in this lecture we're going to discuss um pathogenicity and different ways that microbes are pathogenic and cause infection different ways that they invade the host cells and so on so the first thing we want to do is define pathogenicity this is the ability to cause disease remember a micro being pathogenic means that it's able to cause disease it's able to cause infection virolence is the degree of pathogenicity so kind of like how severely pathogenic is it so first what we're going to do is we're going to talk about portals of entry how do microorganisms enter into their hosts enter into their host cells and then we're going to kind of go through the details and then at the end we'll talk about portals of exit how do they leave the host so one way that they can enter um into their hosts which for example can be us is mucous membranes mucous membranes are basically the inner linings of different tracts in our body for example your mouth is a mucous membrane so any like your respiratory tract is a mucous membrane any opening um to the outside world to your external environment is a mucous membrane um skin um now skin is very very protective there's multiple layers to your skin and it protects everything inside of your body and so if let's say there is a break in the skin a cut or a wound that provides basically an easy access point for a microorganism to enter so they can enter through the skin and they can enter through the parental route um and that's when they directly go into the tissues and again this is going to be when the physical barriers that are protecting our body get penetrated now most pathogens they have their preferred portal of entry like maybe a certain bacteria only enters through the skin or only enters through the respiratory tract a couple of other terms we have to define is ID50 and LD50 so ID stands for infectious dose ld stands for lethal dose so the ID50 is basically a value it's the infectious dose for 50% of a population so the amount for 50% of the population to be infected ld50 the lethal dose that's the lethal dose for 50% of the sample population meaning the dose for 50% of the sample population to basically die from that microbe so here for example we have basillus anthraasis this is the causitive agent of anthrax and so for example depending on how it enters the body different amounts of endospores that it has can lead to 50% of the population being infected so whether through skin inhaling the spores ingesting which means eating the spores like through food and then if you're looking at toxins usually you look at the LD50 so basically how potent that toxin is how strong or um effective that toxin is at doing whatever it's supposed to do and toxins which we're going to talk about today they are part of the defense mechanism of the bacterial cells um so you can see different types of toxins here and whatever amount this is is um this is the amount needed for 50% of the sample population to die from this toxin okay so um adherence is a really really big deal so in order for pathogens to enter into the host cells enter into the host tissues they have to be able to attach to the host tissues this is called adherence or adhesion and they do this with these cell surface molecules that they have called adhesins adhesins are ligans ligans are like signaling molecules so they can be cell surface molecules and they use that to attach to receptors on the surface of the host cells so imagine cell surface molecules on the microbe attaching to cell surface molecules on the host so in that way they can attach because they need to attach in order to actually enter into the host cell and infect it so they can do that with glycoales they can do that with fimbre these are structures that we've learned about already and we also know about biofilms biofilms if you recall these are microbial communities they share nutrients and they release this sticky substance the sticky polysaccharide called EPS and that makes them stick really well to whatever surface they're growing on and so it's really really hard to get rid of them so that's another example of adherence so we talked um a little bit about how they enter now let's talk about how they penetrate the host defenses so the first example are capsules capsules we've talked about before um and it's a type of glo glycoalix that surrounds the cell wall it's external to the cell wall and capsules impair fagocytosis fagocytosis is a process of cell eating so for example if I have a bacterial infection and have bacterial cells around my body my immune system is going to kick in my immune response is going to kick in to try to protect me and kill the bacteria so my immune cells which are my white blood cells actually can eat up the foreign bacterial cells that don't belong in the body and then they can break it down and destroy it and that's one way that they get rid of them and that process is called fagocytosis now bacterial cells that have capsules surrounding them um they evade fagocytosis they can kind of escape our immune system our immune response so some examples of bacterial species that have capsules because not all of them have it these examples are streptococcus pneumonia which is a causitive agent of pneumonia um and many things cause pneumonia this is just one cause himmophilus influenza can also cause pneumonia it can also cause menenitis and menitis is inflammation of the meninges the outer coverings of the brain basillus anthraasis which we already mentioned is the causitive agent of anthrax and your pestis which causes the plague now there are other cell wall components of different um