Your Immune System 101: Introduction to Clinical Immunology

this program is a presentation of uctv for educational and non-commercial use only this is the first time I have done this talk and I am very intimidated by the smart audience so I'm looking forward to your questions and we have hopefully an evening of fun and learning and I hope to learn from you as well so our order of discussion tonight first we'll do just a little bit of history to put things in perspective we'll talk about the cells of the immune system about which you'll hear much more next week from Tony DeFranco we're going to talk about where the action occurs the immunologic strategies of the hosts in general examples of immune system malfunction and then also how the immune system evolves over a lifetime because our experiences as an immune host play a big role in our overall health so I'm going to ask you a question first I don't want to be doing the person doing I don't want to be the person doing all the work up here so if someone came up to you on the street and said what is the immune system what would you say any ideas what would you say if I came up to you with the microphone and said what is the immune system yes yes so the answer is the body's ability to fight off germs and foreign things that shouldn't be there and that's a great general answer and it's interesting because when you ask this question of people we always have an easier time saying what the immune system does as opposed to what it is right that's a hard one it's even hard for me as I try to teach patients about what the immune system is so as I sat down and I thought well what is the immune system and how do I explain it I came up with a really long-winded immunologist definition it's not all that long but let's take a look at it avast communication network of cells and chemical signals distributed in blood and tissue throughout the body human body which regulates normal growth and development of the organism while protecting against disease so clearly this explains why many immunologists are socially isolated please the question is regarding whether the immune system and the nervous system are two sides of the same coin there are definitely some clear relationships of that one place that I can think of it in particular in my job as an allergy immunology specialist is people who have allergic rhinitis often will have involvement of the nervous system if they inhale something they sneeze and that requires a neurologic response in addition to possibly an allergic response but allergy isn't necessarily involved so I'm not sure they're quite two sides of the same coin but they can be very closely related and hopefully we'll get into some more examples of that a little bit later on okay I'd like to shorten this definition to a little slightly more workable one a condition in humans that permits innate which I would call hardwired and acquired resistance to disease and no time saying disease I'm not saying specifically infection although that is certainly a very major part of it so tell me what is this and some of you have correctly identified it as smallpox this was a young girl in Bangladesh who this would picture was taken in the 1970s just several years ago before smallpox was finally wiped out now we're taking a step back in time to look at why it is that people became interested in immunity and trying to understand it if this were your daughter your family member or even if you were a thinking human being you would want to wipe this thing out this is a terrible disease and in fact has been the scourge of mankind for many many centuries this is smallpox which is also known as variola there's another organism that has wreaked a lot of havoc over time and history and it's so bad that it was kind of generically called the plague and it also had a name of black death and you can see why because of the literal death of the fingers of the hand of this person who had it and as we look back through time there's no doubt that there have been many major plagues that have almost wiped humans off the face of the planet some of these plagues may be wiped out 1/3 to 1/2 or 2/3 of the population of whole continents so humans have been trying for a long time through their immunity to overcome some of these nasty diseases and don't forget about tuberculosis influenza it was less than a hundred years ago that 25 to 50 million people died from one variety of influenza and so you understand why it is that so many people scurry around when we get a new virulent type of virus imagine how many more people we have on the planet now than we had then so certainly people were thinking why is this why do humans get some of these horrible diseases and so one thought was maybe this is evil humors that there's something evil in the winds that come in that we catch somehow or that makes us sick it's something that we inhale we didn't know some people thought it was spontaneous generation that it was something kind of rotting from the inside out so there were you can imagine humans wondering why why is this happening one of the philosophies that was held for many many centuries is the philosophy of humor ISM and we'll see this term humor ism a little bit later on in the talk but it was thought for a long time that the body was made up of different fluids in this case phlegm blood yellow bile and black bile these fluids were also associated with personality characteristics and if you had an over balance under balance too much of something not enough of another thing you developed problems with these personality characteristics and you can see some of these terms we still use today melancholic sanguine I don't think I've called anybody phlegmatic for a while but you know this so we still have remnants of some of this terminology and you can also see characteristics of both Indian medicine and Chinese medicine and you can imagine that this information went all around the world as traders brought these different types of ideas to different places but along the way we do have some records of people thinking about what is it that's going on here and sometimes it's just a few careful observations that make all the difference so lucidity x' was an historian and he actually was mostly a military historian but during the plague of Athens which happened to occur during a battle between the Athenians and the Spartans he happened to get the plague at that time which by history we're guessing was probably smallpox he survived lived to tell the tale and he happened to notice that people who got it and lived couldn't get it again they could care for the sick people and it seems very simple but it's actually a very powerful observation and important we know that in 10th century China that there were practitioners who were taking dried smallpox wounds or lesions powdered pox if you will and puncturing it into other people to try to prevent it from happening this is a procedure called variation because smallpox is variola now undoubtedly people died from that but maybe some people became immune by that practice as well and there were Islamic physicians and Italian scientists who thought maybe there's something that's contagious they started thinking about this concept that maybe it's one person communicating something to another person so just a short trip through history to illustrate how some of these thought processes occurred now this is a very interesting lady never underestimate a determined mother this is Mary Wortley Montagu she was the wife of the English ambassador to Istanbul her brother died from smallpox she herself had it but obviously did not die from it and she had two children she did not want them to die from smallpox and she happened to notice that some of the Ottoman trade traders not traitors traitors passing through we're doing this practice of poking people with smallpox and she thought if this prevents it I I want this I want this for my children so she went back to the king of England and said you need to learn about this so the king of England did what all good Kings do and the king of England said to his doctor I want you to do this and so they started doing it learning about it and eventually as you know Edward Jenner was the founder or originator of vaccination the term vaccination which he coined comes from the root of cow which was cow pox which is less virulent smallpox and cow pox you can use it as a vaccine against smallpox in humans because the cow pox doesn't kill humans so the term vaccinate was from vodka from the root cow in case you did not know that and there were some other very important concepts - it's only a hundred and sixty years or so that we thought well maybe it's not a good idea to go directly from the autopsy to delivering babies and hand-washing as a concept came about at that time and when hand-washing was started in that particular ward the rate of infection decreased tremendously some of these things seemed so simple now I mean it's just hard to believe that it's so recent in history so with rapid advancement in the 1800's in the 1800s in particular we made amazing progress in understanding germs and demonstrating in a very systematic manner that there are germs that actually cause disease in people and then can you imagine how exciting it must have been I spot a virus I spot bacteria and even Walter Reed says it's transmitted by mosquitoes you know to have observed these things for the first time and to be able to share them they must have thought we've got it all figured out there's nothing more to learn we know about germs we know about how the body works can you imagine how exciting that must have been at that time and certainly in the 20th century we've had so many improvements in vaccinations and the other key thing is we had an improved ability to look at very small things with advancements