Chapter 15: Mechanisms of pathogenicity

Chapter 15 Mechanisms of pathogenicity pathogenicity means the ability to cause disease virulence is the degree of

degree of pathogenicity. Some microbes are more virulent than others. And so we will talk about this. And for a drug to cause disease, there are a few factors involved. First, they have to gain access to the body, meaning that they have to enter portals of entry, which we're going to talk about in this chapter, include mucous membranes, skin and Panter after the eye will be explaining. And then also they have to be able to adhere to the horse. Cells or tissue? They should be able to penetrate or be able to evade the host's immune system and and then they damage the whole cell and by different means that we're going to discuss. And only then because is so the symptoms are a result from the damage that they have done. And then lastly, we're going to talk about the importance of exit, and that's about the different routes that my troops can exit the body. All right. So we're going to talk about next here. You're looking at the port of entry. That includes the mucous membranes and then skin and then parenteral drought. So those are what you see here. Mucous membranes, skin, Pantanal, notice of mucous membranes are you know that these are in the lining of respiratory tract, GI tract, urinary tract, Geritol tract, and also on the surface, the thin, transparent layer of mucous membranes covering the surface of our eyeballs and also in the lining of islets. So that's.

And so that's some of those pathogens are listed along with their portals of entry, such as the agent that causes pneumonia, streptococcal pneumonia, obviously, as port of entry is through respiratory tract as opposed to GI tract, which, for example, salmonella Latifi and then Geritol urinary tract chlamydia,

HIV and then skin, which would be example's cluster. Tiffany, for example, Clostridium perforations and then parenteral, rather, is it refers to

the disposition of a pathogen beneath the skin and mucous membranes. So that can happen through. Maybe you don't pick anything that's anything that breaks the skin open and and so that therefore the pathogen can enter the same as it can be an animal bite, you know, even even mosquito bites, those are still on their parents or around and then splitting of Solum Solen, part of the body or even due to dryness when the skin spreads because of dryness that is also put into Iraq. So, for example, for example, malaria, that is Pedaler out because it enters the body through the rabies to those animal bites. OK, so let's move on to and before I move on to the next slide, I should let you know that the ports of entry are very important for these microbes because, for example, Common Cold, which is the virus that causes common cold, is portal of entry, is obviously through respiratory tract, through mucous membranes, lining up respiratory tract. If you swallow those viruses that cause.

For example, a common cold or any of these, you're not going to you're not going to have that disease, so they they only cause disease if they have gained access through their preferred portal of entry for many pathogens is just one point of entry. That is their preferred way of entering or gaining access for others. They have multiple portals of entry, for example, for anthrax, the bacterium that causes anthrax. You know that we have inhalational anthrax, we have cutaneous anthrax and we have diarrhea. So that means that the bacterium has multiple ports of entry. So either way, those are the skin is one for them that they can use, but also they can use GI tract and respiratory tract for inhalation. So it depends on the pathogen. The most commonly traveled portal of entry out of all of these is mucous membranes. And all of those are the most common portal of entry, is respiratory tract or mucous membranes, really, of respiratory tract. That is the most commonly traveled portal of entry for pathogens.

Also, pathogenicity not only depends on the gaining access to the body of a host or host cells, but also it depends on the number of invading microbes, how many or if they're just a handful or a few of those microbes, then there's a higher possibility that our immune system can actually overcome that pathogen. But if it's a large number, then they are going to be the pathogens are going to overcome our immune system and then disease as a result would result. So. Identify, which is infectious, those for 50 percent of this population is meant to they tested and then it meant to give us information about the viral virulence or the pathogenicity of a pathogen. You know, the degree of its virulence. For example, I was just talking about anthrax. Notice that it tells you that for bacillus anthraces, which causes anthrax, it can be cutaneous or intonational or GI anthrax. And notice that if it is if for the end of spores to cause cutaneous anthrax, tanto 50 and the spores are enough is enough to cause skin infection in 50 percent of the population. So that's what that identifies of the right infectious those for 50 percent of the

individuals. So skin as little as 10 to 15. And the spores are required to cause cutaneous, whereas for causing GI tract infection with that same pathogen,

the lowest number of the spores that would cause GI tract infection would be 250000, up to one million. So that means that it's easier it's a lot easier to get to come down with cutaneous anthrax as opposed to giant, because only 30 or 50 of the spores enough to end up with the cutaneous one. OK, and then and then the 50, which stands for lethal dose for 50 percent. This is supposed to tell us the the potency of a toxin because this elderly 50 milliliter. Right. So supposedly when they test this toxin is this is gives us the dosage that would kill 50 percent this population, not this obviously they haven't tested on people, but they've tested mice and saw the toxin. These are very potent toxin. Botulinum is actually the most either one of these potent toxin. Only one milligram of botulinum toxin would kill one million guinea pigs. That's how important they are. One milligram would be the amount that you can fit in a period at the end of the sentence. Your textbook. So bottom line, I notice that point. All three nanograms per kilogram kills 50 percent of the. Population.

