Chapter 35: Body Defenses and Immunity   The First Demonstrated Vaccination A. In 1796, Jenner demonstrated that inoculation with cowpox could protect against smallpox. B. Later, Pasteur developed similar vaccinations, which mobilized an immune response. C. Robert Koch was able to link a specific pathogenic microorganism to a specific disease&endash;anthrax. I. Three Lines of Defense A. Surface Barriers to Invasion [of pathogens] 1. Intact skin is an important barrier: The Integumentary System 2. The normal microbial inhabitants of the gut, and vagina keep the growth of pathogens in check. 3. Ciliated, mucous membranes in the respiratory tract sweep out bacteria and particles. 4. Lysozymes, present in tears, saliva, and gastric fluid, degrade bacterial cell walls. 5. Urine, with its low pH and flushing action, keeps pathogens from the urinary tract. B. Nonspecific and Specific Responses 1. Phagocytic cells and antimicrobial substances are in place to defend the body even before pathogens invade. 2. Nonspecific responses are made by leukocytes and plasma proteins to tissue damage in general; some pathogens are recognized by defenders that can make a specific response. II. Complement Proteins A. The complement system is a set of plasma proteins that enhance nonspecific and specific defense defenses. B. About twenty kinds of complement proteins circulate in the blood in inactive form. 1. These proteins are activated in a cascading fashion when defenses are breached. 2. At least two mechanisms are known: a. Some complement proteins form pore complexes which cause the pathogen to lyse and die. b. Chemical gradients of proteins attract phagocytes to the scene. III. Inflammation A. The Roles of Phagocytes 1. White blood cells, produced from stem cells in bone marrow, not only circulate in blood and plasma, but also reside in lymph nodes, spleen, liver, kidneys, etc. where they stand ready to defend. 2. Three kinds are swift to act but do not mount a sustained attack: a. Neutrophils, the most abundant, phagocytize bacteria. b. Eosinophils secrete enzymes that punch holes in parasitic worms. c. Basophils secrete histamine, which sustains inflammation. 3. Macrophages (formed from immature cells called monocytes) are slower to act but can engulf and digest just about any foreign agent or damaged tissue. B. The Inflammatory Response 1. While complement proteins are being activated, basophils and mast cells secrete histamine, which promotes leakage of fluid out of capillaries. 2. Inflammatory response results include: a. Localized warming and redness occur at the site of damage or invasion. b. Fluid seeps from blood vessels causing swelling and delivery of infection-fighting proteins to the tissues. c. Neutrophils and macrophages engulf foreign invaders and debris. d. Clotting mechanisms help wall off the pathogen and promote repair of tissues. 3. Macrophages also secrete interleukins, which are communication signals among white blood cells but in addition can signal the brain to reset its "thermostat" to cause a fever (not necessarily a bad thing). IV. The Immune System A. Defining Features 1. Physical barriers and inflammation may not be enough to check the spread of an invader. 2. T and B lymphocytes of the vertebrate immune system may be needed. a. Interactions among these cells are the basis of the vertebrate immune system. b. This system shows specificity and memory, which involves three events: 1) Recognition of the antigen, 2) Repeated cell divisions, 3) Differentiation into subpopulations of effector and memory cells. 3. Lymphocytes will ignore the "self" markers on the body’s own cells but will respond to "nonself" markers (antigens) on foreign cells by dividing rapidly to form huge populations of effector cells and memory cells. B. Antigen-Presenting Cells&endash;The Triggers for Immune Responses 1. Located on the membranes of the body’s cells are proteins called MHC markers. 2. When antigens enter the body, they are engulfed and destroyed by macrophages but not completely&endash;the antigen becomes attached to the MHC marker to form an MHC-antigen complex, which is then displayed on the macrophage’s surface. 3. Any cell that displays antigen with a suitable MHC marker is known as an antigen-presenting cell and will be noticed by lymphocytes. C. Key Players in Immune Responses 1. Helper T cells recognize antigen-MHC complexes and respond by secreting substances that promote the formation of large populations of effector and memory cells. 2. Cytotoxic T cells destroy infected (viruses for example) body cells and tumor cells in what is referred to as cell-mediated immune responses. 3. B cells and their progeny (effector cells) produce antibodies, which are specific substances that tag targets for destruction; this is called the antibody-mediated response. D. Control of Immune Responses 1. Antigen provokes an immune response, and removal of antigen stops it. 2. Inhibitory signals from cells with suppressor functions may also help shut down the immune response. V. Lymphocyte Battlegrounds: where they originate and how they "know" to take action A. Locations such as tonsils and lymph nodules allow antigen-presenting cells and lymphocytes to intercept invaders just after they penetrate surface barriers. B. Before antigen can reach the blood, it must trickle through lymph nodes, which are packed with defending cells VI. Cell-Mediated Responses A. T Cell Formation and Activation 1. T lymphocytes arise from stem cells in the bone marrow and then travel to the thymus gland where the helper T and cytotoxic T cells complete their development by acquiring TCRs (T-Cell Receptors). 