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00:38 Okay. Okay folks, um turns on martin. Yeah, there we

00:49 . Okay. Um let's see. today we're going to begin the last

00:56 of the course. So uh which going to be aspects of medical

01:03 So looking at the new system basically um we start with kind of how

01:10 body fights disease and the mechanisms you . And then later next week we

01:16 a kind of the actually down it's going to be in the flipped

01:22 form right there and uh okay, the microbial pathogens. Micro pathogens overcome

01:34 defenses to cause disease. So Kind get it from both sides and then

01:39 up with and I'll talk more about next time next week when we get

01:45 26 here in diseases, I don't what's going on there with diseases.

01:52 there's like if you've you've um if looked ahead in the notes um chapters

02:02 . Head at the beginning a couple a couple of slides that list um

02:10 different pathogens. Pathogen list is listed diseases and then by pathogens. So

02:14 kind of goes both ways to look it. So, so you have

02:20 list of pathogens and then the So you're gonna have its heavily grant

02:25 heavily memorization and stuff, but um figure it's it's it's I think it's

02:30 for you, especially for going to school or planning to um or some

02:36 profession at least have some familiarity with of the diseases, infectious diseases.

02:42 and so it's kind of broken, make an easy study guide yourself.

02:46 make a table pathogens on this in column, diseases they cause in this

02:51 and then some interesting features about So it's all detailed in the In

02:56 nose for Chapter 26 and just a up on that. Okay. Um

03:02 and there's like, and the other is I certainly don't cover every disease

03:06 talk about in chapter 26. So sure you stick to that list.

03:10 . There's like maybe a dozen or I think diseases. Um anyway,

03:15 talk more about that next week. uh let's see. So obviously what

03:21 talking about today is not on the . Remember the exam is starting tomorrow

03:26 friday. And so um this is what we're starting to talk about today

03:31 for the next three weeks is just four. Right? So so remember

03:37 is no comprehensive exam here and the quote here is exam four, which

03:42 The material which we're starting today. chapter 23 through 26 is Example

03:49 Okay. Uh and that's not not a month yet. So um let's

03:55 . So what else we have. smart work. There's nothing to do

03:57 smart work Sunday. So that uniform doesn't begin to be turned in for

04:03 couple of weeks yet. So and of that is available to you on

04:06 work as well. Uh let's Um Okay. Blackboard quiz. So

04:13 blackboard quiz this the blackboard quiz will just be what we talked about

04:16 Okay, so it's not gonna be I made five questions that relate relate

04:23 um to today's material which is basically part of one. We do

04:29 like a 1.5 lectures as part one part one in part one and

04:34 So all 23 is like over 1.5 And then we'll go into uh the

04:41 immune system. So uh chapter 24 relatively brief um because that can be

04:48 very complicated subject when you start talking antibodies and antibody production and whatnot.

04:54 do offer a course in department um that goes into great depth but I

05:01 kind of give you an overview of going on there. Um but that's

05:06 for that reason it kind of it's of short, that kind of expands

05:10 on vaccines and what the different vaccines what that's about. Okay, so

05:19 so um so what we're of what we're talking about here in this

05:25 is starting with the innate immune system and you know, the your immune

05:32 of course uh uh and the strength that immune system of course can vary

05:39 times depending on if you're sick yourself you're on antibiotics or um um your

05:48 compromise in terms of immune system that determine certainly how susceptible you are

05:54 to infection. And um and so question of does infection infection there is

06:02 sort of equal disease. Is that ? If you are infected, you

06:10 disease symptoms of disease or you're going get sick? Thank you.

06:16 absolutely. And there are asymptomatic that all familiar with that in terms of

06:21 asymptomatic carriers. Right? And that to a number of countries diseases of

06:26 . Um so remember, that's counter to what the coke thought.

06:31 Cokes postulates about only only diseased animals or diseased individuals have the pathogen and

06:40 that's not the case. Okay. , the the infectious disease you are

06:46 vaccinated for prior, prior to coming school as they're all college students not

06:52 meningitis, that the meningitis vaccine that when there are outbreaks of that

06:59 the the source for The organism is humans because about 50, more than

07:06 of the population naturally carries that in system and their throat critically and they

07:13 have any symptoms of disease. They're carriers. Um, and that's true

07:17 a number of infectious diseases. so questions, not infection does not

07:23 disease. You could have become You may have had the covid virus

07:28 never knew about it because your body took care of it. Okay.

07:32 with the other types of infections. it's just a lot of factors playing

07:38 whether you will succumb to infectious Okay. And so um not only

07:44 your health immune system, the The of pathogen, it is the the

07:49 of pathogen that infected you. And far there's a lot of different variables

07:53 the window that. Okay so um I kind of start this with,

08:00 is mostly stuff we're going to cover chapter 25. Okay I'm not microbial

08:06 but I figured since we're going to spending next 2.5 days talking about your

08:11 system then let's just kind of talk little bit about things that constant factors

08:17 and how they do that. And again we'll revisit this these terms and

08:22 in a in a next week. don't be you don't have to be

08:26 those about writing all this stuff down because you're gonna see it again.

08:30 . But anyway, so we have pathogen. Okay. And obviously I'm

08:34 it's obvious to you that you we're talking about disease, we're talking

08:36 infectious disease. We're not talking you know, non infectious diseases,

08:41 and heart disease, whatnot. So infectious diseases. And so the pathogen

08:46 pathogen um might be any microbe will a an environment where they naturally

08:54 Okay. And we refer to that the source or more correctly than reservoir

09:02 is where if you want to study . X. Okay. And it

09:06 have to be a disease outbreak occurring you to do that. You just

09:10 to study it. You go the of where natural designs is where you

09:15 the reservoir. Okay. Um Does know the reservoir for Covid? It

09:26 it's not a scientist in Wuhan Mhm. You actually got it from

09:31 else or here. Um What do say? What kind of bad?

09:39 it's bad. Yeah. Uh that for um uh well rabies is a

09:48 of different animals. Different mammals type carry rabies. Um And so it's

09:53 vary, it can be an it's very common to be an animal

09:57 be called Zoonotic diseases originate in Um uh It could be soil,

10:02 could be water, it could be , so it's uh different reservoirs.

