| 00:00 | OK, welcome. This is uh 25 when we're looking at microbial |
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| 00:06 | So call, of course, in previous uh modules, we've been looking |
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| 00:12 | the uh innate immune system and the immune system mechanisms by which our own |
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| 00:18 | fight disease, right? So we at a bunch of different um aspects |
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| 00:23 | this through innate immunity and your chemical physical barriers, different types of immune |
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| 00:29 | cells that fight infection, different processes inflammation and fever and others. Um |
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| 00:36 | , for example, then the AAPT system and the uh multi huer immunity |
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| 00:42 | B cells and production of antibodies and cells and T cells. And they |
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| 00:48 | specific for finding a uh dealing with cells. So, a whole host |
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| 00:54 | uh processes we have to fight So now we're gonna turn our attention |
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| 00:59 | the pathogen and look at the mechanisms which these overcome these various immune system |
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| 01:08 | that we have. Ok. So it's a, it's a relationship between |
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| 01:13 | pathogen and our and our own OK. And um you know, |
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| 01:18 | evolving to, to for us to disease and for them to overcome these |
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| 01:28 | immune system barriers that we have. , the um development of the |
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| 01:34 | of course, relates directly to the of the immune system, right? |
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| 01:40 | we going to be more resistant or we gonna be susceptible? So, |
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| 01:43 | course, a number of factors play that, uh you know, determining |
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| 01:48 | healthy your immune system is and, that of course, uh will determine |
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| 01:53 | go a long way to determining how succumb to disease. Ok. Or |
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| 01:58 | we do so, of course, the pathogen perspective, it's all about |
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| 02:08 | factors. And so, uh and genes, it possesses that codes for |
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| 02:13 | factors, right? So, these be of course, chromosomal based um |
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| 02:19 | plants and based acquired through horizon and the various mechanisms we talked about before |
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| 02:26 | including transduction, which can be through p uh integration of phase genome uh |
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| 02:34 | how it can be acquired. all of these are possibilities through which |
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| 02:37 | can be acquired. But it's the collection of rance factors that will enable |
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| 02:45 | pathogen to, to carry out its uh life cycle if you will. |
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| 02:52 | . And so there's different the factors pertain to different aspects of the infection |
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| 02:59 | which begins with um you know, inside the body, there's gonna be |
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| 03:04 | transmission of, of the pathogen to susceptible host. Then in that host |
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| 03:10 | such as adherence, the the pathogen to your own cells or, or |
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| 03:16 | um to be able to persist in body um invasions, some, some |
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| 03:20 | on invasions of your cells. Of course, the viruses do that |
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| 03:23 | their bacterial types do this as Colonization uh uh in your body, |
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| 03:30 | production of toxins can cause damage immune , immune response inhibitors so that |
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| 03:35 | they can produce factors that can that counteract the effects of your various |
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| 03:40 | system defenses. OK. And so , y you know how, how |
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| 03:47 | a pathogen may be, of will relate directly to the, the |
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| 03:52 | and numbers of ri factors it Ok. So a couple of things |
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| 03:56 | , just to remind you, you , the primary pathogen versus opportunistic |
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| 04:00 | And so, uh opportunistic pathogens um of your normal microbiota but then, |
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| 04:07 | then can um become infectious disease causing typically when they uh either are gain |
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| 04:17 | , entry into parts of your body they're not, they don't normally |
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| 04:20 | reside in and, or you some of the checks on their, |
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| 04:25 | their growth, perhaps through other members the microbiota. Uh That, that |
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| 04:30 | some reason are not present maybe through uh administration or something. And then |
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| 04:37 | opportunistic types can proliferate. So uh a case, uh they can cause |
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| 04:43 | but your primary pathogens are, are different. They are, they're |
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| 04:49 | disease causes. If you will, you have a primary pathogen, it's |
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| 04:52 | by accident, it's there because it's a disease. So, a primary |
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| 04:56 | is something like Ebola, for is a primary pathogen. So, |
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| 05:01 | so we're gonna expand upon this as go through this section. And so |
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| 05:07 | of uh again, your checklist, really learning objectives. So we're gonna |
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| 05:10 | at begin with kind of transmission of and how that occurs uh entry into |
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| 05:14 | body in different ways. Um and describing different factors that pathogens have to |
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| 05:22 | your various defenses, uh whether it's penetrate deeper into your body, whether |
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| 05:28 | to cause damage to cells. Um so we'll look at the different aspects |
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| 05:34 | this as we go through here. . And these, this slide in |
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| 05:38 | next really just to show you an of the arsenal of virulence factors pathogens |
