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Cell-Mediated Immune Response Dr. Shaffer A&P II page 1 More immunity stuff: We’ve learned what antibodies are. But I’m sure you’ve heard of monoclonal antibodies. What are they? They’re really just antibodies in the way we’ve learned them. In real life, if you injected a lab animal, let’s say, a mouse, with some antigen, it would produce antibodies. These antibodies would most likely be polyclonal antibodies because the antigen, like many antigens, could have multiple antigenic determinants – each one triggering clonal selections and differentiation of a particular B-cell. Each of those B-cells would make antibodies, and the antibodies circulating in the mouse’s blood would be polyclonal that is, they would result from multiple different clones. Well, back in the seventies it was learned that if you take a B-cell of the type you are interested in and fuse it with a tumor cell, you’ll get lots and lots of those B-cells. (Tumor cells divide and divide like crazy). These hybrid cells grown in culture will produce loads of just one antibody – a monoclonal antibody. So what good are they? We’ve learned that almost anything can be an antigen, right? Usually antigens are proteins, but not always. Let’s consider just one example of the use of monoclonal antibodies. Human Chorionic Gonadotropin (hCG) is a hormone that is found in the urine of pregnant women. Monoclonal antibodies are made that bind to hCG, then they are chemically modified so that they have an indicator dye marker attached. Now, embed some of these modified antibodies on a piece of paper and, viola you’ve got a little piece of paper that can tell you if you’re pregnant. Monoclonal antibodies can be used to identify bacteria, identify blood groups, and even treat cancer. What about those T-cells we’ve heard about . . . You’ve got two main types of T-cells: Helper T-cells and Cytotoxic T-cells. Cytotoxic T-cells destroy cells – more on those soon. Helper T-cells do a lot of things for your immune response. Both types are incapable of reacting to “free antigens” like the B-cells do. Helper T-cells are activated when they interact with self-nonself complexes on the surface of a cell. The complexes can be found on the surface of an infected cell or an antigen presenting cell such as a macrophage. Once activated the helper T-cell will proliferate, and as with B-cells, the helper T-cell that proliferates is the one with just the unique match to the self-nonself complex. Helper T-cells help the immune system in a number of ways, mostly by secreting stimulatory proteins (example: interleukin-2). These proteins act on the T-cell itself stimulating even more division (leaving behind some memory cells in the process). These proteins can affect B-cells, helping to activate them, and they stimulate cytotoxic T-cells. Cytotoxic T-cells destroy infected body cells. Activated cytotoxic T-cells identify the infected cells by the same self-nonself combination that we saw with the helper T-cells. They bind to the infected cell and release chemicals (example: perforin) that destroy the membrane of the infected cell. Injection of some other chemicals through those holes in the membrane results in death of the infected cell. Cell-Mediated Immune Response Dr. Shaffer A&P II page 2 As I’ve stated, T-cells don’t recognize “free” antigens. They only recognize and respond to processed protein fragments on our body’s own cells. In this way they are able to defend us against corrupted cells. MHC proteins are displayed on the outside of cell. T-Cells look for two things on the outside of the cell, self and non-self, before they act. a. MHC proteins are like the cell’s finger prints. 1. They are unique to a individual 2. There are two types b. Class I MHC proteins are made by most nucleated cells. Synthesized in the cell, they have a peptide fragment (8-9 Amino Acids long) 1. fragment may be bits of cellular protein (self) 2. may also have endogenous antigens c. Class II MHC proteins are found on APCs (antigen presenting cells). Macrophages, Langerhann’s cells as well as B-cells and activated T-cells. Class II MHCs help immune cells recognize each other (and not attack!). 1. peptide fragments are longer (14-17 A.A.) and made of 2. cellular and exogenous antigens ************************************************************************************* The five major types of antibodies are: IgA. IgA antibodies are found in areas of the body such the nose, breathing passages, digestive tract, ears, eyes, and vagina. IgA antibodies protect body surfaces that are exposed to outside foreign substances. This type of antibody is also found in saliva and tears. About 10% to 15% of the antibodies present in the body are IgA antibodies. A small number of people do not make IgA antibodies. IgG. IgG antibodies are found in all body fluids. They are the smallest but most common antibody (75% to 80%) of all the antibodies in the body. IgG antibodies are very important in fighting bacterial and viral infections. IgG antibodies are the only type of antibody that can cross the placenta in a pregnant woman to help protect the fetus. IgM. IgM antibodies are the largest antibody. They are found in blood and lymph fluid and are the first type of antibody made in response to an infection. They also cause other immune system cells to destroy foreign substances. IgM antibodies are about 5% to 10% of all the antibodies in the body. IgE. IgE antibodies are found in the lungs, skin, and mucous membranes. They cause the body to react against foreign substances such as pollen, fungus spores, and animal dander. They may occur in allergic reactions to milk, some medicines, and some poisons. IgE antibody levels are often high in people with allergies. IgD. IgD antibodies are found in small amounts in the tissues that line the belly or chest. How they work is not clear.