10:09 It it depends depends on the on pathogen type, but so you have

10:13 source where they're found then the house course has to get to you.

10:17 , so that's the transmission right? can be through the air,

10:21 foodborne. What happened? Okay. then uh you know, susceptible,

10:26 are you going to succumb to it not? Just mentioned, it's gonna

10:29 on your defenses and your health and immune system? Okay, so from

10:34 perspective of the pathogen um it has you know, several steps here.

10:42 it's not just as easy as coming your body and bam you've got disease

10:46 itself, he has to obviously enter host by some means of transmission.

10:54 . Um and then oops wrong button uh get through uh invaded the host

11:03 host. And you know whether it damage or not, you know?

11:06 it all depends on the pattern type keyword here. Virulence factors, it's

11:12 about endurance factors with pathogens. And um the severity, severity or

11:19 lengths, violence related to severity um the pathogen will depend on what the

11:27 factors that has um what do they ? Some can be things like toxins

11:33 obviously that will damage host cells. uh other things and very often it's

11:41 that a passenger will have a time temporal infection cycle, so to

11:49 So of course though it'll still express early in the infection cycle that relate

11:54 maybe be able to stick to a cells. Right. Adherence is can

11:58 a big difference factor for many cells pathogens, so stick to the

12:02 so to speak. Right then it okay breaching host barriers. So back

12:09 the meningitis organisms. You will see that one is um Uh huh.

12:16 has to um it normally resides in what we call the nasal pharyngeal

12:22 10 of them, back back throat , the mucus membranes and um but

12:28 not where it causes disease. It disease when it gets into your central

12:33 system. Okay, so pathogens that that that invade the central nervous

12:38 That's a big hurdle overcome because you your central nervous system obviously, right

12:46 and spinal cord, right? You it has its own kind of

12:50 uh, it's protected by a number different cells that restrict what can have

12:54 to it. And so and then provide the right environment for neurons.

13:00 ? Remember neurons form action potentials. have to have proper uh saw you

13:06 , things like that. So it a whole network themselves that support,

13:10 ? Uh, and so it's restricted to what can get in there.

13:13 pathogens that that that's what they They have to have a certain business

13:19 to kind of get through. It's called the blood brain barrier. So

13:24 the cross that, it's not an thing. So pathogens that do not

13:28 different strategies and meningitis, bacterium is of them. Okay, so

13:34 the bottom line here is the the a business factors are what enable passengers

13:39 college disease and the collection of various they have will determine really how how

13:48 they are in terms of causing Okay, but we're gonna revisit this

13:52 a couple of weeks. So, of course you have various the whole

13:59 of of defenses to counteract, you , the pathogen and that's what we're

14:05 to go into uh, today. . And so again, more terms

14:10 you that you use, of course talking about disease infected disease. So

14:15 the cause of disease, The ideology ideological agent is the cause of

14:22 Pathology. Pathology is kind of the process, right? And it includes

14:27 cause includes um mechanism by which the gets in that causes damage um the

14:35 process if you will. And then course that can be accompanied certainly by

14:40 changes. Right? Um fever, other kinds of symptoms. Okay,

14:49 um or maybe not so much. . It all depends on the pageant

14:52 the infection type. Okay, so look at this question. Alright,

14:58 kind of alluded to this previously when talked about something else that phase

15:04 we talked about the time. in terms of response, because there

15:09 be a difference, maybe there's a between your immune systems and so uh

15:14 I said, we're gonna start today be the innate immune system and see

15:20 that operates. Alright, let's see you think there's a time element

15:34 Okay, Okay, a little Right. So the innate immune system

16:15 just think about it. Pathogen pathogen out here and I want it's gonna

16:20 you. Okay, what are the that's going through to do that?

16:24 , So your adaptive immune system? innate immune system is immediately write your

16:29 is a natural barrier. Okay, the the blinding of your um throat

16:40 , uh mucus membranes we're talking Right? That's another physical barrier,

16:45 ? So um that doesn't require any other than just being there. Right

16:51 then those um surfaces also have secretions different types of antimicrobial chemicals in

16:58 Okay so it's things that are always . Alright. So does that mean

17:02 much of a time parliament with But with the adaptive immune system there

17:07 because it has specificity. And so can look at the innate immune

17:14 What can you get the whole thing as 1st, 2nd and 3rd

17:19 Okay and so again just to visualize pathogen not here. In fact the

17:26 how its layers is going through. certain intact skin mucous membrane and don't

17:33 the microbes already on your body and your body they they to play a

17:37 role In your system. Um 2nd defense I call more specialized cell types

17:47 processes kind of characterized second line Okay so uh white blood cells.

17:55 ? The Vegas of ties Lucas sites and include neutrophils, neutrophils. And

18:00 have other types of macrophages of Vegas is a major process that's used to

18:09 pathogens. Okay. And these cells specialized in that certain ones are uh

18:14 when I turn processes that are involved things like inflammation fever compliment compliment our

18:22 factors in your blood that get activated cause different effects uh antimicrobial substances.

18:30 again uh this character actors. 2nd defense. And so um and so

18:36 third line we called at that Okay. So t cells b cells

18:44 obviously heard of antibody production. That's that's the realm of your third

18:48 defense. Okay. And so this the concept of specificity. Okay.

18:53 which relates to the time element here the immune system, is going to

18:57 a little bit slow to respond because relies on the presence of Anthony.

19:07 . So what's answered? An engine going to be the molecules that are

19:12 are on the periphery of the Right. A and LPS layer of

19:16 gram negative capsule that has that uh you know, any kind of

19:22 biological proteins on the surface despite the . Right. These are all things

19:27 on the surface. So do you of your cells of the adaptive immune

19:33 is having eyeballs? And they're looking see what's out there. Okay.

19:37 so they can only see what's on surface. All right. And so

19:42 so it takes um the Texan recognition two engines and then that induces a

19:55 output. Okay. A production of , you know, antibodies or other

20:02 . Okay. So it's this Right. So that takes time to

20:07 recognize, bind and form whatever the is. So that's why it's not

20:15 . Okay. And that's why Pathogens try to buy time. Right.

