Ch. 43 The Immune System Objectives LO 2.28 The student is able to use representations or models to analyze quantitatively and qualitatively the effects of disruptions to dynamic homeostasis in biological systems. LO 2.29 The student can create representations and models to describe immune responses. LO 2.30 The student can create representations or models to describe nonspecific immune defenses in plants and animals. LO 2.34 The student is able to describe the role of programmed cell death in development and differentiation, the reuse of molecules, and the maintenance of dynamic homeostasis. Overview • Innate Immunity – defenses are activated immediately upon infection; same response for all pathogens. • Adaptive (Acquired) Immunity – defenses based on recognition of the pathogen. Pathogens (such as bacteria, fungi, and viruses) INNATE IMMUNITY (all animals) • Recognition of traits shared by broad ranges of pathogens, using a small set of receptors Barrier defenses: Skin Mucous membranes Secretions • Rapid response Internal defenses: Phagocytic cells Natural killer cells Antimicrobial proteins Inflammatory response ADAPTIVE IMMUNITY (vertebrates only) Humoral response: Antibodies defend against infection in body fluids. • Recognition of traits specific to particular pathogens, using a vast array of receptors • Slower response Cell-mediated response: Cytotoxic cells defend against infection in body cells. Ch. 43.1 In Innate Immunity, Recognition and Response Rely on Traits Common to Groups of Pathogens Invertebrates • Exoskeleton (chitin) • Chitin-based barriers and lysozymes (break down bacterial walls) in intestines • Hemocytes – Phagocytosis – Chemicals – Antimicrobial peptides (disrupt fungi and bacterial plasma membranes) – Specialized recognition proteins Pathogen PHAGOCYTIC CELL Vacuole Lysosome containing enzymes Vertebrates • Barrier defenses – Skin – Cilia: sweep mucus and any entrapped microbes upward, preventing the microbes from entering the lungs – Lysozymes in • Mucus – traps microbes • Saliva • Tears – Acidic • Skin • Sweat • Stomach juices • Cellular Innate Defenses – Phagocytosis after Toll-like receptor recognizes pathogen • • • • Neutrophils: circulate in blood Macrophages: live in cells/organs (spleen) Dendritic cells: tissue in contact with environment (skin) Eosinophils: beneath mucosal surfaces; multicellular pathogens. – Natural Killer Cells: secrete chemical when they come in contact with a pathogen • Antimicrobial Peptides and Proteins – Interferons • Made by virally infected cells to warn surrounding cells. • Inflammatory Response Pathogen Mast cell Splinter Signaling molecules Macrophage Capillary Movement of fluid Phagocytosis Neutrophil Red blood cells – Histamine is released by mast cells in response to tissue damage • Trigger dilation and increased permeability of nearby capillaries • Increased blood flow delivers clotting factors to the injury (marks beginning of repair process/blocks spread of microbes) – Cytokines from macrophages/neutrophils promote blood flow causing redness and increased temp in the area. – Pus—the accumulation of dead phagocytic cells and fluid leaked from capillaries 43.2 In Adaptive Immunity, Receptors Provide Pathogen-Specific Recognition • Pathogens have antigens that trigger lymphocytic responses. – B cells • Binding of Y shaped antigen receptor on membrane to antigen causing it to secrete soluble receptors called antibodies. – T cells • Single rod shaped antigen receptor only binds to already infected host cells that display the antigen. Antigen receptor Antibody Displayed antigen fragment B cell Antigen Epitope T cell T cell antigen receptor MHC molecule Pathogen (a) B cell antigen receptors and antibodies Antigen fragment Antibody C Antibody A Pathogen Antibody B Host cell Antigen (b) Antigen receptor specificity (a) Antigen recognition by a T cell Characteristics of Adaptive Immunity 1. Immense diversity of lymphocytes and receptors. – > 1 million different B cell antigen receptors; 10 million different T cell antigens; each cell carries a specific set of these 2. Self-tolerance. – Lymphocytes are tested; any with “self” receptors go through apoptosis. 