so in this video we are going to talk about innate immunity so we need to start by talking about a couple of definitions so the first definition is going to be immunity and immunity is the ability to ward off disease when we talk about susceptibility susceptibility is the lack of resistance to a disease right we talked about you can be susceptible to an infection and so that means that you don't have resistance innate immunity is the defense against any pathogen it's rapid its present birth so this is your branch of your immune system that is nonspecific it targets any pathogen and it's always there so we call that innate immunity it's built in its president birth it's not directed against a specific pathogen that's in contrast to what we call adaptive immunity and adaptive immunity is immunity or resistance to a specific pathogen so now this is the part of your immune system that is responding to a specific pathogen this is slower to respond and it has a memory component and if you generate that memory that is going to protect you against future infections by that same pathogen this lecture chapter 12 is going to focus on the innate immunity chapter 13 is going to focus on adaptive immunity and so we're going to walk through and talk about innate immunity in more detail so host defenses are a multi-level network of innate nonspecific protections and adaptive specific protections commonly referred to as the first second and third line of defense and so we're going to walk through and talk about what are what are the parts of the first line of defense what are the parts of the second line of defense and so on so the first line of defense think of it just like it sounds it's your first line of defense it's the first thing that a pathogen would encounter and so this is any barrier that blocks invasion at a portal of entry so this is preventing the microbes a pathogen from getting into the body this is gonna limit access to the internal tissues of the body it's not considered a true immune response because it does not involve recognition of a foreign substance again it's very nonspecific it's very general in action so when we talk about our second line of defense our second line of defense again is still nonspecific but it's an internalized system of protective cells and fluids so now we're getting cells involved and so this includes inflammation this includes phagocytosis remember that phagocytosis is the process white blood cells can do it for example where they send out those projections that engulf the pathogen and take it in this acts rapidly at both the local and the systemic levels once the first line of defense has been overcome so if a pathogen gets access to the body now the body gets the second line of defense involved and so if a pathogen is able to penetrate that first line of defense now the second line of defense comes into play the third line of defense is acquired on an individual basis as each foreign substance is encountered by Olympus i'ts again this is your specific branch of your immune system now we're targeting a specific pathogen and the reaction with each different microbe produces unique protective substances and so we'll talk about antibodies for example and so these are directed against a specific pathogen and this branch of your immune system is used to provide long term immunity meaning that hopefully your immune system remembers that pathogen and therefore would respond again if you were exposed to that pathogen again and so this really comes into play now if you think about what's going on with the corona virus scientists are still not sure if once you've already had the corona virus once you've had kovat 19 if you have antibodies which means that you were exposed to the corona virus is the presence of those antibodies enough to evoke that in that memory response meaning if you have those antibodies does that mean that the immune system is going to recognize that pathogen again and is that going to protect you against it getting that disease again and so what you'll see is that not all infections necessarily provoke or cause long-term immunity and so we're still trying to figure out if the corona virus is one that will provide long-term immunity because if it does that comes to a what we call herd immunity and that is that once enough of the population has had the disease then the idea is that it can slow the spread of the disease because people who have already had it or have been exposed to it are now protected and you're not able to pass the disease to that person and so you learned a little bit about this in the epidemiology chapter as well so this is a flowchart basically summarizing the major components of host defenses so again your first and second line of defense are part of your innate immunity again your innate immunity is nonce cific it's not targeting a specific pathogen it's targeting access of any pathogens so your first line of defense is going to be a surface protection composed of anatomical and physiological barriers that keep microbes from penetrating sterile body compartments basically meaning it prevents access to the body and so we're gonna talk about a variety of components of your first line of defense we have physical barriers so physical barriers like skin that protect against entry into the body we're gonna talk about how your maker Beata acts as part of your first line of defense by simply competing with pathogens access to the body and we will talk about chemical barriers as well nonspecific chemicals that the body produces that makes the body able to fight or prevent pathogens from getting in once the first line of defense has been breached so again once the microbe has gotten access into the body that is going to initiate your second line of defense and this second line of defense is a cellular and chemical system that comes immediately into play if infectious agents make it past the surface defenses so again if a pathogen has breached the first line of defense this is going to activate the second line of defense now you'll notice that this light blue box here it says gamma delta T cells and natural killer cells these are a type of cell that can play a role in both innate immunity and acquired immunity and so that's why it's spanning both when we get to our second line of defense we're going to talk about phagocytosis inflammation fever antimicrobial products all of these are nonspecific approaches to targeting a pathogen that has penetrated the first line of defense and then I again the next chapter is going to focus on acquired immunity which again is your specific branch of your immune response so quiet or adaptive this is going to be your third line of defense and this includes specific host defenses that must be developed uniquely for each microbe through the action of specialized white blood cells and so we'll talk specifically about B cells and T cells and how B cells and T cells play a role in your acquired or adaptive immunity so in order for a healthy functioning immune system to be working properly several things have to happen one is that the immune system needs to surveillance the body meaning you have to have cells in the body that are going through the body through the tissues and through the fluids to basically look for foreign invaders so they need to be undergoing surveillance they're out looking for things that have penetrated the body and that are foreign the second part is recognition of foreign material so recognizing that a pathogen is foreign so that it can target it for destruction so you need to have recognition of foreign material this is important because if that part of the immune system fails recognition of foreign material and the immune system starts making mistakes in that aspect and it starts attacking itself meaning it thinks that some part of the body is foreign and it starts reacting and it starts attacking itself that is what leads to an autoimmune disease and so there are lots of autoimmune diseases lupus is one type one diabetes can be an autoimmune response and that is that your own immune system starts attacking your cells because that part of the immune system starts to break down