20:22 by temporarily hiding from the adaptive immune . Right. Remember the phase variation

20:27 talked about in chapter 10 is how pathogens can switch on a different form

20:34 the engine. And so when they that, then it's temporarily invisible.

20:39 that's time one because it has to detected recognized bound to. And then

20:45 put a curse. Right? That time. And we all know how

20:48 bacteria can grow. Okay. And within a couple hours, bam you've

20:53 lots of more pathogens. Okay. they'll do whatever they can to buy

20:58 , right? That's time they can and increasing effect. Okay. And

21:05 , um so well look 1st, at one of the main defenses,

21:14 have This one right here. You're . Okay. So of course.

21:23 it just doesn't appear out of All right. That's what this question

21:26 meant to answer. Okay. So can think. Who can you think

21:32 providing europe microbiota? Yeah, it's have to It's a clicker question.

21:43 , excited there. Yeah, you be. Yeah. Mm hmm.

22:01 . Yeah. I should admit that actually make another correction there, you

22:04 , not addition, not correction addition this. Um mm hmm.

22:16 So I'm pretty sure. But guess ? I think they're going to

22:21 Mm hmm. All right. And answer is mother. Yes.

22:30 Um or I should also on their . So the person who gave birth

22:37 you. Let's put it that Okay. Um through the birth canal

22:43 acquire initially require your uh microbiome Shortly followed Once you're out in the

22:50 outside the room. Um uh Obviously breathing breathing stuff and the beginning eating

22:58 right? Um And that of course the amount and diversity of your

23:04 So you know even at at at early age and again don't memorize this

23:11 . It's just meant to show you of the numbers of of microbes in

23:17 on your body in certain parts mouth G. U. G.

23:21 . Tract. And and the obviously staggering amount in your intestines is you

23:30 pretty remarkable. Um And then also ratio of a roads and a roads

23:35 of anaerobic activity. Okay and so even in a newborn you can see

23:43 differences in the microbiome um babies that born naturally versus cesarean, cesarean.

23:53 miss out. I'm going through that canal right? Um differences in breast

23:59 versus bottle feeding, breastfeeding. Uh course it produces um in the milk

24:06 milk is lactose sugar that baby can and get energy from. But also

24:12 things in there that baby can't necessarily anything with. But what I can

24:17 something with it are the are the in its body. And so they

24:20 of can feed on selectively selectively feeds . And so Um and if there's

24:27 kinds of studies done and it's been been going on for that for the

24:31 1015 probably 20 years now about your and the importance of it and what

24:37 can do for you. Um Something day comes out something new about that

24:43 terms of research. And so uh no doubt if you think about humans

24:48 been evolving for six million years. had that microbiome in the same amount

24:53 time. So obviously they've coexisted with . Coe vulnerable us. Um and

25:00 not surprisingly have lots of benefits. . And so um having I'm here

25:08 convince you if you're a germophobe to not to eat so much of a

25:11 . Okay too. Uh I'm not you to go bask in the in

25:17 sewage to get your bacteria on Okay. But you know have a

25:21 of uh don't don't but don't be much the other way either.

25:24 I think it's good to kind of you know yourself to various various

25:31 Okay. Uh But they know that a diversity of microbiome is better than

25:39 that's restrictive. So that your book about this hygiene hypothesis where that that

25:45 our our ancestors like we had a diverse microbiome um than modern man does

25:53 now we're you know of course our were more out in the open.

25:58 They were more of an indoor type , right? We have developed all

26:06 of hand sanitizers and soap and wash clean and all that good stuff,

26:11 that has taken a toll in terms our microbiome. It's believed and so

26:17 like being less susceptible to allergies and disorders has been correlated to something more

26:26 . Um verse microbiome. So among things. And so um so it's

26:32 good thing. Okay. And as know, I think we mentioned on

26:36 one that um the member of microbes your microbiome outnumber your own cells.

26:44 . And there's uh you know, lots of benefits. We've mentioned some

26:48 these as we go through. And having said, microbes are everywhere,

26:53 in and on your body. They be everywhere. Right. Obviously you

26:57 an infection serious infection if you're seeing in your in your vital organs in

27:02 brain, you know that that's that's normal of course, but they can

27:06 pretty much everywhere else. Okay. so of course it can vary,

27:11 know, because your your health varies over, you know, your

27:15 And geography can play a role in too in terms of how your microbiome

27:20 experience changes throughout your life. Different factors play into that. Um

27:27 one of the main benefits in terms um preventing disease is this you probably

27:35 this uh this term in uh intro basically one of the ecological terms go

27:43 competitive exclusion. I think the ecological is no two species can occupy the

27:51 niche, one has to go either out or killed. Right? So

27:58 is the same idea. Okay um mere fact that microbes are occupying your

28:04 inside and out means that for something come in and take hold, it

28:10 not an easy task because the microbes have are very well adapted to their

28:17 niche on your body. Okay. your body, micro environments can

28:22 right? Um depending on where it's um Some areas are more uh salty

28:29 skin tends to be more more more . So you have to particular microbes

28:33 that are suited for that environment. Others areas are more anaerobic. And

28:39 just just various. Right? But are very well suited for where they

28:43 on your body, right? And is something that really just can't come

28:46 and kick them out normally. so that that this idea of competitive

28:51 is is a good one because it can potentially minimize the uh the pathogen

28:58 taking hold um And so we look symbiotic relationships alright, which can be

29:05 , bad or or no no no foul in terms of these plus

29:10 and zero designations. And so most your in fact I'd say most of

29:16 microbes are in these two categories, als and mutual stick. Okay,

29:22 commence als have no uh you don't benefit or harm. So there's really

29:29 effect on you but they do Of course food, shelter,

29:33 that kind of thing uh mutually Microbes of course can produce things like

29:39 you know asking is that you normally be able to produce certain vitamins uh

29:45 microbes can digest certain foods you would be able to otherwise. Um There's

29:52 system functions. They have um they to be chemicals that they produce that

29:59 interact with immune system selves to kind enhance their activities. They can um

30:05 can minimize the effect of anti inflammatory your body may throw out because of

30:12 response to some allergen or something. so a diverse microbiome. There's members

30:17 there that can that can kind of that effect somewhat. So that's all

30:21 of these being being benefits to Okay. Um and you can enhance

30:30 uh protection enhance with the use of . Okay. Does anybody use programs

30:37 you think it helps you are how I don't think that's this before

30:47 What? Probably back in day I don't know what the answer

30:54 Mm hmm. Uh Yeah, I take my wife takes and I tend

30:59 do lots of things like yoga and like that. So I get bacteria

31:02 way. Um I think um it's certain happening. It's one of those

31:09 test for yourself. Um My wife's mine but uh you know it's uh

31:17 think we're gonna do it I'd say the get the pills that have the

31:21 concentration of bacteria because you know a of are gonna carriage as they go

31:25 your got it. So but they certainly uh benefit they many of them

31:33 the members that you find in Okay. But much more concentrated.