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| 05:44 | possess you don't need to memorize these . But it's just an example of |
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| 05:48 | aureus. Uh on this one staph streptococcus P is on the next |
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| 05:53 | Most of these are our biggest membrane . Uh skin staph can be on |
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| 06:00 | skin. It can be a mucous like your nose. For example, |
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| 06:03 | strep can be of of course mucous inhabitants also on your skin in some |
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| 06:09 | , but they have both pathogens of groups have a large arsenal of different |
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| 06:14 | . You see here with staphylococcus, different types of enzymes that allow them |
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| 06:19 | penetrate deeper into tissues. Adhesions are that allow them to uh adhere to |
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| 06:25 | cell or tissues, um toxins that cause damage as you see there. |
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| 06:33 | uh even from uh factors that can with antibody effects as you see there |
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| 06:39 | G G. So there's uh protein that can counteract the effect of |
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| 06:43 | So they have a wide variety of ways to overcome your immune system |
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| 06:49 | Streptococcus genies as well by this, organism that can cause strep throat and |
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| 06:56 | different types of skin conditions as severe the flesh eating disease. So, |
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| 07:02 | they have different enzymes to penetrate tissues well. Uh different types of adhesions |
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| 07:08 | the M protein has multiple functions uh just adherence. Uh And so, |
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| 07:15 | different types of exercise or substances and . So, uh a wide arsenal |
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| 07:20 | virulence factors and, you know, , don't think that not necessarily no |
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| 07:26 | streptococcus gens, for example, will all the whole entire collection of these |
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| 07:30 | , but they'll certainly have some of . Ok. So we'll go through |
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| 07:34 | explain some of the functions of these various factors. So, first a |
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| 07:39 | bit about um spread of affection. . So, for any uh |
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| 07:48 | there's gonna be a source where you naturally find it. Ok. So |
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| 07:53 | you want to find where is West virus, where is the natural reservoir |
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| 07:59 | that pathogen? Ok. Well, would be in mosquitoes. OK. |
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| 08:07 | um for, for uh other types depends it could be different sources that |
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| 08:12 | see here. Human humans can be actual reservoir where these pathogens normally |
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| 08:17 | Example, is uh meningitis, the organism lives in the throat of probably |
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| 08:26 | of the population of people, Healthy, healthy people not showing any |
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| 08:30 | of disease. Ok. Uh Similarly measles and mumps, hepatitis B, |
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| 08:36 | STD S as well. So all humans are the are the reservoir. |
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| 08:42 | . Um Many patterns are also zoonotic are animal reservoirs. OK. Uh |
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| 08:51 | , obvious example uh as is a um fleet that are on run |
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| 08:57 | infected rats. Um uh I mentioned now virus through insects, uh lyme |
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| 09:05 | through a tick. So a number your types are, are have animal |
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| 09:11 | , then you can have no So, soil and water, |
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| 09:15 | We'll talk about legionella as one of diseases uh that comes from um contaminated |
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| 09:22 | sources that supply uh your H VAC which are, you know, a |
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| 09:26 | air conditioning systems in, particularly in uh commercial uh um commercial operations |
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| 09:37 | a hotel. For example, uh um a tetanus is acquired through |
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| 09:44 | We, we've all heard of uh on a rusty nail. You gotta |
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| 09:47 | a tetanus shot because where do you rusty nails typically in the ground? |
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| 09:50 | ? And you, you, you a puncture wound. So, uh |
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| 09:54 | know, contaminated water supplies, of , can be a um source uh |
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| 09:59 | in. Uh so, you it, it depends on the |
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| 10:02 | the type, of course, the of reservoir they often call the soil |
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| 10:06 | water uh collectively in our environment. ? Um Now it's one thing to |
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| 10:18 | the reservoir infection, right? But of course, the reservoir where they |
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| 10:22 | , then it's going coming from that to a susceptible host, right? |
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| 10:27 | is gonna involve transmission, OK? reservoir to host and it's gonna occur |
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| 10:33 | a variety of different ways. uh through contact, uh director indirectly |
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| 10:40 | what are called vehicles of transmission or vector vectors of transmission. And so |
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| 10:47 | the con contact category, uh direct be obviously just physical contact right through |
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| 10:53 | through uh reproductive structures, through kissing things of that nature. Uh |
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| 10:59 | that's through what's called a fomite. fomite is an inanimate object. So |
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| 11:04 | um a used Kleenex that you touch countertop uh a infected needle, um |
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| 11:14 | kind of an an inanimate object that's that you didn't touch and then you |
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| 11:18 | the infection that's full. The object is considered a full um drop |
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| 11:25 | So this uh typically typically through close contact with another, either through |
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| 11:31 | or coughing. That the definition there drop is typically is if it's less |
