10.1 The Body’s Lines of Defenses Immunity is ability to ______________ against infectious agents, foreign cells, and abnormal cancer cells. The First Line of Defense-The Non-Specific Barriers 1. Four nonspecific defenses include barrier to entry, inflammatory reaction, natural killer cells, and protective proteins. A. Barring Entry 1. ________________________ membranes lining respiratory, digestive, and urinary tracts are mechanical barriers. 2. Oil gland secretions inhibit _____________________ on skin. 3. ________________ lining respiratory tract sweep mucous and particles up into throat to be swallowed. 4. Stomach has a low pH (1.2-3.0) that inhibits ___________________________ 5. Normal bacteria that reside in intestine or vagina prevent pathogens from colonizing. Pathogens are disease causing agents (viruses or bacteria). B. Inflammatory Reaction ● Leukocytes: White blood cells o Produce _________________ o Engulf ______________________ 1 o Granulocytes: One type of white blood cell that contains cytoplasmic granules o Agranulocytes: white blood cells that do not contain cytoplasmic granules 6. Phagocytosis: Process of white blood cells ___________________________________ a microbe. Macrophages: Phagocytic white blood cells (________________) All blood cells are formed in the bone marrow: 1. If skin is broken, a series of events occurs: the _____________________________________ 2. The inflamed area has four symptoms: __________________________________________________ 3. ______________________ occur in loose connective tissues and resemble basophils. 4. When tissue damage occurs, a. This stimulates mast cells to release _____________________. b. Histamine causes ______________________ and increased permeability of capillaries. c. Enlarged capillaries produce redness and local increase in temperature. 2 d. A rise in local temperature reduces invading pathogens and increases phagocytosis by WBCs. 5. Chemicals released by damaged tissue cause __________________and _________________ to migrate by amoeboid movement to site of injury; they escape from blood by squeezing through capillary wall. 6. When monocytes enter tissue, they differentiate into ________________that ingest bacteria or viruses. 7. Connective and lymphoid tissues have resident macrophages that devour old blood cells and debris. 8. Macrophages trigger an explosive increase in leukocytes by releasing colony-stimulating hormones; this diffuses into blood and is transported to red bone marrow to stimulate production of ___________s. 9. Pus is accumulation of dead __________________along with tissue, cells, bacteria and, living WBCs. 10.Aspirin, ibuprofen, and cortisone are anti-inflammatory agents that counter inflammatory histamine chemistry. C. Natural Killer Cells 1. Natural killer cells kill virus-infected cells and tumor cells; they lack specificity and memory. 2. The Complement system __________________________ there are _________________ proteins produced by the liver a. When one complement protein is activated, others become activated in a ____________reaction. b. A limited amount of protein can activate many other proteins. c. Complement is activated when pathogens enter the body. d. It "complements" certain immune responses, which accounts for its name. e. It amplifies an inflammatory reaction by attracting _____________________ to site of infection. f. Complement binds to antibodies already on the surface of pathogens, increasing probability that pathogens will be phagocytized by a neutrophil or macrophage. g. Some complement proteins produce holes in bacterial cell walls and plasma membranes; fluids and salts enter to point where they burst. D. Interferon is protein produced by virus-infected animal cells to warn healthy cells to prepare for viral attack. h. It binds to receptors of non-infected cells, producing substances interfering with viral replication. i. Interferon is specific to a species; only human interferon can be used in humans. 3 10.2 Second Line of Defense-The Specific Barriers If non-specific defenses fail, specific defenses are required against a particular antigen. 1. Antigens are foreign substances, _________________________, that stimulate immune system to react. 2. Pathogens have antigens; antigens can also be components of foreign or _________________________ 3. We do not ordinarily become immune to our own cells; immune system can tell self from non-self. 4. Immunity usually lasts for some time; we do not ordinarily get the same illness a second time. A. Specific immunity is primarily the result of action of B lymphocytes and T lymphocytes. 1. B lymphocytes mature in __________marrow; T lymphocytes mature in ______________. 2. B lymphocytes (B cells) become plasma cells that each produce specific __________________ 3. Antibodies are large globular proteins that combine with and neutralize antigens. 4. Antibodies are secreted into blood and lymph. 5. T lymphocytes either directly attack cells that have antigens or regulate immune response. 