31:39 but certainly uh I would certainly recommend if you've been on antibiotics, right

31:44 gonna wipe out a good portion so take them out or something like

31:48 Um Anybody have a bad experience with . Really bad. Really? Okay

31:55 you're not taking them anymore obviously. . Really. Given any details.

32:00 fine. Um Okay uh What about pathogens? Okay. So even within

32:11 group. Okay. This which most your microbiome was in one of those

32:16 groups. There can be types that cause disease. Okay so that's what

32:23 entrepreneur types are normally not a problem there can be a problem when um

32:31 when they are able to get out their usual environment. Okay so basic

32:39 of that is to say a staph like you have your staff that normally

32:43 in your skin because membranes and you some kind of a mood into the

32:48 for example then they can get into areas that don't normally reside and that's

32:52 the problems can occur. Um a imbalance in your microbiome. You may

32:59 heard of clostridium difficile and causes especially elderly uh and the newborns uh it

33:09 be a very serious diarrheal disease. that organism normally resides in your

33:15 but it's not a problem unless typically you're on antibiotics in your gut microbiome

33:20 of changes or is upset, then guys, those clostridium can take hold

33:26 and and and cause this disease more so an issue and with elderly

33:32 because they tend to be somewhat sickly sometimes and and and and on antibiotics

33:38 things, so but nonetheless, the pathogens. So in contrast or primary

33:45 , you don't have a primary pathogen accident. Okay, If you have

33:49 of those, it's obviously there to disease and examples of that are things

33:55 anthrax Ebola service. Um these kind things that don't live in the body

34:01 , but in fact and and cause . Um Now. Okay, so

34:08 the next question. This gets us the next part. Okay. Which

34:12 going to be um uh first line second line defenses here. Okay,

34:20 let's see uh how we do Okay, um so we'll start first

34:29 the physical chemical barriers. Some of things are mentioned here then. 2nd

34:34 defense or different cell types. A of those are mentioned here.

34:58 mm hmm. Yeah. Mhm. . Okay. Let's see what we

35:35 and good. Okay, if you answered. Gur correct. Okay,

35:43 all these are true. A through for all true as we'll see,

35:46 gonna go through all these um So um of particular importance in terms

35:55 really how your adaptive immune system works . Are these guys? Okay,

36:05 guys here. Okay. Um So you're gonna be able to take something

36:11 not supposed to be in your you're gonna have a system that you

36:15 yourself, Okay, this is supposed be here, right? Because then

36:19 won't be able to make a distinction what's supposed to be there and what's

36:21 . So the MHC system is really barcodes on your cells, right,

36:27 safe, This belongs to you. if something doesn't match that barcode then

36:32 are then they can potentially be taken of. Okay. Um So let's

36:39 so as we go through first line , it's gonna be a little bit

36:44 repetitive in the sense that the physical also produce secretions that double as chemical

36:53 . Okay, so in terms of skin, skin is a fairly pew

37:01 um uh surface. Okay, very would sell sell that liquid cell layers

37:08 has this character. So the character really thick. And your nails fingernails

37:12 here, that's that's keratin. But too there's a layer of this on

37:16 on the skin as well. now there are natural openings of course

37:22 glands towards etcetera. Hair follicles, openings. Um But except for

37:28 you know, it can be fairly a good barrier. Um Of course

37:33 you do have a wound or some of splinter or whatever puncturing and that's

37:37 I call subcutaneous. Um You can into the skin layers. The mucus

37:43 of course are what line your body . And there's a mucus secretion to

37:50 those those cells can be susceptible to out. So you have a mucous

37:54 to keep them to bathe them in , keep them happy. Um But

37:59 you have different things like um hairs , hairs in your nose, Celia

38:06 respiratory tract. The mucosa Salieri Right? That's a big defense

38:11 You have to keep things in your . Okay so it's Celia that are

38:17 moving and mucus produced helps to trap microbes and the moving Celia caused you

38:26 expel them. So it's important defense for uh your rest of lungs particularly

38:32 whooping cough disease is um when that damages that system. And so you

38:41 to a severe respiratory infection. Um any case uh tears and saliva,

38:48 ? You have different kinds of fluids well. So saliva uh you know

38:52 swallow it fairly regular pace. It's about the day. Uh that

38:59 washing over your gums and teeth can wash stuff off um tears of course

39:05 keep your eyes moist and can also off microbes and particulates. Um Other

39:12 like the glass of course covers that so you don't get material in their

39:17 wax. Okay can can trap microbes funny digestion right? Your paris

39:24 Your intestinal tract is moving moving stuff . Okay. But then again as

39:31 these are all both these barriers also chemical factors in them. Antimicrobials.

39:37 In particular what's common to many of is right here. Right.

39:42 I write you see it in the , saliva. Um sweat. Okay

39:50 my design breaks down pepper look like . Right? Which of course is

39:54 cell walls of bacteria. Um Also differences in these fluids. Right?

40:01 gastric juice certainly is very acidic as vaginal human secretions are acidic. Um

40:10 can have antibodies in them. Uh uh I mean coastal secretions will have

40:19 uh I. G. What's called . G. A. A.