and the cells in the immune system stop distinguishing between foreign cells and self cells and so now you get this over stimulation of the immune system and it starts attacking our own cells this is a very important part of a healthy functioning immune system is recognizing foreign materials so recognizing what is foreign versus recognizing what is self and lastly we have destruction of entities deemed to be foreign so once the immune system has recognized that as being foreign now it's job is to target that and break it down for destruction and so that's what you're seeing in this image here so we have our white blood cells and our self cells and when our cells have contact with our own cells no reaction occurs because it recognizes those cells as being self and it doesn't target them for destruction however if we have contact with a foreign cell so we have our white blood cell and now the white blood cell has this pattern pathogen recognition receptor what we call prr and it recognizes a molecule on the surface of the pathogen and that molecule on the surface of a pathogen is referred to as a pathogen associated molecular pattern molecule or pimps and so the receptor is going to recognize those pants which basically tells the immune system that that cell is foreign and that that cell should be targeted for destruction and so again this bottom picture is basically showing you the destruction of that foreign invader and so the white blood cell is going to take in that pathogen and it's going to target it for destruction it's going to break it down so white blood cells constantly move throughout the body searching for potential pathogens and again the the white blood cells need to recognize body cells as being self so that they don't start attacking the body's own immune system the white blood cells will differentiate them from any foreign material in the body so again being able to distinguish that certain cells in the body are non-self right so that the pathogen is recognized as being foreign the ability to evaluate macromolecules as self or non-self is central to the functioning of the immune system and again many many autoimmune disorders are a result of the immune system mistakenly attacking the body's own tissues and organs and so the immune system is not functioning properly and it's starting to attack its own cells and that leads to damage of the cells the immune system is going to evaluate cells by examining molecules on cell surfaces that are called antigens for markers so an antigen is any chemical substance that can elicit an immune response and so these antigens or these markers consists of proteins and/or sugars so they're not always protein based they might be sugar based and these will allow cells of the immune system to identify whether a newly discovered so possesses a threat and should be marked for destruction so again it's that healthy interaction between recognizing if the marker is self or if it is foreign in which case that foreign pathogen needs to be destroyed the most common method of destruction would be phagocytosis so simply engulfing that pathogen breaking it down within the white bloods all it's not the only way which you'll see you later we can use antibodies we can use cytotoxic t-cells there are other ways to target a pathogen but the most common is going to be phagocytosis so we have what are called pathogen associated molecular patterns or Pam's and again these are markers that many different kinds of microbes have in common and so the immune system recognizes these pimps because many microbes have it in common and that allows the immune system to quickly quickly recognize that that is foreign white blood cells have what are referred to as pattern recognition receptors PRRS and so these are used by health host cells with important roles in innate immunity of the second line of defense because these receptors are going to recognize those pimps and so that is what's going to allow the immune system to recognize something as being foreign non-self proteins that are not harmful are generally recognized as such and the immune system is signaled not to react because you have to think about you have normal flora normal microbiota you have plenty of bacteria associated with your body is your immune system constantly attacking all of that bacteria that's found in your body no because there are different markers on different bacteria and that's one of the jobs of the immune system is to recognize what is harmful versus what is not and not mounting an immune response if if that microbe is not pathogenic and so that's an important part of the immune system so we are going to walk through and talk the different parts of innate immunity so again innate immunity is very nonspecific it's not targeting any particular pathogen it has two levels of defense so our first line of defense and our second line of defense are both part of innate immunity and so again we're gonna look at what are the components of our first line of defense which again are barriers blocking entry into the body which could be physical barriers or chemical barriers or microbiota and then also looking at the second line of defense which now involves cells playing a role in this branch of immunity and so this image is just showing you some examples of different parts of innate immunity and so we'll talk about things like sebaceous glands and tears having an enzyme called lysozyme how mucus plays a role how saliva with lysozyme plays a role cilia mucus stomach acid intestinal enzymes defecation so bowel movements urination right flushing out your system intact skin low pH and sweat these all play nonspecific roles in preventing a pathogen from getting access to the body and so we're going to talk talk through and look at how this happens so this slide you don't need to memorize all of this but I wanted to put this on here to kind of break down and talk about which cell types within the body play a role in innate immunity which play a role in adaptive immunity and which play a role in both meaning they crossover between innate and adaptive immunity this goes well with what you guys are learning about in lab where we're talking about different types of white blood cells here are those white blood cell so in innate immunity we have our base of fill again when you see fill think of filled with granules so basophils are a granule site they have those cytoplasmic granules and the function of the basal fill is that it's going to release histamines that cause inflammation this is going to stimulate the inflammatory response so again that's part of innate immunity you have Senna fills fill again it's filled with granules it's a granular site and it kills parasites with oxidative bursts and so eosinophils for example play a role often against Helmuth infections worm infections a mast cell is an a granule site and it kills infected cells often virus or virally infected cells via cytosis and so it's going to kill non-specifically neutrophils neutrophils are going to play a role in both it plays a role in innate immunity and it plays a role in adaptive immunity and so one of the things that you're gonna see is that cells that are phagocytes that are able to do phagocytosis one of the reasons that they cross over between innate and adaptive is because they play a role in innate immunity because of the ability to do phagocytosis it takes in a nonspecific pathogen it's not targeting any one pathogen it's targeting any foreign invader the reason it crosses over into adaptive immunity part of your specific immune response is because many of these phagocytes can do something called antigen presentation so what that means is that those cells that undergo phagocytosis so when they do phagocytosis and they take in that path Hajin they break down that pathogen and then they display those antigens on the surface to tell your adaptive immunity this is what you're looking for go find this in the body and so that's why certain white blood cells again it's specifically phagocytes those cells often play a role in both they do phagocytosis which is part of your innate immunity but they also do antigen presentation which is what