in especially with microscopy so with the new understanding of the concept of germs and improving technology to look at very small things as well as inspiring practical clinical victories scientists started to look inward and ask questions and one question just very basic what is the mechanism of resistance to infection and disease okay so starting to look inward now and looking at very small things so when they started to look at the blood what did they see they saw blood cells and on this slide I've just got a very simple diagram of the blood cells the stem cell in the top left really divides into two different categories the stem cell in the bone marrow which is essentially a baby cell and it's not yet differentiated hasn't yet decided what it wants to do it can become a lymphocyte which are the cells down here or it can become a myeloid cell which then can become any one of these other cells with the exception of the red blood cell the erythrocyte at the top all of these are called white blood cells and the white blood cells are the cells of immunity okay so we'll be talking about some of these cells over the next few minutes and first we'll be talking about some of the cells up above but before we do that when you look a little bit more closely and now we've got even better microscopes you can see some of the different cells in the blood this one for example is a red blood cell and you can see how it's kind of shaped like a lifesaver that's because it bends it can bend a lot so that it can squeeze through a tiny capillary to deliver oxygen and then go back into the veins so arteries down to these tiny capillaries it bends does what it needs to do and then increases in size but the white blood cells are these kind of furry looking cells here and those are going to be our topic for this evening if you look even closer here is a lymphocyte okay now this is not your grandfather's textbook lymphocyte which was just basically a round circle where we had no idea what it does with this view you can see this guy looks like he's ready for business so I have another question for you where is the immune system so if I were to ask you where is the immune system what would you say everywhere is the correct answer I want you to be a little more precise yeah so a lot of different answers but let's take a just a quick look at some of the main places where the action occurs the lymphatic system is a key system related to immunity and you can see bone marrow here which is very important because this is where the cells are born okay now the thymus right up here is a gland in the chest that is quite large proportionately in children but it shrinks down a lot by the time you hit adulthood and the thymus is key because it trains a lot of the T lymphocytes that we'll be talking about and that's where the T lymphocytes are viewed and the decision is made this lymphocyte should die no this lymphocytes ready for primetime and we're going to send it into the rest of the body for action so the thymus is very important and then you can see there are lymph nodes everywhere but especially where there are entrances easy entrances to the body okay and then the spleen is a very important lymph organ as well there's a lot of activity of the lymph system and the immune system specifically within the spleen that takes place and that's one of the reasons that if you have lymphoma you know some people develop lymphoma and they get a really large spleen it's because when you get uncontrolled replication of those cancer cells they're growing in the spleen and that spleen can become huge I'll never forget when I was an intern just just out of medical school starting on hematology oncology one of my first patients was a gentleman who had a type of lymphoma that grows very quickly and over a period of just a few seconds as I was standing talking to him one morning while he was getting ready for his treatment he was telling me how he was doing how he slept overnight and then he said I don't feel too good and you're trained in medical school that when somebody says that you believe him that's bad when someone says I feel like I'm going to die and that's what he said and at that moment his pay his face went pale and he had ruptured his spleen and he died and so the spleen is a very important organ with respect to the immune system we don't know exactly what the appendix is for we know that we can live without it but it's included in the lymphatic system - all right so now we are going to take a wild ride of some hapless bacteria if I were a germ and I were trying to invade you what would I do where would I go how would I try to do that so we're going to pretend that I'm going to try to infect you and let's just see what the immune system does what the body does to try and get rid of me so I call this or why did your breakfast bagel not kill you because if you think about it we don't sterilize things before we put them in our mouths right all day long we have things with bacteria and viruses but those things don't kill us so how is it that that happens so here we're starting to talk about immunologic strategies now there are multiple routes of exposure that I could choose and there's no doubt that there are specific infections that are peculiar to the actual location where I invade you so for example if I am on the outside of your feet and I am a fungus I can cause a Fleitz foot but there really aren't that many major skin infections that people healthy people get you can live your whole lifetime with no skin infections so what is it really that that keeps us healthy is it an appreciation for fine art well in fact it is and I should say right up front that the immune system likes you to be happy so whatever makes you happy is going to be healthy for your immune system eat well of fresh fruits and vegetables that are full of color they have lots of minerals vitamins that are important in the native food for the immune system the immune system likes regular sleep it likes moderate exercise really all the things that grandma told us to do are good for the immune system so even appreciation of fine art but I think really what Michelangelo was trying to communicate to us here is the importance of the skin as major defense against infection okay now if as bacteria I were lucky enough to actually be able to break your skin I would still have difficulty because right underneath the skin are a whole bunch of parts of the immune system now there are several layers to the skin but what I want you to notice is here where it says blood it also says and lymph vessels here's an artery supplying blood to the skin here's a vein that draws it essentially back and right here in the middle is a lymphatic vessel so the lymphatic system is located wherever organisms can go and so if I'm a mosquito and I can poke you or if I poke myself with a needle when I'm sewing anything that breaches that skin will be recognized by immune cells right underneath the skin action will occur and those lymphatics will be used to drain that information to a lymph node where a lot of stuff starts to happen okay so if I as a germ I'm lucky enough to have direct access to the inside of you which is what's happening here I mean this kid just has it right in his mouth okay then there a bunch of other things that are going to happen to me as a poor hapless germ mucous membranes are very important and I must say that I am very pleased and thankful that I have such good friends that I can walk up and say please open your mouth wide I'm going to take a picture and they say okay and that's what happened here but the point is there are mucous membranes that are full of immune defenses so we produce an average of a liter a day of mucus imagine me is a germ trying to make my way around trying to infect you when I'm swimming in this leader of mucus I mean it doesn't seem like that much but that's about right so just the mucus itself and how sticky it is kind of is preventative but we also have mechanical washing chewing you know you're chewing things around and then expulsion I can cough out or I can sneeze out if I'm lucky enough to actually make it down into the stomach then I'm going to be washed around with hydrochloric acid can you imagine this and then even beyond that there's bacterial competition we have probably 10 to 20 times more organisms bacterial and variety of organisms in and on us then we have cells in our human body we are Muni buses for microbes okay and so beyond even that if we happen to make it there are these cilia which are kind of hairlike projections and the cilia are kind of people movers so as a bacterium or germ I might be on top of one of those and these silly at your entire life very quietly all day long say this way please this way please here's the exit over here quietly calmly they just the cilia are they also have a number of other immunologic properties we won't go into those tonight but we used to think they were just kind of hairs that did things but in fact they're very important part of the immune system the the cilia are in a variety of locations in one very important place are the mucous membranes but especially the lungs so you know how after people have been smoking for years they have a lot of mucus and difficulty clearing the mucus one of the reasons is because that smoking destroys their cilia and they have much greater difficulty moving that mucus out so the cilia are located in really mucous membranes almost all over the body but they're particularly important where we inhale things and where we swallow things okay yes sir well so the bacteria the question is where the bacteria trying to get to and that depends on what you are if you're a bacterium or a virus pair you have a particular predilection so let's say I am a as anybody here had a pneumonia vaccine so a lot of people have had