Lecture 19 Immune System

hi everyone this is lecture 19 immune system so today we're going to talk about the nonspecific and adaptive immune responses the nonspecific immunity is also sometimes called innate immunity so there are several components to innate immunity we have external defenses inflammation interferon natural killer cells and the complement cascade then we have adaptive immunity which is triggered by and orchestrated by the lymphocytes the B cells and the T cells so for adaptive immunity we're going to talk about the B cell related antibody mediated immunity and for cell mediated immunity we're also we're going to talk about the T cell related effects so the immune system helps to guard against disease and tissue damage immune cells are distributed throughout the body but as you just heard in our previous lecture of the blood lecture they are highly concentrated in the blood in addition to that they will be highly concentrated in the lymphatic tissues we haven't had much time yet to talk about the lymphatic tissues so let's just remind you of those now so the major lymphatic tissues will be the tonsils the thymus the lymph nodes the spleen the lymphatic vessels which carry lymph fluid and also immune cells peyer's patches which are lymphatic a sope mucosa associated lymphatic tissue in the digestive system the appendix which also has lymphatic tissue and the bone marrow so the bone marrow is important for white blood cell and all other blood cell production the function of the immune system is defense it is to help the body against invading microorganisms it is also clean up the immune system can remove damaged tissue and clean up debris the last function of the immune system is surveillance it can identify and destroy abnormal body cells so again the lymphoid tissues are going to be a primary site of the immune system so unlike other systems these tissues are not connected so it's not like the heart connected to the blood vessels these are all distributed throughout the body so they are more connected by function and by cell type than they are by actual literal connections so the bone marrow is the site of white blood cell production the lymphatic vessels carry lymph from the tissues to the lymph nodes and the lymph organs the lymph nodes tonsils and mucosa associated lymphatic tissue and the appendix will be large collections of white blood cells these lymphocytes for the immune response they will also have white blood cells in the form of macrophages to remove debris the spleen is important for replacing worn-out blood cells but also has a collection of lintel sites for the immune response it will also have macrophages to remove debris the thymus then is one of the sites of t-cell maturation and we'll talk about that in a moment so to remind you white blood cells also called leukocytes are less than 1% of the total blood volume they are the major cells of the immune system so whatever you find white blood cells increasing in numbers you have immune system working they are providing internal defense against foreign cells removing debris and destroying cancer cells five types of white blood cells that we have already covered but here they are neutrophils lymphocytes monocytes basophils and eosinophils they can be distinguished histologically by appearance of both whether they are grainy looking this would be the granular sites granulocytes when they're stained versus non grainy appearance and also the particular morphology of their nuclei the functions of the white blood cells again to review neutrophils are phagocytes lymphocytes are important for antibody production and adaptive immunity we're going to go through all of that today monocytes are phagocytic eosinophils are related to allergic reactions and parasitic infection basophils are histamine from allergic reactions and also can produce heparin okay so let's talk about the targets of the immune system what the immune system is looking for is something foreign that foreign thing is called a pathogen a pathogen is a disease producing microorganism for example a bacteria or a virus bacteria is a living single-celled microorganisms that can reproduce and grow on its own for example ecoli so here's an example of e.coli bacteria a virus is non living but dizzy is causing and it's basically DNA or RNA wrapped in a protein coat I don't want to oversimplify viruses they can be very complex in structure and the only reason they're considered to be nonliving is that they require host cells to reproduce the very complex in structure but they cannot live without a host they will take over the host cell and take over the machinery in order to reproduce themselves there is a term called virulence and that is the disease-causing power of any pathogen so how strong or how effective are those bacteria and viruses at damaging the body causing disease so we're going to talk about several different aspects of the immune response starting with the inmate or nonspecific defensive then we'll move into the adaptive defences to get a full multi-level leveled approach to the immune system so let's start with the innate responses the innate or nonspecific responses are the first and second lines of defense to keep pathogens out of the body so I think of this as you know people say like my body is a temple right or my body is a castle so you have sort of the external barriers to keep things out of the castle keep things out of the body if those fail we can have some general troops that are protecting us against