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Mellon/MCHS Name: Human Biology Immunity/Immunology Objectives: 1. Describe typical external barriers that ward off invading organisms 2. Understand the process of nonspecific inflammatory response 3. Understand how humans recognize and discriminate between self and non-self tissues. 4. Distinguish between antibody-mediated and cell-mediated patterns of warfare. 5. Describe some examples of immune failures and identify as specifically as you can which weapons in the immunity arsenal failed in each case. Intro: A. Jenner (1796) cowpox could protect against smallpox. B. Pasteur (d.1896) vaccinations, pasteurization C. Robert Koch: Discovered the cause of anthrax I. Three Lines of Defense: A. Pathogen: virus, bacteria, fungi, protozoa, parasitic worms that cause disease. B. Surface Barriers to Invasion 1. Intact skin and mucous membranes are barriers 2. Resident bacteria of mucous membranes such as intestine and vagina deep pathogens in check by outcompeting them. 3. Lysozymes: enzymes in the mucous membranes attack bacteria and degrade their cell walls. 4. Enzymes in tears, saliva, and gastric fluid also degrade pathogens. 5. Urine protects urinary tract (low pH) C. Nonspecific and Specific response 1. Nonspecific: white blood cells, plasma proteins, inflammation. 2. Specific: Mounted by lymphocytes, recognize unique molecular configurations on invading pathogens. II. Complement Proteins (C1) A. 20 Proteins circulate in the blood and can be activated in two ways 1. Can bind to a complex of antibody/antigen 2. Can interact with carbohydrate molecules on the surfaces of microorganisms. B: CASCADE effect: 1. Membrane attack complexes become inserted into the plasma membrane of pathogens causing lysis 2. Chemical gradients of proteins attract phagocytes to the scene. 3. Complement proteins coat the surface of invading cells— attracting phagocytes. CQS Comment/Question/Summary Feel free to make a comment in this box: I rediscovered… I learned… I find it interesting that… I wonder… This is important because… Koch established the bacterial cause of many infectious diseases and discovered the microorganisms causing anthrax (1876), wound infections (1878), tuberculosis (1882), conjunctivitis (1883), cholera (1884) Mellon/MCHS Name: Human Biology III. Inflammation A. The roles of Macrophages and White Blood Cells 1. WBC arise from stem cells in bone marrow and can circulate in the blood or reside in tissue. 2. Three types of WBC act swiftly but are not adapted for sustained battles: a. Neutrophils: ingest and digest bacteria b. Eosinophils secrete enzymes that damage parasitic worms; they also phagocytize foreign proteins and help to control allergic responses. c. Basophils secrete histamine, which alters blood vessel permeability. 3. Macrophages (immature form is called monocyte) engulf many foreign agents and do so repeatedly with a big appetite. B. The Inflammatory Response 1. Acute inflammation in a besieged tissue allows phagocytes, complement proteins, and plasma proteins to escape from the blood. 2. Physical signs include redness, swelling heat, and pain 3. The progression of inflammation is as follows: a. Tissue irritation causes mast cells (a basophil) to release histamine and other substances which cause the blood vessels to become engorged and capillary walls to become “leaky.” b. Within a few hours, neutrophils and macrophages leave the blood vessels to begin engulfing foreign materials. c. Macrophages release interleukin-1, which signals other white blood cells, allows body temperature to rise (further enhancing defense mechanisms) and causes conservation of body energy due to drowsiness. d. Clotting mechanisms help wall off the pathogen and promote repair of tissues. Homework Assignment—on your own paper or in the CQS box: 1. What were Jenner, Pasteur, and Koch famous for? 2. List the Three Lines of Defense and describe how they work. 3. What are the four steps in the progression of inflammation? 4. Define the following terms: Complement proteins, Neutrophils, Eosinophils Basophils, Macrophages CQS Comment/Question/Summary Summarize the progression of inflammation: Mellon/MCHS Name: Human Biology IV. The Immune System A. Defining features 1. Sometimes physical barriers and inflammation may not be sufficient to overwhelm the invader. a. Vertebrate immune system is a complex interaction of two types of white blood cells called B and T lymphocytes. b. This system displays both specificity and memory. 2. Each kind of cell, virus, or substance bears unique molecular configurations that give it a unique identity. a. Your own cells (self) bear surface proteins which your lymphocytes ignore. b. Nonself markers from viruses, bacteria, bee venom, organ transplants, etc. bear antigens that trigger immune responses. c. When B and T lymphocytes encounter a nonself marker, they divide repeatedly. 1. Some become effector cells, which will engage and destroy the enemy. 2. Others are memory cells that will be called upon later if the invader strikes again. 3. Immunological memory and specificity involve three events: a. recognition of a specific invader b. repeated cell divisions to form huge populations of lymphocytes d. differentiation into subpopulations of specialized effector and memory cells. B. Antigen-Presenting Cells—Triggers for immune response 1. Any nonself marker that triggers the formation of lymphocytes is an antigen; the antigen binding receptors are antibodies, secreted by B cells. 2. MHC markers reside in the plasma membranes of body cells; some are unique to your lymphocytes and macrophages. 