40:24 serves to buy into pathogens and keep from binding to your cells. So

40:28 so different types of of um Antimicrobial defenses is another one. I I

40:38 these are like um symmetrical shape hollow . If you will uh that kind

40:45 can insert into the membrane and cause of material killing the cells. And

40:52 there's um these defenses are rather small there are hundreds of different types of

40:59 things produced by various cells um including like macrophages, neutrophils but also some

41:05 cell types produced these um as a as a as a defense. Okay

41:12 The. Okay total like receptors. I equate this to um Let's see

41:22 pulling the lever to sound the fire right? Fired you send the smoke

41:28 goes off and you are building pull fire alarm. Alright that's what these

41:34 are full of receptors are the alarm in the body. Okay. And

41:38 when they're triggered so like most everything your body alright yourselves communicate with each

41:47 through binding of chemicals right? Uh yourself are told to grow by the

41:55 of certain kinds of hormones. Um So similarly it's it's chemical signals

42:01 are sent out and that's how your of the immune system responds. Okay

42:05 the trigger is something like this. so this term maps pants or it

42:11 ridiculous but the the the name has and I'm not sure why they changed

42:16 . But um the A. P. S. Part of the

42:20 associated molecular patterns. So M. microbial P. Is panicking associated.

42:27 . Um I used them interchangeably but but what what are you going to

42:34 into that? We're going to buy the things on the periphery of the

42:37 right? And he was basically. and so uh the gentleman cell wall

42:43 . And so you see here in upper corner here a this is actually

42:53 part of a macrophage I think think cell. And so it figures Excel

43:01 course engulfs and digests, microbes and and part one is to bind.

43:07 and so you see the binding here a toll like receptor. Okay so

43:13 there's a number of cells that have just macrophages and neutrophils but other cell

43:18 will have them. And you see so total like receptors on the

43:24 All right as you see here these ones very similar called nod like

43:29 Our internal. Okay so one of things too no um is that packages

43:37 in two types those that do their outside your cells extra cellular pathogens.

43:44 that cause damage part of their their their their things to go inside

43:49 Well we already know viruses do Right so that's obvious but you'll also

43:54 that there are bacterial types that do as well. Okay so the difference

44:00 the bacterial types that do this aren't it to use the cell to replicate

44:06 they're just going inside the cell to out from the immune system or and

44:12 to use it as a as a to get further into your body.

44:17 penetrating different cell layers. Okay. So if that's the case then you

44:23 to have systems that will be able detect both types. Okay you're active

44:29 systems also set up that way to those that are exercisable pathogens and those

44:34 are interested because it required a different kind of strategy to deal detect the

44:39 . Okay so in terms of these so external receptors these T.

44:45 R. S. They will recognize bind to something like this.

44:51 So here's a himself a gentleman contact receptor or maybe it's a spike of

44:58 virus. Okay, internally so remember a virus of kind of course uh

45:05 and maybe maybe viral proteins that are synthesized and assembled will contact one of

45:11 receptors or it could be a bacterial that's inside of it. Maybe it

45:16 a toxin that's inside. So not case, you have a way to

45:21 that as well now whichever one Okay the the effect is the

45:27 Okay so what's gonna happen is a a cascade type reaction occurs but one

45:34 becomes activated and the next thing that activated and then we finally have an

45:39 and in this case it's cytokines. this is a term you will see

45:44 here throughout this whole section. The study is is a generic term

45:51 a number of different chemicals with different involved in some aspect of dealing with

46:00 disease. Okay and so here is a small mess. Okay. But

46:07 these are very common effects of it it will be different cytokines that will

46:12 these different effects about. Okay so of them is chemo attractive. So

46:17 are gonna are gonna, what we'll , it means just themselves to the

46:22 of infection. Okay, um vessel factors. So these are medications that

46:30 with blood vessels to manipulate the permeability blood vessels. So why is that

46:36 ? Because when your main Vegas civic types that deal with infections are

46:42 neutrophils are circulating in your blood. so in order in order for them

46:49 interact with an infection that's occurring outside bloodstream it has to exit the blood

46:55 . And so there's a process that's in doing that and basil active factors

47:00 enable that to happen. Mixed blood more permeable so so that the nutrients

47:04 exit. Okay um that's all part the explanatory response. We'll talk about

47:10 next week um activation of T cells cells um really kind of control the

47:19 adaptive immune response. Okay yes B are part of that but T cells

47:24 also controlled B cells. And so T cells are part of the main

47:29 that control the whole thing. So them. You can really activate the

47:33 immune system um activated macrophages. Macrophages very vague acidic cell types um And

47:41 can actually enhance that ability by by cited kinds to kind of activate

47:48 We'll talk about what that means as . Okay so the point here is

47:53 you know these two receptor types enable of potential of a potential pageant slash

48:01 and the way to alert the body of course through releasing chemicals and specific

48:07 system themselves will respond to those various of chemicals the net result is mobilized

48:14 your immune system get get it ready go into action is kind of the

48:20 what's going on here? Um Any about that? Yeah, basically MlRS

48:32 inside security detail and are pretty much , because again, you're you're trying

48:40 deal with both of these pathogen Internal and external. Right? I

48:47 was some relations to them. They a little bit different. Yeah,

48:50 there is some there is some module the two. You know? Of

48:56 everyone's the same. Yeah. I don't We're going to the structures

49:00 those things. What kind of what's their different functions are in terms of

49:05 they deal with. Um Let's Okay, so here's another question.

49:12 gets us into the different cell types what do you call it?

49:17 Second line of defense can I? adaptive immune system. Cell types

49:25 Of what type? Um neutrophils, ? Macrophages, Your center fields

49:36 Okay, mm hmm. Alright, see what we got. Yeah,

50:21 going to be uh lymphocytes. So B cells and T cells and also

50:28 there are natural killer cells are part those as well. Okay, B

50:35 . Um so here we'll look at different cell types involved system. So

50:43 can look at blood and basically fractionated plasma which is basically protein components,

50:50 and compliments. And then the other being we call formed elements, cells

50:57 different types but also in there are . Platelets aren't are not cells they

51:02 protein fragments, cell fragments uh involved the clotting function. Okay. Um

51:08 clotting function. The rigorous sites are course the red blood cells uh these

51:17 what we call a nuclear itself. don't have a nucleus. They're basically

51:21 full of hemoglobin pretty much. And used to bind oxygen. Okay.