So as opposed to Staphylococcus toxin, which is a higher number, so the most potent is, what, botulinum? All right, so so not only gaining access, the number of invading. Microbes would be important to cause disease, but also adherence to these pathogens need to adhere first. So some have these glycoprotein or lipoprotein molecules on their pillow or maybe it could be on their Shimrit or flagella or even glycol colleagues that they secrete. Those molecules are called adhesives or ligands. So we're looking at a pathogen here with these are representing their adhesive, which could be glycoprotein or lipoprotein. Notice that they actually buying receptors. On the whole cell, so receptors, so the whole cell have receptors for them and those receptors are carbohydrates and so they bind, they find them, they can bind them. So adherence is a first step before colonization. We know that already. And so, again, these are the the areas where you would of the body of a cancer cell that you would find adhesives in addition. Something else that is problematic as far as adhesion is concerned right here, as is concerned, is the formation of biofilm, because many microbes, they can gather together, form these masses that they attach to surfaces that often they must be moist surfaces and also they should contain some organic matter food for them and usually starts with bacteria. There are other microbes that can also, you know, join but usually starts with bacteria. And then so together they are protected within this carbohydrate secretion. And the together they take your nutrients, those nutrients, and also they distribute the nutrients, they get rid of the waste together, and then they're then living together. And that would be that would make them resistant to phagocytes, because our philosophy, white blood cells, they can't they can't recognize them, cannot find them. And also within that carbohydrate rich layer that they are embedded in on surfaces, they're also hiding from antibiotics. And Ossificans would not work against them. And that is a major boy from our major problems in in the hospitals, because these are, as I mentioned, disinfectants to work for them, the antibiotics that work for them. So biofilms are usually about. I think it's more than 60 percent of the infections are actually because of the biofilms, so they can be found, for example, on the urinary catheter, on heart valves. And what we know as TARTA are on our teeth, which are Hardenne, Mineralised, Plax, those are biofilms that aren't mineralised so hard to get rid of. And they cause

major problems, especially with respect to nosocomial infections and biofilms. There's another way that these microbes attach to surfaces at here, including host tissue. Another factor that

has an effect on whether or not a pathogen can cause disease is obviously having capsule's. We've already talked about how capsule's the presence of capsules which are made of polypeptide

or polysaccharide or both. They make phagocytes almost impossible so white blood cells cannot engulf them. So you've heard of heard about the streptococcus pneumoniae. We're the only ones that have capstan cause pneumonia. And here are some other examples. This one is actually Cryptococcus New Foremans, which is the fungus that causes meningitis. And that's that also has that huge capsule that you can see.

And also there are several components. So not just catsuit, but also several components can contribute to pathogenicity, for example, and protein, which is something that exists on the family and the cell surfaces of streptococcus algenis. So naughties here you can see them in protein and this shows the cell that doesn't have any protein. So these have. Without that protein, which is on the cell surface and also on from the eye of partners, partners and protein is resistant to heat and acid won't destroy it. And they also prevent phagocytes losses on white blood cells cannot engulf them. That is another factor that will contribute to the pathogenicity and the virulence of Biogen's. And then also there is Opar protein, which is found on the cell surface in Neisseria GUNDRY, for example. So those are going to really use those to attach onto the cells of of tissues. And they would. And they do. They stimulate the cells, the cells to bring them in. So they induce internalization to bring them in with that protein that they have. And then there is my colleague Acid, that Mycobacterium Acquaviva. They have my colleague Essid as part of the cell. And not only they can be involved, but once they go out, they actually flourish inside the cycle, those phagocytes, because they can't be digested. If they have my folic acid, they can be ingolf, but they're not digestive. So they will. So they will Jupitus producing and multiply example mycobacterium to all mycobacteria know Acquaviva.

All species of mycobacterium general cardio do have high quality assets, so they have that capability.

