Chapter 22 The Lymphatic System and Immunity

well good afternoon the topic of today's lecture is going to be the lymphatic system and immunity the lymphatic system includes the lymphoid organs and tissues the lymphatic vessels which contain a fluid called lymph ly m pH and a population of individual cells called the lymphocytes the cells the tissues the organs and the vessels containing lymph perform 3 major functions in the body the first is at the lymphoid organs and tissues service operating sites for the phagocytes and cells of the immune system that are going to provide the body with protection from pathogens the second is that the lymphatic vessel containing lymph help to maintain blood volume in the cardiovascular system and in addition to the maintenance of blood volume we have fat absorption and the absorption of other substances from the digestive tract that's an important part of how fat are brought into the body from our diet thirdly the lymphocytes are considered defensive specialists they protect our body from pathogens like bacteria viruses but also from foreign tissue cells which is one of the problems associated with tissue transplantation they also the lymphocytes protect us from disease or infected cells or cancer cells that have developed in our body that would otherwise pose a threat to the normal cells and so in this chapter we're going to talk about the lymphatic system and the components of the system and the functions of each of the components we're going to discuss the importance of the lymphocytes and where you can find them throughout the body as well let's talk about the structure of the lymphoid tissues in Oregon and explain the functions of these tissues and organs lastly we're going to talk about the immune system kind of from a broad perspective in terms of nonspecific defenses as well as specific defenses or acquired immunity so again the lymphatic system is composed of lymphatic vessels that contain the lymph and the lymphoid tissues and organs let's see if is pen work here okay so the lymphatic vessels and the lymphoid tissues and organs now some of the functions of the lymphatic system include the transport of fluids back to the blood and an essential role in boxing a defense and resistance to disease due to the presence of those cells called lymphocytes site meaning cell cells in the lymphatic system that are playing a role in in host defense so lymph is itself a fluid so one of the questions you may have is how does it actually move it's not blood it's not moved by arteries and veins so how does it move well it moves through vessels called lymphatic vessels and those vessels are a one-way system that move only towards the heart right so in the cardiovascular system we know that there's a two-way system blood vessels move away from the heart arteries take the blood to the tissues and blood vessels move back to the heart veins right so there's a two-way system would live the one-way system there's no pump like the heart to pump it through its vessel and so the way lymph moved is actually through what we would call a milking action of skeletal muscle around the lymph vessel so when the skeletal muscle contract it would be equivalent to UM if you've ever seen a farm or milking a cow putting pressure from the outside to move the fluid through the vessel so we have a milking action of skeletal muscle and we also have peristalsis that can occur in the in the walls of the lymph vessels due to the presence of smooth muscle so if we're to look at the lymphatic pathways in the body we start our journey with the smallest of all the VM the ducts or the collection centers which would be the lymphatic capillary the lymph is going to flow through that lymphatic capillary to a lymphatic vessel eventually the fluid will move up to what we call lymph node and you may have heard this term before the lymph nodes and they're important in health and you know when a doctor is palpating your your neck region and touching around your throat he or she is trying to get an idea if your lymph nodes are swollen but those are not the only lymph nodes in the body and they're not the only ones that can be swollen but they're often swollen during for example upper respiratory infections but anyway as a nose will drain into vessels lymphatic vessels which will drain into the lymphatic trunk which will empty into a larger collecting duct and eventually be dumped into a vein called the subclavian vein okay so as you can see the journey of lymph starts in capillaries and ends up in veins the veins therefore take that limp to the heart so limp is going to be delivered into one of two large ducts the first is called the right lymphatic duct and it will drain the upper arm and the right side of the head and thorax the upper right arm and the right side of the head at the door acts while the thoracic duct arises from the cisterna chyli and drains the rest of the body okay so the thoracic duct will join the rest of the body and each empties limp into the venous circulation at the junction of the internal jugular and subclavian vein on its own side of the body okay so again the limp is being dumped into veins and again it helps maintain blood volume in that regard it's going to move fat that we're digesting from the gut actually into the heart first and then to the rest of the body so this is an important concept and we're going to look at the wiring and how this is drawn up as we go okay so again if we're looking here at the thorax region here we've got our major lymphatic trunk and duct and how they are connected to veins so the blue colour here and I'm going to point this out maybe it could change the color of my see am I able to no not easily all right so I'm using the pencil in grey so bare with it but here we see the green okay I don't want that exact hold I did change the colour some huh and the blue are the veins and so if you were to kind of put this into perspective if we start here we see the esophagus coming down and trachea is present and so if we look we have the left subclavian trunk the left jugular trunk and so this is where we're going to get lymph fluid draining into the blood vessel okay we also see that if we look at the entrance of the thoracic duct into the vein here okay we're going to get live dumping into the into the vein okay so what's important for you to see here is that whether we're on the left side of the body on the right side of the body this would be the right side of the body if you think about in a comical position okay whether we're on the left to the right ultimately the lymph drains right here right here where I'm pointing and that is called the superior vena cava the superior vena cava now the superior vena cava is going to drain directly into the heart okay so we can see that the lymph vessels are dumping into the venous network and ultimately the place of entry into the cardiovascular system is going to be the superior vena cava the large vein that comes down from the top of the cart into the into the heart okay and so this other vein here that we're looking at a point through the inferior vena cava that also can that also perfuses the heart brings blood into the heart and so the blood coming into the heart is happening through the vena cava we have superior and inferior but the lymph obviously is being dumped into there so I don't expect you to be able to draw a line to everything on this picture but if you were to kind of note some of the important blood vessels obviously we have the subclavian vein and the superior vena cava as important component here if we're to look a little closer at the lymphatic vessel what we see is that they are present in and around the capillary and in this picture that I'm circling they're present they're depicting here by this green looks like a reticular network and so in fact when when the blood is leaving the artery and entering the capillary here any any fluid that leaks out can be collected by the lymph system and eventually we know that lymph system is going to drain into vein but basically the the red is the artery it's branching off into smaller arterioles and eventually into this capillary kingdom that