51:27 now, aside from those guys then have Lucas sites, red blood white

51:31 cells of different types. The distinction granular sites and a granule sites is

51:39 is a historical term number one based the appearance under the microscope.

51:46 so, grand sites have grand mules are typically full of different types of

51:53 . Um And these gradients are quite in granule sites. Okay. A

52:01 house sites, you might think, , well they don't have Granules.

52:04 they do. They're they're just they're not as visible under the microscope.

52:09 that's why you see these two Okay. Um and so we'll focus

52:13 the ground sites. First, neutral , baseball fields, you know,

52:18 , Uh your lymphocytes, dendritic cells macrophages are your ground sites.

52:24 the percentages you see on the slide are are the percentage of their present

52:29 the circulating blood. Okay, so 70% are circulating in the blood every

52:37 . Um I presume the other partner the bone because bone marrow's where these

52:42 were formed. And so that's where remainder would be I guess in

52:47 Um Anyway, so uh are one your main infection fighters early on an

52:54 in terms of the first um stages infection. They're the ones that are

53:00 to the site of infection. They the blood vessels. They do their

53:04 . Ah They're followed by macrophages that of do the rest of the

53:09 Okay. Now this term polymorphous right? That refers to this weird

53:18 of the nucleus. Right? So all that really dark purple is dark

53:24 . Is the nucleus? Okay. has different lobes, it's all

53:29 Okay. But it has it just that appearance. Right? So that's

53:32 they called pony morpho nuclear. Um Bezel fills are not really a

53:41 cell type right? There more about releasing chemicals involved in certainly an inflammatory

53:48 . If you do have allergies, allergies, you can often blame

53:53 Or another cell type. And another type called mast cells. They can

54:00 to different types of allergens and release if you're hypersensitive because you get an

54:08 of those chemicals released and you get watering nose and watery eyes right?

54:12 bad. Or it hasn't really I think the uh the oak pollen

54:16 like through the roof nowadays um that stuff raining down that rains down in

54:23 this time of year, every Um So again a very small proportion

54:29 correctly, other cell types um we see them in um in action when

54:34 look at the inflammatory response, they chemicals that have to do with the

54:38 active factors. Okay. Um The fields A little bit higher percentage.

54:46 . Uh they can have a specific . Their thing is really in um

54:53 dealing with large pathogens, that's something don't think about that much. Can

54:57 think of you know bacterial pathogens, pageants? You don't really think of

55:03 ones? Right? But there can multi cellular worms um large protozoa types

55:10 can that can affect you. Okay so these are the ones that typically

55:14 involved in that. Right? So to kill something that's that large requires

55:21 course a collective effort. Okay so gonna just quickly draw this out

55:27 Don't worry about it cause we're gonna it and that doesn't mean response,

55:31 it's just that we have a large . Okay, like this. So

55:38 order to kill something like that, gotta bring a bunch of cells

55:40 So yes, Center Fields, which are hanging out here will come

55:46 right? And the way to bring bring them together and this is where

55:51 the concept where we'll see this, just with these guys but with

55:55 dendritic cells, they're all that you obviously you have that the immune system

56:02 innate immune system, they do interact in in at certain times.

56:09 And with certain cells. Okay. so by that I mean you can

56:14 antibodies And so antibodies I'm sure you are these white they're kind of Y

56:19 proteins. Right? And one end , they'll have two binding sites,

56:27 ? That will bind to a right to an antigen. Okay.

56:32 then I'll have another side that combined a receptor on the cell if the

56:38 type hasn't. Okay. And so Center Fields have that. And so

56:43 can be made to this pathogen and the other side of the antibody combined

56:50 a single film. So what will is b antibodies will bind and then

56:58 Center Fields bind to the antibody. so now you can bring everything

57:02 Okay, collectively bring these essentials together what will do will really just release

57:10 that these Granules and these toxins were out and then because they're all in

57:15 around this pathogen that it'll kill Right, well it's ready to bring

57:19 way to bring together a number of cells. They have them stick to

57:22 pathogen and do their thing. And so again the association between the

57:28 and innate immune system and we will it again here here with the macrophages

57:33 dendritic cells as well. Okay. so the uh next ones are the

57:44 . Okay, so but a quarter the cervix the blood uh typically in

57:50 manga site mainly the monasteries form. so monasteries will differentiate the modern society

57:56 actually exit the blood and a lymphatic we're talking about that shortly um is

58:03 macrophages and dendritic cells. Will the will mature, differentiate into macrophages and

58:10 cells? And these two cell types types that work with your data immune

58:15 as it says. Right so this called antigen presentation is a big

58:20 They do. Okay. And that's kind of bridges the innate immune system

58:26 the that difficult system. Okay um very specific cell types. They can

58:33 activated to be super specific cell Okay um The other lymphocytes are these

58:43 natural killer cells. Okay um they with infected cells. Right so remember

58:49 gonna have a division here of types interact with intracellular pathogens and extra cellular

58:55 . Okay. And so um natural cells are one of those types.

59:02 , the alpha can seek out sometimes out and destroyed cancer cells are

59:07 Okay um And so T cells and cells will I'll leave the details from

59:17 next week. But I mentioned before interest sailor patrons. Extra sailor.

59:22 differentiation here B cells to their antibodies antibodies combined two extra sensitive pathogens and

59:31 like five or six different effects that when antibody engine bind. We'll talk

59:35 that later. The bottom line is can get rid of them. Okay

59:38 get rid of the past. Uh your t cells there are certain T

59:42 types. Okay, whose job is deal with infected cells similar to natural

59:49 cells but in a different way. um and so things like virus infected

59:55 , remember bacteria can also infect cells , right so you have to have

59:59 way because of the if a pathogen inside of a cell right, it's

60:05 from the immune systems, there has be a way to detect those and

60:08 cells have a way to do Okay, so natural killer cells back

60:13 them. Okay, this is where introduced the MHC these self antigens.

60:20 , so um when a cell is and it's not every cell this happens

60:28 you. So that virus infected itself cancerous cell. Okay. There can

60:34 changes on the surface as a result the infection or the cancer itself.

