this is part 2 for chapter 16 innate immunity as I explained in part 1 your immune system is defending you against infectious disease and cancer and the overall organization of your immune system is as follows your innate immune response also known as your nonspecific immune response is comprised of the first line of defense and the second line of defense all of this is protecting you from microbes in general your third line of defense is the same as your adaptive immune response also known as your specific immune response and this is where your immune system is responding to a microbe that is infecting you at that time last time I went over the whole first line of defense different types of barriers different washing processes chemical factors and your normal microbiota and again the purpose of the first line of defense is to prevent infection to keep the microbes out of your body then after I went through that I introduced the different components of the immune system so lymphoid organs lymphatic vessels lymph nodes and the white blood cells cells to get ready to talk about the second line of defense so this part of the lecture is all about the second line of defense so again second line of defense this comes into play once the microbes have gotten past your first line of defense and they are infecting your body they have gained access to your tissues and this will involve a lot of the different white blood cells leukocytes that I talked about before and it will involve different processes such as inflammation and fever and then antimicrobial substances like complement and interferon just as a review of the different types of leukocytes I went through them so here they are in a different order these are your granule sites granule sites have granules in the cytoplasm so you can see those granules and they are the Isana fills basophils and neutrophils and these are associated mainly with your second line of defense the a granule sites are over here these are the a granule sites a granule sites because they have very few granules in their cytoplasm and the two types are the lymphocytes and monocytes lymphocytes again these are the white blood cells you find in the lymph nodes and they are part of your third line of defense so I'm not really going to talk about them now monocytes on the other hand are immature macrophages and the macrophages are involved in your second line of defense the first process that I want to go over is phagocytosis and phagocytosis of course is so eating so so eating phago means to eat cytosis cells and this is the process by which some of your white blood cells the neutrophils and the macrophages can phagocytose microbes that are entering your body and the obvious benefit is that phagocytosis ends up eliminating killing and eliminating the microbes for phagocytosis you are going to have to know all the different stages of phagocytosis and this image shows you them in order and for this image this big cell is the phagocytic white blood cell either a macrophage or a neutrophil and this is the microbe that it will be ingesting so here is the microbe here to start this process the white blood cell needs to be attracted to the site of infection so that would be chemotaxis when cells move in response to a molecule so the very first thing is that the white blood cell needs to go to the area where the microbe is once it is there that it needs to be able to adhere to the microbe has to be able to attach to the microbe once the white blood cell has moved to where the microbe is and attach to the microbe and the white blood cell will ingest the microbe so it will perform the phagocytosis moving the membrane around to surround the microbe and this will result in a vesicle forming called a phagosome so this is the phagosome there once the phagosome has been formed then the next stage will be digestion in order to have digestion you need to fuse the phagosome to a lysosome and remember lysosomes are vesicles that contain digestive enzymes so in order to have digestion take place the lysosome and phagosome need to fuse together and the resulting vesicle will be called a a lysosome and now those digestive enzymes come in contact with the microbe and start digesting the microbe and this part of the image shows the microbe being broken down by those digestive enzymes once digestion has occurred then there will always be a few parts of the microbe that are indigestible that cannot be broken down and those parts of the microbe that cannot be digest digested will remain in the vesicle and it will be called a residual body and the very last stage is that that indigestible material so this is the process of phagocytosis and it seems very similar to how humans eat because if we want to eat something often we have to move to where the food is we have to adhere to the food we have to be able to pick up the food with our hands we ingest the food by taking it into our body we break it down and then digest the food and then not all of the food can be absorbed by our bodies so we have indigestible material that is then discharged so it's the same basic idea just on a cellular level the second process I'm going to go over is inflammation and inflammation is technically a response to tissue damage whether or not there is actually an infection if you pull a muscle you will have an inflammatory response but there would not be an infection if you cut your skin you will have an inflammatory response and there is also a high likelihood there will be an infection that microbes will be entering through the cut so if there is actually an infection inflammation will provide three benefits the first benefit is that it will confine the microbes to a localized area