anything foreign you know like our bouncers at the door they should keep things out if those fail and the pathogens get inside the body then we will go to the adaptive defences next so let's start with these external barriers and more general cellular responses first the external defensive start with the skin so the skin is a very large organ protecting the outside of the body it prevents entry of pathogens into the body because it has multiple waterproof layers so the keratinized epidermis is impermeable to most not all but most substances so it's going to provide a protective outer barrier to the body there are also immune cells within the skin called the longerons cells that can recognize pathogens that may enter the skin and alert the immune system this is a reminder of skin anatomy but I will not be testing you guys on skin anatomy here if pathogens are able to get past the skin they may have done it through the mucous membranes so not only do we have the external defenses of the skin but where we have to the eyes to the mouth to the nose to other openings lower down in the body vaginal openings etc we will have mucus these mucous membranes are a major site of external defense they are going to line these internal epithelial surfaces to remove debris and prevent pathogen growth so we have to have openings in these regions of the body and if we have to have these openings they need to be protected the digestive tract contains several protective components saliva contains antimicrobial enzymes that's located in the mouth it also contains mucous sticky mucus will trap particles stomach acid down in the digestive system will kill bacteria that the stomach is very very acidic not only to kill bacteria but also to help with protein digestion but it's handy that it's acidic because that kills bacteria there's also good bacteria in the digestive system that helps to suppress the growth of harmful bacteria in some of the lower openings of the urogenital tract we will also have sticky mucus sticky mucus traps particles and prevents entry because of its stickiness it will also be more acidic in these openings so in the urinary openings and in vaginal openings we will have more acidic secretions so urine is acidic which helps to flush out bacteria vaginal secretions are slightly acidic which helps to prevent bacterial growth in the respiratory tract which is also open to the external environment we have mucus throughout this sticky mucus again traps the particles we will also have hair and Celia so the hair will be in the outer portion of the nasal cavity and that will filter particles coming in through the nasal cavity and then throughout the respiratory system we will have tiny little Celia sort of like microscopic little projections that will help to sweep debris out and away from the respiratory passages if something gets down into the respiratory passages way down into the air sacs there are macrophages down in alveoli that will help to clean up any debris we also have a reflex in the respiratory system which can propel irritants out that is the coughing and sneezing reflex that is so uncomfortable when you have a bacterial infection so here's a picture of the Celia and the mucus the mucus trapping the particles and then those tiny little Celia like hairlike projections that will be sweeping the debris out of the respiratory system so those are external defenses skin mucous membranes we have other innate or nonspecific defenses that will just generally provide protection against bacterial growth so inflammation is a nonspecific response to tissue injury or foreign invasion it involves phagocytic cells and plasma proteins that can isolate cleanup and repair the area of injury the important components of inflammation are macrophages and mast cells clotting factors chemo toxin molecule molecules monocytes and neutrophils so the stages and signs of inflammation are like this you will have an injury macrophages will be first to the site of injury and they will immediately come in and phagocytose or eat up any microbes and debris that they find they can then secrete chemicals to alert the rest of the immune system these chemicals will be chemo toxins chemo toxins means that they attract cells and cytokines the mast cells then will be recruited to the site and will release histamine histamine can cause of these Oh Diane okay think back to the cardiovascular system what happens when you have local basal dilation so you're going to go from a normal blood vessel to a dilated blood vessel at this local area of injury the values of dilation actually increases blood flow to the injury that will cause redness as the blood moves in and heat because the blood is warm there's also because of the histamine and other chemical release increased capillary permeability increased permeability of the capillaries is so that more cells can come into the injury so we're going to start to move white blood cells into the injury site this process is called dye appetit cysts and that can cause swelling and pain because not only do the cells move into the tissue but fluid can move into the tissue so increase fluid to the tissues can cause swelling then the swelling can push on the nerves nearby that can cause pain so the four signs of inflammation are redness heat swelling and pain after that we can initiate the clotting cascade so the injury site can begin to be plugged off the chemo toxins will continue to attract immune cells to enter the injury site and the monocytes and neutrophils will