are circled okay giving up nutrients giving up oxygen the blood coming into veins is depicted here as blue to symbolize deoxygenated and any fluid that's lost in that interaction at the capillary will be collected back in through this lymphatic network if you look here this arrow is kind of blowing up one of the one of the lymphatic vessels or what you can see is that we have what we call valves or places into which the fluid can enter and we see that around this lymph vessel you have connective tissue we have cells with this fiberglass we have connective tissue like fibers and proteins that are fixing this duct into the area where where it is in the proximity of capillary and the actual lining of the vessel is made up of and ethereal spell okay so we have looked at excessive than the proximity capillaries and basically their function is to pick up any any lost blood fluid and fluid any of the watery components and eventually dump it back into the cardiovascular system to keep the blood volume relatively constant okay so the lymphatic vessel their purpose is to collect lymph in the lymph capillaries to carry the lymph to away from lymph nodes and to return the fluid to circulatory vein near the heart we did so far with that and so the functions of lymph itself are several I've already briefly mentioned the absorption of dietary back where fat are delivered to the bloodstream directly so that's one important role in the previous slide we talked about the collection of excess interstitial fluid okay excess interstitial fluid that may be coming out of the capillaries needs to be delivered back to the blood stream and then if we have any kind of inflammation remember inflammation is going to require blood coming into the area remove those mobile inflammatories now if there's any inflammation in the area due to a foreign particle like a bacteria or protozoan or you name it any kind of infectious organism the lymph will move those particles to the lymph nodes where we've got lots of lymphocytes that can help us deal with it so the lymphatic capillaries are similar to blood capillaries except they're very permeable so they can take up that cell debris pathogens or in some cases cancer cell remember cancer cells can or very frequently will leave the main tissue and enter lymph right then metastasize to lymph nodes so cancer cells could get in the lymph and in in the in the best situation the lymphocytes will kill the cancer cells and prevent them from moving further and spreading around the body and the cells that are going to make up those lymphatic capillaries are endothelial cells that overlap to form these one-way valves that let the interstitial fluid in interestingly lymphatic capillaries are absent from bone piece bone marrow and the central nervous system and there's a special type of lymph capillaries called lacteals that are found in our GI tract and as I mentioned are involved with bad absorption lacteals are specialized lymph capillaries that are present in the intestinal mucosa and so we're going to see in the digestion chapter that intestinal epithelial cell can have a large surface area due to the presence of these micro villi and within the micro villi we have these these black peels that allow for the absorption of fat so while most of the things that we absorb through oral ingestion via drug or food are going to get into the blood and get taken to the liver or the liver is going to act as a buffer to toxins and such which we're going to learn about digested chapter fat is actually going to not go that way it's going to be absorbed through the lac field and as we saw is going to be dumped into the heart right this is probably one of the functional reasons why high-fat diet it leads to heart disease because the fat gets come from the heart and can accumulate in the heart and too much fat in the heart can result in problems if we look a little bit more closer at the lymphatic capillaries here we basically see that they're blind ended tubes where we've got these endothelial cells that are overlapping with each other and are anchored down to the connective tissue around them and and they form these little one-way directional valves that let interstitial fluid in so limb is going to return certain materials back to the blood like water like blood cells and like proteins so that the consistency of the blood is maintained but we've also mentioned that harmful materials can enter the lymph vessels and be present in length things like microbes cancer cell or cellular debris the lymph nodes are therefore going to filter lives before it gets returned to the blood remember the point of return to the blood is going to happen up towards the heart okay so as the lymph flows from vessels into nose the nose is going to filter that lip and try to sterilize it so the things don't end up going through the heart and getting spreads this definitely so luckily within the lymph nodes we have cells like macrophages which are part of our nonspecific defenses but they also play a role in cell mediated as you'll see later depends we and the lymphocytes which are involved in the cell mediated defenses so one way to look at it is macrophages in the lymph nodes are involved both in nonspecific and specific immunity while the lymphocytes are involved in what we're going to call specific immunity most lymph nodes are actually kidney shaped and less than 1 inch long and you can kind of feel them under your under your throat in your throat region under your chin if you if you feel around obviously they get swollen when certain types of illnesses as an indicator of being sick now the cortex of the lymph node the outer portion is made up of collection of lymphocyte while the middle portion or the lymph node medulla is primarily composed of phagocytic macrophages member phagocytosis is cell eating right eating up debris or eating up bacteria that would otherwise like to spread around the body so here's our typical diagram here's a diagram of a typical type of lymph node what you'll notice first I'm circling here are the afferent vessel meaning bringing live into the node and the lymph is coming into the node and as you notice here this structure is kind of designed to the lymph kind of has to flow all throughout it before it can make its way out of the node through an efferent lymphatic vessel okay so we have a parent vessel coming into the node efferent vessels I think I just said vesicle those vessels efferent vessels leaving the node and in between we've got kind of like a roundabout type of journey that the wind takes and so what you'll see here is things called Qualicum within the lymph node spaces within the lymph node sinuses we can go in Snowden and so within these what we'll call trabeculae within these regions here we're going to have lots of macrophages and within the outer portions here we're going to have lot of lymphocytes okay so the slide you're looking at now shows you some of the many lymph nodes that are found throughout the body and as you can see there are definitely lymph nodes underneath your chin called the cervical nodes but then there are lymph nodes all throughout the body a lot of them in the thorax region right in the abdominal region but also down our arms and our armpit region okay we have high concentration up here so the thoracic cavity node the axillary node the engl in general mowed down by our reproductive organs the pelvic cavity knows the abdominal cavity knows many types of lymph nodes or numerous lymph nodes in the body all giving us defense and protection against image smells of aiding property so you should feel comfortable knowing where axillary lymph node is around your armpit compared to an Ingram inguinal lymph nodes are down by your reproductive tract okay and it just so happens that in most breast cancers that begin to metastasize you know using that as an example obviously the breast is located here in the pectoral region it's a very close by or the axillary nodes which are usually the first site for a breast cancer and they spread just as an example but again we have these lymph nodes all throughout our body and so when they become active they can become