species of bacteria um that serve as these virulence factors one of which is the M protein m protein is another type of molecule that resists fagocytosis streptoccus piogenous has M protein niseria gorrhea which is the cause of gonorrhea it has a protein called opa protein and that allows it to attach to host cells so think of opa protein kind of as like a cell surface molecule that helps the bacterial cell attach to the host cell and then we have micolic acid which we've learned about before um these are by mcoacterium species for example mcoacterium tuberculosis they have micolic acid in their cell wall and it's a waxy lipid and it resists digestion so another example of evading our immune response there are also enzymes that bacterial cells can have they can make they can release them that are protective for the bacteria um and they're bad for us so enzymes um include coagulases coagulases they cause coagulation which is clumping um and so that can cause blood clots in the blood in our bodies kinases do the opposite they don't let blood clot which can also be dangerous cuz then you would bleed out if there's any wound in any of your blood vessels hyaluronidase basically breaks down the sugars that keep cells together so for example all the cells of my stomach they're only in my stomach they're specific to my stomach and they're all attached to each other to make up that organ to make up my stomach um and so hyaluronidase would break down the attachments between cells so the cells kind of separate from each other so that can be dangerous um collagenase breaks down collagen which is really important for a lot of parts of the body and you also have IgA proteasis proteases are enzymes that break down proteins and IgA stands for amunog globbulin a that's a type of antibbody that we have in our body and and antibodies are very very complex protein so if you recall the different levels of protein folding the most complex level was the quatinary structure um and so um antibodies reach that level so they're really complex but antibodies are proteins so proteasis can break them down and that kind of goes against our immune defense now there's also another thing that they can do which is anti-genic variation that's when they can switch up their surface proteins so that our immune system can't recognize them anymore so I'm going to draw this one so here is my microbial cell okay I'm going to draw a before and after okay so let's say it has these surface molecules on its surface it's these purple round ones and let's say it entered my body my immune system was able to um notice it and now it's targeting these and breaking them down well some microbes they can switch these up so now instead of having I don't know that purple circles now let's say it switches it up to another type of surface molecule so is my immune system now going to recognize this one no it recognize this one but now it has to work to recognize this new one so it's kind of fighting against our immune response so this is called antigenic variation surface antigens just think of them as surface molecules for now we're going to learn a lot more about the immune system in the next two chapters okay so um let's talk about some other examples of invading the host cells so there are surface proteins that bacteria produce that are called invasins and what invasants can do is they can rearrange the cytokeleton of the host cells if you recall we defined the cytokeleton as these protein filaments different types of protein filaments that help the cells maintain their shape it stabilizes the cell um and it can also be used for cell movement and so one of those protein filaments are called actin so actin is just a type of protein it's part of the cytokeleton now invasins on the surface of bacterial cell cells can actually rearrange those actin filaments and cause the cell to have a different shape this shape is due to membrane ruffling so if let's say um here's my host cell and you can see my cell membrane is surrounding it what these invasins do is my membrane they cause it to ruffle so it would kind of look like this instead they made these they make these kind of it looks like there's like pockets so this is membrane ruffling and they do this by rearranging the cytokeleton cuz remember one of the cytokeleton's jobs was to maintain the shape of the cell um and so when they do that it makes it easier for them to enter into the cell um they also use actin to move from one cell to the next so they can even manipulate the actin filaments to move from one cell to another host cell so examples of genre that can do this are chagela and lististeria species some bacteria can also survive inside fagosytes so I'm going to go over the process of fagocytosis really quickly give me one second okay let's delete all of these okay so this is the process of fagocytosis so this is that was really bad i'm going to do that one more time all right so this is my host cell okay so this is my host cell it's an immune cell so it's basically a white blood cell and I mentioned that it can perform focytosis to bring in let's say a bacterial cell so here let's say I have my bacterial cell it's a rod and so what can happen here is my white blood cell can basically bring in this bacterial cell okay it'll be bringing in this bacterial cell and basically eating it so when it brings in this bacterial cell it kind of makes this pocket and kind of like swallows it up and when it does that then my bacterial cell is in like this bubble it's kind of like a bubble made from the cell membrane and so that bubble is basically surrounding it we call this