Fundamentals I: 10:00-11:00 Scribe: Joan-Marie Manolakis
Monday October 20, 2008
Dr. Barnum Auditory
Class Monday October 20, 2008
Basic Concepts of Immunology
Slide 1: Introduction
-My name is Scott Barnum. I’ll help you out with any of the immunology.
-Reaching him by email is best, and his email address is and phone: 4-4972.
-He’s happy to meet with anyone to help in any way.
-This morning is a broad overview of immunology, giving the basics and introduction.
-If you haven’t bought the textbook and you’ve never had immunology in the past, I suggest you buy it because it’ll be a good resource that’ll be useful for a lot of classes.
-If you have a book from a previous course, then it should be fine.
-It may help piece some of the topics a little better.
-The big question is, “Why should you study immunology at all?”
-Immunology is important for a lot of reasons for your future as a clinician. You need to know at least some of the major players, how it works in order to treat these individuals, and also to safeguard yourself and the people that work for you.
Slide 2: Immunology is important to you as a future clinician because:
-Most people will come see you because they are having problems with their immune system. Either it’s failed to cope with an infection or trauma that’s occurred, like the little kid that gets his tooth knocked out, his eye poked out or has an infection, gum infections, etc.
-Cavities are basically a bacterial infection in the tooth, so all those components, or all the reasons you see that individual, is because of an immune response. For example, inflammation, trauma, and potential infection of the immune system can’t handle that. You need to understand some of the mechanisms of what is going on in those given settings so that you can treat them.
-When someone says that he/she is immuno-compromised and you have to treat me accordingly, you don’t want to have to say that you don’t know what he/she is talking about. So, you need to be able to understand some of that.
-The immunological status of your patient determines how you treat your patient. For example, if the patient is on chemotherapy and their immune system is wiped out, then they are extremely susceptible to infection. You have to figure out how to treat an individual and that given setting so that you don’t infect them and cause problems.
-You’ll also have patients that have allergies. If you forget to ask and you prescribe penicillin for an infection, they will go and fill it not knowing. Then you get a call and the patient’s in the ER with a massive allergic reaction to penicillin.
-Thus, you must understand the underlying mechanism behind these events in order to treat patients properly.
-You also need to protect yourself and staff because people will come into the office sick. Again, you need to be able to protect yourself and staff so that your office doesn’t become a fantastic place for your patients to get sick.
-You don’t want to be known as Dr. Infection as you try to start your practice.
Slide 3: Immune System Components
-There are a handful of you that haven’t ever had immunology before, so I’ll give you a basic idea.
-It’s an old term from the latin word immunitas, meaning exempt. It originally applied to politicians so that they’d be exempt from being tried. That definition still holds.
-Over time, it came to mean individuals that were exempt from being sick. In old times an infection used to wipe out entire towns, and there’d always be someone who didn’t get sick. So, they were considered immune from that infection. Some of them gained great status because they had special powers.
-Immunology is basically the study of the cellular and molecular events that occur in response to invading pathogens.
-Does it always target invading pathogens? No. Sometimes it targets your own tissues, and then you have autoimmunity.
-Individuals who have autoimmune disease know the full power of the immune system, and it can be extremely destructive because they’ll lose their pancreas, kidney, thyroid, etc., because it will wipe them out when improperly directed.
-Autoimmune diseases are a major focus of study when dealing with immunology.
-You’ll have a lot of lectures on the components of the immune system.
-It can be broken down into a number of different parts: cells and organs. One of the primary organs that you’ll learn about in another lecture is the thymus. It’s a small organ that sits near the throat; it’s the source of T cells and is involved in immune response.
-The spleen is major for filtering immune complexes and sits right next to the liver.
-Lymphnodes are scattered throughout and gather antigens (invading bacteria/viruses) wherever they’ve entered the host and get them in contact with the right type of cell (T cells, B cells, and antigen presenting cells). Then you can mount a very specific immune response to that invading pathogen. You’ll hear much more about them.
-All of the cells involved in immune response come from pleurypotent stem cells that are self renewing. If you end up with cancer and they have to wipe out all of your immune system, they can take out stem cells, wipe out the immune system and then basically give you a new immune system by putting the stem cells back in. They’ll divide and turn into all the different types of cells. Then you’ll hopefully have a fully functional immune system.
-There are a number of different progenitor cells that give rise to all the different cell types.
-T and B cells are involved in adaptive immunity. They’re critical for specific immune response.
-Macrophages and neutrophils are part of the innate immune response. Their job is to eat and kill whatever doesn’t belong there. So, they gobble up bacteria, viruses, and whatever else they encounter.
-Dendritic cells are found in lymphnodes, the spleen and other tissues in the body that are involved in antigen-presentation (APC’s)àYou’ll have some lectures that cover this topic. There are APC’s.
-Dendritic cells (DC’s) are important antigen presenting cells. Macrophages can also serve as antigen presenting cells, and B cells (though they’re the source of antibodies in immune response) also serve as antigen producing cells. Other cells can be when they’re induced, but these are the important ones.
-Mast cells are important in hypersensitivity types of reactions. It’s the mast cells that give those of you with allergies a fit.
-There are a few other types that you’ll hear about as you go along, but these are some of the most important players.
-The other system that I didn’t put up there is the bone marrow.