Enzymes, enzymes also are very important, they contribute to pathogenicity or the capability to cause disease. Here are some enzymes are mentioned here, for example, coagulates, we learn about that in the lab. Staph aureus coagulates blood plasma. So what it's doing is this converting the protein fibrinogen to fibrin, which is what cloth's are made of. And how is that helpful? Well, they they hide it from our immune system. Quiney says these are enzymes that actually break down blood clots, Wallstrip perjurers and Stuff aureus, they have their own kinases that they make and so they break down a blood clot. And the simple kindness I actually use is given to patients who have had a history of heart attack because of what affects because of blood clots. And so they're treated with, you know what, control dosage of streptococcus. Hyaluronic, this is an enzyme that breaks down hyaluronic acid, which is is the chemical that that adheres cells together in tissues. So you can see how something like syrup, Biogenesis or Clostridium beverages, which have this enzyme that breaks on hieratic acid between cells, they can actually spread from the original site of infection colonies, breaks down collagen, Clostridium perforations. Same thing, same purpose. That's how it can spread. Also, you know how the blackening of the tissue that it's observed in Clostridium Frenches infection is due to the enzyme that they produce that high around this enzyme that they produce and they cause them to spread IJA proteases enzymes that break down. As you might remember, EGA is the type of antibody that's found in body secretions, including the secretions from mucous membranes. So if a bacterium can break down, that's important part of our immune system, if it can break those antibodies. Inactivate those antibodies, then they can evade our immune system, so that's what Neisseria both a species of Neisseria that you're seeing here can do that and. Evade our immune system. That was. Others undergo rapid antigenic variation, meaning that something like Neisseria gone awry, which causes gonorrhea, Plasmodium, Trypanosoma, Gambia's and even flu virus. There are examples of those that have high rates of mutation. They activate different kinds of genes to that code for different kinds of antigens and so therefore undersurface. So therefore, our immune system would not and would not be able to identify it as something they has encountered before. They're always they always present themselves as a new pathogen and where the antibodies that our immune system has formed is not going to work against them. Thus, the reason for us giving a flu vaccine every year. So same thing with Neisseria gonorrhea to Plasmodium Trypanosoma means. Also, your textbook indicates that Trypanosoma Gambians has 1000 different antigens, variations of antigens that it can display. And so that's why this disease will last for decades. Plasmodium, because of all the antigenic variation that it has, also is the reason for we don't have a

vaccine yet. All right.

After.

Gaining access and then is penetration into the wholesale invest in our surface proteins and what they do is that they actually rearrange the components of Cytoskeleton, you know, Cytoskeleton, which is composed of we're talking about cytoplasm of eukaryotic cells, which has cytoskeleton. Cytoskeleton are those microtubules of different sizes. And one of those protein fibers that you would find there is acting. So they actually rearrange them so that they would then encourage or stimulate to sell the whole cell to bring them in. And you're looking at some Latifi which hit. This one is Saifi. Both of them separately from the area, but equally does the same thing where they encourage they simulate the whole cell to buy what's called membrane roughly to actually bring them in. So that's due to the rearranging of the components of the set skeleton in the cytoplasm and also shigella to Syria. Both of them, not only they have an effect on hexing, but also they can. Interfere with the glycoprotein between cells that support katherin and so therefore disrupt that, and so therefore they can move, they can go from they can move from one cell into another, therefore distribute, therefore spread different parts of the body.

And yet we have other ones that if even if they're taken in by our white blood cells, if I was any white blood cells, but they won't be they won't die something like Coxiella burnetii, it actually flourishes even though it's acidic inside the phagocytes after the lysosome, the vesicular that contains the bacterium they have fused. So that would be called federalizes. So even in there, even though it's acidic, they survived. And Soozie, some can escape from that and or even prevent fusion of that vesicular with the lysosome. So these are examples of those that can do that. And yet we have other ones that prevent the fusion of lysosome with the phage. So you are not required to memorize the specifics of what shigella the studio can specifically do versus what Coxiella can specifically do or ordenes. But you should know the methods, what is used, such as in the presence of InvenSense, which rearrange Cytoskeleton, or that some can actually survive inside phagocytes.

Direct damage to the host cell or tissue.

Is really what is causing the symptoms of some of these pathogens, they're actually consuming the host cell tissue they're using and can, you know, think about, for example, escalus ascaris that causes malnutrition because it's actually a consuming the host's nutrients.

There are other ones that consume the whole cell and all the tissue. They also produce waste products that are causing the damage. So it's not always because of the pathogen itself, but the metabolism waste that they produce, the enzymes that some of them use in order to penetrate a wholesale or just by their motility, aromatherapy when they penetrate the horse, for example, syphilis, Trypanosoma, Paladium, that causes syphilis, if you remember, that doesn't have any means. Opportunity is just it has in the flagellum. Right. That gives it its corkscrew type opportunities of its own motility that then that penetrates the epithelium cells. And that itself, the ability is. So damaging tissue damaging another once a they multiply inside the whole cell and cause of rupture. Think about Plasmodium inside of cells, which then, you know, they reproduce and they cause some sort of rupture or they interfere with a cell function, for example.