pneumonia vaccine and pneumonia the most common cause of that is a bug called pneumococcus and pneumococcus has a particular predilection for guess what the lungs okay so different kinds of organisms have different sites that they like to infect now you may have heard of an organism called chlamydia but there are different kinds of chlamydia chlamydia can be a genital infection or you can have chlamydia pneumonia chlamydia pneumonia is one of the organisms that causes something called walking pneumonia does that sound familiar yeah so the different bugs all have different places that they like to infect and particular skills as well as we'll see later so I'm sort of talking about a generic germ but you're absolutely right it's a great point that the different organisms are sort of targeting specific tissues and that's one of the reasons why also it's important how they get it get in whether it's through the skin or inhaled or swallowed or maybe with vaginal or even a rectal type of exposures the different exposures sometimes determine the type of infection please keep asking questions like that that's great okay so oh if I've made it that far then I'm wiped out by these these small molecules called defensins and defensins are just these little small molecules that are found all over the body we're just learning about them really in the last 10 to 20 years they do different things in different places and just one example is that if I see that I'm being infected with a germ then one of my white blood cells might have a type of defense and in it that can attach to that germ and then it pokes a hole in it and drains it of all of its essential nutrients how cool is that and that's just one example of what defensins can do but there are a whole lot of other of these small molecules to Catholic ions other enzymes small molecules and toll-like receptors which are also something just in the last 10 20 years that we're learning about and these are sort of the first part of the innate immune system things that happen all the time don't depend on the specific organism necessarily where there's this initial recognition AHA you're a class of this kind of bug and that's important because then it can tell the rest of the immune system maybe this is the signal that we need to think about and how we need to respond so you can see that throughout all of this there are just so many ways that our body is fighting off this poor germ now it gets even worse okay so I want to introduce you to phagocytosis if I've still survived then I'm greeted by somebody who wants to eat me okay so there are professional phagocytes and as we saw before I'm just going to go right forward the professional phagocytes are on this list dendritic cells neutrophils and macrophages and what do these professional phagocytes do if they were to have a slogan I thought it would be recognized ingest and destroy okay they are on a mission so they will ingest me and then they're going to spew all sorts of horrible toxic substances at me so you can see this just gets worse and worse so what I'm going to show you is a professional phagocyte chasing and engulfing bacteria okay and so here we go you can see that poor little bacteria there chase chase chase running around running around other cells and then pretty soon here he's gonna engulf it oh there he goes isn't that cool I mean it's really just awesome but that's what happens every minute of your life and you don't know it because it's just happening it happens automatically it's part of the innate immune system and I wish there were a TV show called prevention okay but there isn't because there are no loud bells that go off there are no Gurney's flying around it just happens and it's beautiful so you can imagine that if you had neutrophils that were not functioning that actually is a kind of primary immune deficiency where people get infections with the kinds of bugs that the neutrophils are supposed to ingest okay so when you see something like this happening it gives you an idea of oh what kinds of things can go wrong and there are genetic types of primary immune deficiencies where neutrophils don't function right in one way or another okay I knew you would like that so this is another one of these professional phagocytes a macrophage and you can see in this picture he's developing I say he I'm so close to these bugs cells where they're developing these pseudo pods where they're kind of reaching out and just looking for troublemakers okay so it's not these just these round static cells that you saw in the old biology textbooks these guys are really busy and looking for troublemakers that are causing infection and here's another one that's really cool too here's a neutrophil engulfing anthrax remember anthrax right after 9/11 very deadly somebody was mailing it to people so in orange is the anthrax and in the yellow is this neutrophil that you can see is actually spreading itself out engulfing the anthrax isn't that just cool so this is one of the many mechanisms this is just one small part of the immune system so that was the neutrophil so we're going to do a brief summary of what we've learned so far and then we're going to refer to this gentleman's questions the innate immune system does all these things that we've been referring to mechanical and physical barriers chemical barriers and antimicrobial peptides those little proteins that are all busy doing things and then you got to compete with billions of other bacteria that just inhabit the system normally and for good measure phagocytosis and then one more thing we're not going to address tonight because next week Tony DeFranco will be talking with you about all this in much greater detail and that's the complement system and that's a really cool part of the immune system that does a bunch of things but one notable thing is it kind of tags bacteria for identification essentially so it goes around tagging these bacteria so the rest of the immune system says aha okay so the complement system is also a very very important part of immunity so you may ask how do the immune cells know where to go right in that film it almost looked like that little bacterium was running for its life didn't it but in fact we don't think that it has legs and runs for its life but the neutrophil does know where to go and this is something that we've just begun also to understand in the last 10 to 20 years and these are substances called chemokines and chemokines are so these the neutrophils of course don't have little eyeballs where they can see things but they almost have little smeller's and chemokines are little molecules that are present where there are invading organisms okay they're kind of like a smell that come out this smell this doesn't belong here and so I've actually got another video for you and what you will see is one of our UCSF researchers who is using his own neutrophil and tempting it with one of these chemokines and here you can see wherever he moves that pipette the neutrophils go in that direction so he's releasing these little sniffers this bad smell that comes from the bacteria essentially you see how it goes right towards the pipette right where he's releasing these little chemicals so that's one main mechanism as to how these immune cells know where to go and and how to sort of chase after those bacteria that's pretty cool too isn't it I knew you guys are going to like this yes ma'am what's the magnification I'm not sure of the exact magnification but it's it's tremendous okay I mean these are very very highly magnified the neutrophil is you have to see it only under a microscope and in this one it's much larger than that so I'm sorry I don't know the exact magnification but I can tell you that this is sped up by seven times okay so this is what you saw there is is actually about seven times faster than it actually occurs in the body okay yes now uh the so the question is how does it how do we clean up or after this mess yes and so that's a great question and so in in general phagocytes after they engulf oh this is if you're obsessive-compulsive you will love phagocytes because the the phagocytes chew these things up and process process them very neatly and then they'll take a piece of one of these little critters and they will take it through the lymph system that I showed you as an example to the lymph node and we'll get to that shortly about how it's processed but in general most of the phagocytes one when they actually ingest the bacteria or whatever it is that they're adjusting the germs they will shoot things at them like nitric oxide type substances and really toxic things that kill it and then they kind of break it up and process it and then the neutrophils of all of the white blood cells the neutrophils have some of the shortest lives then they to die by a natural process that is called a pitocin and I would undoubtedly dr. DeFranco we'll get into that next week but basically what that is is we call it programmed cell death okay so there's death of some of these cells is done in a very neat and tidy fashion okay so there's no actual vacuum cleaner but their vacuum cleaner type actions that are going on here yeah they're all processed and dealt with in a very systematic clean manner okay so to illustrate the principle of chemokines trafficking you can see here that this cell will go in the direction of the greatest concentration of the chemokines so wherever it senses more chemokines that's where that cell is going to go okay so if that's where the bacteria are that's where the chemokines are your neutrophils are going to go right there and just very briefly if for example you're a neutrophil floating around in the bloodstream and somehow I've gotten an infection in my skin or something's invaded my skin there will be a number of chemokines in the tissue in that site and eventually