puts them into the adaptive category as well so we have our neutrophils again fill granule site the function of the neutrophil is that they're used to phagocytize bacteria and fungi remember that the neutrophils are the first responders those are the first on the scene when there's an infection we have our monocyte monocyte is an a granule site does not have cytoplasmic granules and the monocyte is going to be a precursor to macrophages meaning they will differentiate they will become specialized to form those macrophages some macrophages are fixed in certain organs and tissues and others are what we call wandering macrophages and they wander tissues looking for things that are foreign and then they cause inflammation and these different types of macrophages their function is to perform phagocytosis so they're part of the surveillance that's looking for things that are foreign and then doing phagocytosis dendritic cells dendritic cells have these long projections they almost have kind of a neuron type appearance to them and so they are these dendritic cells these are cells that are found in specialized tissues they're found in skin in the respiratory tract in the intestinal mucosa and what their job is is to phagocytose so to do phagocytosis of bacteria and then present antigens to t-cells so again this is why they crossover between innate and adaptive so they're specialized cells in certain tissues their job is phagocytosis and then present antigens to the T cells and the B cells natural killer cells natural killer cells are an a granule site again they're tart they're part of our lymphocytes and so you might recall in the blood lecture for lab that I mentioned natural killer cells they're a type of lymphocyte but they play a role in innate and adaptive natural killer cells specifically kill cancer cells and virally infected cells so again it's gonna target self cells that are infected that need to be destroyed in terms of our adaptive immunity again this is going to be in Chapter thirteen and in our adaptive immunity we have our plasma cells or our b-cells a plasma cell is a type of a b-cell and again this is going to be an a granule site it's a lymphocyte and the purpose of the b-cell is that it's going to recognize antigens it's going to recognize things that are foreign and the plasma cells are going to produce antibodies and those antibodies are used to fight off a specific pathogen and this is why it's part of adaptive immunity because it's targeting a very specific pathogen within adaptive we also have our T cells and there are a variety of different T cells we have T helper cells we have cytotoxic T lymphocytes we have T regulatory cells these are all agranulocytes they are again lymphocytes and t-cells do something different than B cells B cells job is to produce antibodies T cells job is to do something different they secrete what are called cytokines these are chemical signals that tells the immune system what to do so to help ourselves for example you can think of as the commander of the army they're the ones that are responsible for signaling to tell the rest of the immune system what to do and so they're going to basically fight off specific foreign invaders and so we'll get into more how they do this when we get into chapter 13 so I'm gonna keep that brief here so let's start off with our physical factors so again our first line of defense has three main components physical factors chemical factors and microbiota and so we'll start with our physical factors physical factors again are basically barriers to entry basically preventing things from getting into the body and one of the most important barriers to entry is intact skin intact skin most microbes cannot penetrate what I have here in this picture this is what's referred to as a barrier assay and this is done by labs that study skin so my lab as a graduate student studied the function of skin and how different proteins regulated skin development and so one of the things that would that would happen is to test to see if the skin formed properly these are newborn mice that we call pups and the pups are dipped in an ink if it stays like the one on the left where the diet isn't penetrate that means that the skin is functioning properly and it's acting as a barrier and preventing that dye from getting in the picture on the right that mouse has a skin defect where the skin did not form properly and therefore the skin is not functioning as a barrier that's a problem because now that makes the organism the animal more susceptible to infections and so that Mouse on the right that's died the skin was not functioning as barrier and the dye was able to penetrate the skin and get in and so that tells us that there is a problem with skin development in that mouse and that the skin is not functioning as an appropriate barrier it's not blocking entry of things from getting into the body and so intact skin is a really good physical factor in terms of acting as a barrier to entry blocking things from getting in we have mucous membranes and again we're going to talk about these in more detail in a minute so mucous membranes we have other physical factors such as cilia so little hairlike projections that are on for example the respiratory tract that beat back and forth to help move things out of the respiratory tract we have sweat glands and sebaceous glands we have urination and defecation defecation is pooping basically those both work by flushing out things from the body right we talked about how one of the risk factors for a urinary tract infection is being dehydrated because if you are not drinking enough water and if you are not urinating frequently enough what ends up happening is is that your body urinates you urinate to help flush out any bacteria that might be on the opening of the urethra so urination is your body's first line of defense and it's simply there to help flush out any bacteria that might be on the opening to the urethra so trying to prevent access of that bacteria up and into the urinary tract we have normal flora so again if normal flora if there are certain bacteria on your skin they are competing for space and resources with pathogenic organisms so they are also part of your first line of defense and then your reflexes so sneezing coughing etc right so sneezing and coughing is your body's part of its first line of defense to get things out of the respiratory tract for example so we're gonna go through and talk about each of those components of that first line of defense and so let's first start by talking about intact skin so skin is again a good physical barrier so what you're seeing here is this is a cross-section of the skin the top outer layers of skin are referred to as the epidermis the epidermis consists of tightly packed cells that contain keratin and so the different layers of the epidermis have different keratin proteins expressed in them and you might recall what structure do bacteria have that contains keratin and the answer is an endospore remember that that keratin is a tough structural protein it protects bacteria from high temperatures for example right it protects it from a variety of harsh conditions and so that tells you that the keratin is a tough structural protein and so that keratin is there to serve a variety of functions within the epidermis and so let's look at the ways that the epidermis is protective because there are actually a lot of ways that the epidermis is protective the first is the stratum corneum and this is a tough outer layer that is impervious and waterproof it's there to help keep moisture in and again it's difficult for most microbes to be able to penetrate that's the impervious it makes it so that it's unlikely that a microbe can penetrate it your skin is the largest organ in your body in terms of surface area and weight and its job again is to act as a barrier most microbes most microbes cannot penetrate intact skin intact skin serves as a really good barrier the shedding of the skin helps to remove microbes that are on it so what happened for your skin is that these lower levels of cells that line the dermis those lower levels of cells those are the ones that can