6. Lymphocytes are capable of recognizing an antigen because they have receptor molecules on their surface. a. Receptor-antigen fit is compared to a lock and key. b. During our lifetime, we encounter a million different antigens; we need diversity of lymphocytes. c. During maturation, diversification produces a different lymphocyte for each possible antigen. B. B Cells and Antibody-Mediated Immunity 1. Each type of B cell carries its specific antibody as a membrane-bound receptor on its ___________. 2. When a B cell (in lymph node or spleen) encounters an appropriate antigen, it is activated to divide. 3. B cells will: create __________________________________ (in lymph node and spleen) against the specific antigen 4. B cells will: also create _______________________ that do not participate in antibody production but __________________________. 5. Once threat of infection has passed, development of new plasma cells ceases; those present die. 6. Apoptosis is programmed __________________; this is critical to maintaining tissue homeostasis. 7. B cells are responsible _____________________________________ immunity. C. Structure of IgG 1. Most common antibody (IgG) is a Y-shaped molecule with two arms. 2. Each arm has a "heavy" and "light" polypeptide chain. a. These chains have constant regions and variable regions. 4 b. Constant regions have amino acid sequences that do not change; not identical among all antibodies. c. Variable regions have portions of polypeptide chains whose amino acid sequence changes providing antigen specificity; forms antigen binding sites of antibodies (their shape is specific to antigen. ) 3. Antigen binds with a specific antibody at antigen-binding site in a lock-and-key manner. 4. Antigen-antibody complex (or immune complex) marks antigen for destruction by other mechanisms (e.g., neutrophils or macrophages) or it may activate complement. 5. If complement attaches to antigens on surface of pathogens, it renders them more easily phagocytized. D. Other Types of Antibodies * do not memorize-general interest only 1. There are five classes of circulating antibodies or immunoglobulins (Igs). 2. IgG Antibodies a. These are major type in blood; some in lymph and tissue fluid. b. IgG attacks pathogens and toxins. 3. IgM Antibodies a. These contain five Y-shaped structures. b. They appear in blood soon after an infection begins and disappear before it is over. c. They are good activators of the complement system. 4. IgA Antibodies a. IgA contains two Y-shaped structures. b. They attack pathogens before they reach the blood. c. They are main type of antibody in bodily secretions. 5. Role of IgD antibodies is to serve as receptors for antigens on mature B cells. 6. IgE antibodies are involved in immediate allergic reactions. E. T Cells and Cell-Mediated Immunity There are 4 different types of T Cells: 1. Cytotoxic T Cells (Also referred to as killer T cells) a. They destroy _____________________________________ (e.g., virus-infected or cancer cells). b. They have storage vacuoles that contain _____________________molecules. c. Perforin molecules perforate a plasma membrane; water and salts to enter causing cell to burst. 5 2. Helper T Cells regulate immunity by improving response of other immune cells. a. When exposed to an antigen, they enlarge and ______________________________ b. Cytokines (for ex. Lymphokines) are chemical __________________________________ cells to clone and other immune cells to perform their functions. 1. Cytokines stimulate macrophages to phagocytize. 2. They stimulate B cells to become antibody-producing plasma cells. c. HIV (cause of AIDS) infects primarily helper T cells and inactivates immune response. Killer T cells and helper T cells are responsible for CELL-MEDIATED IMMUNITY. 3. Memory T cells remain and can jump-start an immune reaction when same antigen reenters body. 4. suppressor T cells signal the immune system to shut down F. Activation of T Cells 1. Like B cells, T cells have receptors. 2. Receptors of killer and helper T cells cannot recognize antigen simply present in lymph or blood. 3. Instead, antigen must be presented to them by an ____________________________________ a. When an antigen-presenting cell, usually a macrophage, engulfs a microbe, it is enclosed within an endocytic vesicle and broken down to release fragments. b. These fragments are antigenic, each of which is linked to an MHC protein; together they are presented to a T cell. 4. Human MHC proteins are called HLA (_____________________________) proteins. 5. Importance of major histocompatibility complex (MHC) proteins was recognized when it was discovered they contribute to difficulty of transplanting tissues from one person to another. 6. When donor and recipient are histocompatible, it is likely a transplant will be successful. 7. Once a helper T cell recognizes antigen, it undergoes clonal expansion producing memory and suppressor T cells. a. Once a cytotoxic T (or killer T) cell is activated, it undergoes clonal expansion and destroys any cell that possesses _________________ if the cell bears the correct ________________. b. As the infection disappears, the immune reaction slows down and few cytokines are produced. c. The few T cells that do not undergo apoptosis survive as memory cells. 8. Apoptosis occurs in thymus if T cell bears a receptor to recognize a self antigen; if apoptosis does not occur, T-cell cancers result (i.e. lymphomas and leukemias). 