move in to start engulfing and destroying pathogens so again these are white blood cells that will come in and start killing pathogens as an aside a bunch of dead white blood cells because you had a ton recruited to the injury that accumulate at an injury forms pus that's a white eggs excellent that is going to be pushing out of that injury and that causes pus when the white blood cells stick to the injury site that is called margination so let's look at these steps I could draw them for you but actually I think this picture is much better so you have an injury that will cause an increase in white blood cells moving into the injury that's died appetit sense the white blood cells will move in neutrophils mast cells macrophages monocytes they're going to go in to try to clean up that debris that is all caused by the increase in blood flow which brings more white blood cells in and the increase in capillary permeability which allows the white blood cells to push through the capillaries that increased blood flow can cause redness at the injury site that increased permeability can cause swelling at the injury site a result of the increased blood flow is also heat a result of the swelling is also pain so the signs of inflammation are redness heat swelling and pain we call these the cardinal signs of inflammation these are caused ultimately by the vasodilation that brought in more blood flow to the injured tissue and by the increased capillary permeability that brought in more fluid and cells to the tissue that costs falling in pain which increase the phagocytes because of the increase in phagocytes in the tissue you can also get an increase in pus at an injury site if it goes on for a long time but more secretions can also activate the rest of the immune system increase fever and increase tissue repair so here's a macrophage in action so there's a bunch of e.coli there's a big macrophage kind of enveloping and bringing in the e.coli for phagocytosis phagocytosis looks like this you have a foreign particle this huge white blood cell is going to surround it and bring it inside that is phagocytosis bringing the particle in and it will then fuse that phagocytic vesicle which contains the pathogen and the outer membrane surrounded with a lysosome remember that a lysosome is filled with digestive enzymes the digestive enzymes will break down and kill the bacteria they will break it down into pieces and then exocytosed those chunks of now non damaging bacterial parts this debris can build up and cause problems at the injury site if it goes on for too long okay that was inflammation now let's talk about interferons so interferons are anti viral proteins that help cells non-specifically target and prevent viral replication so this is a specific antiviral defense so we had external defences skin and mucous membranes we have a general response to pathogen entry which is inflammation and now we have a general response to viruses so if the body detects viral nucleic acids or it senses that there's a virus then it's going to send out some autocrine and paracrine signals this will trigger a virus blocking enzyme in the body cells that will hibbett viral protein synthesis this will also reinforce the immune responses generally by increasing phagocytic cells and activating other aspects of the immune system it will ultimately slow cell division and growth in body cells as well so interferon looks like this you have a body cell that's been attacked by a virus that first body cell is dead there's no way to save that body cell but before he dies he sends out interferons so this is sort of a hey guys I'm going down don't go down with me so No so he's going to release interferon but he's toast okay because the virus has already replicated within him that interferon though can be sent out to the next cell nearby that interferon will then block infection of the nearby cell by viruses so the nearby cell is now protected because his buddy told him to close his doors right hey there's a virus around close your doors this guy was toast but he saved his friends on the way so the virus then will try to get into the cell but that cell has already been prepared and is able to block the virus from replicating that virus will not be able to replicate and that cell will be saved so interferons are signals that are released from damaged virally infected cells to help nearby cells prevent virus replication okay natural killer cells natural killer cells are specialized to non-specifically detect and destroy virus infected cells and cancerous cells if they find a cell that has been compromised either cancer cell or a virally infected cell then the natural killer cells will release chemicals to kill those damaged cells these chemicals are called her friends and they're inserted in the membrane of the infected cell poking holes in a cell not good right so the natural killer cell releases these preference it pokes holes in the damaged cells and causes those damaged cells to die complement system is similar but it's through a larger cascade of molecules there are 30 proteins involved in the complement system but ultimately it is also going to poke holes in the membrane of a cell and kill those cells so these holes are formed by what we call the membrane attack complex not the per friend so natural killer cells her friends complement system complement proteins membrane attack complex this forms a big channel in the membrane and that disrupts the osmotic balance in the cell blood so the cell is going to lyse