3. Once recognized, increasing the number of specific lymphocytes for an antigen. – Active lymphocyte divides by mitosis making cloned effector cells (begin fighting immediately; B=plasma cells; T= helper T cells and cytotoxic T cells) and memory cells (long lived cells that activate if antigen enters the body again) 4. Stronger and quicker response to previously encountered antigens. – Memory cells 43.3 Adaptive Immunity Defends Against Infection of Body Fluids and Body Cells Cell-Mediated Immune Response (attacks infected body cells) • Active helper T cells secrete cytokines which activate cytotoxic T cells. • Cytotoxic T cells bind to infected host cells – Secretes proteins that disrupt membrane integrity and trigger apoptosis. – Once destroyed, antibodies attach to antigens from within the host cell. Antigenpresenting cell Antigen fragment Cytotoxic T cell Released cytotoxic T cell Pathogen Class II MHC molecule Accessory protein 1 Accessory protein Class I MHC molecule Antigen receptor Antigen receptor Pore Helper T cell Infected cell Cytokines 1 2 Cytotoxic T cell Cellmediated immunity Perforin Antigen fragment 2 Dying infected cell Granzymes 3 Animation: Helper T Cells Right-click slide / select “Play” © 2011 Pearson Education, Inc. Animation: Cytotoxic T Cells Right-click slide / select “Play” © 2011 Pearson Education, Inc. Humoral Immune Response (attacks pathogen) • • • • Helper T cells activate B cells. B cells divide into memory or plasma cells. Plasma cells give secrete 2,000 antibodies/sec! Antibodies: Antigen-presenting cell Class II MHC molecule Antigen receptor Pathogen Antigen fragment B cell Cytokines Helper T cell 1 Memory B cells Accessory protein 2 Activated helper T cell Plasma cells 3 – Prevent the pathogen from infecting cells (neutralization) – Increase phagocytosis due to easy recognition (opsonization) – Complement system of proteins opens a pore in the pathogen causing water to rush in the pathogen to lyse. Activation of complement system and pore formation Opsonization Neutralization Complement proteins Antibody Formation of membrane attack complex Virus Bacterium Flow of water and ions Pore Macrophage Foreign cell Antigen Secreted antibodies Humoral (antibody-mediated) immune response Cell-mediated immune response Key Antigen (1st exposure) Engulfed by Antigenpresenting cell Stimulates Gives rise to B cell Helper T cell Cytotoxic T cell Memory helper T cells 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 Active and Passive Immunization • Active (cell mediated and humoral responses) – Can be induced by vaccinations – weakened, killed, or parts of pathogens to – to create memory cells and can lead to immunization. • Passive (passed on from mother to child for first few months of life) – Injection of antibodies from an immune animal to a non-immune animal. Immune Rejection • Cells from another person’s body can be recognized as foreign due to different carbohydrate found on the cell membranes, causing an immune response. – Blood groups (ABO) – Tissue and Organ Transplant 43.4 Disruptions in Immune System Function Can Elicit or Exacerbate Disease • Allergies – Exaggerated responses to allergens. • Autoimmune diseases – Immune system does not recognize “self-cells” • • • • Lupus Arthritis Diabetes MS Immunodeficiency Diseases • Inborn immunodeficiency results from hereditary or developmental defects that prevent proper functioning of innate, humoral, and/or cell-mediated defenses • Acquired immunodeficiency develops later in life and results from exposure to chemical and biological agents • Acquired immunodeficiency syndrome (AIDS) is caused by a virus Evolutionary Adaptations of Pathogens Antigenic Variation • Changes its antigens so the host does not recognize it – Ex: Flu Latency • Inactive state which does not trigger an immune response (lysogenic cycle). Attacking the Immune System Itself • HIV – attacks helper T cells preventing both cell mediated and humoral responses to infections. Cancer and Immunity • The frequency of certain cancers increases when adaptive immunity is impaired – 20% of all human cancers involve viruses • The immune system can act as a defense against viruses that cause cancer and cancer cells that harbor viruses • In 2006, a vaccine was released that acts against human papillomavirus (HPV), a virus associated with cervical cancer.