Red blood cells contain hemoglobin. We also have transferring that bone bone protein to bind iron in our blood plasma and some microbes that have what's called Cyberforce, they actually by producing spider forms, they steal iron from our hemoglobin or from transparence. And so they use they use that for their own growth. And that way they are interfering with our red blood cells function to transport oxygen back and forth between the tissue and our lungs and other ones produce toxins. So it's really the toxin that is causing the damage to the wholesale of tissue. Many of these toxins are enzymes. You know, some of the enzymes we talked about in the previous slide, and those toxins can also kill yourself. And in addition, depending on type of the cell they can release, this is so therefore looks like and you can see that iron is part of sulfur and that's where it needs that idea. All right. So toxins, many of these bacterial diseases, it's actually the toxin that is causing the damage or causing the disease. There are different kinds of taxes that we will be talking about, but generally

the effects are they have range from the ranges from fever, diarrhea, but destruction of blood cells could be white blood cells. Red blood cells interfere with the function of the nervous system or the cardiovascular system, and protein synthesis is inhibited. So that's just you know, we're not talking about the specifics, but overall, these are what the toxins, the toxin geneste means the ability to produce toxin and which causes intoxication. So toxins are poisons, the poisonous substance. And if a pathogen can produce toxin, then that toxin is present. The disease oftentime is because of intoxication, because of the presence of the toxin, and not because of the bacteria or the presence of pathogen itself. Toxemia is the presence of toxin in in blood. Toxoid are inactivated toxins, they can inactivate toxins by using heat, using chloroform and other chemicals, and then they can use the inactivated toxins as vaccines. So there are still antigens, but they're not because of toxins, but they're inactivated. So they're not going to cause disease, but they're going to provoke our immune system to make antibodies against. And then antitoxins are antibodies of the produce against toxins. So, for example. If anyone receives a tetanus vaccine or diphtheria vaccine, what is in that vaccine is antitoxin, meaning there are antibodies against this and against diphtheria that are given by former vaccines.

Back taxes are divided into two groups, exotoxins and endotoxins, exotoxins majority of the exotoxins mostly are, I should say, majority most of the.

But I'm positive bacteria are the ones that produce exotoxins. Hey, there are some. Gram negative that also produced existence, but the majority of the exotoxins are produced by gram positive bacteria. So I want you to fix that a little paragraph on the Exotoxins in your textbook, because it says that it's mostly produced by Gram Negative, and that's from. As you can see here, is mostly produced by Grandpa XIFAXAN.

And they're called Exotoxins because they're secreted into the surrounding right, they're producing side, but they're secreted into the surrounding their music ground. So you're looking at Clostridium, for example. The botulinum toxin is an excellent toxin, therefore, OK, Clostridium, the grandpa's bacterium. And actually botulinum toxin is the most potent toxin that exists as opposed to and they are pretty exotoxins are pretty endotoxins. However, the lipid that you might remember, which is a component of that also like a polycyclic of gram negative that's repeated. So Liberté I mean, endotoxin is just gram negative that have endotoxins because gram negative have lipid. And and they are only

released when that bacterium is broken open, right? So that means it's just it's broken open and only then the liquid is released and.

For example, here are salmonella you're looking at, which is a gram negative bacteria and produces that this is causing enteral toxin. So let's talk about. So the Exotoxins first, so we know that it's mostly gram positive that we use exotoxins there, there are secreted into the surrounding their protein molecules. Do they cause fever? No. Can they be neutralized by antitoxins? Remember, antitoxins are antibodies that are produced against toxins, right? Can those antibodies neutralize these? Yes. So that means you can actually make antibodies against using those antibodies to neutralize his success. Are they 50 is a small meaning that just a minimal amount of this toxin were killed. It's lethal to 50 percent of the population. Right. And as I mentioned, either one of those exotoxins botulinum toxin is the most potent. So they are protein molecules. They are soluble in body fluids, including blood. So true blood, Ilive, they can be distributed, distributed easily and rapidly to all parts of the body. And these are. The genes that code for Exotoxins, some of them actually are or some bacteria acquire those genes from viruses because it's actually the virus that carries the gene for it. And then once the infected bacteria, that's what they're transferring that toxin producing gene to the bacterium. If you remember the civil rights, the genetic conversion, we're going to have a slight certainty about that or on plasmids. So the genes for producing specific exotoxins are on some plasmids. And you know that bacteria also exchange platform. Also, Exotoxins are named based on what specific tissue or organ they they they can have an effect on, such as hepatic toxins, meaning that those exotoxins that attack liver, Cordia toxins attack the heart, local toxins or exotoxins that destroy white blood cells and other ones are named after the disease that they caused, such as botulinum toxin or arterial toxicity. There are generally three types of exotoxins, those are called AB beatboxes membrane disrupting toxins, subbranches, AB toxins, or most of the exotoxins are actually AB toxins. So they have two components. The component A is an enzyme and component B is what will enable that that toxin to bind. For example, here you're looking at the bacterium that produces that AB toxin exotoxins and noted that it had two parts AB. So A is that enzyme component, and B is the one that actually binds them septum. That's what. And it's here in the U.S. that has it has attached to the wars and is the U.S. the war to bring added?