and die complement is going to come up at the end of the lecture today because it also works together with other immune responses here's a zoom in of that membrane attack complex that pokes holes in those cell membranes okay fever fever is caused by chemicals secreted by macrophages so when macrophages find pathogens or they find foreign invaders they will secrete pyrogens pyrogens will be sent to the bloodstream and reach the hypothalamus when the hypothalamus receives these pyrogens it will elevate the body's temperature and cause a fever a moderate fever can actually be beneficial that's beneficial because a little bit of increase in temperature can increase the rate of chemical reactions so think back to chemistry the more you move a molecule with heat the more active it can be to a certain extent that can actually speed up chemical reactions an enzymatic repair of tissues it can also cause the liver and the spleen to sequester iron and zinc iron and zinc is needed by microorganisms to grow and divide so that will help prevent microorganism growth excessive fever however I should have written that on here excessive fever can be harmful because what happens to enzymes when temperature goes too high right times of proteins so the word I'm looking for is denature right so enzymes denature when proteins are high okay so those were all nonspecific responses so let's list those out and do a summary diagram okay so for the immune response we have the innate or nonspecific defenses these are defenses that are general they are generally going to be active with any foreign pathogen of course there are some subclasses so for example interferons are mainly for viruses but they will be active for any virus not a specific virus so they are general because they are grouped and they will respond with any infection first we have the external defenses which are the skin and the mucous membrane the skin and the mucous membranes are going to prevent entry of pathogens like bacteria then we have inflammation which is generally going to try to increase blood flow white blood cells to an injury site as a byproduct of that we will get the four cardinal signs of inflammation redness heat swelling and pain but ultimately inflammation is a natural response to injury the last three interferons natural killer cells and complement are going to be targeting specifically infected cells so interferons are going to be antiviral natural killer cells are going to use perforin to destroy damaged cells or infect itself and then finally complement is going to use the membrane attack complex to destroy damaged or infected cells alright let's move on now to the adaptive responses the adaptive responses are the third level of response so if the external barriers and the internal general defenses don't work so if inflammation is not enough if the natural killer cells and complement and interferon are not enough then we need to do more so we need to then target specific pathogens that have entered the body and this is where the adaptive immune response comes in the adaptive immune response creates a memory for those very difficult specific pathogens they will then be recognized upon later infection and they will be killed more efficiently so the adaptive responses are two different types antibody mediated immunity immunity Wow antibody mediated immunity which happens through cells and cell mediated immunity which happens through t-cells so for adaptive versus nonspecific immunity the adaptive immune system is specific and we say that it's specific to a particular foreign invader in fact it's specific to a piece of a foreign invader called an antigen so this requires the production of specific lymphocytes b-cells and t-cells and specific antibodies against an antigen it is systemic so it's not restricted to the initial infection site the way that inflammation is and it has memory a second encounter with a pathogen that makes this tiny or has the antigen as its component causes a more rapid and vigorous response so this is driven by the B cells and the T cells the B cells are named B cells because they are born and mature in the bone marrow they are then housed in the lymphoid tissues B cells are going to recognize free pathogens bacteria toxins viruses floating freely in the body they are going to produce and create the antibody mediated immune response T cells are born in the bone marrow but they mature in the thymus so they get their t4 where they mature in the thymus they are housed in the lymphoid tissues just like b-cells they can recognize infected or cancerous cells so the B cells are going to recognize the whole pathogen the T cells are going to look for body cells that are infected they will be involved in cell mediated immunity they are also involved in activating a total and combined immune response so in order to do this B and T cells have to become what's called immunocompetent that means that they display a particular type of receptor that respond to a particular type of antigen I'm realizing that we're using the word antigen but we haven't completely defined it yet so let me show you briefly what an antigen is so what you have is a bacteria this bacteria as a whole is considered a pathogen because it's a disease-causing microorganisms they are very complex and they contain many different molecules around them particularly in their outer walls when a macrophage finds a bacteria it's going to take in the bacteria through the process of phagocytosis when it does that and fuses with the