3. Macrophages can digest bacterial invaders but not their antigens, which become attached to MHC molecules to form antigen-MHC complexes 4. When antigen fragments and a certain MHC marker are displayed together at the cell surface, lymphocytes respond by dividing to produce huge numbers of lymphocytes. C. Key Players: 1. Helper T cells produce and secrete chemicals that promote formation of large populations of effector and memory cells. 2. Cytotoxic T cells kill body cells that have either become infected with intracellular parasites or are identified as tumor cells. (cell mediated immune response) 3. B cells are lymphocytes that produce antibodies. (antibody mediated immune response. CQS Comment/Question/Summary What does specificity and memory mean ? What is an antigen ? Mellon/MCHS Name: Human Biology D. Control of Immune Responses 1.When antibodies have "saturated" the binding sites on pathogens, fewer exposed antigens translates into less production of antibodies. 2.Inhibitory signals from cells with suppressor functions shut down the immune response. V. Lymphocyte Battlegrounds A. The antigen-presenting cells and lymphocytes interact in lymphoid organs (tonsils, adenoids), lymph vessels, and lymph nodes. B. In lymph nodes, cells are organized for maximum effectiveness with antigen-presenting cells in the front line, engulfing invaders. VI. Cell-Mediated Responses A. T Cell Formation and Activation 1. T cells arise from stem cells in the bone marrow, then travel to the thymus gland where they differentiate into helper T and cytotoxic T cells and acquire receptors for MHC markers and antigen-specific receptors. 2.Virgin T cells ignore both unadorned MHC markers and free antigen but do bind antigenMHC complexes on presenting cells, which stimulates division of the T cells to form clones. B . Functions of Effector T Cells 1.Some clones, effector helper T cells, secrete interleukins that stimulate cell divisions of virgin T cells and virgin B cells. 2.Effector cytotoxic T cells recognize MHC markers on viral-infected cells and tumors and kill the cells by secreting perforins that punch holes in the cell membranes. C. Natural Killer Cells 1.Other cytotoxic cells such as natural killer (NK) cells also kill tumor and infected cells. 2.They do not require an antigen-MHC encounter. VII Antibody-Mediated Responses A. B Cells and Targets of Antibodies 1. B cells also arise from stem cells and eventually produce copies of a specific antibody. a. Antibodies are proteins with binding sites for a single antigen. b. The Y-shaped antibody is embedded in the B cell membrane with the two arms extending as antigen receptors. 2. When its receptors lock onto an antigen, the B cell will undergo repeated cell divisions IF there are also present secretions from a helper T cell already activated by the same antigen. 3. The clonal B cells differentiate into effector (formerly known as plasma) cells and memory cells; effector cells produce antibodies that recognize antigens and mark their possessors for destruction by phagocytes. 4. The main targets of antibody-mediated responses are extracellular pathogens and toxins. B . Immunoglobulins 1. All five classes of antibodies have binding sites for antigen but the ones in each class have special sites for specific functions. 2. The different classes are the protein products of gene shufflings: a.IgM antibodies set the complement cascade in motion and bind invaders into dumps. CQS Comment/Question/Summary I rediscovered… I learned… I find it interesting that… I wonder… This is important because… Mellon/MCHS Name: Human Biology b.IgG antibodies neutralize toxins, are long lasting, can cross the placenta, and are found in mother's milk. c.IgA antibodies are present in the mucus of respiratory, digestive, and reproductive tracts. d.IgE antibodies bind to basophils and mast cells where they act as traps for antigen. IX. Immune Specificity and Memory A. Formation of Antigen-Specific Receptors 1. Immunological specificity lies in DNA recombinations. a.All T and B cells have the same genes coding for the polypeptides in each arm of the antibody molecule. b.Many 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 of a primary immune response is explained by the clonal selection theory. 2. Some B and T memory cells will continue to circulate for years and make secondary response to any subsequent encounter of the same antigen. 3. This later response will be more rapid, greater, and of longer duration than was the primary immune response. X. Immunization and Other Practical Applications of Immunology A. Immunization 1. Immunization involves a deliberate production of an immune response and memory cells. a.In active immunization, the first dose of vaccine elicits a primary immune response; a second dose ("booster") elicits a secondary, and more long-lasting, response. b.Passive immunization involves injections of antibodies to persons already infected with pathogens. 2. A vaccine can be made from killed or weakened pathogens, inactivated toxins, or genetically engineered viruses. B . Monoclonal Antibodies 1. Monoclonal antibodies are obtained by techniques that produce large quantities of antibody from B cells. a.A mouse is immunized with a specific antigen; B cells are extracted and fused with cancerous cells known as myeloma cells to produce a hybridoma cells. b.The hybridoma cells produce the desired antibody indefinitely. 2.Monoclonal antibodies are being used commercially in home pregnancy tests, screening for prostate cancer, and passive immunity. C. Cytokines 1.Signaling molecules produced by lymphocytes are called cytokines. 2.Tumor necrosis factor secreted by cytotoxic T cells has been used experimentally to treat malignant melanoma of the skin. 3.Interferons have been used to suppress viral diseases. CQS Comment/Question/Summary I rediscovered… I learned… I find it interesting that… I wonder… This is important because…