a fagosome it's basically a vesicle okay so now the bacterial cell is in the fagosome it's a vesicle that's holding on to it and then the bacterial cell is sent to one of our and I'm going to do this just to make it look different it's sent to our lo and once the fu the once the bacterial fagosome this vesicle fuses with the loone now we make something called a fagago and then you have that bacteria in there and we already know what losomes do they're going to degrade they're going to break down and so now this bacterial cell is going to be destroyed so this is fagocytosis so I'm going to go over it just one more time so here is my bacterial cell here's my immune cell it can engulf and eat up this bacterial cell it makes like a pocket it brings it in in a vesicle and this vesicle is called a fagosome the fagosome fuses with loss which are one of the organels in our cells to make a fagosome and in that way we put the bacterial cell in a lo for it to be destroyed that is fagocytosis so I'm going to go back let's exit this i'm going to go back here so different ways that bacterial cells can survive fagosytes and fagosytes are the white blood cells that do fagocytosis um so some of them can tolerate the low pH inside of a faglyosome remember that there's uh there's enzymes that degrade there's an acidic pH all to destroy things inside of the lossome some of them can escape that fagosome even before it fuses with the lysosome and some of them can even manipulate the fagosome to never fuse with the loone so these are different strategies that they use inside of cells okay so here you can see membrane ruffling you can see it has like this wavy appearance to it which is not normal um and then salmonella is one of the examples different salmonella species can cause membrane ruffling and it allows them to enter into the host cell biofilm we've already talked about a couple times already biofilms play a role in evading fagosytes meaning they escape fagosytes they escape fagocytosis um and we already know bofilms are really resistant so they're also resistant to fagocytosis and I already mentioned the EPS substance that makes them really sticky to whatever surface they're bound to they're attached to and it also protects them it kind of shelters them um away from immune cells attacking them okay now let's talk about ways that bacterial pathogens can damage host cells one example of this is citaphores citeraphores are proteins that pathogens release out of their cells and the job of citaphores are is to bind to iron iron is one of the main nutrients one of the important nutrients that cells need not only do microbial cells need iron but our cells also need iron and so whenever there's iron in the external in their environment around them then they can release these proteins these molecules called citaphores that will go and find iron they'll bind to iron atoms and they'll bring it back to the cell and citraphores can bind more tightly to iron compared to our cells so they kind of get the upper hand um and so we're kind of competing for iron so here's the structure of a citraphor so again a microbial cell will will send it out mainly bacteria bacteria send it out it binds to iron in environment brings it back into the bacterial cell that's damaging to us because we also our cells also want to use that iron okay um other ways that they can directly damage they can disrupt the host cell function um they can use up our nutrients and kind of compete for our nutrients a lot of pathogens they produce a lot of waste products with all the um chemical reactions that happen there's a lot of side products and waste products and when those build up inside of a cell they impair the functioning of the cell um we already know that um viruses for example and even some bacteria sometimes when they're multiplying in the host cells um they can rupture the host cells when they leave and that basically kills the host cells okay moving on to toxins toxins are poisonous substances that microorganisms produce it's protective for them but it's negatively going to impact us okay now toxins can produce pretty serious side effects or issues um they can cause fever they can cause cardiovascular problems cardiovascular refers to the heart and your blood circulation they can cause diarrhea they can cause septic shock the toxygenicity of an organism is its ability to produce a toxin toxia we've already defined before toxin inside of the blood intoxications are presence of a toxin without microbial growth now most of the time the symptoms and signs that someone gets are from the toxins and not from the path uh not from the microbe itself it's about the toxins that the microbe produces so an intoxication is when a toxin is present even though the microbe is not really doing anything so we're going to first talk about exotoxins and then we're going to talk about endotoxins so exotoxins they're proteins right they're toxic proteins produced by bacteria they release it into our body as their own defense mechanism and exotoxins are soluble in bodily fluids so for example in the bloodstream they can travel through the bloodstream and go to different parts of the body they can destroy host cells they can impair the metabolic functioning of the host cells and so on now um in vaccines a lot of times vaccines carry exotoxins but they're inactivated exotoxins so they don't really cause anything but they're like just think of like a dead version of an exotoxin and those we call toxoids so toxoids are the ones that are used in vaccines okay we're going to look at some categories of exotoxins because they can act