now there are actually certain dedicated what we call lymphoid organs in the body and these sites are particularly important in terms of lymphocyte protection and function the first of them is just lean the spleen is a blood filter and it plays an important role it actually destroys worn out red blood cells so you know a typical red blood cell has a lifespan of 120 days as it works and as it goes through the circulatory system under all that pressure eventually wears out becomes what we call a feet and so a feet red blood cells get destroyed in the spleen the spleen also involved in blood cell formation and the developing baby and acts as the blood reservoir okay so what spleen isn't important liquid organ assignment assignment is located low in the throat it overlays the heart and it functions at its kind of peak levels during childhood it produces a hormone like thymosin which helps the program lymphocytes and is needed for the maturation of esau so the thymus is needed for mature teeth now the tongs hold they play a role in trapping and removing bacteria and other foreign materials tonsillitis or inflammation of the tonsils is usually due to a congestion of that tissue with bacteria and lastly we have lymphoid organs in the gut called peyer's patches peyer's patches will capture and destroy bacteria in the intestine all right so a that contaminated piece of food and building bacteria you may never develop symptoms because the peyer's patches are helping to protect your body from those pathogen all right so the clean the thymus the tonsils and the pirate patches are what we will call lymphoid organs and so here's a photograph of the spleen in its normal position in the abdominal cavity and this is an anterior view here you can see the spleen you can see the diaphragm right so let's play dress up against the diaphragm you can see the adrenal gland here very important gland in the sympathetic nervous system and the fight-or-flight response here is down at the left kidney big blood vessel here that supplies the spleen with blood called the splenic artery and of course the pancreas which is involved in digestion as well as an regulation of blood sugar and intricately involved in when it works well protecting us from diabetes okay so again am I going to ask you to draw this clean but this is just a picture of where it sits in the body kind of up against the the diet plan itself okay so immunity what is immunity you know the name itself it refers to resistance to disease being resistant to getting sick okay so if you have a compromised immune system you're very likely to get sick on the other hand if you have an immune system which is healthy you're likely to do you know fend off an attacking pathogen and so immunity refers to resistance to disease and there are two intrinsic systems that contribute to immunity the innate or the nonspecific immune system innate means you just have it just there's an eight part of you and innate just refers to from birth you have it from birth adaptive is the other type of intrinsically or more specific defensive so two major types the innate immune system or the adaptive immune system sometimes that's called the nonspecific immunity versus specific immunity so just FYI innate immunity involves things like macrophages and I'm just going to abbreviate that here with the Greek symbol apply macrophages and adaptive immunity is going to involve felt like t-cell and b-cell for example so this slide kind of puts it all together it talks about the innate defenses depicted for you here by this purple diagram versus the adaptive defenses the innate defenses things you're born with include things like barriers right we have barriers we talked a lot about the skin for example in this class already by protecting us from our environment from bacterial viruses or other things that would like to hurt us we also have mucous membrane mucous membrane that line the respiratory tract of that line the nasal passages that line the gut they're going to trap pathogens or prevent physical injury by particles right so these are just things that are in a like you're born with them there's nothing particularly specific about them they're not different from one bacteria to a different virus they're just there at surface area similarly we have internal defenses like Vegas ice and natural killer cells which are intimately involved in destroying infection inflammation the process is inflammation which we've introduced in an earlier chapter where we get increased blood flow to the site of injury or to the site of infection that's going to bring in blood cell blood cells of the white high white blood cells that are going to be involved in resolving injury including Vegas I'd like neutrophils and macrophages cooing the natural killer cells there are certain time microbial proteins one example would be lysozyme life so design and lysozyme is a protein found in various places among others your saliva but in other places within the body that will cause lysis of foreign pathogens lastly we have fever fever is an internal defense as well we just innate it's indicative of your immune system working hard to combat and infect the organism okay so fever is an internal defense by your body temperature getting hotter than normal a microbe is presumably not going to grow as quickly right because bacteria have a temperature at which they prefer to grow which is your body chemically but if you're by tempor goes up by two or three degrees Celsius which is pretty serious but clear don't glow as well so when I'm growing as well these cellular defenses are involved perhaps there's mucus trapping them to get all these kinds of cool innate defenses in terms of adaptive defenses or specific defenses then we have cells like b-cell which are going to make something called antibody so I would write that down and when is B cells make antibodies and T cells of various types the various types of T cells that are going to be involved in cellular immunity so again the body has two defense systems for for material nonspecific defense system which are going to just protect against a variety of possible invaders it's going to respond immediately to protect the body from foreign materials while specific defenses are going to be required for each different type of pathogen so you'll need a certain type of defense against the bacteria compared to against the virus compared to against the proteins all in okay and so that's a specific defense is required for each type of invader it's also known as the specific immune system or the acquired immune system acquired because you acquire immunity to each and every one of these single pathogen as a result of exposure and these different cells becoming activated so again the nonspecific body defenses things like the skin the stomach mucosa the saliva and the lacrimal fluid your tears that that hydrate the surface of your eye they contain lice design so when you put your finger in your mouth or you put your finger in your eye that that increases your risk of exposing yourself blue bacteria if you haven't washed your hands but won't always result in an illness because of life on of course if you have a particularly pathogenic strain that you introduced to those tissues or new systems a little bit run down or or you didn't wash your hand then of course you know the mouth and the high off sights of exposure to certain pathogen but nonetheless there's a there's a level of protection there delightful time and of course mucus mucus that lines your gut mucus in your upper respiratory tract and so on so the defensive cells who are they what we've mentioned them some of them at least by name the natural killer cell these cells lights or kill viral infected cells and cancer cell and they tend to be nonspecific because they they use a type of agent to attack called a preferring perforin and that perforin punches hold into the membrane of the virus infected cells cancer cells a killer so it's kind of a a missile shooter that shoots missiles at the pathogen those missiles being the purloined macrophages we can have free or fixed macrophages fixed would be those which reside in the tissue three