Example of a bit of zoom is gene autopsying and the general toxins are produced by for that. An example of a bacterium that produces toxins, Helicobacter, Helicobacter Gram negative. And general toxin's, what they do is that they actually break from their DNA chromosomes containing DNA. And so that's how they interfere. They cause changes in chromosomes by breaking the DNA and also interfering, therefore, with cell division. And that can also lead to cancer. And then Membrey disrupting toxins are the ones that disrupt the cell membrane function. They loyce the host cell, the cause of a cell, therefore to die, and local sedan's, which are exotoxins that break down with blood cells and hemolysis red blood cells. They're both produced by streptococcus and staphylococcus. So both are membrane disrupting toxins and they disrupt the membrane by either actually creating a channel, pull through the membrane cell membrane, or by binding the phospholipid in the membrane and then causing disruption and eventual outcome is the same lysis of the cell. Super antigens are called superagency with these Exotoxins Allport parameters because they can provoke an immune response that is beyond what's considered normal. And it's actually so intense that we can even lead to death of the host. So. Because these provoke intense immune response in a way that excessive cytokines are produced by Kissel's and that would lead to fever, vomiting, intense, not nausea, diarrhea, shock, which is sudden drop in blood pressure and even death. So when you think about Sobrante, just think about Staphylococcus aureus toxin produced in cases of toxic shock syndrome or even food poisoning or even food poisoning is due to super allergens.

And the stable, you can see the bacteria with their exotoxins that are produced and this is is that because our mission here, this is a toxic toxin and I was just talking about staph aureus that makes us look around. Pigeon food poisoning is super antigen. Notice that majority, the majority of the exotoxins are actually AB toxins, which have two components.

Helicobacter, which is a gram negative, but produces Junon toxin that I talked about earlier, and you know how Helicobacter pylori can lead to stomach cancer. That's because general toxins that they produce. And what I was going to say is that we already talked about neurotoxin, which, you know, it has an effect on the nervous system or on the nervous system. For example, botulinum is a good one where it's a neurotoxin that causes a paralysis of muscles, are involved with the respiratory, with respiratory muscle. So would really. Houses of those muscles, and that's why that results or toughness, which we have talked about before. That's also a neurotoxin that they produce, which also causes muscle spasms. So that's how they are also interfering with nerve with the central nervous system, psycho toxins or toxins like yourselves by preventing protein synthesis and then enter a toxin. I was going to make sure that I mentioned this. Anthrax toxins are exotoxins that specifically affect the lining of the GI tract. And so those bacteria that produce and a toxin, they also cause diarrhea. That's because this causes secretion of large amount of fluid, diarrhea as well as electrolytes. That's you know, if it's not treated, that's what can actually lead to shock, which is sudden drop in blood pressure. And those electrolytes losing electrolytes is dangerous. So it's a toxin. Is that toxin we talk about? I think you covered them all, do you? Yeah, not a function of these toxins. So, you know, I already talked about what toxin does. And then over here, what do I have? Yeah, and then, you know how these are named, obviously look autopsied by some white blood cells and things like that.

But, you know, the function of these toxins that I have talked about on.

Endotoxins or Liberté, we already talked about that, and that's the component of utter lack of polysaccharide membrane, so it's only found in gram negative and they are are only released once that gram negative bacterium is broken, broken open, and then it's lipid and like exotoxins, which are proteins. Do they induce fever? Yes. So endotoxins have pathogenic effects. Can they be neutralized by antitoxins? Know the antibodies that are produced against endotoxins are not effective. So no, they can't be always by antitoxins. Elvie, 50, is large compared to Exotoxins. That means that endotoxins are less potent than Exotoxins. You need a large amount of endotoxins to kill 50 percent of the test population. That's a lethal dose means. So they're not as important as Exotoxins are. And we are looking at the pyrotechnic effect of an autopsy. You're looking at a gram negative bacterium that's being engulfed by a macrophage broken down into pieces. And that is the Liberté is going to induce the macrophage to make Interleukin one. Interleukin one is a cytokine. That macrophage makes for uses only after the order, the effect of the lipid, then interleukin one is going to be secreted into the blood circulation through that is going to reach the hypothalamus of the brain, which is going to then affect the hypothalamus to make tumour necrosis factor alpha. So is our hypothalamus. That makes tumour necrosis factor alpha. Which then.