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| 11:36 | a meter um then that's dropped it infection. So um vehicles of transmission |
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| 11:47 | be water, air food can also bloodborne. It could be uh through |
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| 11:52 | contaminated drugs. Uh Waterborne air food probably the most common vehicles. Uh |
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| 11:58 | can be through uh contaminated water Of course, this is what we |
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| 12:02 | the fecal or oral route. Um uh when the water treatment system is |
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| 12:09 | in some way that doesn't provide the water, then uh becomes contaminated. |
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| 12:16 | that can be a source of, waterborne infection, waterborne transmission um |
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| 12:24 | Ok. So airborne is gonna of be traveling more than a meter and |
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| 12:29 | uh dust particles. Pet dander is uh food borne, of course through |
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| 12:35 | food. Ok. Uh Also through various means of food production that are |
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| 12:43 | being where standards are not being So uh keeping foods in their proper |
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| 12:49 | , not in their not refrigerated or but out too long on a at |
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| 12:54 | temperature. For example, can allow microbes to grow uh undercooked food. |
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| 12:59 | course, uh unsanitary handling, not gloves or hearing that these things, |
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| 13:05 | kinds of practices you see in the services where they prepare food. Uh |
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| 13:12 | food borne outbreaks can occur in this um accidental transmission. So this typically |
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| 13:20 | when uh humans uh enter in an on a particular life accidentally and acquire |
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| 13:29 | disease. The example of this is disease was acquired accidentally. So humans |
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| 13:34 | in the course of their economic development going into areas, forested areas where |
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| 13:42 | two uh but it hadn't been And in these, uh this was |
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| 13:46 | happening in Connecticut in this area, areas, there is a, a |
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| 13:51 | cycle involving a, a tick which course is, is carried on a |
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| 13:56 | and, and animals in the, these forests areas. Uh And so |
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| 14:03 | the going from um from um and dear to, to uh rodents, |
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| 14:11 | humans inject themselves into this life cycle became bit and uh and then contraction |
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| 14:19 | lyme disease occurs. So, uh is typically how accidental transmissions occur |
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| 14:24 | they become part of the way they the life cycle of a pathogen and |
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| 14:27 | acquire the infection um vertical transmission. the mother of the child. So |
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| 14:33 | can general type of condition that can . Um Vector born is typically through |
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| 14:40 | . Uh mosquitoes is very common for like uh transmission of Zika virus. |
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| 14:48 | uh of course malaria, um West um a number of different uh |
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| 14:56 | The um and so you could break retro bone uh metro transmission through mechanical |
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| 15:04 | biological um mechanical transmission is kind of very random kind of a process where |
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| 15:11 | is like AAA fly on a on on garbage and it um just through |
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| 15:21 | sitting on a contaminated, you source, it then goes on to |
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| 15:27 | and those body parts kind of transmit to your skin or hands or something |
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| 15:30 | then you ingest it. Uh that's of just the mechanical transmission is what |
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| 15:35 | refers to um uh biological transmission. course, involves a very specific type |
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| 15:41 | life cycle. Uh You see this the, the the parasites that many |
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| 15:45 | are often use insects as part of cycle as well as other animals. |
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| 15:50 | , and um so malaria is an of this that involves life cycle involving |
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| 15:57 | mosquito and um humans as part of cycle. And um transmission occurs this |
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| 16:05 | . Ok. Um So assuming, we have, so we have a |
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| 16:14 | disease uh then transmission from the reservoir a susceptible host. Then what are |
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| 16:20 | steps? Ok. Well, the are of course, entry, |
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| 16:25 | So, pathogens have a preferred, called a preferred port of entry into |
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| 16:29 | host. In order in order for to effectively cause disease. Thereafter, |
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| 16:34 | um uh adhesion, different factors that then play a role in in determining |
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| 16:42 | the onset of infection can be adhesion the pathogen to your tissues. Uh |
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| 16:48 | can't forget also how many infectious units actually entering the body can have an |
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| 16:54 | ? Certainly. Is it one cell is it 1000? Ok. Um |
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| 17:00 | tractor is involved in uh penetrating through tissues, different types of enzymes evading |
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| 17:07 | of fences. So a capsule I uh I can be part of adherence |
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| 17:13 | well. Uh Capsule can hide the pathogen from the immune system temporarily. |
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| 17:21 | may uh enable it to be less to be focus times less easily, |
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| 17:28 | damaging the host of things like toxins cause damage to host cells. |
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| 17:32 | Uh and of course, exiting the , OK. And usually the mode |
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| 17:37 | which a pathogen enters the host is they'll exit the host as well. |
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| 17:42 | . So what are portals of Well, think of the the physical |
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| 17:48 | that a patron would have to right? So you have, you |