would be those which are going to come into the tissue due to inflammation the neutrophil our Vegas eyes whose levels lies very shortly after exposure and then will fall after after the the pathogen is put under control so the neutrophils account the first wave of phagocytes followed by macrophages usually the critic cells are defensive cells that will carry foreign bodies the lymph node so that lymphocytes can get involved and destroy the foreign particle or the foreign cell so moment a moment about phagocytosis just a brief word about it theta cytosis would call it cellular eating and it actually involves certain steps it observed it involves a step called opsonization optimization which helps the pegasi to adhere to the thing it's going to eat whether it's a bacteria or particle it's going to engulf the bacteria or the particle by the process of phagocytosis and then it's going to destroy that which it has eaten with lysosomal enzymes okay this is not lysozyme per se lysosome remember that organelle and your cell but is made up a lot of toxic things like protease is that can break things down okay so lysis so mole is not the same thing as lysozyme that may be obvious but I just feel like I should point that out places so mole refers to the organelle within the macrophage the toxic waste dump of itself so here we've got a macrophage depicted for you in purple and it's using its cytoplasm to kind of extend and move itself around these invading particles in this instance the particles of bacterial cells you can see that the macula is like grabbing on to them right well in the very beginning of the endocytosis process well grabbing on word hearing and then we're going to internalize and then those bacteria will be destroyed so a few things about the innate defenses and an inflammation so are if you look up here in the upper left corner we've got a person who could a nail into there again right maybe they were working with a nail gun laying down tiles in the roof will put down carpet or something and so basically this is going to be a type of injury that's going to immobilize your internal defenses because now you've got it the inside of your body exposed to the external non sterile environment so here we've got injury we've got inflammatory chemicals coming out of the inflamed site okay so we've got releases of chemicals and those chemicals are going to have a special name called chemokines but for the moment it's just important to know that this chemicals released from the injured cells which are going to recruit white blood cells to enter into this area that's called leukocytes close to step one down here where the neutrophils will enter the blood from the bone marrow all right so here they come they sense that there's injury they're coming towards the site of injury but how do they actually leave the blood vessel and come into the site of injury the way they do that is through a process called margination and diaphoresis in margination the neutrophils cling to the capillary wall very tightly and in dive diseases they actually squeeze through the space in between endothelial cell right so they stick tightly to the inside of the wall may squeeze through the space between your Mobilio claws and then they continue to move towards the site of injury and that movement called chemotaxis or movement towards a chemical signal all right so here they come and they're going to start to eat up some of the cellular debris some of the damage is going going on in the area alright so in terms of an injury this could also be you know a pocket of bacteria that's gotten into the skin maybe it was a scratch scratch by a cat wasn't cleaned immediately wasn't sterilized but we're starting to grow down to the skin a single injury like that nail could be physical damage that tore up themselves or could be pathogens that have access the otherwise sterile environment okay so leukocytosis margination diabetes is chemotaxis so what are some of the chemical defenses that we have well we heard about one of them from our guest speaker last week interferon interferons a protein that are secreted by virally infected cell that will go and move to healthy cell and bind those cells and cause those cells become resistant to the virus in fact that the name interferon was given that name because it's a protein that interferes with viral replication right so we have interferon in addition to interference we got something called complement proteins complement proteins those are 20 proteins in our blood that when activated can actually punch holes and infect itself blow them up and destroy them complement protein complement proteins float around in our blood be usually not active but in response to an infection that you come active and they can destroy the cell that's been infected and certainly we have chemical called collective which are proteins that recognize foreign structures or sugar arrangements and they stick to them the collectin are like a molecular signal they see something far and they stick to it and in une system sees that they're sticking to something they really shouldn't be sticking to anything if there's no infection so they're sticking to something that through the signal for the immune system so interferons and if your viral replication complement is a whole series of proteins that can destroy pathogen protected cells and holding them and collectin are going to be I don't know what you want to call them tattletales but look we've got a problem they do that by actually binding to the surface of the infected cell and acting as a signal to the immune system so if we look here for example at interferon right we've got two cells got fell over here it's a little spot by without snow over here and this cell we've got an infection of virus has come in and it's replicated and it's shedding and it's releasing up here it's releasing new viruses and those new viruses would like to go to this next cell and inspect it but because the virus has entered the cell the cell has a chemical defense called interferon and as you heard last time let the guest lecture main types of interferons but the interferon gene will get activated in response to the virus infection and the cell will start to make and release lots of interferon that will be able to travel to the nearby cell and turn on mechanisms that prevent that virus from being internalized okay so if we start at step one over here the virus enters the cell but yeah it's coming in and it's replicating and it's causing problem but by the same token it's cell is responding by producing interferon and it produces them and releases them and so the interference get released by that host though are going to then bind to the surface of the adjacent cell and that adjacent cell is going to turn on genes that are going to be used to prevent that virus from coming in or prevent that virus from from reproducing or replicating itself so to simplify this you know the infected host cell is making interferon it's going to die and be killed by the virus but the interferon that it released protects that second cell that second otherwise that otherwise second spell that would be inspected it gets stimulated by interferon to synthesize genes that will defend it from further infection okay so one example here of a chemical defense now again if we talk about the complement pathway and I probably I probably should tell you about this even though it's a little bit more detailed because I'm not sure where else you get it in your curriculum so there's two types of complement pathway remember over 20 about 20 protein would be considered complement proteins we have the classical pathway and the alternative pathway now in the classical pathway we have something from the invading organism called the antigen that forms a complex with an antibody made by your B cell and certain complement protein complement protein 1 complement protein 4 complement proteins 2 are depicted here that complex is going to coat the pathogen surface and it's going to make phagocytosis easier for the neutrophils or the macrophages and that's the classical pathway the alternate pathway is we've got spontaneous activation