signals are sent that that neutrophil will make its way through the wall of the blood vessel right into the tissue okay and then it follows the chemokines to the site of the infection and then it does its stuff so when you say the immune system is everywhere it you really mean it because these things can go in many many different parts of the body where ever we have tissue essentially yes ma'am well there are chemokines almost there are chemokines almost everywhere and they're chemokines that are actually emitted as well there chemokines that are it's hard to explain exactly but they're chemokines wherever they're a bacteria and the bacteria also give off a variety of other signals that the immune system senses so they might sense they might not know exactly what kind of bacteria you are but they can look at your face and kind of know what class of bacteria you are and then the cells that recognize that start sending out signals okay those can be chemokines yes and that's just one example but there are a lot of others but I'm using the chemokines because it is a very important example and one that we're just learning about in the last 10 20 years okay all right so key makind trafficking is that clear okay so now very briefly let's bridge the innate and the adaptive immune system so the innate immune system is all the things that happened to me a regardless of my identification I come in there's mechanical washing if I'm a big particulate matter I might get coughed out if I make it to the stomach there's hydrochloric acid but that doesn't really make any difference whether I'm a virus or bacteria or whatever my identity is those are things that just happen that are designed to kill miscellaneous invaders but how do we know exactly who this germ is and what do we do about it so if we have some of the skin breached somewhere in this face and this is a super old illustration from the original one of the original Grey's Anatomy textbooks about a hundred years ago and you can see they knew a lot about lymph nodes and where they were but if if I do break the skin if I am as a germ able to get in the phagocyte may or may not pick me up but what will happen is any of this sort of debris that's left over gets drained through one of these through the lymphatic system into one of these lymph nodes and it's there in the lymph nodes that the real business starts to happen okay you ain't seen nothing yet so now we're going to be talking for just a couple minutes about lymphocytes and specifically T and B cell type lymphocytes so when the lymphatics drain into this lymph node which is seen here in cross-section so all the debris and whatever the innate immune system wants to present to the lymphocytes drains into the lymph node and then there are different places in the lymph node where different types of action occur and I'm not going to go into great detail except to say that you have T lymphocytes which are absolutely key to determining the adaptive response so it's T lymphocytes that get communication that says aha I recognize you as this particular invader that specific identification and then there's communication that occurs from there and so with this one when the t-lymphocyte recognizes what's going on the t-lymphocyte is kind of have you have you ever been to London in the the war room where Churchill had his command center and all of the commands go out from there and this is kind of what happens in the lymph node where the T lymphocyte can send out specific directions about what to do now if the T lymphocyte says this is pneumococcal pneumonia potential for that this is a pneumococcal organism we need to make antibodies specifically because it's antibodies that are the best at attacking pneumococcal organisms so the T lymphocyte might give that instruction to the B lymphocyte and one of the ways it does that we've now learned is they essentially attach to each other through receptors I mean physically there's a physical attachment where they're communicating back and forth and so thank you to another one of our faculty I should say that the neutrophil chemotaxis video that I showed you that was a Ryan whiner his video I wanted to give credit where credit is due was also his neutrophil too this one is from Jason's sister and this one shows b-cells attached to t-cells and the B cells are in red the T cells are in green and the T cells are essentially communicating to the b-cells this is he mentioned specifically this is the activity that occurred after this lymph node this individual was vaccinated okay so after the vaccine you can see how the red and green cells some of them are physically attached to each other and that's where the T cells are communicating to the b-cells we need to make antibodies we need to make antibodies okay so there's a very clear signal that's going on that involves multiple steps and processes but that's actually happening in a lymph node it's super cool and then the b-cell will mature and start to make antibodies which will specifically attack pneumococcus again this is an introduction to next week so you can see what you're in for next week yeah so the question is then with respect to the process of the phagocytosis the connection of that with what we're talking about now so the phagocytes the macrophages dendritic cells and neutrophils they all have slightly different mechanisms of doing things but as an example the one that I showed you the macrophage which had the pseudo pods that we're forming when that engulfs something the macrophage will chop it up and then express a little bit of it on its surface it then takes it to someplace where it can communicate with these lymphocytes and then the lymphocyte particularly the T lymphocytes decides what needs to be done about it so yes much of the destruction that's done in the peripheral tissue as the innate immune processes are first trying to do battle up front it's kind of like the Marines or the army at the frontline trying to hold things while decisions are being made about how best to plan the attack so that is communicated into the lymph node and we'll talk about the timeline of all that in just a second into the lymph node and then the lymphocytes make decisions about what to do about that so to reiterate after identifying the invader the lymphocytes generate an immunological response that specifically and maximally targets that pathogen okay so this is the important point about the part of the immune system that knows specifically Who I am is a germ and when that happens watch out okay I'm just toast so importantly they also generate memory cells for future protection and that's important and a principle that you're familiar with with vaccination okay the first time with vaccination the body thinks oh I'm being exposed to measles I better make some antibodies the process that I showed you is similar to that process that occurs okay so you make some antibodies so that the next time the next time that the body actually happens to see it it has a much greater response sorry let me just back up for a step here got ahead of myself for a moment answering the question so lymphocytes can do different things lymphocytes can choose to directly kill infected cells okay so that's called as you can have a cytotoxic response so there can be lymphocytes that just shoot things at it and kill it or a lymphocyte here can choose a helper lymphocyte for example T helper lymphocyte can choose to tell the B cell we need antibodies against that organism and then the B cell produces all of these antibodies that are specific for example to pneumococcus this is really important because most of you probably have somewhere in the order of 1 to 10 billion specific antibodies to different things to which you have been exposed throughout your lifetime ok so that's one of the things that helps us to understand when you're exposed to something why your body just battles it off no big deal we can handle that no big deal I've got antibodies against that okay and these antibodies are what is induced with vaccines okay so yes the B cell that I showed you in that previous picture matures into something called a plasma cell and it just becomes an antibody producing machine that is very specific it matures in that lymphocyte and I know that you'll learn more about this next week but that b-cell matures and it starts it has this signal about what its job is and then after that it just starts producing antibody after antibody specific to that one particular organism okay so what is an antibody let's answer that an antibody you may have turned heard also the term immunoglobulin there they're synonymous it's the same different terms for the same thing it's a large y-shaped protein produced by the B lymphocytes and the antibodies can identify and neutralize the germs and they can do that by several different mechanisms that you'll learn more about next week but the antibodies essentially can glom on to these germs and and also target them for destruction so yes oh what a great question so the question relates to whether people who have gone through treatment for cancer radiation therapy chemotherapy are they able to retain memory and the answer is a qualified that depends and I'm sorry to sort of bow out of it that way but there are different types of treatments and some will affect the immune cells more than others but I can tell you that as an immunologist I am totally amazed by people including a very good friend of mine who had lymphoma and had his immune system wiped out then had an autologous stem cell transplant and just has really not gotten sick you know so I think that that there are parts of the immune system that really are completely wiped out but I think there are things that we still don't appreciate including some of the innate immune defenses that aren't necessarily wiped out so the answer