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| 17:52 | physical barriers which are your mucus membranes skin. So, uh there are |
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| 17:57 | openings in the skin, obviously, Foles, sweat glands, uh your |
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| 18:01 | , conjunct eyes. So, um of course, you can have a |
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| 18:07 | route when in which the uh micro infectious agents are deposited under the skin |
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| 18:13 | a, to a needle stick through a splinter or something. So, |
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| 18:17 | is a way to introduce um a pathogen into the skin, uh mucous |
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| 18:25 | . Of course, when they align various body cavities, respiratory tract, |
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| 18:29 | cetera. Um And so when we about preferred pole. So, um |
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| 18:35 | know, for example, E coli 157 that causes foodborne illness, this |
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| 18:41 | acquire through ingestion of contaminated uh it's foodborne disease. So, through ingestion |
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| 18:45 | contaminated food and um it's an intestine and that's how it causes disease. |
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| 18:51 | , if you take that same E and try to rub it on your |
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| 18:55 | , that's not its preferred portal of . So the worst, you're gonna |
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| 18:57 | gets a rash. Uh but you're gonna come down with foodborne illness in |
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| 19:02 | way. So that's what we mean preferred portal of entry, right? |
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| 19:06 | uh an organism that's, that's acquired sexual transmitted disease to reproductive structures. |
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| 19:11 | is not gonna generally be of no if you, if again, if |
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| 19:15 | lands on your skin. So it's this is what we mean by a |
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| 19:17 | portal of entry. If it the pathogen doesn't have access to its |
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| 19:24 | mode, then it likely will not disease or very mild symptoms. |
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| 19:30 | Um Now, in looking at uh , right. So attachment pattern can |
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| 19:35 | important uh back again to the 0157 coli strain. Um The uh presence |
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| 19:44 | fibri are important for it to attach intestinal cells and to cause disease mutants |
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| 19:49 | are lacking a fibri um do not disease. So it can be very |
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| 19:54 | for certain pathogens uh beyond piri. , adhese is is kind of a |
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| 19:59 | term that applies to any of these that are involved in adhesion. |
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| 20:04 | They can be they, but they be just proteins or like our proteins |
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| 20:08 | the, on the cell surface that to specific uh receptors on the post |
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| 20:15 | cells. OK. Now, um couple of examples of these are uh |
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| 20:25 | you mentioned, the E coli and uh the M protein and O |
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| 20:29 | A protein. OK. Uh For coccus and NIA respectively. Let's take |
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| 20:34 | look at that here. So the protein is um up at the top |
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| 20:42 | uh has these uh like little hairs are on the surface of the |
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| 20:45 | So, streptococcus has this uh this particular streptococcus pneumonia that causes pneumonia, |
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| 20:52 | . And this is one that has of a diplococcus shape, two cocci |
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| 20:56 | kind of a bean shaped. Uh streptococcus is famous for the M protein |
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| 21:03 | factor. And so this is involved adhesion but also has antihero properties. |
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| 21:09 | it can interfere with comp activation. so um uh quite a potent ambulance |
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| 21:16 | uh for streptococcus to avoid um the system um and to attach to your |
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| 21:25 | , excuse me, the um among those pathogens in Nigeria are the |
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| 21:31 | organism, uh gonorrhea and that causes STD. So the O P A |
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| 21:37 | is one that's involved in adherence. so you can see the, you |
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| 21:47 | see in the illustration here at the here are the O P A proteins |
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| 21:53 | here, the little dark um knobs the top of the cell surface and |
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| 21:57 | too has a diplococcus uh arrangement. then you see the longer pill |
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| 22:02 | OK. So the pill eye provides uh like a loose anchoring to, |
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| 22:09 | the cells. OK. So here's the epithelial cells for mucous membrane uh |
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| 22:15 | which Niya pathogen is um attaching And so pill, I provide a |
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| 22:21 | Anchorage as you see here. And the O P A proteins provide for |
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| 22:26 | tight adherence as you see here. . So you see the binding of |
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| 22:32 | P A provides for a very tight . And this actually induces this invasion |
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| 22:38 | the cells. You see how the is gonna become engulf it. |
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| 22:41 | after having a bound those O P proteins and it ends up coming out |
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| 22:46 | other side. So the net movement from outside to end. So it's |
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| 22:52 | the tissues. This is what is the trans. So being transported through |
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| 22:59 | cell out the other side as you here. And then this can go |
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| 23:03 | to an effect, endothelial cells. make up blood vessels, ok. |
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| 23:08 | they can end up traveling to the . Uh other cell types types like |
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| 23:12 | blood cells like a neutrophil. They occupy end up being inside of a |
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| 23:18 | or a monocyte which becomes a macrophage differentiate into a mac face. So |
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| 23:23 | is how uh lyra can gain entry into the body travel throughout the body |
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| 23:30 | um being inside uh your cells. So very uh both in protein and |