stabilizing factors coming together no inhibitors on the pathogen surface that are going to enhance inflammation okay so they're going to come in they're going to stimulate histamine release and there'll be more more blood coming into the tissue or blood vessel dilation or permeability Vega size chemotaxis and so to make a long story short complement proteins to simplify this and maybe oversimplify this in some way but basically there's two pathways a classical pathway an alternate pathway that's going to lead to cell lysis and the infected cell will die and not be able to perpetuate the virus or the or the I should say pathogen because not supply receipt but also bacteria yeast can activate these pathways so for the purposes of now just understanding that there are these proteins called complement proteins that are going to protect you from invaders they there are many of them they can activate various pathways one called a classical one called an alternative the net effect is slowing down the growth of the pathogen or or killing the pathogen infected cell fever remember fever is elevating the body temperature and that's going to be protected why is it protected because high temperatures of the body will inhibit release of iron and zinc from the liver and spleen which bacteria would use for their metabolism right so the bacteria aren't getting things like iron and zinc in some cases bacteria aren't growing as well because this is increasing the temperature by one or two degrees slows down their growth dramatically okay just like you don't feel good when your body temperature is elevated many bacteria don't feel good if their body temperature is elevated fever also increases the speed of tissue repair and you know we could discuss that point but the cytokines that get released or an inflammation caused increased vascular permeability more of the blood cells and command respond to the infection resolve the infection and so a fever is caused by a class of molecule released from macrophage called a pyro Jen pyro meaning fire Jen meaning synthesizing pyro Jen is the macrophage release product that causes fever only released from the macrophages there's a we've talked about the inflammatory response chemical signal involved in that response are things like histamine and histamine is released in large amounts by basophils and mast cell so tissue is injured basophils mast cell two types of white blood cells releasing lots of histamine that's going to cause dilation of blood vessels increased permeability of the capillaries and now things like neutrophils are going to move into the site of injury so if you were to follow this flowchart from the top down we see injurious agent causing ourselves to get damaged causing the release of cytokines a molecule like histamine that's going to trigger increased vascular permeability the block is going to dilate in a leaky those cytokines internet cause neutrophil and then monocyte which are type of macrophage to come in to the area of damage right so the blood vessels dilating becoming leaky going to cause redness and heat right those but tissues going to feel hot for the touch the swelling of the capillaries and the leakiness is going to cause swelling into the tissue that's called edema and that's going to put pressure on the nerves in the in the tissue and cause pain and they limit the movement of the tissue or of the joint for example and so the neutrophils are going to come in maybe the other white blood cells like the monocytes we're going to differentiate if the macrophages are going to remove the dead or damaged tissue and so this is going to all contribute to the process of healing now turning our attention over to specific community everything we've talked about those five nonspecific immunity well here we have a pathogen specific response something about the pathogen is being recognized by the immune system a little piece of the pathogen a small molecule with a molecular fingerprint a molecular signature is called an antigen right so the body might not have eyes to see that something has come in and infected it but it can sense surface molecules on various things like bacteria and parts of those surface molecules that activate the new system are called antigen there should to be antigenic so the specific community is going to be pathogen specific your immune system might recognize a small portion of a surface molecule of a micro bacterium tuberculosis compared to you know small portion of a molecule on the surface of the coli all right those two bacteria both bacteria but they're going to elicit very different type of antibody formation by immunity right so we're not getting too complicated let's just say that each pathogen has its own molecular fingerprint called an antigen and so the immunity is specific to that antigen when we see that signature or that motif or that antigen we know that there's a certain pathogen in the body okay so it's antigen specific it's systemic I involve the whole body which wants a systemic circulation and we say it has memory because usually subsequent exposure results in less illness because of the formation of memory cell that can make anybody right so maybe the first time you get a virus feel really sick and you're kind of out of it for five or six days so if you were to be exposed to that virus two or three years later you might not even be pick at all because your immune system has developed memory to those antigens and very quickly now has been able to eliminate the virus the second time with the third time around now in order for the immune system to be specific it has to distinguish self you from non-self invading pathogens when the new system fails to distinguish self from non-self you start to attack your own body those are called autoimmune diseases but I digress so there's two types of specific immunity that we can talk about humoral means fluid and that's going to be mediated by the antibodies to get secreted into the blood by B cell and then cellular immunity which is mediated by cell in particular T cells so humoral and cellular immunity are two arms of a specific response to the specific immune response allergies allergies are not antigenic alone but linked up with our own protein or what I mean by that I didn't really say that correctly hey allergies are caused by something called haften which are not necessarily on their own going to elicit an immune response but when it mixes up with some of your own protein it forms like a novel antigen that your body responds to so for example a hay fever right being exposed to pollen the pollen may be what we call an incomplete antigen but when it interacts with proteins in your nose when you breathe it in the interaction forms an antigen that your body now responds to so if you remove the pollen you don't have this happen interacting with your own clothes and just form a true bona fide antigen haptens are are an interesting topic and I don't I don't I think they're a little bit more complicated than what I want to get across today because sometimes you actually use happen in vaccines to get a stronger immune response though maybe for the moment we can you can put that one aside and so let me keep going down because it's cells here right so we have humoral immunity we have cell mediated immunity both types are mediated by lymphocytes but there are different types of lymphocyte B lymphocytes T lymphocytes both types actually originate from matter poetic precursors in the redbone level okay so there they come to us from bone marrow so this explains why people who take drugs it suppress bone marrow get infection like cancer chemotherapy drug certain types of cancer chemotherapy drugs can hurt your bone marrow increase a patient's risk of of infection so the cell of specific community our lymphocyte B and T cells B cells make antibodies P cells are involved in cell mediated immunity now this slide talks a little bit about two antigen receptors on lymphocyte because lymphocytes are detecting antigen antigen something foreign in the body and so there are receptors for those antigens on their surface and what's pretty amazing and again this might be something you