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3/14/2014 Essential knowledge 2.D.4: Plants and animals have a variety of chemical defenses against infections that affect dynamic homeostasis. a. Plants, invertebrates and vertebrates have multiple, nonspecific immune responses. Students should be able to demonstrate understanding of the above concept by using an illustrative example such as: • Invertebrate immune systems have nonspecific response mechanisms, but they lack pathogen‐specific defense responses. • Plant defenses against pathogens include molecular recognition systems with systemic responses; infection triggers chemical responses that destroy infected and adjacent cells, thus localizing the effects. • Vertebrate immune systems have nonspecific and nonheritable defense mechanisms against pathogens. b. Mammals use specific immune responses triggered by natural or artificial agents that disrupt dynamic homeostasis. Evidence of student learning is a demonstrated understanding of each of the following: 1. The mammalian immune system includes two types of specific responses: cell mediated and humoral. 2. In the cell‐mediated response, cytotoxic T cells, a type of lymphocytic white blood cell, “target” intracellular pathogens when antigens are displayed on the outside of the cells. 3. In the humoral response, B cells, a type of lymphocytic white blood cell, produce antibodies against specific antigens. 4. Antigens are recognized by antibodies to the antigen. 5. Antibodies are proteins produced by B cells, and each antibody is specific to a particular antigen. 6. A second exposure to an antigen results in a more rapid and enhanced immune response. ✘ Memorization of the structures of specific antibodies is beyond the scope of the course and the AP Exam. Essential knowledge 3.D.2: Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling. a. Cells communicate by cell‐to‐cell contact. To foster student understanding of this concept, instructors can choose an illustrative example such as: • Immune cells interact by cell‐cell contact, antigen‐presenting cells (APCs), helper T‐cells and killer T‐cells. [See also 2.D.4] • LO 2.29 The student can create representations and models to describe immune responses. [See SP 1.1, 1.2] • LO 2.30 The student can create representations or models to describe nonspecific immune defenses in plants and animals.[See SP 1.1, 1.2] Reinforcement: • LO 3.34 The student is able to construct explanations of cell communication through cell‐to‐cell direct contact or through chemical signaling. [See SP 6.2] • LO 3.35 The student is able to create representation(s) that depict how cell‐to‐cell communication occurs by direct contact or from a distance through chemical signaling. [See SP 1.1] I. Pathogens, agents that cause disease, infect a wide range of animals, including humans II. The immune system recognizes foreign bodies and responds with the production of immune cells and proteins How does recognition occur? 1 3/14/2014 Pathogens (such as bacteria, fungi, and viruses) III. All animals have innate immunity, a defense active immediately upon infection A. Present before any exposure to pathogens and is effective from the time of birth B. Involves nonspecific responses to pathogens IV. Vertebrates also have adaptive immunity (acquired immunity) A. It involves a very specific response to pathogens INNATE IMMUNITY (all animals) • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors • Rapid response ADAPTIVE IMMUNITY (vertebrates only) • Recognition of traits specific to particular pathogens, using a vast array of receptors How do vertebrates develop adaptive immunity? • Slower response I. Innate Immunity of Invertebrates A. Exoskeleton made of chitin B. Lysozyme, protects digestive system, breaks down bacterial cell walls C. Hemocytes circulate and carry out phagocytosis, ingestion and digestion of foreign substances • Pathogen PHAGOCYTIC CELL Vacuole Lysosome containing enzymes Include skin and mucous membranes of the respiratory, urinary, and reproductive tracts o Mucus traps and allows for the removal of microbes o Body fluids including saliva, mucus, and tears o Low pH of skin and the digestive system Barrier defenses: Skin Mucous membranes Secretions Internal defenses: Phagocytic cells Natural killer cells Antimicrobial proteins Inflammatory response Humoral response: Antibodies defend against infection in body fluids. Cell-mediated response: Cytotoxic cells defend against infection in body cells. A. Innate defenses include: 1. barrier defenses 2. phagocytosis 3. antimicrobial peptides 4. natural killer cells 5. interferons 6. inflammatory response Which of these are unique to vertebrates? • Phagocytic cells recognize EXTRACELLULAR Lipopolysaccharide FLUID pathogens by TLRs, Toll‐ Helper protein Flagellin like receptors TLR4 PHAGOCYTIC o Uses lysosome to CELL destroy the microbe TLR5 o Types of phagocytic cells: 1. Neutrophils 2. Macrophages Dendritic cells 3. Eosinophils • VESICLE CpG DNA TLR9 TLR3 Innate immune responses ds RNA Natural killer cells also involved 2 3/14/2014 • Peptides and proteins function by attacking pathogens or impeding their reproduction o Interferon interfere with viruses and help to activate macrophages o About 30 proteins make up the complement system causes lysis of invading cells helps trigger inflammation Pathogen Mast cell Macrophage Movement of fluid Capillary Red blood cells • How do cytokines help the immune response? 