Which then? Excuse me, I said that was wrong, so it produces interleukin one Antillean across the sector. Both are produced by macrophage into the circulation. They reach our hypothalamus. Hypothalamus produces crustal. Prostaglandin is produced by our hypothalamus unpossible and then is it is it it will set our body at a higher temperature. So that's how they develop fever. And if you remember, we have talked about how, for example, Tylenol, which has a them in acid acetaminophen, what it does is that if it prevents production of prostaglandin and that's how it brings the fever down.

We'll see.

Oh, and so something else about and toxins that are produced by only gram negative bacteria, the Grampa's, it cannot produce the. They all produce the same endotoxins that are produced, the same signs of symptoms in the patient, regardless of what that endotoxin is, which would be fever, chills, septic shock, which would also lead to death because of sudden drop in blood pressure, general weakness in aches, and that also the one that can cause miscarriage and death of the tissue, which is called necrosis, because of the blood clots that form, and therefore they interfere with the blood and therefore oxygen reaching that area and further reaching that. That's why necrosis or tissue death. And then, of course, they are called Speaker Hydrogenics. So these are common to excuse me, Orlinda toxins.

Regardless of the pathogen.

And this table is kind of summarizes the properties of. The traits that we associate with the Exotoxins versus endotoxins, and I'm just looking at it quickly to see if I miss anything. Some representative diseases are mentioned in each one.

Remember that endotoxins are only produced by gram negative bacteria that are due to the salmonella equally, Proteus can cause you're interacting fictions so that one of the alternatives are going to make you the same as.

Meningitis, whereas exotoxins mostly gram positive, but also we have a few gram negative bacteria such as Helicobacter pylori that I mentioned before, that produces the exotoxins called general toxins.

Psychopathic effects of viruses. Well, some of these we have already covered in Chapter 13.

What damages the viruses cause? How do they cause disease of cells? Right. Psychopathic, the different. Hematological changes to cells.

One, inclusion bodies, inclusion bodies are. Little granules that would be found in the cytoplasm of the cell, those infected by a virus or even in the nucleus or so those are, what are they? They are usually just water parts, for example, before assembly, for example, protein, you know, the capsule and DNA or RNA nucleic acid of the words that are supposed to then assemble together. But they're not assembled yet. That's what inclusion bodies contain and they serve as a diagnostic, they have diagnostic purposes, they can be used to diagnose the disease, for example, in case of. Any of them they can do if they see these specific inclusion bodies inside their nucleus or cytoplasm. They can diagnose a viral infection.

Another one is like, for example, Sehar.

Papillomavirus is one that induces formation of inclusion, what is adenovirus, the virus that's also cytomegalovirus, so you don't have to know the names of these viruses. But I'm saying is that let's just give you some examples that if they see these inclusion bodies, for example, in specific types of cells,

tissues, then they can tell that the person is infected with cytomegalovirus. So this would be a naive picture. So that's what they would look for, as opposed to something like rabies, which if they see inclusion bodies in the brain cells, that is an indication of rabies infection, HIV. So in conclusion, wisemen, another one is formation of these giant or seeing these giant cells, which they are. They have multi nuclei. So what those are they're actually called. You just have to slightly measure their costs and CTM here, so CTM, which is what it is, is that these viruses cause adjacent cells to fuse together so that you just see a giant cell. But it has multiple many nuclei because really it was many cells that fused together as a result of that. And then another one is, of course, actually morphological changes to the cells. For example, you might remember from anatomy that fibroblasts are kind of slender and they have these pointed ends, whereas normal fibroblasts I'm talking about, whereas here you can see how this rounded and it doesn't look. This is not normal. So morphological changes to cells as well as chromosomal abnormalities and other things that we have talked about is loss of contact, inhibition of growth. What is that is when, you know, normal cells, they come into contact with one another and they start multiplying, but not these. So if cells are infected with viruses, they lose that contact inhibition of growth. And so therefore, that means they're just reproduce and multiply. And that leads to cancer. Also confident that this one actually activate, they can activate oncogene oncogenes. If you remember, there are our own genes, but they can be activated by some viruses. And once they're activated, the outcome is cancer. A chromosomal abnormalities that we have talked about before. They can cause resistance to mix, to release their enzymes, enzymes that are released by looms inside the cell. They kill the cell itself. Our own cells I'm talking about. And then.