60:39 in all viral infections or all cancers in many that that happens that there's

60:46 and changes to the service can be by certain immune system selves natural killer

60:51 is one of those. Okay, what's what's the MHC thing all

60:56 Well, in a second. so in in natural killer cells that

61:02 these abnormal cell types because of the surface changes they have, they want

61:10 get rid of them because obviously the to the body is something that's not

61:14 and get rid of it. And so they have these molecules called

61:21 , which means to perforate, Very similar to defenses in terms of

61:26 their like cylinders with like a holding in like a straw emotion. So

61:30 kind of uh can insert into the and cause license. It can also

61:35 enzymes they produced these grand times. So apoptosis. Right. That's that's

61:42 a process that potentially everyone of yourselves do. Right? When when it's

61:49 to do that, you know what call a programmed cell death. And

61:55 yourselves would do that if they were a state where they weren't functioning really

62:01 well anymore. Older cells you kinda to get those out of the

62:05 Okay, if you've been somewhere you've gotten rid of you know,

62:10 peeled right. Those are basically cells were undergoing apoptosis because they've been mutated

62:14 UV light. You want to get of it. So um so but

62:18 are cases where you can actually make cell do that and this natural fuel

62:24 can do that to these damaged cells these chemicals. So um so again

62:33 go back to this MHC and what is all about. Okay so again

62:38 stands for major history compatibility complex. So um the term probably likely came

62:48 uh huh. So organ donation, ? You have someone wants to receive

62:52 organ. All right, some of tissue transplant, you gotta make sure

62:57 the donor and recipient are compatible. and so this is what you're looking

63:03 in terms of compatibility? What's the of chemical nature of the MHC complex

63:08 donor recipient? Right. Um Obviously change for these you inherit from your

63:14 . So obviously you look at that most closely related to the recipients,

63:20 ? Siblings etcetera because they're likely to the most commonality between these things.

63:26 . And so what they are they're the membrane, right? They are

63:30 and nature. They are equate them like barcode. You have a column

63:36 for your body and that barcode is stamping all yourselves? That's kind of

63:40 this represents. Okay because you have have a system if you if you

63:44 to know what's your own if you're detect something that's different coming into your

63:49 . Okay. And so don't obviously for effect but you know so it

63:55 be lined with these MHC antigens we them self antigens. Okay. You're

64:01 with the blood type A. O. Blood type. So red

64:05 cells have their own system and that's they euzebio they'll have those engines on

64:11 surface. Okay. Um And so do we differentiate those two classes?

64:17 . So the easiest way to This is let's define class to

64:22 Okay so these are just these cell ? Dendritic cells macrophages and B

64:30 Okay these are also what we call presenting cells. Okay, we're going

64:34 talk about that in a second. um Class one is basically everything

64:41 not skin cells, your brain your liver cells, kidney cells and

64:47 of these that are new created. ? So that's to distinguish from red

64:52 cells have their own system, the system. So basically everything else uh

64:58 not a dendritic cell. Macrophage or cell is in class. Why?

65:06 if they have a nucleus. So so the um and makes the receptors

65:17 be our embassy molecules can be recognized T cells. Those candidates will have

65:23 for MHC molecules and T cells. some T cells that recognize class one

65:31 . Mhm. And other T cells class too. And um so remember

65:37 natural killer cell. Alright, it for these. All right. So

65:44 they sell us lacking those, it's going to be a cell as a

65:48 cell. The rosella nobody sell basically cell we call it. And so

65:55 that is lacking these class one molecules says oh this is not normal.

65:59 get rid of it. That's what killer cells look for ourselves lacking in

66:03 Class one types. Okay, so so here's the virus infected cell.

66:09 , So again, it's not a thing where every virus infected cell will

66:14 these differences, but many do. . And if they do they may

66:18 some kind of lack MHC engines or we have a weird looking membrane

66:25 Okay. So um any questions about . All right. So it's really

66:33 about setting up a system in your that your cells are marked as yours

66:38 that you can find something that doesn't there. Okay. All part of

66:42 detection recognition binding aspect. Okay. of course if things can go wrong

66:50 your cells may think your own cells not supposed to be there.

66:54 That's autoimmune disorders. That's how that occurs. Okay. Um Now lymphatic

67:03 . Okay, so the lymphatic system of course a system of vessels.

67:10 . It's of course obviously not carrying that's carrying lymphatic fluid but it's but

67:16 vessels of the lymphatic system are closely proximity to blood vessels. Um fluids

67:25 through lymphatic vessels by gravity by muscular probably by contractions of circulatory system.

67:34 vessels as well to push stuff Um So you're only revival organs.

67:41 got a picture here. So all vital organs Have calculus three beds in

67:47 . Right? So your veins and will meet up in this very thin

67:53 vessels capillaries and that's how materials So your tissues receive nutrients.

68:00 Your tissues release waste gets picked So exchange occurs and that's what we

68:05 interstitial fluid. Right so it's it's the cells in the area of these

68:11 beds. Right. So you that's course a loss of volume from your

68:17 system and you wouldn't get that Right. And so that's where lymphatic

68:22 comes in. Right? So those kind of pick that up and then

68:26 return it to your circulatory system. around appear by your clavicle right,

68:32 in back, dumps back into your system. So again so you don't

68:36 a lot of blood line that Okay recover material that you've gotten rid

68:41 . So um but in lymphatic tissues can they can become very thick in

68:52 parts of the body like your armpits groin area, your tonsils um spleen

69:00 parts of your skin underneath in your wall there can be dense collections of

69:06 these lymphatic tissues and in there are of B cells and T cells

69:12 As well as macrophages dendritic cells. and so um but these can protect

69:20 inhaled ingested organisms. Your spleen has tissue that will kind of filter out

69:26 and T cells. B cells. there will kind of grab hold of

69:31 . Okay um so many things that know slide in your mouth,

69:35 Your tonsils are there that they can stuff in your saliva as well.