1. Which of the following defense mechanisms is incorrectly paired with its function? a) gastric juice– kills bacteria in the stomach b) fever– may stimulate phagocytosis c) lysozyme– attacks the cell wall of viruses d) histamine– causes blood vessels to dilate Splinter Signaling molecules Inflammatory response, such as pain and swelling, is brought about by molecules released upon injury of infection o Mast cells release histamine • Activated macrophages and neutrophils release cytokines • Phagocytosis Neutrophil The adaptive response relies on two types of lymphocytes o T cells mature in the thymus o B cells mature in bone marrow 2. Which of the following statements best describes an insect’s immune system? a) Insects rely on the barrier defense of an exoskeleton. b) Hemocytes can carry out phagocytosis of bacteria and foreign substances. c) Lysozyme and a chitin‐lined intestine with a low pH protect an insect’s digestive system. d) All of the above are part of an insect’s innate immunity. Antigen receptors How are pathogens recognized by lymphocytes? • Antigens are substances that can elicit a response from a B or T cell o B and T cells have antigen receptors Bind to part of the receptor called an epitope Mature B cell Mature T cell 3 3/14/2014 Antigenbinding site Antigenbinding site Disulfide bridge A. Each B cell antigen receptor is a Y‐shaped molecule with two identical heavy chains and two identical light chains 1. Constant regions of the chains vary little 2. Variable regions differ greatly providing antigen specificity Variable regions B cell antigen receptor C Constant regions C Light chain Transmembrane region B. Binding of a B cell antigen receptor to an antigen is 1. an early step in B cell activation 2. gives rise to cells that secrete antibodies or immunoglobulins (Ig) Heavy chains B cell Antigen receptor Cytoplasm of B cell Antibody B cell Antigen Plasma membrane Epitope Pathogen (a) B cell antigen receptors and antibodies A. T cell and B cell antigen receptors are functionally different B. T cells bind to antigen fragments displayed/presented 1. antigen fragments are bound MHC molecules T cell antigen receptor Antibody C Antigenbinding site V V Variable regions C C Constant regions Disulfide bridge Transmembrane region Antibody A Antibody B chain Antigen T cell chain Plasma membrane Cytoplasm of T cell (b) Antigen receptor specificity • MHC (major histocompatibility complex) molecules are host proteins that display the antigen fragments on the cell surface, a process called antigen presentation. • A T cell can then bind both the antigen fragment and the MHC molecule. This interaction is necessary for the T cell to participate in the adaptive immune response A. The adaptive immune system has four major characteristics: 1. Diversity of lymphocytes and receptors 2. Self‐tolerance; lack of reactivity against an animal’s own molecules 3. B and T cells proliferate after activation, clonal selection a. effector cells act immediately against the antigen b. memory cells that can give rise to effector cells if the same antigen is encountered again 4. Immunological memory 4 3/14/2014 Antigen Primary immune response Secondary immune response to to antigen A produces antigen A produces antibodies to A; antibodies to A. primary immune response to antigen B produces antibodies to B. Antigen receptor Antibody concentration (arbitrary units) B cells that differ in antigen specificity Antibody 104 103 Antibodies to A 102 101 100 0 7 14 21 Plasma cells 3. Which of the following statements correctly describes the main difference between innate immunity and adaptive immunity? a) Innate immunity responds only to free pathogens in a localized area; adaptive immunity responds only to pathogens that have entered body cells. b) Innate immunity involves only leukocytes, whereas adaptive immunity involves only lymphocytes. c) Complement proteins participate in adaptive immunity but not in innate immunity. d) Innate immunity recognizes molecules common to a set of pathogens, whereas adaptive immunity reacts to specific microbes on the basis of their unique antigens. 