cover more in it in a full-blown immunology class but what's really amazing here is that lymphocytes make up up to a billion and that is a B different types of antigen receptors so lymphocytes have the ability to make lots and lots and lots of different antigen receptors and without getting into the genetic there's something called dumb automatic recombination that allows them to do that okay so that's what we mean when we talk about antigen receptor diversity and that's all I'm going to say about that now each antigen will have a particular molecular shape that will stimulate a b-cell to secrete anybody to interact specifically with that particular shape and that acted Pope and so the B and the T cells recognize specific antigens through their plasma membrane bound antigen receptor and at any given time at single lymphocyte and there are hundred thousand receptors for an antigen that all have some more specificity okay and so although it may encounter large set of B cells and T cells a microorganism only going to interact with the lymphocyte that has the receptor for its antigen right so you're going to have thousands of B cells and people floating around in your blood at any given time but the one that's going to start the cell mediated response it's going to be the one that interacts the right receptor on the B cell wall on the T cell so in the world of B cells and kind of categorize them into two broad classes the plasma cells the plasma cells are those that are going to secrete antibody molecules at the rate of up to two thousand molecules per second over the cells four to five day lifespan those the plasma cells are big time antibody producers now let's say that the infection has subsided the body will retain some of the plasma cells but then get rid of some of the others the ones that are no longer needed so the cells would say develop into what we call memory cell so now if it's that memory cell encounters a similar antigen it's ready to go there's no scaling up the process the memory cell can quickly proliferate into many memory cells and eliminate the epitope of the applied to the epitope of the antigen and so the reason why that can happen is called clonal selection the first encounter is called a primary immune response the users take longer then the second and subsequent encounters which are called secondary immune responses which are usually very quick and a patient may not even experience okay so the secondary immune response it's stronger than the first the response is much faster much larger and more prolonged and so this secondary immune response we call immunologic memory and it's the basis of vaccine and again will briefly discuss this in our other class and Public Health System ester when we talk about vaccine so they feel comfortable knowing the difference between a primary immune response and a secondary immune response if you do let's keep going if you don't just go back and think about that again before we move forward because that's the important context so here's what the process looks like in terms of pictures so here we've got our primary response up here in the upper left the initial encounter with an antigen so these little red balls will be the antigen and the antigen binds to a receptor on a specific b-cell those these cells don't have that particular receptor so remember we said it may be 100,000 b-cells and only one or two may have the right receptor for the antigen but that's good enough because once that receptor is bound that cell starts to proliferate and clonally expand we say clonally expands that was banding the exact same cell making copies and copies over the clone of the original and they are going to expand into plasma cell the plasma cells are going to make antibodies that are going to bind to these antigen on the invading organisms and so most of the plasma cells will get formed are going to be used to make antibodies but some of the plasma cells will be retained as a memory cell and that memory cell will be there for the second time there's an infection okay so those antibodies that get to big time important because they help neutralize the invading pathogens that make sense so we start with lots of b-cells only one might have the right receptor for that antigen but once it's stimulated it starts to expand it proliferate some Colossus of cells we call plasma cells and then usually a small but significant quantity of those plasma cells are retained as memory cells or secondary infection detection and they form into memory details okay so your immune system has memory and so if we were to look at a graph here of the antibody concentration versus time after exposure to an antigen will see that it might take anywhere from 7 to 14 days in really 14 days or so to make a lot of antibodies to the antigen and then those antibodies are going to help resolve the illness and then it will be scaled down that production will retain a few memory cells and that's about it now the person has been exposed a second time to the same antigen and boom there anybody formation is much faster you know usually within a week they've already made much more antibodies and in new systems much more confident in fighting that infection the second time let's imagine though at this point in addition to being exposed back to that first pathogen they get exposed to a second snail needs on them that have a different type of virus well immunities to that second virus is an apology same passage the original it's going to take anywhere from you know 7 to 14 days and produce antibodies and multiple days resolved and so upon second exposure to that second antigen it would look more like this class because of the memories from the mixer and collectin okay coming to you live from st. John's campus in Rome so the cell mediated immunity we have B and T cells that are involved and they mature in the bone marrow and in the assignment and their antigen receptors are tested in those issues for potential self reactivity okay we don't want to be sending out cell that have an ability to destroy thing if the things are going to destroy our earth and our tissues because that would lead to injury and so in situations where there's a failure of self tolerance we can say that that's a scenario where we can develop autoimmune disease where you know T cells and B cells get produced that react against our own antigen epitopes our own epitope shouldn't be a minnow genic but they are being immuno genic and their clothing and immune response so T cells do have a crucial interaction with one important group of native molecule whereas B cells do not and what is that group of native molecules but so B cells think of them as the antibody makers pista are going to interact with a group surface marker called MHC major histocompatibility complex and so these are cells surface proteins that kind of give your style its own signature right all of the cells in our body have built different proteins that are dependent upon our genetic the Col major histocompatibility alcohol P so these cells are looking for these MHC and when they see one that's foreign it activated the idea they're being and the problem arising when people start to react against the hosts own na T and again I don't want to go into this too much in terms of what is autoimmune disease because that will be a topic you learn about in pathology but the idea here is what's normally happening normally the B cells and the T cells are maturing in the bone marrow and assignment and they're being quality controlled tested before being put out into the circulation and usually the standard is that if they're going to react against itself they'll be destroyed because they never have to go out to systemic circulation cause problems but problems can occur if that was to happen right so failure of self always again I think I said all I need to say about that right now you will revisit this in a future course I'm not going to go into the VM HD monitors for the moment I will tell you this the MHC molecules are one of the reasons why organ transplants fail from you know person B the person a that's why tissue matching is important so if you got somebody from