divide and those are going to turn over and they're going to move up as the cells divide and your outer layer of skin is dead and so those top layers of skin are dead and they slough off and they shed and they take any microbes that are on it with it so that helps you remove microbes by simply shutting of your skin the dryness of the skin also inhibits microbial growth because again most microbes can't tolerate desiccation or drying out and we talked about this for example when we were comparing staph and strep staff is resistant to dryness it can tolerate that dryness of the skin whereas streptococcus species cannot it's sensitive to dryness so the dryness of the skin also inhibits microbial growth unless bacteria have an adaptation that allows them to survive the hair shaft is periodically shed and the follicle cells are just disc wanted and basically the hair follicle when it's shed just like the skin that's gonna help flush out any particular pathogens as well and so the hair shaft plays a role as well as sweating so sweat is going to just flush out and remove microbes and so again this is nonspecific it's not targeting a particular pathogen but it's targeting microbes in general so now we're going to talk about the mucous membranes and the mucous membranes are an epithelial layer that wines the gastrointestinal so the GI tract the respiratory tract and the genitourinary tract and so these mucous membranes can produce mucus and mucus is a viscous glycoprotein that traps microbes and prevents the tracks from drying out and so this is very nonspecific it's not targeting any particular microbe but it's targeting non-specifically and so that mucus coat impedes entry and attachment of the bacteria so it prevents the bacteria from getting into the body now in addition as part of your mucous membranes you have something called the lacrimal apparatus and the purpose of the lacrimal apparatus is that it drains tears and it washes out the eye so in the eye there are these glands that are called lacrimal glands there in the upper outermost portion of the eye they produce tears and they pass them under the upper eyelid so tears come out and when you blink it pushes the tears towards the inner corner of the eye and to to small holes that lead through what's called the lacrimal canal and to the nose think about so you can see this lacrimal canal so think about if you've ever gotten something in your eye and your eye becomes irritated what is your eyes response to that irritant well it's going to produce tears because when it produces tears it's flushing out the eye it's producing those tears and it's draining it out of the lacrimal canal and getting that substance out of the eye so it's job is to wash the eye and so this these are all part of mucous membranes and so lastly we have other physical factors right other physical factors that impede entry into the body we have our we have our ciliary escalator and the ciliary escalator are the cells that have cilia on them and the cilia beat back and forth and they help to push microbes away from the lungs so it's gonna transport microbes trapped in mucus away from the lungs and so the ciliary escalator the cilia are gonna beat and it's going to cause the microbe to be pushed out of the body now if you think about smoking right people who smoke sometimes get get what we call smokers cough right they start coughing as a result of smoking one of the reasons that the happens is that smoking causes damage to the ciliary escalator it causes damage to the cilia if the cilia aren't moving it's gonna have problems moving things out of the lungs and so again your body's other response to things being in the love is that you're gonna cough and so a response to a damaged ciliary escalator it's gonna be coughing and so this is why people who smoke get this smoker's cough because coughing basically helps to get those things out of the respiratory tract sneezing also helps getting things out of the respiratory tract and so the ciliary escalator is going to help move things out of the respiratory tract next we have earwax earwax is going to prevent microbes from entering the ear because that thick wax in there is going to block and treat to the ear this is why you don't want to be overzealous with cleaning out your ears having that little bit of ear wax in your ears is actually part of your body's first line of defense and so if you are cleaning out all that earwax constantly that's actually not helpful that's actually hurting your body you need that ear wax to help prevent microbes from getting into the ear urine urine is going to again clean the urethra be a flow so it's just again gonna flush out microbes we have vaginal secretions right vaginal secretions are there to help move microbes out of the vaginal tract again through a flushing action we also have peristalsis the movement of the stomach we have defecation right so going number two is going to help flush out bacteria that are in the GI tract vomiting diarrhea those are your body's response to something foreign and something not useful being in the GI tract right so if you've ever eaten food and gotten food poisoning you've probably at some point experienced you know vomiting and diarrhea that's your body's natural response to try and get that bacteria or to get that pathogen out of the GI tract so we talked about our physical factors as part of our first line of defense and now let's look at our chemical factors so our chemical factors as part of our first line of defense again are going to be chemicals that are nonspecific they're not targeting any particular pathogen and so the first one is going to be sebum sebum is going to be oils and this oil the sebum is going to form a protective film and it also lowers the pH of the skin makes the pH of the skin about three to five and so that is going to help because the sebum has these fatty acids think of acids acidic they decrease the pH which inhibits the growth of certain pathogenic bacteria and fungi because remember that most bacteria are neutrophils they prefer a neutral pH so if you have a lowered pH that is going to inhibit many microbes from growing and so the function of the sebum is that it prevents hair from drying and becoming brittle and it also forms a protective film over the surface of the skin and again when it forms the low pH that is going to inhibit pathogens from growing we also have what's called lysozyme lysozyme is found in perspiration tears saliva and urine and the way that lysozyme works is that it destroys bacterial cell walls specifically more commonly against gram-positive because it has an effect on peptidoglycan and so this is there as a nonspecific way it targets bacteria non-specifically and so again it's produced in a variety of tissues in the body and in a variety of fluids in the body and it nonspecifically is there to inhibit bacterial cell growth we have our low pH so the gastric juices the juices in the stomach are between 1.2 and a pH of 3 and that low pH of gastric juices is going to destroy most bacteria and toxins low pH of vaginal secretions also will inhibit microbes so in addition to vaginal secretions being used to flush out the genitourinary tract the secretions themselves also have chemicals in them that inhibit microbes from growing there are antimicrobial chemicals in semen and so semen is going to have antimicrobial chemicals in them we have specialized glands of the eyelid that lubricate the conjunctiva with an antimicrobial secretion and so we have these Maya bohmian Glantz or what we call tarsal glands and they are a special kind of gland at the rim of the eyelid inside the tarsal plate and they're responsible for the supply of Mipham so produces and oily substance that prevents clips that prevents evaporation of tears and so it prevents the evaporation of the eyes tear film and it prevents tear spillage prevents tear spillage onto the cheeks which traps the tears between the oiled edge and the eyeball and it makes the closed eyelids airtight and there are approximately 50 glands on the upper eyelids and about 25 glands on the lower eyelid and so this produces these specialized chemicals that basically