a little differently the first one we're going to talk about is AB toxins now AB toxins have two components and the A component and the B component the B component just remember B is for binding so this helps that toxin attach to whatever cell it wants to infect and the a part of it is the enzyme part of it that's the part that does the toxic effect to the cell whatever that toxic effect might be an example of an AB toxin is diptheria toxin um dtheria toxin causes dtheria um and that's found and you can see that the toxoid is actually found in the tap vaccine okay genotoxins are toxins or exotoxins that damage DNA geno just think of genes DNA it can cause mutations in the DNA it can mess with the cell division process and it can even transform cells to become cancerous we also have membrane disrupting toxins these as you can guess can disrupt the plasma membranes they can lice host cells um and basically cause the cells to die there are different examples of membrane disrupting toxins for examples for example luccoidins these kill fagositic luccoytes luccoytes is another word for white blood cells so white blood cells that do that fagocytosis that we mentioned that's part of our immune response um there are exotoxins released by some bacteria called luccoyins that would kill those white blood cells hemolycins would kill red blood cells so the other word for red blood cell is arythroy and then streptoly are basically the same thing as a hemoly but it's specific only to streptococcus species okay the last exotoxin that we're going to discuss are super antigens super antigens cause a really really huge intense immune response and this is because they cause the release of cytoines from the host cells so let's define what cytoines are and we're going to talk more about them in the next couple of chapters cytoines are the signaling molecules of your immune system so anytime there is one of your white blood cells comes across a bacterial cell or a foreign pathogen that's infecting you it wants to signal that out to the rest of the immune system and it does that by releasing these signaling molecules called cytoines cytoines will go on and they'll alert the rest of your immune cells that hey there's something foreign in here there's a pathogen and we have to fight against it one of the cells one of the types of immune cells that release cytoines these are called TE-C cells we'll be learning more about this later on um but what super antigens do is they cause a cytoine storm they cause way too many cytoines to be released causing a really huge overreaction of the immune response and that can be really dangerous um you never want something to be that intense or last that long so um this can cause fever nausea vomiting diarrhea septic shock and even death so it can be very very serious now these next couple of slides I put a star next to the ones that we have to know and you have to know the first three columns of any of them that are starred so for example for the disease botulism the causitive agent is the bacterium called claustrdium botulinum and we have to know the type of exotoxin that it produces which is AB exotoxin same with tetanus tetanus is caused by clustrdium tetany and it has an AB exotoxin dtheria is caused by coronabacterium dtheria that releases that toxin that we mentioned before which was an example of AB toxin so it's diptheria toxin toxic shock syndrome is caused by stafylocus orius and this exotoxin is a super antigen anthrax we already learned is caused by basillus anthraasis it's an AB has AB exotoxin gastric cancer or um gastric ulcers they're caused by helicoacttor species of bacteria um and they have an AB toxin and lastly antibiotic associated diarrhea which occurs a lot in long-term antibiotic use in the hospital this is clustdium difficil or maybe you've heard of it as CIFF this has a membrane disrupting exotoxin so you do have to know the ones that have a star next to them and it's the first three column so you have to know the disease the bacterium and the type of exotoxin they have the next one we're going to talk about um is endotoxins now endotoxins we're only going to learn about one type of endotoxin which we've talked about before which is lipopolysaccharide or LPS if you recall LPS is found in the outer membrane of gram negative bacteria and LPS has LPS has a specific structure so it's lipopolysaccharide so it has a polysaccharide that's part of its structure and it also has a lipid now the lipid part is the toxic part of LPS and it's called lipid A so that's the bad part that's the one that is toxic to us um and so whenever gram negative bacteria die and that outer membrane breaks up then LPS can be released and that again like we've learned about before can lead to septic shock it can lead to death um and this is because it causes a lot of cytoines to be released um and it can also cause what we call disseminated intravascular coagulation disseminated means that it's spread intravascular means inside of the blood vessels and coagulation means clumping blood clotting so it can get pretty serious so the endotoxin example here is LPS and again the toxic part of it is the lipid A this table just goes over the differences between exotoxins and endotoxins okay so that was mainly about bacteria we're going to talk a little bit about other microorganisms for example viruses now viral infection of a host cell causes different effects in the host cells that are called cyopathic effects site means cell pathic means something pathogenic causing infection causing disease so let's go over some cytoopathic effects that viral infection can have