The Immune System ✔Inside your body there is an amazing protection mechanism called the immune system. ✔ It is designed to defend you against millions of bacteria, microbes, viruses, toxins and parasites that would love to invade your body. To understand the power of the immune system, all that you have to do is look at what happens to anything once it dies. That sounds gross, but it does show you something very important about your immune system. ✔When something dies, its immune system (along with everything else) shuts down. In a matter of hours, the body is invaded by all sorts of bacteria, microbes, parasites... None of these things are able to get in when your immune system is working, but the moment your immune system stops the door is wide open. ✔Once you die it only takes a few weeks for these organisms to completely dismantle your body and carry it away, until all that's left is a skeleton. Obviously your immune system is doing something amazing to keep all of that dismantling from happening when you are alive. ➢ The immune system is complex, intricate and interesting ➢ And there are at least two good reasons for you to know more about it. ➢First, it is just plain fascinating to understand where things like fevers, hives, inflammation, etc., come from when they happen inside your own body. ➢You also hear a lot about the immune system in the news as new parts of it are understood and new drugs come on the market --knowing about the immune system makes these news stories understandable. ➢In this session, we will take a look at how your immune system works so that you can understand what it is doing for you each day, as well as what it is not. Seeing your Immune System Your immune system works around the clock in thousands of different ways, but it does its work largely unnoticed. One thing that causes us to really notice our immune system is when it fails for some reason. We also notice it when it does something that has a side effect we can see or feel. Here are several examples: ● When you get a cut, all sorts of bacteria and ··viruses enter your body through the break in the skin. When you get a splinter you also have the sliver of wood as a foreign object inside your body. Your immune system responds and eliminates the invaders while the skin heals itself and seals the puncture. In rare cases the immune system misses something and the cut gets infected. It gets inflamed and will often fill with pus. Inflammation and pus are both side-effects of the immune system doing its job. ● When a ··mosquito bites you, you get a red, itchy bump. That too is a visible sign of your immune system at work. ● Each day you inhale thousands of germs (bacteria and viruses) that are floating in the air. Your immune system deals with all of them without a problem. Occasionally a germ gets past the immune system and you catch a cold, get the flu or worse. A cold or flu is a visible sign that your immune system failed to stop the germ. The fact that you get over the cold or flu is a visible sign that your immune system was able to eliminate the invader after learning about it. If your immune system did nothing, you would never get over a cold or anything else. ✔ Each day you inhale thousands of germs (bacteria and viruses) that are floating in the air. Your immune system deals with all of them without a problem. Occasionally a germ gets past the immune system and you catch a cold, get the flu or worse A cold or flu is a visible sign that your immune system failed to stop the germ. The fact that you get over the cold or flu is a visible sign that your immune system was able to eliminate the invader after learning about it. If your immune system did nothing, you would never get over a cold or anything else. ✔ Each day you also eat hundreds of germs, and again most of these die in the saliva or the acid of the stomach. Occasionally, however, one gets through and causes food poisoning. There is normally a very visible effect of this breach of the immune system: vomiting and diarrhea are two of the most common symptoms. ✔ Finally, we sometimes see the immune system because it prevents us from doing things that would be otherwise beneficial. For example, organ transplants are much harder than they should be because the immune system often rejects the transplanted organ. The immune system protects organisms from infection with layered defenses of increasing specificity. Most simply, physical barriers prevent pathogens such as bacteria and viruses from entering the organism. If a pathogen breaches these barriers, the innate immune system provides an immediate, but non-specific response. Innate immune systems are found in all plants and animals. However, if pathogens successfully evade the innate response, vertebrates possess a third layer of protection, the adaptive immune system, which is activated by the innate response. Here, the immune system adapts its response during an infection to improve its recognition of the pathogen. This improved response is then retained after the pathogen has been eliminated, in the form of an immunological memory, and allows the adaptive immune system to mount faster and stronger attacks each time this pathogen is encountered.Innate Immune System Adaptive Immune System Response is non-specific Pathogen and antigen specific response Exposure leads to immediate maximal response Lag time between exposure and maximal response Cell-mediated and humoral components Cell-mediated and humoral