4. What accounts for the huge diversity of antigens to which B cells can respond? a) The antibody genes have millions of alleles. b) The recombination of a light and a heavy chain gene during development results in millions of possible antigen receptors. c) B cells have thousands of copies of antibodies bound to their plasma membrane. d) The antigen‐binding sites at the arms of the molecule can assume a huge diversity of shapes in response to the specific antigen encountered. Helper T cells triggers both the humoral and cell‐mediated immune responses B. To activate adaptive immunity: 1. a foreign antigen must be present 2. the foreign antigen must be displayed on an antigen‐ presenting cell using the class II MHC molecule 3. cytokines are released from both the antigen‐presenting cell and helper T cell a. the helper T cell is activated and proliferates b. cloned helper T cells activate: i. B cells (humoral immunity) ii. Cytotoxic T cells (cell‐mediated immunity) 28 35 42 49 56 Exposure to antigens A and B Exposure to antigen A Memory cells Antibodies to B Time (days) • Acquired immunity has two branches: o Humoral immune response o Cell‐mediated immune response How do the two types of responses differ? • In the humoral immune response antibodies help neutralize or eliminate toxins and pathogens in the blood and lymph • In the cell‐mediated immune response specialized T cells destroy affected host cells Antigenpresenting cell A. Antigen fragment Pathogen Class II MHC molecule Accessory protein Antigen receptor 1 Helper T cell Cytokines Humoral immunity B cell 3 2 Cellmediated immunity Cytotoxic T cell 5 3/14/2014 A. Cytotoxic T cells are the effector cells 1. recognize fragments of foreign proteins produced by infected cells 2. possess an accessory protein that binds to class I MHC molecules 3. activated cytotoxic T cell secretes proteins that a. disrupt the membranes of target cells b. trigger apoptosis A. The humoral response is characterized by secretion of antibodies by B cells B. In response to cytokines from helper T cells and an antigen 1. B cells proliferate a. differentiates into memory B cells b. antibody secreting effector cells, plasma cells Cytotoxic T cell Released cytotoxic T cell Accessory protein Class I MHC molecule Antigen receptor Antigen fragment 1 Antigen-presenting cell Pathogen Antigen fragment 2 B cell Cytokines Activated helper T cell 2 So what do antibodies do?!? Plasma cells 3 Antibodies do not kill pathogens; they mark them for destruction Opsonization Neutralization Memory B cells Helper T cell • 3 Accessory protein 1 Dying infected cell Granzymes Pore Infected cell Class II MHC molecule Antigen receptor Perforin Secreted antibodies Activation of complement system and pore formation Complement proteins Antibody Formation of membrane attack complex 1. Neutralization ‐ antibodies bind to viruses/toxins preventing infection of a host cell 2. Opsonization ‐ antibodies bind to antigens on bacteria creating a target for macrophages/neutrophils, triggering phagocytosis 3. Activation of complement system ‐ antigen‐antibody complexes may bind to a complement protein triggers a membrane attack leading to lysis of the foreign cell Virus Bacterium Flow of water and ions Pore Macrophage Foreign cell Antigen 6 3/14/2014 Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) Engulfed by Antigenpresenting cell B cell Helper T cell Stimulates Gives rise to A. Active immunity develops naturally and can also develop following immunization, called vaccination B. Passive immunity provides immediate, short‐term protection. It is conferred when: Cytotoxic T cell 1. IgG crosses the placenta from mother to fetus Memory helper T cells 2. IgA passes from mother to infant in breast milk 3. artificially by injecting antibodies Antigen (2nd exposure) Plasma cells Memory B cells Memory cytotoxic T cells Active cytotoxic T cells Secreted antibodies Defend against extracellular pathogens • • • • • • Defend against intracellular pathogens and cancer Monoclonal antibodies – used in medical diagnosis and treatment Immune rejection – antibodies are important part of blood, tissue and organ transplants Allergies – exaggerated response of the immune system Autoimmune disease – loss of self tolerance Immunodeficiency disease – lack of response by the immune system Cancer – can result when adaptive immunity is inactivated 5. Clonal selection is responsible for the a) proliferation of effector cells and memory cells specific for an encountered antigen. b) rearrangement of antibody genes for the light and heavy chains. c) formation of cell cultures in the commercial production of monoclonal antibodies. d) recognition of class I MHC molecules by cytotoxic T cells. 6. A transfusion of type B blood in a person who has type A blood would result in a) the introduced blood cells being destroyed by innate defense mechanisms. b) no reaction; B is a universal donor blood type. c) the recipient's anti‐B antibodies reacting with the donated red blood cells. d) the recipient's B antigens reacting with the donated anti‐B antibodies. 7