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| 23:38 | P A protein kind of have multi in terms of bri factor. Uh |
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| 23:44 | course both writing A but then we these other feature as well for |
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| 23:50 | Um Now penetrating host defenses. extra cellar enzymes that they synthesize uh |
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| 24:00 | lead to this sore staph, staph . Uh many of these produce are |
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| 24:05 | positive that are pathogens. And so will act upon your bodies natural components |
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| 24:14 | are involved in clotting. So far or soluble factors that you have in |
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| 24:18 | blood and they come together to form , which is a network of fibers |
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| 24:22 | begin to form a clot. And uh this leads to the whole |
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| 24:29 | process. Your body undergoes to, then you know, firing form a |
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| 24:34 | , you can form a scab and kind of things part of part of |
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| 24:36 | healing process. Uh but bacteria can coagulate and to form those clots as |
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| 24:44 | . This is uh often seen when staph infection that produces like boils, |
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| 24:49 | say. And so the ability to clot blood allows it to kind of |
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| 24:54 | a cocoon around itself, isolate it the body and it begin can proliferate |
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| 25:00 | there. Um Conversely, you're gonna bacteria that destroy blood clots, they |
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| 25:06 | kis. So streptokinase is an example one produced by streptococcus that can break |
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| 25:13 | of blood clots. So this can it to gain entry into the body |
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| 25:17 | , by removal of the clot. how you grow out of these. |
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| 25:23 | this uh chemical is what uh helps kind of connect your, your cells |
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| 25:29 | your connected tissue. OK. So the bacterium can break those connections |
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| 25:34 | it allows it to penetrate and spread the body. Uh she coccus can |
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| 25:40 | is I think staff can as Uh again, that too uh serves |
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| 25:47 | um bind connective tissue. And if can break it apart, which is |
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| 25:52 | collagen A does again, allows for penetration into the tissue, uh proteases |
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| 25:58 | enzymes that can destroy of both proteins prime of those pri prime. Among |
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| 26:03 | are things like I G A I A is the antibody that's prevalent in |
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| 26:09 | secretions. So, and and has neutralization effect. So will not allow |
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| 26:16 | pathogens from binding to the mucosal So if it has a prote, |
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| 26:20 | can destroy those antibodies and then allow to adhere. Um So let's just |
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| 26:25 | a quick look and how that So here is kind of a cross |
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| 26:32 | of the skin. Here would be bacterium pattern that's producing extra or |
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| 26:39 | And so here is how the, would work. So you have uh |
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| 26:45 | or particular cells that are connected through hyaluronic acid. And the enzyme can |
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| 26:53 | these connectors apart line for penetration. the foundation for where the cells are |
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| 27:00 | is through collagen fibers. So they call this the basement membrane. So |
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| 27:05 | rich in collagen fibers and then high collagen A can break those apart. |
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| 27:10 | again, so you see that the is getting deeper, penetrating deeper and |
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| 27:14 | into the tissues. And so, know, your flesh eating disease. |
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| 27:18 | is the strep oxide that do this this, this arsenal of different enzymes |
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| 27:24 | can penetrate a part layers of the . And that's essentially what's happening as |
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| 27:29 | produces these enzymes. Uh Here's the of K. So here might be |
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| 27:34 | blood clot uh that naturally occurred uh a result of a wound or some |
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| 27:42 | . And now here comes a streptococcus its streptokinase and it can use it |
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| 27:48 | break that clot apart and gain entry the body. Ok. So |
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| 27:51 | all, all these are factors that for penetration in the host tissues. |
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| 27:58 | . Now, toxins um uh specifically we're talking about here are synthesized |
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| 28:07 | the uh pathogen and then secreted into surrounding environment. So they can circulate |
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| 28:14 | , and, and, and uh to their target cells. And these |
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| 28:17 | have of course a variety of different . And so the A B structure |
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| 28:21 | very common. Uh So these A toxins, uh the B of course |
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| 28:25 | a part of the toxin that binds the target. And the A has |
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| 28:29 | activity that um works internally in the to bring about whatever the effect |
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| 28:36 | Ok. Many toxins are placid based through horizon and transfer or through phases |
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| 28:43 | transduction and they can then be through uh forming a prophage um in the |
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| 28:51 | . Uh again, their action typically going to be damaging to the |
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| 28:57 | Ok. Oftentimes lethal. Uh there anti tos. So remember that toxins |
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| 29:03 | also produce a immune response. And A toxoid uh works against those uh |
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| 29:11 | E as a vaccine. Um So the reaction of the A B |
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| 29:17 | the synthesis of the exotoxin and it and then bin into a specific target |
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| 29:24 | receptor and then in that cell, toxin comes in and the eight portion |