lysosome it's going to break down the bacteria when it breaks down the bacteria the bacteria will now be in pieces those pieces will include molecules that originally made up the bacteria those pieces are antigens so an antigen is a molecule that causes an immune response and it can come from pieces of pathogens that have been broken down in this process it can also come from pathogens that are just floating around in the body that has previously caused immune response that an antigen is basically a molecule it's not a complete pathogen it's just a portion of a pathogen and the important piece here is that one pathogen can have many antigens one pathogen broken down into many molecules those molecules specific to the pathogen will be the antigen so to become immunocompetent the B and C B and T cells need to have receptors that will find these antigens so these are receptors that are specific for that molecule they need to become immunocompetent before they encounter the antigens so they can actually recognize those antigens once they do that they will be exported to lymphoid tissues where the antigens will be encountered once they actually encounter their antigen they will become fully functional and be activated so for B cells and T cells the pathway is slightly different they're both made in the bone marrow B cells will stay in the bone marrow and get their receptors or become immunocompetent in the bone marrow T cells will leave the bone marrow and obtain their receptors and become amino competent in the thymus they will then both circulate to the peripheral lymphatic or lymphoid tissues here is the antigen definition antigens are any molecule or partial molecule that triggers an immune response these can be solved proteins carbohydrates lipids that are part of bacterial cell structure they can also be toxins released by bacteria B and T cells will then have specific receptors for specific antigen molecules B cell receptors we're going to abbreviate btrs t-cell receptors will abbreviate TC RS we could spend an entire class on immunocompetence it's a very complicated series of interactions that ensures that B and T cells have receptors for foreign antigens and not molecules in our own bodies there are two trillion lymphocytes in the body and each lymphocyte can only recognize one out of a hundred million possible types of antigen okay B cells so we're going to first talk about antibody mediated immunity and what the B cells do so here's what happens the pathogen invades the body and the specific b-cell with its specific receptor because it's now immunocompetent recognizes a specific pathogen the b-cell will then differentiate into plasma cells and memory cells plasma cells produce antibodies memory cells store a memory of that antigen so that if you have a later infection weeks months days years later then they will be ready to produce antibodies quicker the next time so this is how your book diagrams it but we're going to draw it out so you have a bacterium that has invaded the body this is a free-floating pathogen circulating somewhere in the body tissues that bacteria is going to have on it some molecules that will be specifically recognized by our b-cells so we have B cells with specific receptors for those specific portions of the pathogen so these are antigen receptors and let's just follow this pink B cell so this particular V cell has a specific receptor for this molecule on this bacteria it's going to go near the bacteria and recognize that molecule when it recognizes that molecule the B cell is going to be activated in other words it found its soulmate it found its specific antigen right so they could go their entire lifetime without ever encountering the antigen that they have been built to encounter but once it does it will become activated so this is a b-cell with its b-cell receptor once it becomes activated two things happen the first thing that happens is it produces plasma cells plasma cells are going to produce antibodies the second thing that's going to happen is it's going to produce memory cells memory cells are going to remember that antigen later so instead of having just one B cell or one small group of B styles it recognizes with antigen we're going to now have a collection of memory cells that can recognize those antigens upon a later infection so what is the significance of these antibodies that are produced by the plasma cells so here's your bacteria here's your B cell with a specific receptor for the antigen on that bacteria other B cells with other receptors will not be activated that specific B cell will become activated and make plasma cells plasma cells will make antibodies and the antibodies are also called immunoglobulins they are y-shaped proteins that recognize specific antigens there are five types of antibodies that are created in the body the most common is IgG ITT's will be secreted to respond to most antigens look for example you're infected with disease bacteria X site well we made this up dbx you will have a specific type of b-cell that specifically recognizes dbx that will activate plasma B cells to produce the IgG specifically for a cellular protein on dbx and then what happens this is the structure of an antibody so you have to wait for what happens for me to show you this structure sorry I forgot this slide was in here so antibodies are y-shaped proteins and they recognize specifically the antigen okay so then what happens we have the antibody mediated responses it's important to know that the antibodies do not