second benefit is that it will destroy the microbes that have entered into the tissues and the third benefit is that it will then facilitate tissue repair which will repair the breach to your barriers your first line of defense so again inflammation is triggered by tissue damage in this case you have a thorn that is damaging the skin on a person's finger which will trigger an inflammatory response the four signs of inflammation first sign is ruber and this is Latin but ruber means red so in that area where you're getting an inflammatory response it will turn red the second sign of inflammation is Keller Keller is Latin for heat so that area will turn red and it will become warm the next sign of inflammation is tumor tumor means swelling so that area that is inflamed will begin to swell and the last sign is doler which is pain so the four signs of inflammation if you are having an inflammatory response is that the area will turn red it will be warmer than the other areas of your body it will swell and you may have pain this slide will go through the process of inflammation in more detail and it will talk about the white blood cells that are involved and also how the whole process works so the very first thing that happens is injury so that's injury to the skin and in this case a pin or a needle is breaching the barrier of the skin and all these little green things are microbes that are on that pin or needle so it was not a sterile needle when the injury happens that is going to stimulate the cells that are damaged so the epithelial cells that are damaged and mast cells mast cells are a type of white blood cell both of those cells are going to release chemical mediators signal molecules like hormones and the major chemical mediator that is released is histamine so histamine is going to be what triggers the inflammatory reaction once the histamine is released that will have an effect on the blood vessels that are in the area and the two effects are that they are going to dilate you're going to have vasodilation and they are going to become more permeable more permeable means that the plasma is going to be able to seep out of the blood vessels so vasodilation increased permeability means that you are going to get more blood to the area and the plasma is going to be able to leak out and that is that yellow stuff that is leaking out so histamine is going histamine release is going to be triggered by tissue damage and it's going to stimulate the blood vessels to dilate to bring more blood to the area and to become more leaky increase the permeability so the plasma can leak out this diagram shows in a little bit more detail what is happening during the first stages of inflammation so down here somewhere damage has been done maybe microbes have entered the tissues and the damaged cells or other cells are releasing histamine so that's the chemotactic factors so these blue molecules would be those cytokines probably histamine that have been released by those damaged cells so that histamine is going to trigger this blood vessel to dilate to bring more blood which includes more white blood cells and more antibodies and more complement to the area and then the histamine is also going to stimulate the blood vessel to become more permeable to become leaky so then those blood vessels white blood cells can leave the blood vessel and go to the site of infection and of course the first white blood cell that will be there are the neutrophils because the neutral neutrophils make up the highest percentage of white blood cells in the blood you have a lot of them and they will rush they will charge into the site of infection and they're attracted to that area of infection by the chemotactic factors the histamine all right so you had the damage was done microbes have entered into the tissues at the damaged cells and the basophils have released histamine that's made the blood vessels dilate made it leaky so that the neutrophils can leak leave the circulation and go start fighting the infection so as this progresses what you will have is a lot of neutrophils arriving to the scene to ingest the microbes that have entered through that damaged part of the body and you will also start having Puffs formation so pus formation the pus is basically composed of plasma the liquid part of the blood that has leaked out of the blood vessels the neutrophils and lots of dead neutrophils because remember once they in just one microbe then they die and also it will contain microbes so pus usually contains plasma neutrophils lots of dead neutrophils and the microbes and of course during this whole process you're getting blood clotting so blood clotting scab formation and also that serves to isolate the microbes so it remains localized in this area confining the microbe to the area then at later stages of inflammation what you have are macrophages moving in so at the very end of the inflammatory process you have the macrophages coming in and the macrophages big eaters they are going to come in and clean everything up so they are going to ingest the dead neutrophils and they are going to ingest the remaining microbes and they also ingest the plasma so they basically come in and ingest phagocytose all of the pus and everything that's there now the macrophages it takes them a relatively long time to come in because these are wandering Mike McAfee ages and wandering macrophages are found only in the tissues so macrophages are never found in the blood they are only in the tissues so it takes them a long time to get there because they have to crawl through the dense tissue to get there neutrophils get there very quickly because remember they're in the circulation so they are circulating throughout