to your question is yes you can impair some long-term effects of the immune system and some you kind of need to reacquire again there is vulnerability but I'm actually kind of amazed that it's not more than than it is why that is I don't know and dr. DeFranco may be able to address that better too the thing I wanted to address very simply on this slide of an antibody here is this right here this is what is specific with every single antibody this is called the variable region and that is exactly what is adapted to a specific germ so every antibody that comes out of a plasma cell is identical okay for a specific germ but this is the part on every antibody that's different okay so your antibodies you'll learn about this more but you'll have I G aig G IgM IgE different kinds of antibodies this part is pretty much always the same but this varies depending on the organism and the immune system has a remarkable way of making this on the spot okay and then remembering it over time to be able to target that specific organism this is just illustrating the concept of learning where to begin with it might take a number of days before you get your first - body response but then I feel sorry for that poor hapless organism if a first cousin or another one like it comes along because the next response is floom because you already have antibodies you're ready you're primed and that's why vaccinations work okay so another important concept how do lymphocytes communicate their orders okay so we know that these T lymphocytes are giving out orders I want you to do this I want you to do that how do they do that one of the mechanisms by which they do that is some chemicals called cytokines and basically I was thinking how do you explain a cytokine and the best way I could think of is it's kind of a text message that induces your friends or your buddies to do specific things so if for example the the germ is tuberculosis then a cytokine will be sent out by the lymphocyte to other specific cells specifically to put out chemicals for tuberculosis okay so cytokines are like text messages that go to other parts of the immune system saying this is how we're going to coordinate the attack so cytokines are absolutely key for communication about how to coordinate the attack very very quick explanation of a complicated principle so if I is a German unfortunate enough to be a parasite then I'm going to be overwhelmed by a number of other cells that we're up on that slide and we're not going to go into that tonight but probably most key for most of the parasites are eosinophils which are amazing cells that can keep these parasites at bay so let's summarize before we get into some of the fun clinical stuff what we've done innate immunity some of the defenses that are there for almost any germ that comes into the body the adaptive immunity and if it's the first time for exposure then it'll take a little while and there's a directed specific response and memory is formed if it's not the first time and the immune system has previous memory there's going to be a very big very fast directed response because the immune system has already seen that memorized it ready and just waiting for you to come along and then none of this would be possible without the help of chemokines and cytokines okay whew yeah so the question is how the lymph system is regenerated after it's been destroyed so within the case of the stem cell transplant and that's exactly the the topic that you'll hear in the six weeks is how does bone marrow and stem cell transplant work but basically what you do is you start all over again you start with new baby cells and you let the cells mature now you don't lose all of your defenses especially those innate defenses but you essentially are starting with baby cells again like I showed you on that slide of all the cells where you had the stem cell up in the very top corner so that those cells just kind of start all over again okay so it's a very intriguing complex process but in some cases it really works well it's not for the faint of heart it's quite a procedure and any of you who have been through it or have family members or friends who've been through it know that it's not for the faint of heart but it can help tremendously where no other things help and that's why I wanted dr. Cohen to come talk with you too because there's so many people who themselves or their friends have been through things like this it's important that you really have a good understanding of that that you take home and devote some time to that okay so just as a general time course of all of this the innate immune system zero to four hours the early induced immune system some of the early recognition sort of a few hours to a few days adaptive immune system generally the first time around is going to take a number of days okay so that's why you want to have really good innate immune responses to hold the fort until your lymphocytes can give directions and address the problem yes the question is regarding colds cold viruses are the sneakiest thing for one there are lots of different cold viruses and so if your body has seen that particular virus before you may not get that cold at all remember how I said that for much of your life you don't even notice when your body battles something off that's the case with a lot of viruses to which we're exposed but if you're exposed to that cold virus for the first time you may not have the immediate defenses to battle it off so there are a lot of cold viruses and the other thing that happens which we talked a little bit more about in a few minutes if you'd like is the sneaky ways that some of these germs have of disguising themselves or looking like somebody else not what the immune system is expecting and many of these viruses kind of change their appearance a little bit so just when the immune system thinks it knows who you are you change your appearance and it says oh I don't know you I can't respond to you that way so you have to respond to it another way so that's one of the sneaky ways that a lot of germs have of getting around the immune system is sort of subverting a lot of these defenses or changing their appearance before the immune system the other problem is there are so many different cold viruses that throughout a lifetime you can be exposed to a lot of different ones so very briefly the concept of tolerance tolerance is hugely important in the immune system so why is it that I don't kill myself all the time how is it that my immune cells know that my cells are me and germs are not me okay so remember I was telling you about the thymus the thymus is what trains the lymphocytes the T lymphocytes in particular and the T lymphocytes go through this sort of testing process it's kind of like they need to show the right papers in order to pass and become a lymphocyte that will be working in the body so a T lymphocytes needs to be able to recognize me okay but it also needs to be able to recognize a foreign invader but I don't want to T lymphocyte to recognize me so much that it sticks to my cells and then starts to destroy me okay so if I have a lymphocyte that's attaching to my cells instead of germs that's a problem that's called autoimmunity okay so if my cells are attaching to me thinking I'm germs I start destroying myself I get autoimmune diseases and you're all familiar with many autoimmune diseases lupus multiple sclerosis most common thyroid problems are a type of autoimmune disease where the body is making antibodies that are attacking the thyroid gland so this concept of tolerance is very important we see it also for in allergies so why is it that dust mite and cat dander for most people are no problem but if you're allergic to it the immune system freaks out the immune system should say uh dust mite cat dander who cares right and just pass it by so you need to be able to have tolerance to be able to focus on the important things and leave the unimportant things alone and also not attack yourself you do not want your own immune cells attacking yourself so that's the concept of Tolerance and again you'll learn more about this next week yes ma'am so the really the question is how does autoimmunity happen and that's a question of great research right now and if you have nothing else to do please become an immunologist and study mechanisms of tolerance but I can give you an example in some of my patients who have primary immune deficiencies where they have parts of the immune system that are not functioning they have either no b-cells at all so they're not making any antibodies at all so for the patient who for example is invaded by pneumococcus that pneumonia bacteria they have almost no adaptive defense against that but those people have also a greater chance of having autoimmune diseases they might have their own antibodies attacking their thyroid gland or their own antibodies attacking some of their blood cells so we don't know exactly why that happens and it's it's a huge topic of research why right now why is it that some people develop cells that attack themselves and why is it that some people are healthy for 45 55 60 years never have any evident autoimmunity and then all of a sudden develop an auto immune disease in the old days it was blamed on God's more recently we've blamed it on viruses it's probably multiple mechanisms but it's an area of very active research and we need all the help we can get so tolerance is an important concept ok now if you were to come see me I would be taking a history from you to find out all of your where you've been where you've lived what kinds of exposures you've had what's your occupation because all of things these things affect your immune system so of course your genetic influences start at conception you're born you're conceived and you have the genes from your parents not much we can do about