kill the bacteria the antibodies cause a couple of things that can prevent the bacteria from doing more harm or can downstream lead to the destruction of the bacteria these three major processes are neutralization agglutination and tagging for destruction so antibodies can physically surround a pathogen to prevent it from interacting with other cells so can form a barrier around that pathogen so it will bind to the outside of that bacteria for example and prevent it from interacting with cells it can also clump molecules so it can clump bacterial cells together so antibody will grab onto one cell another to another cell that all clump together and it can cause them to precipitate out of solution the last is that antibodies will tag a style for destruction by something else so the antibody itself doesn't do the destroying the antibody will tag it and say hey I found something and then the complement the phagocytes and the natural killer cells can come in and either gobble up the bacteria or poke holes in it so that it dies here's agglutination so this is antibodies clumping together several bacterial molecule so here in brown these are the bacteria here in red is the particular portion of the bacteria the antigen and then here is the antibody clumping all of these together here's the activation of complement so the antibody activating or scuse me the antibody binding to the antigen will lead to active complement and then through the cascade complement will form the membrane attack complex around that bacterial that was found and cause lysis or rupture of that bacterial cell so the complement does the killing the antibody is just the flag activation of phagocytes happens in a similar way where they will be attracted to the antibody bacterial complex and they will surround the bacteria and phagocytose the bacteria natural killer cells very similar but they use preference instead of the membrane attack complex so how long does this take antibody response time depends on whether it's your first exposure or a later exposure the first exposure to an antigen is very slow it can take several weeks before antibodies can reach their peak concentration and the bacteria or other pathogen invasion can be held back in the meantime symptoms can get worse and sometimes death can occur before the antigen has been neutralized the secondary response is the second or later exposure to the antigen where you now have memory cells and the memory cells can respond very quickly and much more powerfully so memory cells can make enough antibodies within just a few days the secondary response to that antigen may not even create symptoms so you might not even know that you got sick the second time and later exposures after this primary response will be completely contained so this is the basis of vaccination so the idea of vaccination is to mimic the primary response so what you do with vaccination is you take a piece of a pathogen something that cannot cause disease remember that an antigen is just a molecule it's a chunk of that bacteria or a piece of that virus it cannot fully cause the disease but it can cause an immune response the non-pathogenic vaccine then will be the primary exposure to that antigen it might take weeks after that vaccine to develop immunity but after that you will have memory cells and because that portion of the bacteria or virus cannot make you sick then you've created memory cells without getting sick so you skip the primary infection and go right to having memory cells and you're then prepared for any other exposures so this will be done for diseases in which the primary response could create enough damage or could be fatal in that case it's very important to get a vaccine to prevent that initial infection and to guard against any exposure to the antigen in the future so this is the time of exposure to a first antigen and it takes a couple of weeks for that to get enough antibodies to make a difference this is the second exposure and you can see within just a couple of days so before the first week is over you have a much larger response because of the memory cells let's put these two together then so here you have the first exposure to an antigen which can take a couple of weeks to create enough antibodies we will then guard against that pathogen and the antibodies will go back down the pathogen will be destroyed then if you get a second infection it will take only a couple of days to mount a much bigger and more powerful response and make enough antibodies to ward off the infection this is what we call active immunity b-cells and counter antigens to produce antibodies against them this can be natural natural in response to a regular bacterial or viral infection or it can be artificial in the case of a vaccine but either way the patient is exposed to a bacteria or virus molecule or a portion of that bacteria or virus that is either natural or artificially put into the body and that will cause memory cells to help against infection later passive immunity is different passive immunity is when you give a patient antibodies so in this case the cells are not challenged by the antigens b-cells are not activated so you don't get memory but you can protect someone by artificially giving them a bunch of antibodies that will help to neutralize a gluten a tor tag the bacteria for destruction so these can be natural this happens with breast milk from mother to baby there are antibodies that are passed on to the baby or it can be artificial where a clinician will inject