the body there on the highway system of the body so they can get anywhere very quickly but the macrophages it's going to take them a lot longer to get there the third process I want to talk about is fever and you should know fever is an elevated body temperature fever is actually a response to infection so the fever response is much different than an inflammatory response inflammatory response is a response to tissue damage fever is actually a response to infection and the benefits of having the fever are as follows first it's going to inhibit the microbes and it inhibits microbes in two ways it's going to inhibit the microbes ability to replicate and that would be both cellular microbes prokaryotes eukaryotes and also viruses second benefit is it's going to inhibit the microbes ability to take up nutrients and that mainly affects the bacteria it would not affect viruses of course because viruses don't metabolize the next benefit is that a fever and elevated body temperature will actually stimulate your leukocytes so it actually stimulates the leukocytes makes them more active and inhibits the microbes which is what you want when you have an infection you want to inhibit the microbes from functioning and you want to stimulate your white blood cells so they can fight the infection so now the process of fever and for fever the main cell that is involved is a macrophage so macrophages are the white blood cells that are going to stimulate or trigger a fever and what basically happens is that the macrophage is going to phagocytose a microbe so here is your macrophage it's phagocytosis a microbe and when that macrophage recognizes molecules on the microbes such as endotoxins remember endotoxins basically lipid a that will stimulate the macrophage to produce cytokines so that will stimulate the macrophage to produce cytokines and cytokines are molecular messengers between white blood cells and the main cytokine it's going to produce is il-1 an Iowan stands for interleukin interleukin interleukin enter between leuco white blood cells so aisle one and there are many aisles aisle one il-2 aisle three and so on these are molecules that white blood cells use to communicate with each other so once the macrophage endocytosis a microbe it's going to trigger the production of cytokines by that macrophage those cytokines are going to diffuse into the circulatory system and they are going to diffuse all the way to the hypothalamus of the brain and they are going to stimulate the hypothalamus to raise the body's temperature so this is the process of fever it is triggered by a macrophage that has ingested a microbe that macrophage secretes il-1 yeah aisle one diffuses through the blood vessel until it gets to the hypothalamus of the brain where it stimulates the hypothalamus to increase body temperature compliment compliment is a really really important part of your second line of defense but probably you have never heard of compliment before so I want to take a little bit of time to go through compliment compliment is basically a group of serum proteins and so complement the word itself is a plural because it's referring to many different types of serum proteins they're about 20 different serum proteins and serum of course means the blood so complement is found in the plasma the liquid part of the blood the serum in complement is activated in a cascade manner that means if you activate just one serum protein that one protein will activate another protein usually more than one and each of those will activate more proteins so that is your cascade manner of activation and to activate complement there are three different pathways which I will go over in a minute and once you have activated complement there will be three results that will benefit and help you fight an infection now I will go through the three different pathways of complement activation and the first pathway is called the classical pathway of complement activation so in order for this to occur you have the microbe here this is the microbe and you have certain molecules on the surface of the microbe called antigens and for the classical pathway you need two antibodies bound to the microbe when you have antibodies bound to the microbe and the antibodies always have this Y structure and they're always drawn in green when you have two antibodies bound to the microbe then that allows the first complement protein c1 to bind to those antibodies and cascade manner of activation if c1 is activated this way it will activate c2 and c4 which will then split and lead to activation of other complement proteins you do not have to know the different numbers and orders of the complement proteins but what you have to know for the classical pathway of activation is that it requires a microbe and antibodies so having the antibodies bound to the microbe that will activate the first complement protein the second way to activate complement is called the alternative pathway and for the alternative pathway you just need the microbes so only the microbe will activate the complement and in this pathway three different complement proteins called B D and P you don't have to know what they stand for they will bind directly to the microbe and then that will lead to activating a complement protein which will lead to its splitting and activating other complement proteins the last way to activate complement is by the lectin pathway and lectin is a molecule that you find in blood and so for this activation all you need is the leptin in the blood to bind to the microbe and that will activate the complement proteins so as long as you have lectin binding to the microbe that will activate some of the complement proteins which again in a