that yet in most cases but for example if you have two parents if both your parents have allergies say allergies causing asthma allergies causing eczema as a kid you are probably 50 to 70% have a 50 to 70% chance that you will have some type of allergy so there's genetic predisposition to some immunologic disorders we know that prenatal influences so if I have peanut allergy and I am pregnant should I eat peanuts or should I avoid peanuts will that have an influence on my child and that's a great question right now we don't quite know the answer to that because we know that perinatal so around the time of childbirth before and even after childbirth the exposures that that child has are important in helping to shape the immune system in the long term those immune systems and those little kids are just working as fast as they can learning from day one we actually have a little predilection I'm giving you a hint of Homer Boucher's talk here when we're born we actually have a little predilection towards the allergy kind of immunity and we think that exposure to a lot of the viruses and maybe even to the things that we've wiped out like well TB is not wiped out it's still around but most of us are not exposed to TB as youngsters and most of us don't get it as youngsters smallpox some of the things that people got before probably they trained the immune system in a way to respond properly we don't exactly know about that but it's um again something that's being researched right now and key really at the core of this hygiene hypothesis lifetime exposures to microbes we do know that some bugs can lead to some diseases so for example if you have strep throat and your strep throat is not properly treated some people will then develop a couple two three four or five weeks later kidney failure not related to the strep but related to a sort of an aberrant immune response that can occur after that and some of the questions related to autoimmune diseases is rheumatoid arthritis related to an infection so again this is an area of active research birth order if you are a first child you are more likely to have hypersensitivity disorders such as allergies than if you're the fifth kid is this the hygiene hypothesis well think about it if you're the first kid mom and dad are keeping everything clean and everything's in order and there are no germs anywhere but if you're the fifth kid imagine what the place looks like you know there's a dog and a cat feces everywhere and kids spitting all over you you get exposed to so many germs as a fifth kid that there is some evidence that the first kid become maybe because they're so clean is more likely to develop allergies than the fifth kid okay again that's part of this hygiene hypothesis that's going to be a great talk your occupation so if you're if you have a predilection to asthma you may not get it at all in your lifetime unless you're a baker in which case you might be inhaling wheat flour and if you have say grass allergy you might develop asthma to wheat flour okay so your occupation plays a role in how your immune system turns out where you live I have a patient with a severe immune deficiency but he almost never gets pneumococcal pneumonia or any of these other bugs that we pass around because he lives out in the Nevada desert it almost never sees anybody you know so where you live makes a difference I'm going up and down in the elevator all day with twenty people coughing on me you know so I guess I could say my immune system stronger because you know I've had the opportunity to all of these antibodies to things and how to age gracefully and this is a little bit of what we were talking about before how we care for ourselves is very important to the immune system if I get enough sleep if I eat well if I exercise with moderation all things that are good for a healthy immune system okay so the immune system evolves throughout our lifetime examples of things that can go wrong and we'll discuss a couple of these more in a few minutes and talk about some of the things that you would like to discuss so microbes can outsmart the immune system for example many of these viruses are very sneaky rather than being outside like that poor little hapless bacterium that got engulfed by the neutrophil they sneak into a cell they sneak right in there and then they hide and then they use that cells machinery to multiply so that's an example for with HIV HIV is a virus that gets inside the cell and then HIV can replicate okay so viruses many of them are very sneaky trying to bypass many of the immune defenses by getting into a cell and then kind of hiding pretty clever cancers can grow unchecked I talked about this concept of programmed cell death our cells have a normal turnover rate and programmed cell death is a very neat process but if you have an abnormality in programmed cell death and as a cell you don't grow but you keep multiplying multiplying multiplying and you don't get those signals to die properly you can develop cancer okay so some cancers are a particular kind of cell that keeps multiplying multiplying multiplying itself and not dying properly that's a very simplistic explanation but I hope conveys the concept neutral visitors are viewed as foes that's the cat dander dust mite allergy type thing who cares you know why should you have this horrible allergic response to cat dander okay so sometimes the immune system has hyper sensitive responses as opposed to not reacting enough to things or the body attacks itself and that's immune diseases so in summary we've looked at a short history of diseases that have plagued humankind we've looked at based the basics of cells and anatomy of the immune system and principles of things that can go wrong and evolution of the immune system throughout a lifetime and the importance of those influences so at this point what I would like to do is just open it up to case discussions and clinical questions and some fun things that you guys probably think about on a regular basis so questions first and then I know that we're theoretically supposed to go for another half an hour but we'll take some questions and when we're done we'll break yes ma'am so the question is related to the effects of medications on the immune system and that depends entirely on the medication some medications are no problem whatsoever for the immune system some medications can actually cause suppression of certain parts of the immune system so for example prednisone is probably the classic example prednisone kind of suppresses multiple parts of the immune system particularly as pertains to some of the lymphocytes but it can be very very helpful for nasty diseases such as autoimmune diseases and others but because it's non-discriminatory it affects multiple parts of the immune system altogether that's one of the reasons why we've now developed targeted immune therapies that go directly for the source of a particular problem so most medications are probably not a problem for the immune system but some of them certainly are and that's something that your doctor should be able to communicate with you if you're starting on a particular type of medication whether or not it's a problem with the immune system so it's a generic response because it depends entirely on the medication yes yeah so gamma globulin is another term as an example for antibodies and one specific kind of antibody might be the IgG antibody and the IgG antibody member I showed you that y-shaped antibody and the b-cells putting out the antibodies well a hundred years ago it was noted that you could just administer not the blood cells but but the serum the rest of the blood to someone and they would have protection against certain types of diseases and that's because they were getting the benefit of people's antibodies the problem is we now know that if you get somebody else's blood or body tissue into you what happens you reject it okay you reject it so people could get very sick one illness called serum sickness it seemed to work and it would work but then you would get serum sickness which is a kind of a rejection or immunologic process but we do use gamma globulin specifically the IgG antibodies in for example my patients who have a primary immune disease where they don't make any of it so 2530 years ago the most common way to give that was an intramuscular injection but that didn't work too well because it had to be absorbed just right and it was hard to get the right level now for people who have primary immune deficiencies I give them prescriptions for intravenous gamma gamma globulin or we can put it right under the skin and that essentially replaces the immune system that they're missing the antibodies so if you think about it it's great for them because there are blood donors you know how there are some donors who are there every week donating and they might be donating more of the plasma as opposed to just the red blood cells and so these people who receive gamma globulin or intravenous IgG immunoglobulin these terms are all mean the same thing they are actually getting the benefit of many many people's immune systems because there are many people's blood who goes into purifying that IgG and so my patients come to me and they say you know not only have I not had pneumonia for a year but I'm not really getting sick at all everybody else around them is getting sick and these are people who've had recurrent sinusitis pneumonia sinusitis again maybe colds other bad infections that they get but then when they suddenly get the donation of all of these antibodies from other people who've donated them many of them are leading very healthy lives but there's a lot of variation in these immune deficiencies but some people really just don't make antibodies and they do well when they're infused with antibodies and that's a treatment that's well-known