a serum that contains antibodies in both of these cases though because the b-cells are not challenged and do not bind to antigens we skip that step and just go straight to the antibodies there's no memory so this doesn't help the long term immunity it only helps while the antibodies are being administered okay so that was the cell immunity we're going to finish up now with t-cell related immunity so t-cells are going to search for infected body cells so b-cells are searching for bacteria t-cells are searching for damaged or infected body cells if the pathogen has been successfully able to get into a body cell the not body cell is going to send out signals this requires both the recognition of self cells and infected body cells and this is done through MHC proteins okay so MHC proteins are on the surface of cells and they can signify a self cell they are also used on antigen presenting cells and we'll talk about those in just a second but the idea here is to coordinate and enhance other immune responses so there are three types of cells used in the t-cell response there are cytotoxic t-cells helper t-cells and regulatory t-cells so let's talk about the antigen presenting cells so what happens is that t-cells cannot recognize free pathogens the way that b-cells can they can only recognize antigens displayed by MHC proteins so there are two possibilities one is that a pathogen infects a body cell the pathogen will be broken down inside that body cell in the lysosome an MHC one protein will be used to display the pathogen on the cell surface this is a body cell saying I have been infected and this is what I'm infected with MHC proteins are also used on cells we call antigen presenting cells these are specialized macrophages that will phagocytose pathogens or bacteria break them down in their lysosomes and then display them on an MHC 2 protein we now call those macrophages which the name for those are dendritic cells we now call them antigen presenting cells so they are hovering around the body looking for pathogens when they find a pathogen they will grab it break it down and use an MHC 2 to display it and say hey I found something here it is so here is a dendritic cell engulfing a bacteria this looks very much like the same phagocytosis process we talked about so the dendritic cell engulfs the bacteria bring the enzyme breaks it down with lysosomes and then pieces of that bacteria these antigens will be displayed and they're displayed by MHC 2 molecules now the MHC 2 molecules will be recognized by the t-cells so those two general classes of MHC found in the body class 1 MHC signals a self body cell that is infected class 2 MHC signals an antigen presenting cell that is flagging a pathogen has been found okay so let's begin to draw this out because it's getting complicated yes ok ok you have a bacteria that bacteria is engulfed by a dendritic cell it is the dendritic cells job to find foreign invaders and it found one so it brings it in and breaks it down it breaks it down and then uses an MHC 2 protein to display it so this is an antigen being displayed by a dendritic cell on an MHC 2 protein when the dendritic cell is displaying an antigen it is now called an antigen presenting cell once the antigen presenting cell is displaying an antigen it's going to be recognized by a helper T cell this is one of these T cells that is involved in the response to these displayed antigens so the helper T cell has its own T cell receptor so this is our helper T cell it's going to be floating around and looking for antigens on antigen presenting cells when helper t-cell finds an active antigen presenting cell it's going to release signals that will activate the rest of the immune system they're going to activate b-cells so that the b-cells can look around for the same bacteria floating around and make antibodies and they're also going to activate something called cytotoxic T cells the cytotoxic T cells are going to then take that information and start to look in the body for infected cells so the cytotoxic T cells let's draw them in pink actually so now the site of toxic T cells armed with information that there is an antigen to be found are going to look for that same antigen that was found by the helper T cell when they find that antigen they will recognize it by binding to an antigen that was on an MHC 1 protein MHC 1 will be attached to an infected body cell so this is a cell that has been infected and has displayed the cause of its infection the antigen on its surface so the cytotoxic T cells and activated by the helper T cells start to circulate and look for infected body cells once they find infected body cells they're going to destroy those body cells those body cells have been infected so they're on their way to being damaged by the bacteria and we want to make sure that they don't create any more damage so the cytotoxic T cells are going to call lysis of these infected body cells we've already heard about two ways that lysis can be induced perfer ins from natural killer cells the membrane attack complex from complement now here's one last way granzymes so they the notch alula the cytotoxic T cells release granzymes to induce lysis of infected body cells now these can be virus infected cells they can be mutated unhealthy cancer cells they can be transplanted donor cells in any case that the cytotoxic T cell finds an antigen on an MHC one it's going to kill that body cell this was helped by the activation of helper T cells so helper T cells activate B cells they activate