BISC 307L 2nd Edition Lecture 31 Current LectureInnate Barrier Defenses1. The skin is a barrier to invasion of the body and infection. The outer layer, the stratum corneum, is very dry and has an acidic pH and is covered with toxic oil as well as sweat, which has antibacterial agents in it. 2. Other epithelia, which are in contact with the outside (including the respiratory or digestive tracts, which are particularly being exposed to pathogenic organisms through inhaled air or particles or food, and the urinary or the genital tracts, which are also subjected to pathogens) will secrete: 3. Mucus, which is sticky to trap foreign matter, contains lysozymes & IgA, and may be moved bycilia.4. Normal Flora, which are bacteria that have colonized and lived commensally with us to protect the body from pathogens. Immune System CellsBrief overview of all the cells of the immune system. These are all “leukocytes”, or white cells(not white blood cells). White cells can spend all their time in tissues, in blood, or travelling back and forth. The ones that are in the blood most of the time are basophils, neutrophils, eosinophils, monocytes (which differentiate into macrophages). The tissue leukocytes are mast cells, dendritic cells, natural killer cells, and most of the organ-specific phagocytes.A number of these cells are phagocytic. Neutrophils and macrophages are very active phagocytes. Neutrophils have very short lives of a few hours during which time they can ingest 5-10 bacteria, and die. Macrophages live longer and can ingest maybe 100 bacteria before they die. Although they are mainly blood cells, they sometimes travel to the tissue, and this is where they do most of their phagocytosing. Neutrophils will go into the tissue, ingest bacteria, and die.Whereas macrophages will enter the tissue, phagocytose, and possibly move back to the blood.Eosinophils mainly attach to parasitic worms and attack them. Among the lymphocytes, B lymphocytes are phagocytic and have some overlap of function with macrophages. Dendritic cells are very phagocytic cells that are fixed in the tissue. There are three types of Glia in the brain: astrocytes, oligodendrocytes, and microglia. Those areall diverse groups – there are several types of each. Kupffer cells in the liver are a fixed phagocyte. There exist fixed phagocytes in the spleen as well. There are cells called granulocytes from the appearance of granules in their cytoplasm – the granules are vesicles. Neutrophils and eosinophils are considered granulocytes, as are basophils and mast cells. They are very important in inflammatory responses. Lymphocytes – the B type secretes antibodies, and the T type has a number of different functions, one of which is to be cytotoxic and attack and kill other cells directly. And cytotoxic T lymphocytes share a lot in common with the natural killer cells. One of the main differences between them is how they select the targets to kill. The cytotoxic T lymphocytes are part of the specific immune system, and the natural killer cells attack a wide variety of things because they are part of the nonspecific immune system. Traditionally, the cell types marked with asterisks are part of the nonspecific immune system. Mast cells function in both the specific and nonspecific. However, it has recently been pointed out that the specific immune system incorporates many aspects of the nonspecific immunesystem – for example, the lymphocytes would not be able to recognize and attack threats unlessthe nonspecific cells were helping them to recognize the threats in the first place. The cells of the nonspecific immune system have receptors on their membranes that recognize molecular groups that are associated with pathogens. They recognize a broad array of bacterial species – things that bacteria in common share. They are called PAMPS or pathogen associated molecular patterns. The receptors on the surface of these nonspecific cells are called pattern recognition receptors or toll-like receptors. They recognize and kill bacteria, fungi, and even viruses by recognizing common molecular groups on the surfaces of those pathogens that bind to the toll-like receptors on their membranes and that activates the attack on their cells.Innate Chemical Defenses• Lysozymes in mucus/saliva attack bacterial cell walls. Mucus also contains IgA.• Gastrointestinal Tract: gastric acid & protease in the stomach kill most bacteria, but not all. bile salts are detergent like molecules created by the liver and stored in the duodenum, and they help to emulsify fat and attack bacteria membrane.• Urinary Tract: acidic urine keeps the tract clean• Cytokines: In general, they are hormones of the immune system. Communication between cells are as complicated as communication through synapses in the nervous system. But they utilize cytokines as signals instead of electrical signals. They can work asparacrine, autocrine, or endocrine agents. • Chemokines are one type of cytokines that are attractant molecules. So for example, a phagocyte like a macrophage or neutrophil travelling in the blood would be in a rolled up formation. If chemokines were released near them, they would cause the phagocytes to become sticky and to flatten out. They begin adhering to the walls of the capillaries, flatten out and become motile and crawl around, and they will look for a space between endothelial cells and push their way out and crawl out, looking for the source of the chemokines which would be the source of infection. • Fever - endogenous pyrogens (which are cytokines that specifically bind to receptors in the temperature controlling region of the brain to cause fever, which would be a defense) or bacterial endotoxin (membrane component of many bacteria, which does the same as above)• Complement – A group of 20 plasma proteins that are synthesized in the liver and they circulate it in inactive form. When activated, different components of the complement complex will work together and self assemble into a MAC, a large water filled pore, called a membrane attack complex. It kills the cells by osmotic lysis, allowing water to rush in through the pore it creates. A complement can attack bacteria by itself, but the action of attacking is tremendously enhanced if the cells have antibodies bound to them.• Interferons (a, b, g) – They are cytokines, there are three classes, alpha, beta, and gamma, and they are important in defense against viruses. Cells