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.

Pathogens (such as bacteria, fungi, and viruses) 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) • Rapid response Recognition of traits shared by broad ranges of pathogens, using a small set of receptors • Recognition of traits specific to particular pathogens, using a vast array of receptors • Slower response 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. ADAPTIVE IMMUNITY (vertebrates only)

Invertebrates Exoskeleton (chitin) 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 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 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 Pathogen Splinter Mast cell Macro- phage Capillary Red blood cells Neutrophil Signaling molecules Movement of fluid Phagocytosis

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. Antibody Antigen receptor B cell Antigen Epitope Pathogen (a) B cell antigen receptors and antibodies Antibody C Antibody B Antibody A (b) Antigen receptor specificity Displayed antigen fragment MHC molecule Antigen fragment Pathogen Host cell T cell T cell antigen receptor (a) Antigen recognition by a T cell

Characteristics of Adaptive Immunity 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 Self-tolerance. Lymphocytes are tested; any with “self” receptors go through apoptosis. 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) Stronger and quicker response to previously encountered antigens. Memory cells

Cell- mediated immunity 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. Antigen- presenting cell Pathogen Antigen fragment Class II MHC molecule Accessory protein Antigen receptor Helper T cell Cytokines Cell- mediated immunity Cytotoxic T cell 2 1  Cytotoxic T cell 3 1 2 Accessory protein Class I MHC molecule Infected cell Antigen receptor Antigen fragment Perforin Pore Gran- zymes Released cytotoxic T cell Dying infected cell

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: 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. Pathogen 3 1 2 Antigen-presenting cell Antigen fragment Class II MHC molecule Antigen receptor Accessory protein Helper T cell B cell Cytokines Activated helper T cell Memory B cells Plasma cells Secreted antibodies  Opsonization Neutralization Antibody Virus Bacterium Macrophage Activation of complement system and pore formation Complement proteins Formation of membrane attack complex Flow of water and ions Pore Antigen Foreign cell

Humoral (antibody-mediated) immune response Cell-mediated immune response Antigen (1st exposure) Engulfed by Antigen- presenting cell Helper T cell Memory helper T cells Antigen (2nd exposure) B cell Plasma cells Secreted antibodies Defend against extracellular pathogens Memory B cells Memory cytotoxic T cells Active cytotoxic T cells Defend against intracellular pathogens and cancer Cytotoxic T cell Key Stimulates Gives rise to 

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.