help to prevent this bacteria from getting into the eye and so these are the variety of chemical factors next we come on to our normal microbiota and our normal microbiota will compete with pathogens via microbial antagonism and so this normal flora plays a role in several ways one it produces substances that are harmful to the pathogen it can also alter conditions that the pathogen survival maybe the normal flora produces acids which basically affect another pathogen survival and then lastly they can also block access of the pathogen to epithelial surfaces think of if you've ever played basketball boxing out right so basically it's like the bacteria are occupying that space so that pathogens can't occupy that same space they're boxing out and so those are some of the ways that the normal microbiota or the normal flora play a role in innate immunity they are competing with pathogens so if we look at some other types of interactions we have what's referred to as commensalism one organism benefits while the other the host is unharmed and so sometimes we'll see that type of interaction between the normal flora and the host probiotics probiotics are live microbial cultures administered to exert a beneficial effect and so taking a probiotic sometimes is recommended when you have when you are prescribed a broad-spectrum antibiotic and that's because when you take a broad-spectrum antibiotic you're not just targeting the bad bacteria the ones that that's causing the infection but you're also targeting good bacteria and you're killing off some good normal flora and so taking a probiotic is going to include these live microbial cultures that can be used to exert a beneficial effect along this line a treatment so it's obviously not part of your own immune system but a treatment that affects your normal microbiota also can include a fecal transplant so if somebody has a problem with a c-diff infection Clostridium difficile and they have problems with their gut bacteria being disrupted meaning their normal flora is not intact one of the things they can do is they can do a fecal transplant and actually put bacteria back into the gut to help compete out the bad bacteria and so that would affect that normal microbiota and so this would be an example so question for you which of the following is or are not a first line of defense is it red skin yellow tears green saliva or blue fever so which of the following are not part of your first line of defense so pause your video think about it and then when you're ready push play to hear the answer if you said blue whoops if you said blue you are correct fever is not part of your first line of defense you're gonna see that fever is part of your second line of defense it is still part of innate immunity it's still nonspecific but it's not part of your first line of defense in that it's not acting as a barrier to block entry it's now getting cells involved in this response so skin is part of your first line of defense tears saliva those are all part of your first line of defense your tears in your saliva for example right they contain light the time which break down peptidoglycan inhibits microbes tears are involved in flushing of the eyes etc so the top three are part of your first line of defense but fever is not and so now we're going to move on and start to talk about our second line of defense our second line of defense are generalized and nonspecific defenses that support and interact with specific immune responses so they're there to support adaptive immunity but again they are still nonspecific and so there are four main categories that we're going to talk about in more detail we're going to talk about phagocytosis we are going to talk about inflammation fever antimicrobial proteins etc and so we're going to look at now the second line of defense so in our second line of defense we are going to talk first about cellular components of your second line of defense and so of your cellular level we have what are called phagocytes phagocytes are cells that are responsible for phagocytosis and so there are some generalized activities of phagocytes one is they're there to survey the tissue compartments and discover microbes particulate matter were injured or dead cells so this is the surveillance component of your immune system their job is to ingest and eliminate these materials so again to do phagocytosis and to destroy that bacteria and then lastly their job is to extract immuno genic information or antigens and participate in what is referred to as antigen presentation presenting the antigen on the surface and showing that information to your adaptive immunity show it to B cells and T cells now when we talk about types of phagocytes we have our neutrophils neutrophils again are the first responders these are the most phagocytic white blood cell these are the first on the scene there they to destroy any organism that has penetrated the first line of defense we have art eosinophils which are phagocytes these are used or toxic against parasites and helmets so they target a specific type of foreign invader we have our monocytes which can differentiate or become specialized to give rise to our macrophages and if we talk about macrophages they can be broken down into two categories we have our fixed macrophages fixed means that they're fixed or they stay within a particular tissue or organ so these are residents and tissues and organs they're not wandering they stay in that particular tissue free or wandering macrophages just like the name suggests these are macrophages that roam tissues and then gather at the site of infection so they play more of a role in surveillance they go looking for things that are foreign and then if they find something foreign then they're going to gather at the site of where that infection is and so this slide we are going to look at how phagocytosis occurs so one of the first thing that happens during phagocytosis is what is referred to as chemotaxis and you might recall the chemotaxis if we were talking about let's say positive chemotaxis would mean that the microbe is attract or I'm sorry the white blood cell is attracted to some chemical substance that the microbe is the microbe is producing and so the Micra or the white blood cell is attracted to that chemical signal and it's following that pathogen if you recall when I showed the video of the white blood cell chasing the bacteria you might recall that you saw the white blood cell chase the bacteria it knew where the bacteria was and that's because the white blood cell was exhibiting chemotaxis it was recognizing a chemical signal that was produced by the bacteria and that's how it knew where the bacteria was and was able to chase it so first thing in phagocytosis is we have Kempe chemotaxis the white blood cell is going to chase the bacteria and the next thing that has to happen is adherence of the microbe to the phagocyte now how does that happen well again on the bacteria we have those pants those packagin associated molecular patterns and these are signals signal molecules found on microbial surfaces that are recognized by phagocytes and other defensive cells these molecules are shared by many organisms but are not present in mammals and so this is what allows the immune system to recognize them as foreign those pants serve as red flags for phagocytes and other cells of innate immunity bacterial pants are typically either peptidoglycan or LPS lipopolysaccharide which remember is found in the outer membrane of gram-negative viral Pam's often include double-stranded RNA now on the surface of the white blood cell we have those pattern recognition receptors or in this case TLRs these pattern recognition receptors are found on phagocytes they're found on dendritic cells they're found on endothelial cells and lymphocytes and again they're going to recognize and bind to those pants which is how they know that that substance is foreign South possessed those pattern recognition scepters whether they have encountered the pants before or not so that is always going to be present this is why this is part of innate immunity its present at birth these cells are going to produce those