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| 29:31 | the active portion that works on whatever target is inside the cell. |
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| 29:34 | So what are the different effects of of a uh exotoxin? Well, |
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| 29:39 | can of course disrupt a cell membrane a lysis. These are things like |
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| 29:43 | and leucocytes. Leucocytes are specific for blood cells. Hemos target red blood |
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| 29:49 | . The end result is to um the cell membrane causing a lysis protein |
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| 29:57 | , destructors work on, you the the components of protein synthesis, |
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| 30:01 | are gonna be ribosomes typically. diphtheria and she toxins uh work on |
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| 30:09 | uh ribosomes. Uh shica toxins are by um G I tract uh |
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| 30:16 | pathogens of your gut. Uh The of course is a a respiratory illness |
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| 30:24 | the toxin affects those cells in your system. Um Secondary messenger pathway |
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| 30:32 | these typically alter the flow of ions the cell membrane. So remember this |
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| 30:38 | osmosis, then remember water flows to high salute side. So you're setting |
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| 30:43 | ionic balance around the cell, then can lead to loss of, of |
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| 30:50 | from the cell. This is very for the G I tract infections that |
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| 30:56 | toxins that the cholera toxin. For , uh we all know the symptoms |
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| 31:00 | G I tract infection typically are loss water, diarrhea, these kind of |
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| 31:05 | . And that's due to the many the action of these kinds of toxins |
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| 31:09 | similar type toxins. Um super So these tend to cause an over |
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| 31:16 | of the immune system. So think an inflammatory response that occurs locally in |
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| 31:21 | conditions but then becomes a body wide when it's through the action of these |
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| 31:28 | antigens. Ok. Uh proteases are that can include certain proteins. |
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| 31:35 | tetanus toxin, for example, and is one that uh toxin as well |
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| 31:41 | neurotoxins that affect um um the messenger uh that interact between neurons and |
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| 31:52 | So motor neurons uh speak to so to speak through different neurotransmitters. |
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| 31:59 | uh tetanus toxin is tactic can actually some of these different neurotransmitters causing uh |
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| 32:06 | effects as a result. Ok. Now, endotoxin uh or basically found |
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| 32:18 | gram negatives, right? So they're, they are associated with the |
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| 32:22 | S layer of the gram negative, ? The outer membrane layer, specifically |
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| 32:26 | lipid a portion. Now, when gram negative cell is intact, there's |
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| 32:32 | issue. It's when the cell dies lies when this material becomes released from |
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| 32:40 | . And um you can see salmonella is a gram negative gram negative |
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| 32:48 | has endo can have endotoxin activity only the cell membrane disrupted. So as |
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| 32:54 | , when it's when it's killed in and in lies then that lipid material |
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| 32:59 | available. And you can see here , for example, is a macrophage |
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| 33:03 | a gram negative and then by breaking that gram native and of course lies |
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| 33:12 | releasing that material. And so that trigger that can then um travel through |
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| 33:20 | blood and over stimulating, you um immune system cells. Um And |
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| 33:31 | of course, it can also trigger the macro itself to release lots of |
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| 33:35 | , ok? And create uh a wide effect, you know, including |
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| 33:44 | of fever. Ok. So it's of a step by step here. |
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| 33:47 | here would be. So for a a sepsis occurs when you have |
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| 33:50 | that are entering the blood. And so the anatoxin effect can be |
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| 33:55 | dangerous if it's an issue where the negative infection has gone septic. In |
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| 33:59 | words, the gram negatives are in blood, ok? And traveling throughout |
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| 34:03 | body. So, you know, the course of the infection, maybe |
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| 34:08 | immune system begins to kill your native and this lipid material then become spread |
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| 34:15 | the body and they can contact things T L R S on, on |
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| 34:19 | system cells like macrophages and that triggers release and then this will lead to |
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| 34:27 | effects we've seen before of production The uh vasoactive factors which work |
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| 34:35 | on blood, um blood vessels to them more permeable, which means you |
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| 34:40 | fluid and loss of blood volume drop blood pressure, clotting factors are |
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| 34:48 | So, capillaries can be effective. remember, your vital organs are supplied |
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| 34:53 | capillaries which are very thin walled, vessels. So you exchange nutrients. |
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| 34:58 | so if you have clotting factors that being activated, these can block the |
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| 35:04 | and block nutrient feeding of your tissues cause tissue death. Ok. So |
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| 35:11 | , you know, when the gram infection has gotten this bad, then |
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| 35:16 | got to be careful in terms of antibiotics to kill the gram negative. |
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| 35:22 | because collectively the all these effects can to shock and death. Ultimately. |
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| 35:29 | again, the endotoxin effect is it on, on on the severity of |
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| 35:33 | gram negative infection. And so if granary infection has gotten septic and you |