69:40 these are mechanisms to kind of trap . Okay? Um in different locations

69:46 Here's an example here of what we gut associated lymphoid tissue. So these

69:52 called pirs patches. Okay here you a cross section of the intestine and

69:58 purple blobs here are where these pirate located that are like this, this

70:03 the cartoon of them. So this be intestinal cells here remember the micro

70:08 they have on top to absorb nutrients there will be interest first with these

70:13 patches trap microbes you don't have um macrophages on one side that will then

70:20 them. Um Here's the other example that testing the wall. This will

70:25 a pirate's patch. These areas that trap microbes, potential pathogens and your

70:30 . Now conversely the pathogen can kind depending on the passage of time they

70:35 kind of exploit that and actually get macrophages and survive in them and then

70:42 out of them and then you know infections. So we'll see an example

70:45 that next week. But nonetheless you these are a defense mechanism. We

70:50 have these similar kinds of things in skin different properties that we call salt

70:55 associated with tissue. Okay it's all you know dense lymphatic tissue full of

71:01 cells B cells. Macrophages, dendritic to kind of help trapped in the

71:07 get rid of potential pathogens. Okay um so the figures psychosis of course

71:16 a primary function of your infection. cells particularly neutrophils. Macrophages. Dendritic

71:26 in particular macrophages really And neutrophils. so your macrophages um can be of

71:33 type that is stationary for the most of basically resides in in in one

71:39 of your body. So like al macrophages or in your lungs patrolling.

71:46 up any kind of patterns that maybe are other microbes. Um But you

71:51 have also wandering those that kind of throughout the body will calm wandering

71:55 Okay. And so um in terms the process process, okay it's going

72:03 follow this pattern of chemo taxes chemicals draw them to the site of

72:09 Adherence. So obviously a figures Excel when you're going to adjust what can

72:17 do, what it sticks to engulf ingested and then digested internally. Okay

72:24 so here's an example of if there an excel type, this could be

72:29 macrophage. And of course the presence these pseudo pods. Right? And

72:35 when you mentioned earlier about activating a , what you're basically doing is increasing

72:42 number of these membrane folds, These pseudo pods. You're increasing these

72:47 greatly because that's how we can contact engulf stuff. So you have more

72:52 these arms, so to speak. you become much more uh powerful fake

72:59 agent. Okay and so and so we saw before the collect receptor so

73:05 can bind there. So you have double whammy. So you get the

73:10 mint of the pathogen but then you the release of these cytokines that can

73:13 other uh communities themselves to the Okay so following. Um so let

73:19 go along here. So we have tactics signals to bring um more so

73:25 the site adherence. Right, so adherence. Um that will bring about

73:30 of sort of kind certainly been So we ingest right from your

73:35 That's going to be that Figo Right figure zone. So it forms

73:40 license zone can then fuse with it the license zone will bring about

73:45 So there's digestive enzymes, it can induce perhaps have oxygen radicals and peroxide

73:51 kill the agent and then uh material cannot be digested, it can be

73:56 , expelled. Okay, But there's other function. Right, This is

74:00 the pathogen presentation comes in. so this would be what you see

74:05 a macrophage for dendritic cell? Right, so these would be a

74:12 of the microbe that was digested. ? So it could be proteins,

74:18 have you here? Right. And that solar produced MHC molecules. So

74:26 macrophages following into class too category. , they will produce self antigens of

74:31 type two. Okay, and they'll those MHC antigens will bind these self

74:38 will bind these guys and then we'll it to the body. Right?

74:45 now this so in this form, this form they're not visible.

74:51 But now in this form they Okay, and that's where a certain

74:57 cell types Okay, will recognize that two receptor bind to it, recognize

75:05 antigen bind to it and then the is typically released satisfies activate the adaptive

75:13 system etcetera etcetera. So but that's another big function. So again we're

75:18 the and Nate an adaptive immune systems by allowing to interact with the cells

75:25 the but that that means that T in particular. Okay. Um and

75:30 that's that's an important function to get you want to get all hands on

75:34 in the in the situation get innate adaptive immune system working together right?

75:39 both going to be a powerful defense fight infection. Okay. Um and

75:47 the the and we'll see that also that B. B cells we'll talk

75:54 this next week. B cells that antibodies also also can present Angela interact

75:59 T cells that help to activate them make antibodies. So all these things

76:03 together time. Um So the Estonians are uh so not every microbe

76:14 amenable to being digitized. So figure relies heavily upon be able to bind

76:20 that microbe and ingest it. If that microbe is not easily bound

76:27 it doesn't work very well. Okay that can happen for microbes that have

76:31 capsule. That's what you see This is a very thick capsule surrounding

76:36 cell. Right, Streptococcus pneumonia The meningitis bacterial also very thick

76:42 OK so those don't make this so susceptible to binding and figure cited

76:48 So how do you enhance that? do it through optimization. Right,

76:53 you involve antibodies? You involve compliment just protein factors. Okay,

77:00 here's an example where we're gonna look antibodies. Ok, so this may

77:04 a form that's not very able to it easily and fix it ties.

77:09 what do you do? Well, produce these options. So antibodies to

77:15 capsule platform if that's a capsule surrounding and it combined to that.

77:21 so now the macrophage or neutral Phil have receptors. That's what the fc

77:29 is that I mentioned earlier, this what combined to the actual macrophages or

77:34 itself. Right through a receptor. , so this is the this end

77:38 the antigen binding portion. This in here is what combined to one of

77:43 . Okay. And so collectively now becomes let's say call it more it's

77:48 this form more slippery. Right? form is more sticky. Okay,

77:53 so now that can that can be to the in this case macrophage and

77:59 whole thing gets engulfed. Right? now you've greatly enhanced the ability to

78:05 the tires to these cells where it it happened that well before.

78:09 so that that's what so the option is the antibody optimization is this

78:16 Okay, and so not only can do this, but complement for a

78:21 protein factors can also bind to the of the cell and your own cells

78:26 receptors for those as well. And very similar fashion. You can take

78:31 cells clearly complement, right? Makes much more easier to figure out the

78:35 . Okay. Um Any questions about ? Yeah. Alright. I think

78:43 yeah, that's a good spot. do this one. We'll start with

78:46 next class with that one. So are yeah, we're up against it

78:50 we're good. So thanks folks. you next

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