your family who can donate a kidney to you much more likely that their surface molecules are closer to yours then totally unrelated person but nonetheless when they look for a match when looking for a match if a working person place has got similar MHC markers on their cell to you so the immune system won't pick up on the foreign and may seize and destroy them so you'll learn about different technology again an aura not belabor the point but it mates these are one of the reasons why pshoo transplants can fail because they're too different from your own I may see structures on your own cell and your immune system can detect them as far and destroy them it's one of the reason actually like people who get organ transplants and put on immunosuppressive therapy it can reduce the risk of tissue rejection the other thing that can tell you on this slide that might be new in this discussion is that there are different types of T cells so you know how we said we have D cells their plasma cells in memory cells move T cells we have various subtypes you have helper T cells which do a lot of the job but you also have cytotoxic T cells we also have memory T cells so we'll briefly talk about them okay I'm going to keep this slide and I'm going to skip this slide I'm going to skip this slide and I'm not skipping this because it's unimportant but this idea of antigen presentation major histocompatibility complexes I think is going to be better served after you've had a course about chemistry and you know what these proteins are you know and the kinds of things that surface proteins are able to do so keep going so this slide is one that I'll just briefly talk about and I'll talk about it in the context of cell mediated immunity versus humoral immunity okay and so again without going into every single detail of the slide we know that in the cell mediated response in the cell mediated response we're going to have T cells involved and we're going to have B cells and follow the T cells can be of different types to be helper T cell in the cytotoxic T cells but basically what they do is they work together with macrophages over here to help with T cells work with macrophages to activate States the cytotoxic killer T cells and the B cell so basically what happens is the cytotoxic killer T cell is going to destroy the infected cell to kill it and the B cell is going to make antibodies and those antibodies are going to help in neutralizing it spread of the pathogen so these responses are called cell mediated responses because first of all they're specific there needs to be an antigen a specific antigen response finding through a receptor on the on the surface of the T cell right so it's not like neutrophils coming in anything that's different they eat it up yum-yum-yum here a specific antigen activates a specific receptor and our cellular response event that occur because of that receptor activation okay so without moving too deep into this there's two different types of responses here you have the T cells doing cell mediated immunity with their tack the effective style we have the B cell making anybody's that neutralized antigen slow down the spread of the of the pathogen okay so as an overview we can see how we have humoral responses and film mediated responses antigens coming into the body through injury or infection getting eaten up by macrophage the macrophage is going to interact with a helper T cell which is going to stimulate a cytotoxic T cell to do toxic things to the infected cell going to stimulate the B cell make plasma cells and antibodies in both cases we're going to retain some memories down and so the next time we're exposed the ramune response is much more quick and much more strong once they're much more strong but much more quick more antibodies get made faster and so usually the patient might not even experience symptoms and that's really why we do vaccinations to establish memory cells so how can we acquire immunity right how can we acquire immunity remember we talked in public health about a disease called aids acquired immunity deficiency syndrome right so we know that if we don't have acquired immunity we're in trouble so how do we actually acquire immunity well there are different ways but they all involve exposure you need to be exposed to things now how do you acquire knowledge you be exposed to things right how do you acquire mates to get exposed to things so you can have naturally acquired immunity or artificially acquired immunity naturally acquired is infection or contact with pathogen artificially acquired is vaccination and then we have active versus passive in both types so active me is like an accident section right making the acquire immunity passive immunity is actually something that happens to little babies but they they get anybody from their mother going breastfeeding does anybody come provide infection protection for the nurturing infant going to breastfeeding process so one of the good things about breastfeeding is that you actually give your child passive immunity it gives them extra protection from illness when you breastfeed which is not part of the deal when you use formula if there is no antibodies in the formula on the other hand in terms of artificially acquired passive immunity would be something like injecting serum into a patient like what they're doing with Ebola now they're rejecting people's serum from people who have survived is that people who are infected and that serum contains antibodies in neutralizing the virus working so without getting too complicated here the main concepts are acquired immunity how do you get immunity naturally or artificially naturally can be active or passive you should know an example of each artificially can be active or passive and if you know an example of each now antibodies these are y-shaped proteins they're completely specific and have many uses for immunity and for science research in general they're also commonly referred to by their category in terms of what they are their immunoglobulin poky i G you know globulin protein you know globulin they're secreted by b-cells carrying the blood plasma capable specifically binding to an antigen and there are five main types made up of four amino acid chain linked by disulphide bonds and so here I'm talking about okay we have five pain two heavy chains two light chains and a stem Y shape it looks like the letter Y this portion is what's going to bind to the epitopes and neutralize them okay we have a heavy chain a light chain constant chain this is sometimes called the FC region portion down here which acts as a lichen for a receptor on macrophages okay so max page will eat these things up and break them down lots of disulfide bond which you're going to learn about and cloud cams on top and what about them the point here is the structure is important for the function like this thing acts like a clamp it climbs to the epitope and then the bottom portion brings it to the macrophage for elimination of clearance it's just another picture of immunoglobulin structure again without getting too much detail at this point now this five types of immunoglobulin very important for immunity all of them actually but idg is involved in defending is bacteria viruses and toxins IgA is also involved in fighting against bacteria and viruses and there's three other types IDM IgD and IgE IgE really important in allergic reaction so these are immunoglobulin IgA IgG mmm by far the most commonly used immunoglobulin clinically and therapeutically are IgG IgE s are involved in inflammation so you want to keep that in mind promote inflammation allergic reactions and IgM are involved and things like complement activation and they can react with antigens on red blood cells following certain blood transfusion so point be told there are several types of immunoglobulin that you know the actors antibodies and it has different function IgG is by far the one most associated with what we're talking about today in terms of you know fighting infection and eliminating infection ok so these are the different types of neural globulin along with description of what they do and I'm not going to hold you to all of