receptors whether or not they've actually seen it before so we have to have adherence the receptor on the white blood cell is going to recognize the pathogen and we get adherence then we get ingestion of the microbe by the phagocyte so again we have these pseudopods that come out these are controlled by actin and those pseudopods are going to come out they're going to engulf that pathogen and they're going to take that pathogen into the cell and so the next step is going to be the formation of a phagosome right it's going to be this phagocytic vesicle that phagosome is then going to fuse with a lysosome and remember that a lysosome is an organelle and it contains digestive enzymes its job in the cell is you can think of it like the recycling center it's going to produce those digestive enzymes and when the lysosome fuses with the phagosome it forms something called the phago lysosome and the Fagor lysosome is then going to begin to digest that microbe and so we get digestion of the ingested microbe by enzymes and then formation of residual body containing indigestible materials and those indigestible materials are then discharged or released from the cell as waste and so this is going to be how phagocytosis occurs now this is showing you how that pathogen is destroyed but what you also have to realize and you'll see this again in Chapter 13 when we talk about an adaptive immunity is that these phagocytes often can also then take these molecules that they've broken down and they do something called antigen presentation they're actually going to present the antigen on their surface to show the acquired adaptive component of the immune system this is the antigen that you're looking for right because obviously that antigen is present if the phagocyte just destroyed that foreign invader and so this is why phagocytes often are going to be the bridge between innate and adaptive their innate because they target any pathogen they're not targeting a specific pathogen and so that's what makes this part of the innate immunity so microbes have evolved ways to be able to evade phagocytosis so one way that microbes are able to evade phagocytosis is that some microbes can inhibit adherence basically these microbes produce things like the EM protein if you think about streptococcus for example they produce capsules etc and those structures remember the M protein is like velcro capsules are sticky also and so that allows the microbe to stick to surfaces which then makes it more difficult for the white blood cell to adhere and stick to the pathogen to do phagocytosis and so these structures that inhibit adherence basically the M protein the capsules etc they make the bacteria sticky which makes it so that it's less likely for five cytosis to occur some microbes can kill phagocytes they can produce chemicals called Lukas items Luco refers white buds all think of seidel means kill so leukocyte ends are chemicals that kill phagocytes or kill white blood cells an example of this would be Staphylococcus aureus Staphylococcus aureus can be pathogenic because it can produce these leukocyte ends which kill white blood cells some can evade phagocytosis by lysine phagocytes what they do is that they form what's called a membrane attack complex an example of this would be Listeria monocytogenes which remember causes listeriosis one of the things that you're gonna see is that your immune system targets microbes by forming a membrane attack complex and it causes destruction of bacteria for example but certain bacteria have also evolved to produce this membrane attack complex and then use it against us and so it would cause lysis of the phagocytes some are going to escape the phagosome so that vesicle that can form so Shigella rick sedia etc some are going to prevent phagosome lysosome fusion so what that's gonna do is that's going to inhibit the breakdown of that microbe while the microbe can be ingested by phagocytosis it's going to inhibit its breakdown so we've talked about this before when we talked about Mycobacterium tuberculosis TB is gonna cause scar tissue in the lungs because this bacteria is able to prevent the lysosome from breaking it down and so you get scarred tissue in the lungs as a result HIV can also evade phagocytes by this method some bacteria can survive in the phago lysosome so they're able to survive within that structure coxiella brunetti is an example of this and so this is just some examples of ways that microbes have evolved to overcome phagocytosis and so whenever we have an immune response you have to think that oftentimes bacteria are going to evolve also and they're gonna find unique ways to try and evade the immune system next we have our as part of our cellular component in addition to phagocytes we also have our natural killer cells and again our natural killer cells are a type of lymphocyte so again they are a white blood cell and they play a role in this case in innate immunity and that's different than other lymphocytes like b-cells and t-cells which play a role in adaptive or acquired immunity this type of lymphocyte plays a role in innate immunity and natural killer cells are going to be used to kill chemically they are used against protozoans fungi virally infected host cells cancer cells etc so notice that they're used primarily more for eukaryotic cells and not as much and not for bacterial cells the next part of our second line of defense is going to be our inflammatory response and the inflammatory response is in response to tissue damage and there are several symptoms that are associated with the inflammatory response and so symptoms of inflammation would include redness pain heat and swelling or edema these would be symptoms that inflammation is happening and so like if you get a cut for example and the cut gets red or feels warm or there's pain that is a signal that your body is mounting an inflammatory response in response to that tissue damage in response to that cut the chief function of the inflammatory response is to mobilize and attract immune components to the site of the injury so letting the body know that foreign invaders have penetrated the first line of defense their job is also to set in motion mechanisms to repair tissue damage so it's going to repair tissue damage and to localize and clear away harmful substances before the tissue is repaired and so lastly it's there to destroy microbes and then block further invasion so to block additional pathogens from getting access to the body and so we're gonna walk through and we're going to talk about the three basic stages of inflammation and so we're gonna talk about these stages so I'll just put them here in summary and then I will walk through them in more detail so the first stage of inflammation is going to be vasodilation and increase permeability of the blood vessels we have phagocytic migration and diabetes and we have repair so I'm going to walk you through and talk about how these three Agis work so again stage one of the inflammatory response is going to be vasodilation and increase permeability of blood vessels so let me walk you through and talk about how this works so let's say you are cutting meat to make dinner and you make a mistake and you accidentally cut yourself with the knife so you get tissue damage right the knife is going to penetrate the skin and bacteria that are on that knife are going to be able to penetrate that first line of defense right the skin is now broken it's not acting as barrier so bacteria now get into the body and so the immune system is going to start to recognize that or the body recognizes rather that the skin has been damaged and the cells in the area are going to release a variety of chemicals to signal to the body and so those damaged cells will produce chemicals such as histamines kinase prostaglandins leukotrienes and cytokines they're gonna release these variety of chemicals leukotrienes and prostaglandins tell you about pain cytokines cause cells to move to the site of the infection and so what's going to happen is is that these chemical signals are going to attract cells to where the damage occurs and so what's going to happen is is that a blood clot is going to