well-established and works really well yes sir yes so the question is using radiation treatment for curing cancer so I'm not an oncologist but really what radiation does is radiation is there to destroy those cancerous cells so remember how I mentioned sometimes with cancer the cells are replicating themselves in the same cell over and over and over and that's how you get these big tumors there's no turn off mechanism there's no mechanism that's turning that tumor off so it just grows and grows and grows and radiation is one mechanism by which you can actually kill those tumor cells and so one of the big challenges of radiation therapy is how do you kill the tumor without killing the host and so that's why you try to really target radiation to a specific spot but certainly there can be adverse effects with radiation treatment because it's hard to only get the tumor say inside the breast and not get the tissue that that leads you there also so radiation oncology is a field that has really made tremendous strides in recent past but the principle of it is to try to specifically kill those tumor cells okay yes ma'am okay so the question relates to use of vaccines in people who have autoimmune disease and I think it's really a very good and interesting question I think that vaccinations because they actually use parts of the immune system that are a little bit different than this auto antibody process I don't have a problem with for the most part for patients with autoimmune diseases using vaccination they can still benefit from it a lot and remember that when you get vaccinated you're going to be making antibodies that are just very specifically to that germ okay so that antibody is not going to turn around and start attacking tissue because it's very specifically to that germ now that said it's kind of complicated because sometimes some of our tissues have a slight appearance like the surfaces of some germs and it is possible for antibodies to get confused but when you think about the fact that we probably have 10 billion specific antibodies the few extra antibodies that we get for vaccines probably are not going to be related really to autoimmune diseases now that's actually a good question for the talk that we have on autoimmunity and I'd be interested to hear what he has to say about it as well ok yes yes so the question is what's happening with the body if you have a nasty reaction to something like a tetanus shot so a tetanus shot goes as you know goes into the arm and many of us have reactions to those tetanus shots part of that is your immune system reacting to it so number one before you swear because it you know it hurts which it does that's right you can say well thank you to begin with that I have an immune system that's capable of reacting so you have an immune system that's there that's reacting and that's called a localized response as opposed to the systemic response that you'll get from the vaccine but yes that is an immunologic response and some of us have a more sort of fulminant localized response by parts of the immune system that we were talking about earlier and why that happens we don't know but some people do have very sensitive skin and whatever you do with the skin seems to give a sort of a hyperactive response but that is the immune system reacting so some people say that when they get the flu shot they get the flu what they actually get is they get an immune response and that immune response can manifest with a little bit of fever a little bit of body aches but that's your immune system working it's not influenza influenza is not a live vaccine okay so the question is regarding what causes it when these are there are some people who have no b-cells don't make them or don't make antibodies and I'm glad you asked because that's an area of interest of mine and currently I'm working with a geneticist and an infectious disease doctor here at UCSF and we are asking some of our patients who have this immune deficiency to you donate some blood so that we can do genetic analysis so far we have identified about not we but we in the generic sense others have identified about five to ten percent of the genetic abnormalities that are the reason that some people just make no b-cells and we can measure this in the blood I can do a blood sample just draw a blood sample from you and I can count your b-cells and see if you have them or not and some people just don't make them and there are different types of primary immune deficiencies that will result in loss of b-cell but as you can see they're all different processes that are involved in actually getting to antibodies you know there are many signals that are involved before you actually get production of antibodies so if you have no IDE and two-body in your blood it could be that you're not making b-cells and therefore you're not making antibodies or it could be you've got all sorts of B cells but the B cells aren't functioning right they're there but they're just sitting there doing nothing and if they're doing nothing you're not making antibodies so there are lots of signals and lots of processes to get to that point to make antibodies so you can see how complicated all this is yes and you will hear a little bit more about that with Andy grosses talk his focus is autoimmune disease but the principle is actually the same with some of the cancers and what you want to do is you want to find something in particulars as one mechanism you can find something in particular on the surface of that cancer cell it might have a particular it's let's say the equivalent of a nose you know exactly what that nose looks like and so you can target the immune system to start attacking noses that look like that okay so what you want to be able to do is you want to be able to find something in that cancer cell that you can specifically target so that when you get your immune cells primed it will go exactly to that cancer cell that has that identity because each cancer cell each cancer is its own specific kind of cancer cell and if you can identify something that's peculiar about that then theoretically you can induce immunity to attack that particular cancer okay so yes those those treatments are available now and some of them are in process there's one that many of you have probably heard about we can use this as kind of a case for example some of the b-cell lymphomas where some people have lymphoma where they're making the B cells the B lymphocytes that we talked about but the B lymphocytes one of them has become a cancer cell so it's replicating itself over and over and over and over and so you're getting masses of these tumor cells that are all these being lymphocytes all over the body that's one kind of lymphoma and so just for as a case example there is now a medication called rituximab Rituxan some of you may be familiar with it that specifically targets an identifying marker on the outside of B cells okay so the B cells will have one marker that is a hallmark that says hey I'm a b-cell and rituximab is designed so that it only identifies cells that have that marker so it only kills those B cells okay now you can imagine that that is probably not with completely without other problems because remember you need B cells to be able to make antibodies and so we would like to be able to target just that cancer cell but rituximab targets B cells in general because all the B cells have that marker but as time passes we're starting to come up with medications that will target the specific cancer cells all right okay so let me ask you this question what is pests now that you've heard this whole talk what do you think pests is all about white blood cells phagocytes yes so pus is this process where these phagocytes come in and they chew these things up and then there's a bunch of debris left over okay and that's pus so on the one hand you look at it you say if that's but then you should say oh that's awesome it's okay because your immune system is working now obviously if you have a lot of pus that can be a hallmark of a bad infection but pus can actually be a good thing okay because that means that your phagocytes are working and but you're going to have a lot of debris left it takes the body awhile to clean that up okay so what is inflammation well so one answer is inflammation is swelling and that's actually a correct answer inflammation has swelling because whenever you have an immune reaction like this occurring you need to get blood there and in and you need to get fluid to the site of the tissue where that the immune system has to work that needs fluid and that causes swelling okay so yes that's swelling but in general it's the immune system at work it's an inflammatory response which means that you have white blood cells doing things now inflammation can be good because when you get a sore throat you get inflammation in there right you've got your white blood cells are doing what they need to do but sometimes inflammation can get a little out of hand and you can get inflammation as a consequence of autoimmune disease too inflammation as in arthritis where you get an inflammatory arthritis and you get a lot of immune cells in a joint maybe where they don't belong so inflammation can be good or inflammation can be bad okay so but in general it means that you've got an active immune system so I also wanted to ask you do you want to let's say that you are having some problems with infections and you want to make yourself healthier especially in cold and flu season do you want to take something that calls itself an immune booster this is a loaded question isn't it well especially if you're an autoimmune patient you do not want to take something that's called an an immune booster but you can see how something that's labeled an immune booster is just so simplistic okay you guys have now sat through this