2. Virgin T cells ignore both unadorned MHC markers and free antigen, but they do recognize and bind with antigen-MHC complexes on antigen-presenting cells; this causes them to divide repeatedly to form clones. B. Functions of Effector T Cells 1. The effector (clones) helper T cells secrete interleukins, which stimulate further cell divisions and differentiation. 2. The clones of cytotoxic T cells recognize the antigen-MHC complexes on infected cells and kill them by punching holes in their cell membranes with proteins called perforins. 3. The main targets of cell-mediated responses are cells infected with intracellular pathogens, tumor cells, and cells of organ transplants. B. Regarding the Natural Killer Cells 1. NK cells appear to be lymphocytes (but not B or T) produced in the bone marrow. 2. Natural killer (NK) cells kill tumor cells and virus-infected cells spontaneously, without the presence of antibodies. VII. Antibody-Mediated Responses A. B Cells and the Targets of Antibodies 1. B cells also arise from stem cells and proceed along a path to full differentiation which includes the production of proteins called antibodies. a. Each antibody has sites that will match up with only one kind of antigen. b. Each antibody is Y-shaped with the tail embedded in the B cell membrane and the two arms (bearing the antigen receptors) sticking outward. 2. When a "virgin" B cell makes contact with an antigen, it becomes sensitive to communication signals from helper T cells that have been activated by antigen-presenting cells. a. In the presence of interleukins (from the helper Ts), B cells sensitized to the antigen will divide rapidly to produce clone cells, all making the same antibody which will tag invaders for destruction by the phagocytic cells. b. Part of the clone population differentiates into effector cells that continue to make antibody; other cells become memory cells. 3. The main targets of antibody-mediated responses are extracellular pathogens and toxins, which remain outside the body’s cells. B. The Immunoglobulins 1. B cells produce four classes of antibodies known as the immunoglobulins. 2. All have antigen-binding sites, but each class also has other specialized functions: a. IgM, the first to be secreted during immune response, trigger the complement cascade. b. IgG antibodies activate complement proteins and neutralize many toxins; they are long lasting and can cross the placenta to protect the fetus. c. IgA, present in saliva, tears, and mucus, helps repel invaders at the start of the respiratory system. d. IgE triggers inflammation if parasitic worms attack the body; it also works with basophils and mast cells to secrete histamine. VIII. Focus on Health: Cancer and Immunotherapy IX. Immune Specificity and Memory A. Formation of Antigen-Specific Receptors 1. All B cells have the same genes coding for the polypeptides in each arm of the antibody molecule, but different polypeptides can be made by shuffling the genes into millions of combinations to produce antibodies against numerous agents. 2. The clonal selection theory proposes that a lymphocyte activated by a specific antigen will divide and give rise to a clone of cells that are specific only to that antigen. B. Immunological Memory 1. "Immunological memory" is the basis of the secondary immune response to a previously encountered agent. 2. After a primary immune response, some B and T cells continue to circulate for years as memory cells, which can divide when they meet the antigen again. 3. The secondary response is more rapid, of greater magnitude, and of longer duration. X. Defenses Enhanced, Misdirected, or Compromised A. Immunization 1. Immunization involves a deliberate production of memory cells by a vaccine that is made from killed or weakened bacteria or viruses. 2. It is also possible to incorporate antigen-encoding genes from one pathogen into a different organism. 3. If a person has already been exposed to bacterial pathogens, passive immunity can be temporarily conferred by injecting antibodies. B. Allergies 1. An allergy is a secondary immune response to a normally harmless substance. 2. Exposure triggers production of IgE antibodies, which cause the release of histamines and prostaglandins. 3. A local inflammatory response results; death can even occur due to anaphylactic shock, a condition in which air passages leading to the lungs constrict, fluid escapes too rapidly from capillaries, and blood pressure drops. C. Autoimmune Disorders 1. In autoimmune disorders, lymphocytes turn against the body’s own cells. 2. Grave’ s disorder is an overproduction of thyroid hormones, which elevate metabolic rates, heart fibrillations, nervousness, and weight loss. 3. In myasthenia gravis, antibodies are directed against acetylcholine receptors on skeletal muscle cells causing weakness. 4. Rheumatoid arthritis is an inflammation of the joints caused by antibody that treats the body’s own IgG molecules as if they were antigens. C. Deficient Immune Responses 1. When cell-mediated immunity is weakened, infections that would normally not be serious become life-threatening. 2. In acquired immune deficiency syndrome (AIDS), the cause is the human immunodeficiency virus (HIV). XI. Focus on Health: AIDS&endash;The Immune System Compromised AIDS is caused by a retrovirus, which has RNA instead of DNA.