components No immunological memory Exposure leads to immunological memory Found in nearly all forms of life Found only in jawed vertebrates✔ Both innate and adaptive immunity depend on the ability of the immune system to distinguish between self and non-self molecules. ✔ In immunology, self molecules are those components of an organism's body that can be distinguished from foreign substances by the immune system. ✔ Conversely, non-self molecules are those recognized as foreign molecules. ✔ One class of non-self molecules are called antigens (short for antibody generators) and are defined as substances that bind to specific immune receptors and elicit an immune response. ✔The body’s immune defenses normally coexist peacefully with cells that carry distinctive “self” marker molecules. But when immune defenders encounter cells or organisms carrying markers that say “foreign,” they quickly launch an attack. ✔In abnormal situations, the immune system can mistake self for nonself and launch an attack against the body’s own cells or tissues. The result is called an autoimmune disease. Some forms of arthritis and diabetes are autoimmune diseases. ✔ In other cases, the immune system responds to a seemingly harmless foreign substance such as ragweed pollen. The result is allergy, and this kind of antigen is called an allergen. Structure of the Immune System ✔The organs of the immune system are positioned throughout the body. They are called lymphoid organs because they are home to lymphocytes, small white blood cells that are the key players in the immune system. ✔ Bone marrow, the soft tissue in the hollow center of bones, is the ultimate source of all blood cells, including white blood cells destined to become immune cells. The thymus is an organ that lies behind the breastbone; lymphocytes known as T lymphocytes, or just “T cells,” mature in the thymus. ✔ Lymphocytes can travel throughout the body using the blood vessels. ✔The cells can also travel through a system of lymphatic vessels that closely parallels the body’s veins and arteries. Cells and fluids are exchanged between blood and lymphatic vessels, enabling the lymphatic system to monitor the body for invading microbes. The lymphatic vessels carry lymph, a clear fluid that bathes the body’s tissues. ● The spleen is a flattened organ at the upper left of the abdomen. Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and work, and serves as a meeting ground where immune defenses confront antigens. ● Clumps of lymphoid tissue are found in many parts of the body, especially in the linings of the digestive tract and the airways and lungs—territories that serve as gateways to the body. These tissues include the tonsils, adenoids, and appendix. ● B cells and T cells are the main types of lymphocytes. ● B cells work chiefly by secreting substances called antibodies into the body’s fluids. ● Antibodies ambush antigens circulating the bloodstream. They are powerless, however, to penetrate cells. The job of attacking target cells—either cells that have been infected by viruses or cells that have been distorted by cancer—is left to T cells or other immune cells (described below). ● B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response. ● Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a “non-self” target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and presented in combination with a “self” receptor called a major histocompatibility complex (MHC) molecule. ●There are two major subtypes of T cells: the killer T cell and the helper T cell. ●Killer T cells only recognize antigens coupled to Class I MHC molecules, while helper T cells only recognize antigens coupled to Class II MHC molecules. These two mechanisms of antigen presentation reflect the different roles of the two types of T cell. ● A third, minor subtype are the γδ T cells that recognize intact antigens that are not bound to MHC receptors.[41] ● In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface, and recognizes whole pathogens without any need for antigen processing. ● Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture.● Humoral Response (Cont...)Cell Mediated●Each B cell is programmed to make one specific antibody. For example, one B cell will make an antibody that blocks a virus that causes the common cold, while another produces an antibody that attacks a bacterium that causes pneumonia. ●When a B cell encounters its triggering antigen, it gives rise to many large cells known as plasma cells. Every plasma cell is essentially a factory for producing an antibody. Each of the plasma cells descended from a given B cell manufactures millions of identical antibody molecules and pours them into the bloodstream. ●Antibodies belong to a family of large molecules known as immunoglobulins. Different typnties play different roles in the immune defense strategy. ●Immunoglobulin G, or IgG, works efficiently to coat microbes, speeding their uptake by other cells in the immune system. ●IgM is very effective at killing bacteria. ● IgA concentrates in body fluids—tears, saliva, the secretions of the respiratory trac t and the dig e stiv e trac t—g uarding the e ntranc e s to th e b o dy. ● IgE, whose natural job probably is to protect against parasitic infections, is the villain responsible for the symptoms of allergy. ● IgD remains attached to B cells and plays a key role in initiating early B-cell response. C ytokine s ● Components of the immune system communicate with