9. Once the battle is won suppressor T cells signal the immune system to ____________________ 6 10.3 Malfunctions of the Immune System A. Autoimmune Diseases ● Autoimmune diseases result as an attack on tissues by body's _______________________. ● Cause is not known but autoimmune diseases often appear following recovery from an infection. 1. In multiple sclerosis (MS), ____________________________of nerve fibers is attacked. (Advanced MS results in the destruction of the insulation of the nerve cell provided by the myelated sheath 2. Rheumatic fever results from an _______________________________ that leaves scared heart tissue. 7 3. Type I diabetes occurs when an immune response is produced against the __________________ of the pancreas 4. There are no cures for autoimmune diseases but they are ________________________by drugs. B. Allergies 1. Allergy results from an immune system forming antibodies to ____________________________ 2. A response to these antigens, called ______________________, usually involves tissue damage. 3. Immediate and delayed responses are two of four possible responses. 4. ________________________________Allergic Response a. Immediate responses occur within seconds of contact with an allergen. b. Cold-like symptoms are common. c. A severe systemic reaction is ___________________________, a sudden drop in blood pressure. d. IgE antibodies are attached to plasma membrane of mast cells in tissues and basophils in blood. e. When an allergen attaches to IgE antibodies on these cells, they release large amounts of _____________________________________, which cause symptoms or anaphylactic shock. 5. Allergy shots sometimes prevent the onset of allergic symptoms. a. Injections of the allergen cause the body to build up high quantities of _____________________. b. These combine with allergens received from the environment before they have a chance to reach IgE antibodies located on the plasma membrane of _________________________. 6. Delayed Allergic Response a. Delayed responses are initiated by sensitized T cells at site of allergen. b. It responds to antigens that _________________________________ before. c. Tuberculin skin test is example: positive test shows prior exposure to TB bacilli but requires some time to develop reddening of tissue. 10.5 Induced Immunity: Active and Passive Immunity A. Two Types of Immunity 1. Immunity is acquired naturally through infection or artificially by medical intervention. a. Active immunity is where persons make their _____________________________ 8 b. Passive immunity is where an individual receives ___________________________. B. Active Immunity 1. Active immunity sometimes develops naturally after a person is infected. 2. However, active immunity is often ____________when a person is well so future infection is prevented. 3. Immunization uses vaccines to provide antigen to which immune system responds. 4. To prepare vaccines, pathogens were treated so they were no longer __________________ 5. Genetically engineered bacteria can produce proteins from pathogens; protein is used as a vaccine. 6. After vaccine is given, immune response is measured by antibody level in serum-the ____________________ (or concentration of antibody) a. After first exposure, a primary response occurs with _____________ and then a ____________ in titer. b. A gradual decline follows as antibodies bind to antigen or simply break down. c. After second exposure, a secondary response occurs and antibody titer rises rapidly to a level much greater than before; this is a "_____________________" d. Higher antibody titer is expected to prevent disease symptoms if individual is infected. e. Active immunity depends on memory B and T cells responding to low doses of ____________. C. Passive Immunity 1. Passive immunity occurs when an individual is given ________________________ to combat a disease. 2. It is short-lived because antibodies are not made by individual's B cells. 3. Newborn infants are immune to disease because mother's antibodies have crossed ________________ 4. Breast-feeding promotes passive immunity-antibodies are in mother's milk. 5. Passive immunity is needed when a patient is in immediate danger from infectious disease or toxin. 6. A person may be given a gamma globulin injection (serum that contains antibodies against the agent) taken from an individual or animal who has recovered from it. Monoclonal Antibodies 9 1. Monoclonal antibodies: antibodies secreted by hybridomes: new cells created by the fusion (or cloning of two cells) 2. Monoclonal antibodies can be produced in vitro. a. B lymphocytes are removed from body (usually mice) and exposed to a particular antigen. b. Activated B lymphocytes are fused with _____________________ (malignant plasma cells that divide indefinitely). c. Fused cells are __________________because they result from two different cells and one is cancerous. 3. Monoclonal antibodies are used for quick, reliable diagnosis of various conditions such as ___________ 4. Monoclonal antibodies can be used to treat various diseases such as __________________ 5. They can distinguish between cancer and normal cells and can carry isotopes or toxic drugs to kill _______________________ 10