discussion of just the basics of the immune system and now you can see how complex it is okay so it's like saying do you want to boost the weather well maybe sometimes if you want more sunshine and it's too cold but you know boosting weather might give you a hurricane so it's just too simplistic and there are things that you do not want boosted in your immune so and one of your take-home messages for tonight is the immune system is all about balance you need to have things balanced you need to have enough of this and not too much of that and you need to have these things working in concert with each other if you have way too much of some of the immunoglobulins or antibodies that are IgE antibodies then you may have lots of problems with allergies do you want to boost that so this is one of the things that one of the reasons that I took this job was to be able to communicate concepts such as that that the immune system is very complex it's all about balance and when people are trying to sell you products you just have to be careful about what the claims are they may or may not be good for you okay so how about tonsils if a little kid has tonsils child this big has these big tonsils is that good or bad so you think it's good and for the most part it is because those tonsils are what they are working lymph nodes okay so there is an awful lot of B cell B lymphocyte activity occurring in tonsils and the normal role is for those B cells to be working away in those little kids developing memory fighting off germs they're working hard so yes we can live without tonsils and tonsils can be problematic if they're too big they can get inflamed there's that word and you can get pus there's that word and sometimes rarely they have to be taken out but actually the presence of tonsils in a very small child tells us that that child has an immune system okay so if I have an infant with no tonsils that's one of the hallmarks of an infant with a primary immune deficiency okay because we expect them to have lots of B lymphocytes in tonsils and then as you grow older they start to fade because our immune systems are more mature now here's another good question for you that's related to a woman who delivers and she has a normal childbirth and the child is healthy and I want to know from you why is that child who's never been exposed to the world why does that child really for the most most kids will stay healthy even in those first six months of life when they have no immune experience how does that happen oh you guys are so smart so mom passes some of those IgG antibodies in particular through the placenta to the kid and those IgG antibodies are going to last for maybe six to eight months or so so that kid has got a lot of protection from a mature immune system six to eight months but then it starts to wear off and that kid is in kind of a vulnerable period where the child has not yet really developed a lot of immune defenses and mom's antibodies are wearing off so sometimes we see kids right in that six to eight month period that present with their first bad infections and that's a time when we often identify primary immune deficiencies because that child might be protected if the main problem is no antibodies might be protected until he or she is six to eight months old okay so infants gain protective immune function from their mothers and that's pretty awesome - yes ma'am so the question really is to inheritance it depends on the kind of immune deficiency some of them have very clear inheritance patterns some of them do not so for example with the many of the patients who lack the antibodies or immunoglobulins especially if we first identify them as adults and the oldest patient I've identified with the primary immune deficiency was 92 okay and she was just not happy because she was getting these recurrent infections colds and flus she had had pneumonia a bunch of times and so we talked about it turned out that her immune system and it's hard to tell sometimes because by that age sometimes a lot of the normal immune function that we test isn't working quite so well but she clearly had an immune deficiency and had always been the sick person her whole life so when we discussed the option of possibly her using immunoglobulin as we were talking about before either intravenously or infused through the skin which has to be done once a week if it's infused through the skin she just didn't know about that it was going to interfere with her social life you know she just I don't know two or three extra hours a week to get that treatment but once she got on it she was very happy she did because she was much healthier and she's a very vibrant woman who's now I think she just turned 95 and she's very active very vibrant and just a delightful lady so the answer is some of these immune deficiencies are inherited and some of them seem to occur sporadically and that's why we're trying to understand what is it that you know how many of these are sporadic and can we identify ahead of time who is going to develop that problem yes ma'am well that's the nursing does give you some passive protection but it's not like antibodies going right through the placenta so yes you can get some protection through nursing and that's one of the reasons why you know why nursing is a very good idea but it's not going to be like the antibodies that come through the placenta that provide really very specific protection especially the first six to eight months yes yes ma'am I knew probiotics would come up tonight yeah yes yeah yeah so that's a great question because a lot of people do take these organisms so called friendly bacteria so when do you need it well we are loaded as I mentioned before we are just loaded with different types of organisms and most of those organisms do have a role and do have a function in the health of our bodies and dr. Boucher will be talking that's one of his favorite topics he loves that topic so he'll be going into that in some detail but yes there are some times when our normal bacteria get out of balance and so although I think many of the people who take probiotics probably don't really need them in general if they're taken in a conservative fashion they're probably not going to be harmful the challenge is is that we have many many different kinds of bacteria in our gut and what you buy over-the-counter is likely just to be one or three or four or five different kind and we don't know exactly how what they do differs from what's normally in the gut so there are some circumstances for example if you're taking an antibiotic that's a broad-spectrum antibiotic and you're prone to yeast infections you might be someone who benefits from at the same time supplementing with normal bacteria now will that interfere with the with the antibiotic and there are some things that we don't know but yes in some cases where the normal gut flora has been interfered with either because of a disease process for example Crohn disease which is a kind of autoimmune inflammatory bowel disease some people who have that have gut flora that doesn't function quite right and there may be some other things such as those little defense and molecules I was showing you that don't work right we're just in our infancy of learning about these things but for some people it may be appropriate to take probiotics to try to restore normal gut flora exactly who should get it we don't quite know yet there are a lot of clinical trials going on for example for eczema atopic dermatitis allergic disorders so far they've not been all that exciting but if it works hey I'm all for it we just need to know if it does work and then how does it work we need to figure it out so yes in some cases it may be appropriate yes a winner antibiotics called for so in an optimal situation you would want to have antibiotics when whatever the germ is is getting out of hand and your own immune system cannot handle it so for example if you have invasion into tissue like with pneumonia where that germ is not held just in the bloodstream or not just it's superficially but somehow it's been able to invade and actually set up shop in tissue sometimes you actually need antibiotics to battle that off the antibiotics go in the bloodstream and then they can go directly to the site of the infection and can really help to kill those germs directly so in the right situation antibiotics are really really helpful and obviously save lives the challenge is not giving antibiotics when they're not needed so for example cold viruses that we were talking about before antibiotics don't help cold viruses but when you have a patient who comes into the office and says I'm so sick and I really need an antibiotic you have to kind of decide on the spot is this a viral infection is this a bacterial infection is there any evidence of pneumonia or more severe infection that would require antibiotics and so sometimes it's pretty obvious and other times it's a judgment call so in the optimal situation you want to reserve the antibiotics for a situation where the where the infection has a threat of getting worse and potentially even killing you and pneumonia would be one example of that kind of situation yeah prophylactic benefits of antibiotics it depends on the disease condition sometimes for example if we know you've been exposed to something that could be really nasty for you and kill you it might be appropriate to use prophylactic antibiotics so it's totally dependent on the specific condition so and I'm happy to answer any more specific questions that I can afterwards but thank you all so much and I look forward to seeing you next week

Channel: University of California Television (UCTV)

Views: 331,286

Rating: 4.7694182 out of 5

Keywords: immune system, health, immunology, allergy

Id: _oI0jVN4TTI

Length: 88min 41sec (5321 seconds)

Published: Thu Jun 02 2011