one another by exchanging chemical messengers called cytokines. These proteins are secreted by cells and act on other cells to coordinate an appropriate immune response. ●Cytokines include a diverse assortment of interleukins, interferons, and growth factors. ● Some cytokines are chemical switches that turn certain immune cell types on and off. ● One cytokine, interleukin 2 (IL-2), triggers the immune system to produce T cells. IL-2’s immunity-boosting properties have traditionally made it a promising treatment for several illnesses. ●Clinical studies are ongoing to test its benefits in other diseases such as cancer, hepatitis C, and HIV infection and AIDS. Other cytokines also are being studied for their potential clinical benefit. ●Other cytokines chemically attract specific cell types. These so-called chemokines are released by cells at a site of injury or infection and call other immune cells to the region to help repair the damage or fight off the invader. Chemokines often play a key role in inflammation and are a promising target for new drugs to help regulate immune responses. Phagocytes and Their Relatives ● Phagocytes are large white cells that can swallow and digest microbes and other foreign particles. ●Monocytes are phagocytes that circulate in the blood. When monocytes migrate into tissues, they develop into macrophages. Specialized types of macrophages can be found in many organs, including lungs, kidneys, brain, and liver. ● Macrophages play many roles. As scavengers, they rid the body of wornout cells and other debris. They display bits of foreign antigen in a way that draws the attention of matching lymphocytes. And they churn out an amazing variety of powerful chemical signals, known as monokines, which are vital to the immune responses. ●Granulocytes are another kind of immune cell. They contain granules filled with potent chemicals, which allow the granulocytes to destroy microorganisms. Some of these chemicals, such as histamine, also contribute to inflammation and allergy. ● One type of granulocyte, the neutrophil, is also a phagocyte; it uses its prepackaged chemicals to break down the microbes it ingests. ● Eosinophils and basophils are granulocytes that “degranulate,” spraying their chemicals onto harmful cells or microbes nearby. ● The mast cell is a twin of the basophil, except that it is not a blood cell. Rather, it is found in the lungs, skin, tongue, and linings of the nose and intestinal tract, where it is responsible for the symptoms of allergy. ● A related structure, the blood platelet, is a cell fragment. ●Platelets, too, contain granules. In addition to promoting blood clotting and wound repair, platelets activate some of the immune defenses. Complement ● The complement system is made up of about 25 proteins that work together to “complement” the action of antibodies in destroying bacteria. ● Complement also helps to rid the body of antibody-coated antigens (antigenantibody complexes). ● Complement proteins, which cause blood vessels to become dilated and then leaky, contribute to the redness, warmth, swelling, pain, and loss of function that characterize an inflammatory response. ●Complement proteins circulate in the blood in an inactive form. When the first protein in the complement series is activated— typically by antibody that has locked onto an antigen—it sets in motion a domino effect. Each component takes its turn in a precise chain of steps known as the complement cascade. ●The end product is a cylinder inserted into—and puncturing a hole in—the cell’s wall. With fluids and molecules flowing in and out, the cell swells and bursts. Other components of the complement system make bacteria more susceptible to phagocytosis or beckon other cells to the area. Mounting an Immune Response ● Infections are the most common cause of human disease. ●They range from the common cold to debilitating conditions like chronic hepatitis to life-threatening diseases such as AIDS. ●Disease-causing microbes (pathogens) attempting to get into the body must first move past the body’s external armor, usually the skin or cells lining the body’s internal passageways. ●The skin provides an imposing barrier to invading microbes. It is generally penetrable only through cuts or tiny abrasions. ●The digestive and respiratory tracts—both portals of entry for a number of microbes—also have their own levels of protection. ●Microbes entering the nose often cause the nasal surfaces to secrete more protective mucus, and attempts to enter the nose or lungs can trigger a sneeze or cough reflex to force microbial invaders out of the respiratory passageways. ● If microbes survive the body’s front-line defenses, they still have to find a way through the walls of the digestive, respiratory, or urogenital passageways to the underlying cells. ● These passageways are lined with tightly packed epithelial cells covered in a layer of mucus, effectively blocking the transport of many organisms. ●Mucosal surfaces also secrete a special class of antibody called IgA, which in many cases is the first type of antibody to encounter an invading microbe. ● Underneath the epithelial layer a number of cells, including macrophages, B cells, and T cells, lie in wait for any germ that might bypass the barriers at the surface. ●Next, invaders must escape a series of general defenses, which are ready to attack, without regard for specific antigen markers. These include patrolling phagocytes, NK cells, and complement.