65:18 potential antigens. Okay and so so kind of two viewpoints here in terms

65:24 the binding. Okay so we have to an energy. Right? But

65:31 Epic Tope is within the engine. the episode is actually where the actual

65:37 occurs as we see here. All . So the gray area here's the

65:43 . The red is the actual spot it binds. That's what we call

65:47 episode. Epic Tope smaller binding occurs of the larger. Okay okay.

65:56 . And so and it can also you don't have to be a bacterial

66:00 . It can be a virus can a protozoan and it can be what

66:04 can be appalling. All right all things are antigens that can produce an

66:09 . Okay um Now in terms of structure of antibodies. Right so again

66:15 kind of wide shape but there's actually subjects here. Um We call heavy

66:21 light change. You can guess what is. Right. So that's based

66:25 size and heavy chains, bigger. chain smaller. Of course you have

66:31 sulfide linkages holding it together. Uh you have different binding sites. Okay

66:39 the classes. So I G. for immunoglobulin. I am a Okay

66:49 now you know you have what are engine and binding sites you have two

66:53 those minimum per antibody we'll see that um antibody types can actually come together

67:03 form polymers. Ok so I G for example can can put two of

67:08 together to form something that looks like it's. Okay so it actually has

67:20 121234 per molecule if you will per er Okay, it forms a dime

67:30 Um IgM can form a Pentagram That makes 10 binding sites. So

67:35 can happen with those two types of . Okay, um now the there's

67:42 another binding site which is down Okay, so of course antigen binds

67:49 these two sites. Okay, you there? Okay, at the

67:55 but this site down here can be to a particular cell type.

67:59 You have to have the receptor. we talked about optimization. Right?

68:03 is how it happens this side buys pathogen. This side binds to the

68:10 or neutrophils. Right? And brings the optimization process. Okay, um

68:19 , uh in terms of the more , so more technology really. So

68:25 I G uh so we have two molecules and one high G G.

68:31 , so how can you, at molecular level distinguished these I G G

68:38 from I G A s. How can you determine if an idea

68:42 an idea? A right was all criminalizing sequence of various regions here.

68:48 , so you have what are called types? Okay. Which differ in

68:54 heavy chains? Okay, so an G A will be the same in

69:01 um uh constant regions. Right, , idiot types. So I G

69:05 media types. Okay, will be , similar the same in these heavy

69:15 regions. Right? Um But they differ in the Andean binding sites.

69:21 can be the same but they can you produce you can't just ig antibody

69:25 the same engine, they'll all be same. Right? Same heavy region

69:29 managing body sides. But they can be I. G. S.

69:33 different antibiotics sites. Okay. Excuse . But the constant the but what

69:41 them all together as being IJ is the same in this area here.

69:46 course I G differs in that All right. So there is a

69:50 type. Okay so you have a D E. M. Aisa

69:55 Okay. And so um so that's differentiates these classes. So the Intertype

70:01 within the class. Okay. And the ice A type are the different

70:06 . Okay. Um The main question that. Okay so um video types

70:16 an ice type. So ice you can have multiple media types.

70:21 . That differ in antibiotic sites. . Um So if you look at

70:28 , what happens when you have antigen fighting? What are the consequences of

70:34 ? Right. So here's one we illumination clumping basically what this is clumping

70:43 . So um but basically what you're is because anybody's have two binding sites

70:50 can clump together multiple what they're calling units? Right, infectious unit could

70:56 a microbe. Of course. And uh what you're doing is you're

71:02 the number of effects just you So here you see 123 pathogens on

71:08 own maybe three separate microbes. But clumping or illumination reaction with antibodies basically

71:16 them into one unit. So easier the body to deal with.

71:20 That's why your I. G. . Alright. That can form that

71:26 inform the my pen is not working . Can form the dime. Er

71:32 , you can have four binding sites diamond. Uh Gm can have

71:37 So that can really clump together a of units in the ones that's why

71:40 very effective in that function. observation. We already know about

71:46 Right neutralization. So that's what the vaccine produces neutralizing antibodies. Okay.

71:55 so what that does is basically coats pathogen. Okay. And prevent it

72:00 adherence adherence to cast into your tissues very often a virulence factor. They

72:08 be able to do that. Obviously can you can see that the virus

72:11 need to do that because step one recognize host. Buy into it and

72:15 entry into it. Right? So you're if you're blocking that through the

72:19 neutralizing uh antibodies then you effectively are reducing the capacity of the virus that

72:27 infection or or battery but also remember toxins produced many patterns produce toxin tetanus

72:35 botulinum toxin etcetera. These are dealt also by antibodies that bind because the

72:42 needs to also bind to a target . Get inside and cause damage.

72:47 if you can not allow it to by putting everybody's on it, then

72:51 effectively neutralized the toxin. Okay, of complement. Already talked about

72:57 Right? So that that's the effect antibody binding. And then this we

73:01 about as well early last time. the in the in the context of

73:07 function of fields, right center field deal with large pathogens, multicellular types

73:15 this. So something like this to bring this down. It takes a

73:19 effort. Right well, 11 cell this is likely not going to be

73:23 a lot of damage. She brings lots of immune system cell types to

73:28 it down. That's what this antibody cell mediated toxicity. Way too many

73:35 . Um 80 cc uh so we antibodies introduced to the passenger binds two

73:45 . And then remember the fC portion to a cell continue receptors. So

73:51 can have those can be found on macrophage on fields. And so it's

73:57 way to kind of bring them together the large pathogen here. And then

74:04 response by the cells is to release of different types of different types of

74:08 chemicals to kill the pathogen. But point here is using hand buying to

74:13 all these cells together right on top the pathogen because it's so big,

74:18 gotta get to bring all these cells and their toxins to kill it.

74:23 again, all effects of potential effects antibodies find it. Okay.

74:31 you need questions biography, just like , visible. How? Oh

74:41 they're not. They're not, they're , but they're not that big.

74:44 parasite. Yeah. The large parasite could be it could be visible to

74:50 it up. Yeah. At first could be okay, all different than

74:59 . Okay, so it's like strategy . Okay. Yeah. Thanks

75:09 See you on

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