the details beyond that for IgG at the moment you're going to have a whole course on immunology so I presume you're going to learn about all of the IDs but here idg very important it crosses the placenta it confers passes immunity onto the developing baby it protects against bacterial viruses and toxins in the blood and limb and it triggers the action of the complement system ok so very important immunoglobulin and I'll leave it at that ok so in your study if you know what IG G is and what it does and its role you've gotten what you need but also just realize or other types of immunoglobulins and they all do certain things ok and sometimes those things can be over activation of the immune system causing a severe allergic reaction like IgE all right so here's our antigen forming an antigen antibody complex with the antibody which is going to be inactivated the antigen going to being activated by neutralization by the antibody by gluten ation those cells are going to come and bind around the antigen by precipitation might precipitate out lots of these microbes and phagocytosis clearing these things away in addition to that antigen antibody complex activate complement pathway and the complement pathway can lead to cell lysis can enhance the effect ptosis and cannon information okay so the antibody is critical to all of these things the antibody is not there these things don't happen and hence this idea of antigen antibody complexes and effects on immunity now grab in terms of transplants for tissues issues like a kidney issues like bone marrow heart valve what it what you will we use terms to describe the types of transplant that's I so graph which would be an identical twin with the identical surface molecules in major histocompatibility complexes so this would be a bone marrow transplant from a healthy twin the twin who has for example leukemia that would be called an I so graph so be comfortable knowing what with that term mean compared to an autograph an autograph is something where in for example from one part of your body would be used to replace burned skin so maybe a person has burned a bad burn on their part of their face or their hand and and skin is used from another body reason we wrapped it onto those burn site to promote the healing process autograft grafting part of yourself on one place to another okay allograft allograft is from the same species so a kidney transplant from a relative or a closely matched donor I thought maybe a first cousin has a similar major histocompatibility complex gene as the person who needs the tissue and how would they know that they would do a molecular now they would do blood sample and look at the DNA and get an idea for how similar the tissue surface molecule may be an allograft okay so an allograft is one of the first cousin or you know an uncle donate a tissue that gets put into the recipient it's different from the self is different from an identical twin but it's close and last amount leaf is Reno grass you know means foreign xenograft is going to be a graph like pull different species so using for example heart valves out of a pig's heart replace a heart valves a detective heart valve in human as you know by the term autoimmunity self is when the immune system does not distinguish between itself and foreign and so the body makes antibodies and sensitize the lymphocytes that attacks itself so it sees it seems to join the synovial joint and rheumatoid arthritis is foreign and it's to attack the joint causing pain and inflammation autoimmune disorders are numerous and I'm not going to go through them all but some of the big ones like type 1 diabetes is considered by some to be an autoimmune disease where the pancreatic beta-cell of the beta cell the pancreas is destroyed by the host immune system to a mechanism that's not very clearly understood ok so that's one and Islam prevalent examples see lots of cases of type 1 diabetes used to be called juvenile onset but now we realize it's not just children anymore we can develop that but usually interestingly enough develops after a viral infection when it happens ok but if you look down the list the other one I'll point out is rheumatoid arthritis leading to joint pain or joint deformity and usually antibodies are developed against the cells that line the joint it's a know yourself and co-star get damage to the joint and as you know to join it while perfused well innervated and can cost which leads to edema or inflammation of the joint I should say really inflammation of the joint not just edema and pain so I'll be comfortable knowing those two examples of autoimmune disease and just realize that there are many others lastly allergic reaction and this is going to be really relevant for you as a pharmacist future pharmacist because wall avoid these in your patient and there are four different types and again I know you're going to go into the molecular mechanisms behind these in in your immunology class but just I would be amiss to overlook this so there are four main types type one allergic reaction is the most serious this one can kill you it's an immediate reaction allergy it could present as hives or it could present as anaphylactic shock where a person you know has difficulty catching their breath severe bronchoconstriction laryngeal spasm can die Oh anaphylactic shock been associated with certain drugs like penicillin in some patients bee sting and some patient's serious thing and some patients that allergic to these things actually carry around epinephrine injection an injectable pen if you know hasn't forbid they're far from that medical help they could it we inject themselves until medical help a lot they're out camping or you know so they're skiing or something all right so type 1 is the most severe type 2 is antibody dependent cytotoxic reaction usually going to develop over a few hours and it's often associated with blood transfusion reaction implementation type 3 our immune complex reaction this is where the antibody complexes that are formed can't be cleared from the body and can lead to damage particularly of your kidneys and type 4 are delayed reaction allergy so they might develop you know one to three weeks after an exposure might might presented as a skin rash or something to that expect but by most standards the type one would be considered the most serious and so this is immediate reaction allergy IgE antibodies are being stimulated on mat cells not so there's something out lots of histamine and this could be a medical emergency and you could read a little bit about that more detail about that few slides back where we talk about different I GE but again I'm not here to get into all the mechanism of this really I want to hear the overview today of the lymphatic immune system so hopefully because we've gotten to the end of our slides here hopefully you've um you've developed an appreciation and an awareness of the relationship between lymphocyte and nonspecific cell talked a little bit about the anatomy of the lymphatic system lymph vessels lymph nodes we talked about absorption of fat via lacteal and the importance of doing statics in that process and then we talked about some of the lymphocytes to key players in cell mediated immunity or humoral immunity like the B cells or anybody production and humoral immunity and the T cells or cell mediated immunity so I'm very glad that I was able to record this for you it's a very important topic is I hope we have showed you here and of course is there any questions I'm going to be available to try to help you through this material the best I can so I will be giving you an assignment like a quiz related to this information which probably homework quiz and so I could have any difficulty please let me know have a great day see you soon I'd like to stop you I have no idea exit I hope is recorded I just been a long time you eliminate the giggles

Channel: Biaggio della Pozza

Views: 37,936

Rating: 4.7777777 out of 5

Keywords: Lymph (Biofluid), Lymphatic System (Literature Subject), macrophages, T cells, B cells, lymph, lacteals, fat absorption, Immunity

Id: FNNOhiAgz_k

Length: 92min 48sec (5568 seconds)

Published: Thu Feb 12 2015