cascade way will activate other complement proteins so again you do not have to know the order of the different complement proteins what you need to know is that the lectin pathway involves lectin binding to the micro to activate the complement so lectin pathway lectin binds to the microbe classical pathway antibodies bind to the microbe an alternative pathway the complement proteins directly recognize and bind to the microbe once compliment is activated it's going to lead to three benefits so these are the outcomes of complement activation so the three benefits that will help fight infection the first benefit is opsonization an obstinate is an important word for the immune system opsonization is basically defined as having proteins coat a microbe so all these little red things are the proteins in this case the complement proteins coding a microbe so this brown thing is the microbe and once you have all these proteins coding the microbe that makes it much easier for phagocytosis to occur so having a microbe covered in proteins will make it easier for the phagocytic cells the macrophages the neutrophils to phagocytose the microbe and in this case having complement proteins bind all over the microbe will make it much easier for the phagocytic white blood cells to adhere to the microbe and phagocytose the micro second benefit the second benefit is triggering inflammation so here's inflammation once one of the complement molecules is activated that will lead to activation of other complement proteins which will stimulate mast cells and basophils to release histamine which will trigger an inflammatory reaction so that is a second benefit of complement activation the third benefit of complement activation is site ala sious lysis of the microbes and this basically occurs by Mac formation so Mac a/c this is called this stands for membrane attack complex and this is the membrane attack complex here it is composed of complement proteins and what these activated complement proteins do is they wedge into the microbes cell membrane and they create pores in the membrane they can create hundreds of pores in the microbes membrane and all the cytosol leaks out and of course that leads to lysis of the microbe and death of the microbe so that's called Mac formation membrane attack complex and that's done by the activated complement proteins so the three benefits of complement activation can be abbreviated by oil oh I L so o IL o stands for opsonization I stands for triggering inflammation and L stands for lysis by Mac formation the last thing I'm going to talk about in this lecture are interference interferons are a type of cytokine so again cytokine those molecular messengers they send signals again another way to refer to cytokines are inter Lukens Lube khun's so interference can send signals to white blood cells or to other cells so interference they are signals signal molecules an interference are only antiviral so they're not effective against bacterial infections or eukaryotic microbe infections they are just specifically against viral infections but they are still part of your nonspecific immune response because they're against or they're effective against all viruses not just one particular type and the purpose of the interference is to protect uninfected cells so that way can limit a viral infection it can prevent uninfected cells from becoming infected and this will be a diagram of what happens or how interference work so here you have the virus and the virus is going to infect a cell so you are going to have an initial cell infected and that virus is going to start going through its lifecycle remember the life cycle of viruses you have attachment penetration biosynthesis maturation and release so this host cell has been infected by the virus being infected by the virus is going to trigger this host cell to produce interferons so there are two types alpha and beta you can just refer to them both as interference but being infected by a virus is going to trigger the production of interference and not only is the cell going to produce the interference but the cell is going to secrete those interferons out so that those interference can go to the neighboring cell and stimulate that cell to produce antiviral proteins so this signal molecule is going to stimulate this neighboring cell to produce anti viral proteins so that when a virus particle that either buds off or is released by lysis from the host cell and that virus particle attempts to infect this neighboring cell that will be stopped so anti viral proteins it's going to stop the infection so interference our signal molecules that are produced by a virus infected host cell to send the signal to the neighboring cells so that the neighboring cell can produce anti viral teens as a review for what I have covered in chapter 16 we have gone over specifically the innate immune system which is also called your nonspecific immune system and it is composed of the first line of defense and the second line of defense first line of defense is meant to prevent infection and it involves how your body is structured the physical factors the types of tissue that cover the outside of your body and their chemical factors their washing processes and your normal microbiota if those microbes get past your first line of defense then they have entered into your tissues and now it is up to the classical parts of your white of your immune system the white blood cells to defend you and processes like inflammation fever and antimicrobial substances such as complement and interference the next chapter chapter 17 will be focused on your adaptive immune response how your immune system adjusts to a microbe that is currently infecting you