on a host cell so it can cause the host cell to stop dividing it can cause losomes to open up and release all their acidic um destructive enzymes into the cell and basically destroy the cell they can create things called inclusion bodies inside of the cell inclusion bodies just think of them as like buildup they're like these big masses that kind of build up inside of the cell and then they're going to impair the cell functioning think of for example someone coming into your house and um just filling up trash they fill up trash they keep eating they trash your house so now your house is filled with just like a million trash bags and it's basically going to get in your way right inclusion bodies are like that um they can also make cells fuse together so they can cause different host cells in our body to fuse together into this one giant multi-ucleated cell called a sensitium they can change the functions of the host cell they can change change the genes of the host cell so the host cell is acting differently than what it would act like they can cause antigenic variation on the cell surface so that it goes undetected by our immune system and they cause loss of contact inhibition which we've learned about before and that leads to cancer right if cells do not have that contact inhibition anytime they come into contact with another cell they're still going to divide it's not going to stop them and it's going to create a tumor now there are these molecules called interferons some examples of interferons are alpha interferons and beta interferons whenever a host cell is infected by a virus it starts producing and sending out these interferons to its neighboring host cells and this is to let the neighboring host cells know hey I'm infected by a virus save yourself okay um and so then the neighboring cells can protect themselves um and the infected host cells undergo apoptosis basically they plan their own cell death so that the virus doesn't keep spreading so this is kind of like a zombie movie right so if someone gets bit by a zombie they turn into a zombie and they say they basically need to die or else they're going to start attacking their friends and turn them into zombies and so on okay now let's talk about some other microorganisms like fungi there are a few different toxins that fungi release one of which is aphotoxin so there is a genus of fungi called aspiggilis and aspergillis species release a toxin called aphltoxin this toxin can be pretty serious it is carcinogenic meaning that it can cause cancer um other fungi like mushrooms they release mcotoxins such as foidin and amanitin so these are examples of micotoxins and these are neurotoxic that means they're toxic to the nervous system so they can cause nervous system impairments if we look at prozzoa prozzoa um include the parasites um now the main negative impact of prozzoa are their waste products as prozzoa and parasites go through their life cycle inside of the host they create a lot of waste products that build up and then cause symptoms in us in the host um now they can also avoid our immune system and escape our immune system by digesting cells digesting tissue fluids they're able to grow inside fagosytes without getting killed and they also have the ability of antigenic variation which we defined earlier helmans remember these are parasitic worms they use the host tissue to grow um helmans have different stages of their life cycle they have microscopic stages and then they can grow into larger worms essentially um so they produce large masses they can cause damage to the cell and this is another one that builds up a lot of waste products that cause the host to have uh experience symptoms now there are some algae that produce neurotoxins the example here we're going to learn is saxtoxin so saxtoxin is a neurotoxin that's produced and released by algae so if you've ever heard of paralytic shellfish poisoning that's actually not the shellfish that's poisoning you um it's the algae inside of the shellfish so before the shellfish died it ate some algae and that algae released saxotoxin and so if someone's eating that shellfish later um they can undergo they can get this saxotoxin neurotoxin which remember it's toxic it's affecting the nervous system and so it can cause paralysis now lastly we're going to talk about how they exit the host so portals of exit include the respiratory tract so when you cough out or you sneeze out they can leave the host and then find another host the gastrointestinal tract your digestive tract they can leave through the feces they can leave through saliva the genital urinary tract they can leave through urine they can leave through secretions from the penis secretions from the vagina they can leave through skin so every time if let's say the skin is infected and your skin cells are constantly being like um worn off your body and they kind of contribute to the dust around you um it can wear off with your dead skin cells and of course blood as well so if someone's using needles syringes um if someone's being stung by an arthropod like a mosquito or a tick that's other ways that they can exit the body so here we basically went over portals of entry how they enter into the body remember they have to attach they have to adhere um they invade the host they evade the host's defenses they penetrate they cause damage to the host cells and then they exit usually the way they exit is the same way they came in so if um someone got infected through the respiratory route then they leave then the microbe will leave through the respiratory route for example so this concludes chapter 15