form and that blood clot is going to trap microbes to prevent further spread right because as they form this blood clot it's going to prevent other invaders from getting in now what's going to happen is is that an abscess is going to start to form that's this dark yellow area and neutrophils are going to aggregate at the inflamed site they're involved in phagocytosis and destroying bacteria dead tissue and particulate matter and so you get this pus that can accumulate and a pus is the accumulation of a whitish mass of cells liquefied cellular debris and bacteria and so some bacteria are what we call pyogenic streptococcus staphylococcus gone okok i mention NGO cocci these are bacteria that will help stimulate the formation of pus now when this blood clot forms and this abscess starts to form we have vasodilation blood vessels dilate so the blood vessels are going to increase in diameter and if you think about it the reason that your body is going to increase blood flow you might think it's counterintuitive because you think well don't you want to stop bleeding yes but that's the job of the the blood clot is to stop the bleeding but the reason you want to have blood vessel dilation is that you want increase blood flow because remember that your immune cells are found in the blood your white blood cells are carried to the site of the infection through the blood vessels and so we get these these blood vessels dilating so that we get blood flow to the site of the infection which will help bring phagocytes antibodies and clot forming chemicals to the site of the infection and so now these defensive materials are delivered from the blood to the infection so we get vasodilation and increase permeability what that means by increased permeability is that blood vessels start to become leaky so they become more permeable which means that things that are in the blood can get out of the blood vessels and into the damaged tissue where the infection is and so that's stage one vasodilation and increase permeability step two step two is going to be phagocytic migration and diocese so what's gonna happen in stage two is we get what's referred to as margination and that is that the white blood cells begin to stick the phagocytes begin to stick to the blood vessels so they stick to the blood vessels in response to cytokines at the site of the inflammation so again those cytokines are produced by the damaged cells which causes the white blood cells to know where to go and so they're gonna stick to the blood vessels that's that margination and then the white blood cells are going to squeeze between the endothelial cells into the tissue from the blood via diocese so diabetes this is when the white blood cells are going to squeeze their way out of the blood vessels and again that can happen because the blood vessels get increased permeability so the white blood cells are going to do diocese they're going to squeeze through the endothelial cells so squeeze through the blood vessels and get into the tissue fluid where the microbe is found and now those cells are gonna target those foreign invaders and so again this is gonna have neutrophils first there are first responders followed by our macrophages both of those cells are phagocytes and their job is going to be to engulf that those foreign invaders in the site of the infection and then lastly we have our repair and the repair of tissue cannot be completed until all harmful substances are removed or neutralized so it takes the body time the immune system time to fight off all those pathogens and then it can begin to repair so the stroma is the supporting connective tissue that's repaired and the prank ama is the functioning part of the tissue that is repaired so the epidermis and so when we get to shoe repair tissue repair happens from the inside out we fix the inner layers first and the last part to be repaired is the outer layer so think about if you've ever had like a scab on a on a wound right if the scab falls off oftentimes the tissue underneath could already be repaired and it's just not finished with its repair meaning the outer layers are not fully complete but we're gonna get tissue repair from the inside out repair the inner cells first outer cells last so question for you which white-blood-cell dominates during the initial phase of a bacterial infection is it red a neutrophil yellow a monocyte green a lymphocyte or blue an eosinophil so which white blood cell dominates during the initial phase of a bacterial infection so when you're ready pause the video and then once you thought of your answer push play so if you said neutrophil you are correct remember that the neutrophil is our first first responder it's going to be the first on the scene and so this is why in lab when we talked about an elevated number of neutrophils is likely an indication of an infection because if you have an excess of neutrophils you get that excess of neutrophils because of that infection monocytes will go to the site of the infection monocytes remember give rise to macrophages lymphocytes are typically not there in the first phase of the infection because most of our lymphocytes play a role in acquired immunity except natural killer cells but the others are all in in part in response to acquired immunity eosinophils are not typically used against a bacterial infection they're used more against eukaryotic cell type infections and so in a bacterial infection the white blood cell that dominates at the initial beginning would be the neutrophil so moving on along our second line of defense right so we just finished talking about our cellular components so our phagocytes for example our natural killer cells we talked about inflammation now we're going to talk about the metabolic response of the host and so the host is going to produce a fever and a fever is initiated by what are called pyrogens think of if you ever hear somebody referred to as a pyro they like heat or they like fire in essence right so think of pyrogen as being basically something that's gonna turn up the heat in the body it's gonna initiate a fever we can have what are called exogenously gens these are products of infectious agents such as viruses bacteria protozoans fungi endotoxins blood blood products vaccines or injectable solutions that come from outside of the body so eggs Aegina smiie --nz that they're not produced internally they are exogenous meaning from outside the body so there are other things that come into the body that initiate a fever we also can have endogenous pyrogens so endo means within meaning that our own body stimulates a fever and these endogenous para genes are liberated by monocytes by neutrophils and macrophages during phagocytosis such as interleukin 1 and tumor necrosis factor so this is basically your immune systems way to turn up the heat think about why a fever is useful to your body and so we talked about this right and so when a fever is brought on by chemicals like parabens these are substances that reset the hypothalamic thermostat to a higher setting Mesa files may slow down in their growth when body temperature goes up right because Mesa files prefer our body temperature to be 37 degrees Celsius if it goes up it's going to inhibit their growth or in some cases potentially caused proteins to denature so a fever is our body's own natural way to inhibit microbial growth and so the benefit of the fever is that it inhibits multiplication of temperature sensitive microbes such as poliovirus cold virus herpes zoster virus and systemic and subcutaneous fungal pathogens these organisms are particularly sensitive to a fever and so a fever can be protective now you probably know that yes a fever can be a good thing however if a fever goes too high if the fever for example goes above 104 that then 104 being Fahrenheit if that happens that can cause damage to the cells especially in kids if you've ever heard of a kid having a febrile seizure that basically is when their fever gets too high they have a seizure as a response and that's because that if your temperature goes too high it's going to denature your own proteins and this can cause brain damage or hearing loss etc if the fever