-T cells come from the thymus, and B cells come from the bone marrow, but lots of other cells types come from bone marrow (macrophages, dendritic cells, neutrophils, etc.)
- It’s a major source of cells involved in immune responses.
-Humoral/Soluble components: The most predominate known is antibody. There are many types or isotypes of antibody. You’ll have a lecture on their generation.
-Cytokines are one of the most important components. The number of them is about 100 or so, including chemokynes.
-These are small molecules that are critical for sending signals for development of different lymphoid lineages, all the different leukocyte lineages, cells involved in activation of T cells and B cells, and other types that participate in immune responses. They all get their signals from cytokines.
-The complement system is part of the innate immune response. It is critical for killing invading pathogens and actually punching holes in them by a protein complex called a MAC.
-They target invading pathogens by covalently attaching proteins to the surface of that pathogen so that they can be taken up by macrophils or nuetrophils. It also produces small molecules that are important in inflammation, and a number of the acute phase proteins also do this. They basically rev up the body to eliminate invading pathogens by making more cytokines by changing the number of cells that are produced, like macrophages and neutrophils, to get their numbers to go up. All of this is done to help eliminate invading pathogens and turn on the immune response.
-There are lots of different enzymes, and some are found free floating in serum or at sites of tissues, and others are inside the cells (like macrophages and nuetrophils) that have these vesicles inside so once they’ve engulfed the bacterium, for example, they have every class of enzyme to chew up proteins, lipids, DNA, etc. to almost nothing.
-The body produces its own antibiotics, defensins (produced by a number of cells in the body), and some are bacteria static and prevent it from growing. You won’t hear too much about those, but they come into play in a variety of settings and cell types.
-That’s an overview of the major components of the system.
-I mentioned this term innate and adaptive immunity.
-The immune system has been broadly classified into innate and adaptive immunity. There have been discussions about relative importance of one part of the immune system when you classify them this way.
-Both of these parts of the immune system are interrelated, and you can’t have a great immune response without both of them.
-If you’re missing components that are part of the innate immune system, like the complement system, you’re going to have serious immuno-deficiency. If you’re missing T cells or B cells you might still have a fully intact innate immune system, but you’ll be seriously immuno-compromised.
-Both of these arms are necessary in mounting good efficient immune responses to eliminate invading pathogens. They work together to do so.
-The innate immune system is responsible for early elimination of pathogens. It’s also important in antigen presentation so that pathogens can be presented to T cells to mount a good response. So, this response is a little later in eliminating pathogens.
-We’ll talk about that a little later.
Slide 4: Innate Versus Adaptive Immunity
-Are you using adaptive interchangeably for acquired? Yes, we’ll talk about the goofy nomenclature later.
-This slide breaks down the components of the innate and adaptive immune responses.
-If you get a cut, the innate immune system will be at work immediately because once it’s cut, you’ve torn open vessels and activated cells in the immediate side of the cut like mast cells. Mast cells will be activated and cytokines will be activated. Immediately the innate immune system will try to eliminate that pathogen. If it can do so efficiently because there’s not a lot of bacteria, you might not need the adaptive immune response engaged under those circumstances, but that doesn’t always happen.
-The adaptive immune response takes days because it’s extremely specific. The innate immune response will go after whatever it finds and it doesn’t care what it’s going after. The adaptive is very specific in what it targets. You have to get whatever invaded you in contact with the specific B or T cell immediately.
-If you have cut on your wrist, for example, and the T cell that was specific for that invading pathogen is in the lymphnode in the back of your left leg, it’ll take time for the two hook up. You don’t have a million T cells specific for everything you come in contact with. You might have hundred. It takes time to get the two together to mount a specific immune response. It takes longer to do that.
-The innate immune response is specific for molecular patterns, aka PAMPS (Pathogen Associated Molecular Patterns).
-These are things like lipopolysaccharides, cell wall materials, peptidoglycans, single and double stranded RNA, etc.
-It allows the innate immune system with a few receptors to recognize millions of different pathogens based on these common structures in bacteria, yeast and other pathogens that might invade.
-The adaptive immune response is extremely specific. The adaptive immune response can discriminate between molecules that are very subtly different. Just the shift of an amino group can yield antibodies that recognize one structure and not the other. It is extremely specific in what it recognizes.
-In the innate immune response there isn’t much diversity. The diversity lies in the receptors that recognize these PAMPS. There’s not a lot of these receptors, maybe 20 or 30, that will allow you to recognize lots of bacteria and viruses.
-The adaptive immune response you have a highly diverse repertoire. At any given moment your body is churning out millions of T cells and B cells, all of which have a single specificity for a single invading pathogen. You have a massive diversity that’ll allow you to recognize anywhere up to 10^8 or 10^9 different microorganisms. The adaptive immune response has clones for everyone. It allows you to eliminate them very efficiently.
-Innate immune responses have no memory so the next time you encounter the same thing it’ll respond with the same vigor as the first time around because there isn’t any memory component or cells there.
-Adaptive immune response has persistent memory. If you develop a good antibody response to an invading pathogen, you make a lot of B cells that will produce that antibody and they’ll go hide in the bone marrow and continue to chunk out antibodies for years after that. You’ll have memory B and T cells. There will be great numbers of them compared to before you encountered the pathogen, so the next time you encounter it’s much faster response than before (a few days instead of a week or two).
-This is a point that sometimes gets a little tricky: self vs. nonself immune responses