Inducing antigenic variation was seen as. I don't know what it is, but here here we have you inducing antigenic variation so viruses can actually it as can induce

the cell to display these proteins antigens. Right. But there are Berlanti on the surface. And when that happens, those cells are actually then targeted by our own immune cells to kill the. So but it's our own cells that die, right? That's not a good thing. And then and also we've learned about how cells interfere. Our own cells produce interference, alpha, beta, interferons. Which we talked about before, how they have the capability to. Prevent viral multiplication in the adjacent cells, but they don't do any good for the cell that is infected, they actually use it pop tosses of the cell and so therefore the cell dies. And then lastly, the genetic convergence, which

is lysergic a bacterium, viceversa genic is one that it carries viral genes its own in its own DNA. Right. So therefore, that bacterium is Vasiljevic. Now it's transformed. It's carrying Prophage, and so therefore, whatever the Prophage genes are calling for, that bacteria will also produce. So here are some of the those toxins that we've been talking about before. That. Produced by these bacteria, but notice that these toxins are only produced by those bacteria if they are Genetix bacteria, meaning that if only these bacteria are effected by virus and therefore there they are carrying Prophage in their DNA, only then they can produce these toxins. Why? Because the genes that code for these toxins are the Prophage or the viral genes that are calling for them. So, for example, if you have a corona bacterium, bacteria that does not have a Prophage, it will not be able to produce cytotoxic. Just sells.

And so so in reality, the genes coding for these toxins are really origins, so supervisions of staph aureus is really because a virus enter a toxin, you know, the one that causes diarrhea, apologetic toxins, that causes hydrogen, it causes fever. This is staph aureus gram positive. It's not gram negative yet. It has pathogenic effect because it's producing pathogenic toxin. Only if it has, it carries perfect.

Lastly, which, you know, that certain caucus narwani, I have capsule's, they can cause pneumonia. What is the gene that codes for capsule come from only?

So to focus on the money that have undergone a gynaecology meaning that they're infected with the virus, the Warren Prophage is now. In their DNA is the Prophage virus gene that is calling for the presence of GABSI

pathogenic properties of fungi.

Some probably allergic response, you know, those fungal spores, for example, April, allergic responses, some people some produce these proteases, protease enzyme, three different ones. These enzymes can break down the host or alter the membrane of the host cell so they can adhere to such as Candy Arkan's, which is pathogen sleepify, which is pathogen

capsule's. So some have like cryptosporidium performance. This is actually cryptosporidium. Newfoundland's with a giant capsule they have, which therefore cannot be Girlfight. That's how it can cause disease. We talked about. This from the affirmance, which is really. The most well, not the most, but one of the most dangerous and fatal fungal infection, toxic metabolic byproducts that they produce as a result of their metabolism, such as Aagot, which is actually is the source of ALYSSE, which is a hallucinatory toxin that's produced by clever purpurea, is the fungus that produces these fungi were actually they every once in a while they can contaminate wheat and other grains, not in the modern day, because modern day milling and processing these grains is it can remove the parts that would cause that would carry that aagot. But in the old days, such as in 2006, in hundreds or something, the witch hunt in witch hunt in Salem, Massachusetts, and I'm sure you've heard of where you know the. There were a few thousand young girls who actually they accused a few people of.

Big wishes, you know, and they they they said that they were bewitched by them. Well, they think that now they think that they will actually have consumed bread that was made with these wheat, the wheat that had Aagot had these virus fungus growing on them so that there therefore they actually were suffering from ergotism, which is a hell of hallucination. They were actually expressing frustration that that's that's what was happening because of excessive rain that they had received that year. And therefore, these fungi contaminated the wheat that they had used to make.

Try Courtice is another. Metabolic byproducts of these two fungi, fusarium and stachybotrys that we talked about before, this one growing on weight, I believe, and this one, they have found that growing nowadays in inside houses where the water has damaged the walls in the walls. They found them and noticed that these actually also these are the ones that actually are fatal to infants, inhibit protein synthesis, that toxin. And can even this one can be fatal to. Infants, aflatoxin, again, I've talked about that before, where it causes a mutation due to Aspergillus Flavors that specifically goes on, for example, peanuts or other cheek nuts. It's a carcinogen, it causes a mutation that leads to cancer and mycotoxins, such as phalloides and amenity that are neurotoxins and their produce. But Amanita, this is a different species of America. But this genus of mean, the ones that produce these or Amanita phalloides, and they actually cause that and commanded and that's why they're called death care. They look like regular mushrooms. I mean, if you go where most people can't tell them apart from regular mushrooms. Next, pathogenic properties of protozoa for those are eukaryotic. They're seeing itself and they produce not only by their presence, just being there in the in the host, but also the metabolic waste that they produce they symptoms and some of them, they actually digest our own cells and tissue fluids, such as NameA, which causes the ulcers, something like Plasmodium. You know, there are several species of Plasmodium, for example, Plasmodium memex, you know, the plasmodium that cause malaria. They killed those red blood cells. Other ones can grow inside our macrophages, such as Toxoplasma gondii that induces miscarriage and even stillbirth in women who are infected. Other ones by undergoing antigenic variation. Multiple, many mutations and therefore changing the surface of the gender for evading our immune system. Such as all these examples, including Javier.