these cytotoxic T cells they will also generally attract macrophages that includes neutrophils to help to find more antigens and more debris there are also some cells called regulatory t-cells I don't have an image for these they are currently under research but regulatory t-cells are thought to keep the immune system in check so they are thought to reduce immune responses and they are currently being researched for autoimmune disease so when the self vs. pathogen signals get mixed up then the body can mistakenly in attack its own healthy cells regulatory t-cells can keep that immune response lower and hopefully prevent autoimmune disease okay there are some summary diagrams in your textbook for this but let's take a moment to put them back together for b-cells and t-cells so here's our b-cell response B cells recognize free-floating pathogens with their specific antigen receptors when they find those free-floating pathogens they will induce production of they will activate production of plasma cells and form antibodies they will also form memory cells that will remember the antigen later t-cells are here they are going to recognize antigens only as displayed on MHC proteins so T cells will first be activated by antigen presenting cells antigen presenting cells will activate helper T cells which will overall enhance the immune response in the body that will also increase B cells and macrophages but primarily for the T cell response it's going to increase cytotoxic T cells those cytotoxic T cells then based on MHC 1 interactions will kill any infected body cells so T cells kill infected cells that's why the T cell related is called cell mediated immunity and B cells are going to kill bacteria with antibodies so that's why the b-cells is antibody mediated immunity you have a summary diagram in your textbook which talks about the differences between B and T cells one example of antibody use clinically is individual blood type so individuals have particular proteins expressed on their blood which mark it as self versus non-self if you are blood type O you don't have any of these proteins if you are a blood type a you have a antigens if you're blood type B you have B antigens if you're blood type a B you have a and B antigens if you are an a containing blood cell then your body will only recognize a as self if it encounters anything else namely B it's going to make anti-b antibodies the same goes for B type blood if you are a B type blood then your body recognizes B as self and if it encounters anything else it will make antibodies to that namely anti a antibodies if you don't have any cell markers then both a and B will be recognized as foreign and you will make anti a and anti-b antibodies in any of these cases whatever is recognized as non-self will be attacked by the immune system that can cluster and cause clumping of donor blood if you give a patient the wrong blood type and that's the agglutination response that we see normally with antibodies applied here to blood type hypersensitivity is an abnormal or extremely vigorous immune response that it can occur within seconds to minutes this can occur with allergies and with asthma so this can happen when plasm cells produce IgE antibodies which attach to mast cells mast cells then release histamine causing a huge inflammatory response they can also release a leukotrienes that causes a slow substance that causes smooth muscle contraction in the airways that will constrict the airways and cut off air flow this can be treated though with antihistamines and newer drugs that block leukotrienes such as singular immunodeficiency is the opposite it's when you don't have enough of an immune response immunodeficient deficiency can be caused by lacking our abnormal production of immune cells so you can have something called severe combined immunodeficiency disease which is deficiency of both B and T cells and then out in the media discussed a lot is aids so acquired immune deficiency syndrome happens because HIV specifically destroys helper T cells helper T cells are necessary for activating cytotoxic T cells to kill infected body cells they're necessary for activating B cells so the entire immune response will be lowered by the destruction of helper T cells so you don't die from AIDS you die from a secondary infection that you weren't able to fight because your T cells were destroyed an autoimmune disease happens when the body when the immune system does not sting distinguish well between self and non-self in this case something on a self cell will become an antigen and the body will produce antibodies and cytotoxic T cells that are going to tackett's own tissues there are many possible causes for autoimmune diseases but the research here still is very ongoing some of this could be inefficient lymphocyte programming for example a problem with the immuno competence development this could also be the appearance of new self antigens something new that's created in the body or it could be the antibodies produced against a foreign antigen could begin to react with a similar self antigen okay we are finished with the immune system please take a moment to review the nonspecific defenses the B cell mediated antibody response and the t cell cellular mediated response let me know if you guys have any questions

Channel: Physiology for Students

Views: 161,155

Keywords: anatomy, physiology, immune system, white blood cells, antibodies, vaccination

Id: 3L7eM81CTzA

Length: 67min 15sec (4035 seconds)

Published: Mon Jul 18 2016