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| 35:40 | through throughout the body, then potentially entire body think of it as a |
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| 35:43 | wide inflammatory response, right? The response is meant to the acute inflammatory |
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| 35:49 | is meant to work in the local in different parts of the body, |
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| 35:52 | not, not throughout the whole Because now you can involve a number |
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| 35:56 | all your immune system cells, potentially , that the effect is overwhelms the |
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| 36:02 | and this is what can result. . So uh so again, certainly |
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| 36:07 | when you, I gram negative this this is something you have to |
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| 36:10 | one has to be aware of in it this potential effect. So it |
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| 36:16 | involves close monitoring of the patient. here we can look at uh intracellular |
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| 36:23 | . So we're all familiar, of , with viruses that that's their mode |
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| 36:30 | , that's their life cycle is to the cell and, and and exploit |
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| 36:34 | and replicate itself inside the cell. there's also bacterial types that exploit this |
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| 36:38 | as well for the purpose of avoiding immune system. So you can break |
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| 36:42 | down what we call intra pathogens into are called alate types that are required |
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| 36:48 | do this. Like Kezia is a that's um evolved in a way such |
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| 36:55 | it doesn't really have a lot of . So it, it, so |
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| 36:58 | relies on being a parasite and living side cells to perpetuate themselves. |
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| 37:06 | Kezia are uh species of these cause mountain spotted fever carried by a |
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| 37:10 | for example, but they can be types of pathogens like should get on |
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| 37:15 | same node that, that temporarily hide cells to avoid the immune system in |
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| 37:22 | . Yeah. What they do uh that do this have what are called |
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| 37:28 | . So invasion is a collection of proteins that basically exploit the cyto |
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| 37:34 | elements in in the eukaryotic cell. . And so things like acting, |
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| 37:40 | example, think of an intestinal the micro bili are formed by extensions |
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| 37:47 | acting. So these invasions can actually these fibers, these filaments and cause |
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| 37:54 | to engulf the pathogen. So this this is how it gains entry inside |
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| 37:59 | cell. Ok. Again, through injection of these collection of invasion |
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| 38:05 | there's probably about a dozen or so these that are, are injected that |
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| 38:09 | bring about these effects inside the OK. And so, one of |
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| 38:17 | effects is called membrane, roughly that's manipulation of these acting filaments. So |
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| 38:21 | can see how the uh cell is has more membrane folds in, it |
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| 38:27 | now able to engulf and take in um uh pathogen. OK. So |
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| 38:37 | , OK. Now, um another we see uh from these intracellular pathogens |
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| 38:46 | some of them is the ability to not, but inside the cell, |
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| 38:51 | can utilize these acting monomers uh bind uh bind them to themselves and then |
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| 38:59 | them. So they can polymerize these . And as they do, |
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| 39:05 | as they increase the length of they're propelled forward. OK. So |
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| 39:10 | can use the acting as a way make themselves mottos or moving in that |
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| 39:22 | . So you can see so many you'll be, these will be um |
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| 39:30 | a um inside a endo zone, , a zone rather, right, |
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| 39:38 | break out before it fuses with a that can digest it. And so |
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| 39:43 | doing so, you can form these rockets that will propel it forward, |
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| 39:49 | in, in staying in the same or breaking over into other cells |
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| 39:54 | and moving this way. Ok. again, all about exploiting the act |
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| 40:01 | components to, to bring about a type of motility what's called an acting |
|
| 40:07 | . OK. So she and Listeria capable of doing this and both are |
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| 40:12 | nonmotile bacteria but are made moon by action of exploiting these act and monitors |
|
| 40:18 | this way. OK. Um And the strategy of the of a |
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| 40:27 | right. So it's inside of a via the formation of a zone, |
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| 40:34 | , as you see here, Or in the zone. And so |
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| 40:39 | course, what can happen is I fuse with a lysosome. But before |
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| 40:47 | , as we saw previously, you break out, simply break out and |
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| 40:51 | the active motility can spread to other . And beyond now, the other |
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| 41:00 | for intracellular pathogen is to prevent the of prevent the fusion of the lysosome |
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| 41:14 | the right. And so and secretes that interfere with that process. And |
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| 41:20 | it survives by not binding with that that will digest it. And then |
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| 41:25 | can actually come out the other side the cell in the trans cytosis process |
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| 41:30 | penetrate deeper into the body, entering lymph node. And the lymphatic |
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| 41:34 | et cetera. OK. A third is to simply just tolerate the |
|
| 41:39 | So the fiz can combine with the but the bacterium just survives, can |
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| 41:46 | that acidic uh condition with those digestive . And there is this Coxnet that's |
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| 41:53 | strategy. OK. And so um can survive and it basically just sits |