gets too high and so yes a low fever you don't need to suppress it with you know Tylenol or ibuprofen because in fact that fever is your body's not in response it wants to turn up the heat to try and inhibit that microbe another metabolic response of the host is by doing something called iron removal and so the body will produce this lactoferrin which removes iron now you might wonder why would the body want to remove iron well it impedes nutrition of bacteria by reducing the availability of iron and so if the bacteria can't get get access to iron it's going to slow down their metabolism and then the last part of this that we're going to talk about is going to be chemical components of the second line of defense and so we're going to look at interferons as well as the complement system so let's start with our interferons interferons are produced by virally infected cells so if you look at the cell on the left the saw on the left has been infected by an RNA based virus this RNA based virus virus is going to get in and it's going to turn this host cell into a virus producing factory and so the virus is going to get in and the host cell is going to be turned into a virus producing Factory and so it's going to start producing these virus particles so it's going to replicate the RNA it's going to produce the capsid it's going to produce all the components of the virus for the virus now what happens is is that sometimes the cell can recognize that it has been infected and what happens is is when it recognizes that it's been infected it's going to produce this interferon and this infected cell produces interferons it secretes the interferons out of itself and the interferon is gonna go into the neighboring host cell so it's going to go into a cell that is adjacent to the already infected cell and what that does is that signals this uninfected cell the one that has not yet been infected to turn on transcription of antiviral proteins so it's basically the immune systems way to say like the virally infected cell to say hey I'm infected you want to prevent being infected start producing these anti viral proteins and so the cell that's already infected secretes interferon and our fear on is going to go to the neighboring cell it's gonna turn on production of these anti viral proteins and these anti viral proteins are then going to block or inhibit viral replication so now this neighboring cell can prevent being infected and so these interferons are used to enhance an immune response it's produced by an already virally infected cell it signals to neighboring cells to tell the neighboring cells hey a virus is present start making anti viral proteins and that uninfected cell produces those anti viral proteins which blocks that cell from also being infected and so it helps prevent the spread of the virus to adjacent cells and so again these are produced by virally infected cells and they're going to block the infection of neighboring cells these are not microbe specific so again this is why they are part of in the community they're not targeting any one type of virus they are very nonspecific and so interference can be a valuable treatment for a number of viral infections it can be something that is stimulated to help fight off to help fight off viral infections and so this is a chemical component for the innate immunity and then lastly we have our complement system and the complement system is a group of serum proteins produced by the liver that assists the immune system in destroying the microbes and so these act in a cascade in a process called complement activation so it's basically this signal transduction pathway this this complement protein activates this one the next one activates the next one that one activates the next one and so on and so forth and so that is what's called complement activation it's used to dilate arteries so again to increase blood flow during inflammation for example complement also acts as a chemotactic agent helping to attract other microbes to where an infection is occurring the proteins are designated with an uppercase C and are numbered in their order of discovery and so what that means is that when you look at this complement system it doesn't mean that one activates two two activates 3 3 activates 4 because they were numbered in the order of their discovery the activated fragments meaning once they've been activated to stimulate the next one the activated fragments are indicated with a lowercase a and B because what you'll see is that sometimes you need those activate compliment proteins to come together to then stimulate the next part of the response so when you're looking at this diagram I do not care that you memorize the signal transduction pathway meaning I don't care that you know that three compliment three inactivate a compliment three splits in two activated c3a and c3b I don't care that you know the steps in the signal transduction pathway but what you want to notice is that you get this series of activations so this red one activates into this these two red ones one of those two red ones activates into this yellow one which splits into two which activates this blue one etc so this is what we call a cascade or you'll also hear it called a signal transduction pathway what you want to take from this slide is what is the outcome of complement activation what does complement activation stimulate within the immune response and so one thing that happens one of the outcomes of complement activation is something called optimization and that is that that complement that activate a compliment protein is going to attach to the surface of that microbe and what that does is when that compliment protein attaches it helps enhance phagocytosis it's going to make phagocytosis more likely because that complement is actually signaling to the phagocyte that it's foreign and it's helping to enhance phagocytosis so we call that opsonization it's basically marketing its marking that pathogen for destruction it's going to enhance phagocytosis another thing that compliment system activates is it it activates something called cytolysis Saito refers to cell lysis is breaking and so what ends up happening is is that the complement proteins themselves will form what's called a membrane attack complex and this membrane attack complex basically produces this pore or this hole in the membrane of the pathogen and when it creates this hole in the membrane of the pathogen you're gonna have this fluid that goes in or out and it causes the cell to be destroyed so this is cytolysis it's going to break down the pathogen by forming this membrane attack complex and again some microbes have evolved to also form a membrane attack complex but have the effect on the white blood cells but our immune system does this so complement proteins are used to activate cytolysis and lastly the last outcome of the complement system is by initiating inflammation so again helping to initiate inflammation and that's because these complement proteins activate a cell called a masked cell a masked cell is going to release histamine and histamine is going to initiate inflammation and so again it's going to attract the white blood cells to the site of the infection it's gonna make blood vessels leaky etc and so these are the three outcomes of the complement system optimization cytolysis and inflammation and so this is just putting into words what I just explained so again outcomes of complement activation we have cytolysis you get this activated complement protein that creates that membrane attack complex which puts a hole in the membrane of the pathogen which causes it to lyse opsonization is going to promote the attachment of a phagocyte to a microbe because it's going to mark that microbe for destruction and then lastly we have inflammation the activated complement proteins bind to mast cells mast cells release histamine and histamine is going to stimulate the inflammatory response and so this complement plays a role in several aspects of innate immunity it is still nonspecific it's not targeting a particular pathogen but non specifically it's targeting foreign invaders through these variety of different avenues