Helmet's parasitic worms, their large their presence alone is interfering with the function of the host tissue, and they also produce waste products. They also can consume the horse itself, you know, not the whole host tissue or cells such as askaris that actually consumes all of our food or McArtor Americana's, which causes iron deficiency anemia because they're actually, you know, taking

taking Iten feed on blood and also an amoeba. Well, that's not what we're talking about here. So one basic thing is that there multicellular big. Organisms. And so when you have so much of them, for example, all those askaris blocking the GI tract looking intestine, they're they're causing malnutrition. So not only by the feeding on our nutrients, but also by just their mere presence. Same thing with which area bankruptcy, which also same thing they are blocking our lymphatic vessels and also the metabolic byproduct damages those valves in the lymphatic vessels. And so all of those will cause severe damage and grotesque changes in tissues. And that's so that's what they do. That's how helmets, in addition to, you know, all the time you think this is all we've talked about in Chapter 12, but these are some kind of it's a summary of what they can do. Algae neurotoxic, we thought we have talked about genus Alexandrian before the toxin that the neurotoxin they produce is called sexy toxin. So we all know it causes paralytic shellfish poisoning, and that is as a result of consuming like oyster clams, mussels, you know, all of those that if they have been consuming genus Alexandrian algae so it wouldn't do anything to them, that toxin. But if we consume those shellfish, then we can end up with paralytic shellfish poisoning. That can be fatal because that's paralysis of respiratory muscles. Diatoms, which is only a certain species of the items that produce domoic acid. The condition is called the acid intoxication, also known as amnesic shellfish poisoning. So that is even though it's called shellfish poisoning. But it's not just shellfish. So it's all those muscles, but also it could be fish or shrimps that have been consuming those diatoms. So, again, the items are not toxic to them, but they would. They would they would consider my guess, the intoxication in us that would be

would cause the least that can happen is

short term memory loss

is gone, but also it can lead to that.

Portions of exit.

These microbes, usually pathogens, they exit the body. Using the same rules that they entered that they used to enter the. So, for example, common cold. Right, common cold or flu?

The way that they enter is through the mucous membranes lining the respiratory system, we inhaled them, but also they exit the same way through respiratory tract by coughing, sneezing, and those drops of mucus, small drops of mucus, that's how they exit the body. Right.

So common cold, flu, measles.

Well, that's. So anyway, discharge from those the. Pneumonia, right? And then genital gastro intestinal tract. That would be those pathogens that enter because we know that because we ate we ingested those. They also will exit the body through GI tract, which would be saliva is part of a drug secretion and also feces. So excretion as the pressure of the GI tract. So, for example, you know, all those that cause food poisoning, those that cause poisoning or salmonella that causes typhoid fever by, you know, eating contaminated food or drinking contaminated water, they also are excreted in feces.

Amoebic dysentery, cholera, salmonella. And then. And of course, Survivor, which I talked about, is also one

survivor, can also contain something like maybe rabies virus. They exit that way, they can infect someone else

and and your urinary tract. So that's from a urine. So an example of what can exit through urine.

Typhoid fever, typhoid fever, the salmonella that causes typhoid fever, also it's secreted the urine. So not only is feces, but also in urine.

All the diseases, the sexually transmitted diseases, those are in this category

secretions.

And then also.

I at to the reporters exist for those kinds of diseases, skin or drainage from wounds, so skin, for example, of a disease of skin such as fungal infection of the skin, like ringworm, herpes, like the one that causes so courser herpes simplex that causes Saunders's skin infection. And it's existed that way through those, you know. The lesions are they cause.

The drainage of those that contain active viruses that can that can infect someone else or worse, you know, those are also found on impetigo, skin, bacterial infection. And so they can they can be spread through contact directly with the skin or contact with brain. It can be even from a wound. And then, of course, blood, blood. That would be anything that like Plasmodium vivax that has introduced the that has been introduced into our blood by a mosquito, that mosquito bite, but also the exit the body through that mosquito bite, also right through blood. So biting insects or also contaminated syringes, needles that can also transmit HIV hepatitis.

So those is are in this group of.

All right, that was the last slide. Oh, and I should say that the most traveled portals of exit are two of them, respiratory and gastrointestinal tract. Both of these are.