|
| 41:58 | there and, and multiplies within these iso songs. OK. Um Now |
|
| 42:08 | about those that are not intracellular They're extracellular pathogens. Well, |
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| 42:14 | they have mechanisms too to survive. so compliment and antibodies of course, |
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| 42:21 | with cellular pathogen. And so you have the secretion of a thick capsule |
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| 42:25 | can cover the surface proteins that that these molecules will normally bind |
|
| 42:31 | So a capsule can help with that a hydronic acid capsule. So there's |
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| 42:36 | streptococcus pneumonia, afro gavil can form capsule of Hyaluronic acid. So it's |
|
| 42:42 | similar to the material that hold your connect your your cells together, |
|
| 42:49 | So your body, the body is gonna see that as uh as being |
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| 42:53 | . So it's not gonna matter, very strong immune response to that |
|
| 42:57 | So that's another way to avoid the system, right? Produce something that |
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| 43:00 | like the body and the body won't an immune response to it or a |
|
| 43:06 | weak response. Um We saw the of proteases that can degrade antibodies, |
|
| 43:14 | ID E antibodies, for example. that can happen just destroy the antibodies |
|
| 43:19 | are, that are um formed to . Uh The protein A is a |
|
| 43:25 | , a little bit of a different . So, Staph aureus has a |
|
| 43:28 | A that can bind to the F portion. Ok. So these would |
|
| 43:35 | the protein A will coat the surface Staph and uh antibody to, it |
|
| 43:42 | bind the F C portion or the C portion. It's not the an |
|
| 43:45 | antigen binding site, right? It's opposite end. So, in that |
|
| 43:50 | , it basically counteracts the effect of antibody and is, is not harmed |
|
| 43:56 | it, right? Um Syria, I mentioned, has the I G |
|
| 44:00 | protein that can destroy the uh uh G antibodies. And this meningitis in |
|
| 44:08 | is one that uh requires adherence to membranes. And so mucus secretions are |
|
| 44:14 | in I G A. So this enables it to be able to counteract |
|
| 44:19 | and to adhere to the mucosal Uh but then the phase variation, |
|
| 44:26 | is another we talked about that in context of, of uh per period |
|
| 44:32 | gene regulation, right. So phase is a mechanism to alter surface |
|
| 44:37 | And so um in doing so, can, it can hide from the |
|
| 44:42 | . Uh So in the body, it changes the next generation of cells |
|
| 44:47 | , will have the antigen form that's readily recognized. And of course, |
|
| 44:51 | buys a time and then during that of course, can multiply and, |
|
| 44:54 | cause infection. Uh Other types can apoptosis in Figo cells through release of |
|
| 45:02 | chemicals. I remember remember that apoptosis this programmed cell death. OK. |
|
| 45:09 | let's just look at summarize some of um mechanisms of hiding. Here's an |
|
| 45:16 | of the phase variation which we talked before. Uh this would be like |
|
| 45:20 | pro type doing this here. So you see the protozoal types, one |
|
| 45:27 | the surface engines which are the triangular , one has the square type. |
|
| 45:34 | so the types are triangle are the that are being shown right now and |
|
| 45:45 | are recognized, but then they are care of by the immune system |
|
| 45:52 | But the other types are not right? The ones carrying this form |
|
| 45:58 | then those are the ones that then proliferate because they're not being recognized by |
|
| 46:03 | immune system. And then they become predominant type and multiply and cause |
|
| 46:10 | of course. And then there is strategy of the intracellular pathogens which we |
|
| 46:19 | here. So here's an example of , for example. And so the |
|
| 46:29 | to a self, the intestinal the introduction of invasions. All |
|
| 46:35 | let me see here. And this particularly through a specialized pill eye that |
|
| 46:40 | occurs and then the invasions and manipulate blood, uh I'm sorry, manipulate |
|
| 46:44 | acting filaments and now it becomes Ok. So now we have entry |
|
| 46:49 | the cell through cytosis, it can , come out the other side. |
|
| 46:54 | can lead to disruptions in, in movement of ions. Of course, |
|
| 47:00 | this can, can lead to loss water, the typical symptoms of G |
|
| 47:04 | tract distress. Um and then of , someone can come out the other |
|
| 47:10 | , they can exploit other cell types get in them and they kind of |
|
| 47:17 | . And here's, that's nonmotile. these can also be an entry again |
|
| 47:23 | the injection of invasions, then the of the cell and then these types |
|
| 47:33 | also form these acting rockets as we'll here like. So, so here's |
|
| 47:39 | binding of active monomers and the polymerization them, it then allows him |
|
| 47:45 | to move around. So the act rockets right to movement into other cells |
|
| 47:51 | well and spreading. OK. So so um so to summarize, then |
|
| 48:05 | a collection of all the factors right . So you can use this as |
|
| 48:08 | of a summary of various variance factors in adhesion, uh extracellular enzymes, |
|
| 48:16 | , endotoxin, intracellular pathogens and their , extracellular pathogens and their strategies. |
|
| 48:23 | kind of just a summary of all variance factors. Um So you should |
|
| 48:27 | familiar with, familiar with these. and it's summarizing. So again, |
|
| 48:33 | looked at, we began with looking um uh the source of infection. |
|
| 48:39 | the reservoir and how it's the various in which it can be transmitted to |
|
| 48:42 | susceptible host, what's in the susceptible ? Um What does the pathogen do |
|
| 48:47 | terms of, you know, what's preferred port of entry? What |
|
| 48:51 | you know, is adherence important. So, uh the, the tractor |
|
| 48:57 | called adhesions and what their role is penetrating invading host defenses as you see |
|
| 49:02 | , uh capsule, um various enzymes of penetration, um um phase variation |
|
| 49:09 | avoid the immune system, uh So that's the, that's what your |
|
| 49:15 | or pathogens will have our invasions to inside your cells and hide from the |
|
| 49:19 | system, damage the host cell. things like toxins, for example, |
|
| 49:24 | and then of course, portal of . So generally the way pathogens come |
|
| 49:28 | , there's a way they'll, they'll , you know, among the |
|
| 49:31 | probably the most common portals of entry gonna be your respiratory system. That's |
|
| 49:36 | be part of the most common port entry. Simply because of the ease |
|
| 49:39 | access. We're always, we're always . And so we're always taking in |
|
| 49:44 | microbes. So it's very uh probably that, the food born, maybe |
|
| 49:51 | of the next, next uh uh uh prevalent uh but certainly respiratory tract |
|
| 49:57 | a very common um port of if not the most common type. |
|
| 50:03 | Anyway, so we look here at a number of different ways in |
|
| 50:06 | uh pathogens can overcome immune system So it uh so we'll conclude this |
|
| 50:13 | by looking at different types of infectious and kind of putting them all |
|
| 50:18 | you know, what are the for disease, what are your defenses and |
|
| 50:21 | , what do the pathogens do to around those offenses? And so uh |
|
| 50:26 | you ever looked already, there's a of pathogen pathogens will, will |
|
| 50:30 | So you wanna be treated with the , the disease that they cause um |
|
| 50:34 | some features about it. And so , we'll begin covering that in the |
|
| 50:38 | module. So this, so chapter will cover different diseases, infectious diseases |
|
| 50:44 | we'll cover that in, in uh two parts. OK? So we'll |
|
| 50:48 | part one in the next module. ? Thank |
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