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This chapter explores how animals defend themselves against pathogens using innate and adaptive mechanisms. It discusses the recognition, activation, and effector phases of the immune response, as well as the distinctions between innate and adaptive defenses. The role of physical barriers, phagocytic cells, antibodies, and toxic molecules is highlighted. The chapter also emphasizes the coordination between innate and adaptive defense systems in vertebrates.
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39 Immunology: Animal Defense Systems
Chapter 39 Immunology: Animal Defense Systems • Key Concepts • 39.1 Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • 39.2 Innate Defenses Are Nonspecific • 39.3 The Adaptive Immune Response Is Specific • 39.4 The Adaptive Humoral Immune Response Involves Specific Antibodies • 39.5 The Adaptive Cellular Immune Response Involves T Cells and Their Receptors
Chapter 39 Opening Question • How can a person survive an infection and be resistant to further infection?
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • Animals have various means of defense against pathogens—organisms or viruses that can cause disease. • These defenses are based on the distinction between self—the animal’s own molecules—and nonself, or foreign, molecules.
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • Response to invaders occurs in three phases: • Recognition phase: The animal must be able to discriminate between self and nonself. • Activation phase: Mobilization of cells and molecules to fight the invader. • Effector phase: Mobilized cells and molecules destroy the invader.
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • Two categories of defenses: • Innate defenses—nonspecific, 1st line of defense, rapid response • Include physical barriers such as skin, molecules toxic to invaders, and phagocytic cells that ingest invaders • Some are present all the time, others can be activated quickly
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • Adaptive defenses—aimed at specific pathogens; activated by innate systems • Slower to develop and long lasting • Example: Cells make antibodies—proteins that will recognize, bind to, and aid in the destruction of specific pathogens
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • Immunity:when an organism has sufficient defenses to successfully avoid biological invasion by a pathogen
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • All animals have innate defenses. • Barriers include physical, chemical, and biological mechanisms, such as hard exoskeletons.
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • Cells include phagocytes that ingest microbial pathogens by endocytosis and destroy them by hydrolysis, such as amebocytes in the blood of the horseshoe crab.
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • Toxic molecules: horseshoe crab blood cells release molecules that can disrupt bacterial cell membranes or bind to bacterial surfaces and cross-link them.
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • Vertebrates have both innate and adaptive defense systems—they work together as a coordinated system. • The main factors in immunity are specific cells and proteins. • These cells are produced in the blood and lymphoid tissues and circulate throughout the body.
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • The recognition and activation phases of innate immunity evolved very early in animals. • Animals from humans to fruit flies have Toll-like receptors that recognize and bind to pathogen molecules, such as components of the bacterial cell wall. • Binding sets off a signal transduction pathway that ends with expression of genes for anti-pathogen molecules.
Concept 39.1Animals Use Innate and Adaptive Mechanisms to Defend Themselves against Pathogens • White blood cells (leukocytes): • Phagocytes—large cells that engulf pathogens and other substances by phagocytosis • Lymphocytes—B cells and T cells are involved in adaptive immunity; natural killer cells are involved in both innate and adaptive immunity
Concept 39.2 Innate Defenses Are Nonspecific • Innate, nonspecific defenses are general mechanisms—the first line of defense. • They are genetically programmed and “ready to go.” • In mammals, they include physical barriers, cellular defenses, and chemical defenses.
Concept 39.2 Innate Defenses Are Nonspecific • Skin is a physical barrier—bacteria can rarely penetrate it. • Saltiness of the skin is not hospitable for bacteria growth. • The normal flora—bacteria and fungi that live on body surfaces, compete with pathogens for nutrients and space.
Concept 39.2 Innate Defenses Are Nonspecific • Mucus secreted by mucous membranes traps microorganisms. • Beating of cilia continuously move the mucus and debris towards the outside of the body, such as in the respiratory tract. • Lysozyme in mucus attacks bacterial cell walls and causes them to lyse.
Concept 39.2 Innate Defenses Are Nonspecific • Mucous membranes also produce defensins, peptides with hydrophobic domains that are toxic to many pathogens. • Defensins insert themselves into the plasma membrane of the pathogen and make it permeable to water and solutes. • Defensins are also made in phagocytes, where they kill pathogens trapped by phagocytosis.
Concept 39.2 Innate Defenses Are Nonspecific • Harsh conditions in the internal environment, can also kill pathogens; for example, the acids in the stomach.
Concept 39.2 Innate Defenses Are Nonspecific • Pathogens that do penetrate the body surfaces encounter more innate defenses. • Activation of defensive cells; involves recognition of nonself molecules by pattern recognition receptors (PRRs) on phagocytes and natural killer cells. • Toll-like receptors are PRRs.
Concept 39.2 Innate Defenses Are Nonspecific • Molecules recognized by PRRs are pathogen associated molecular patterns (PAMPs)—molecules unique to classes of microbes, such as bacterial flagellin and fungal chitin. • Binding of PAMPs to PRRs stimulates signal transduction pathways that lead to many responses: • Production of defensins and cytokines • Phagocytosis of invaders • Activation of natural killer cells and complement system
Concept 39.2 Innate Defenses Are Nonspecific • Phagocytes recognize pathogenic cells, viruses, or fragments of invaders and ingest them by phagocytosis.
Concept 39.2 Innate Defenses Are Nonspecific • Natural killer cells—lymphocytes that can distinguish between healthy cells and tumor cells or virus-infected cells • Initiate apoptosis in tumor cells • Can interact with adaptive defense mechanisms by lysing cells that have been tagged with antibodies
Concept 39.2 Innate Defenses Are Nonspecific • Complement system:antimicrobial proteins that act in a cascade—each protein activates the next • One complement protein binds to surface of invading cell, marking it for phagocytosis • Another protein activates the inflammation response and attracts phagocytes to site of infection • Still other proteins lyse the invading cells
Concept 39.2 Innate Defenses Are Nonspecific • The complement system can be activated by mechanisms in both the innate and adaptive immune systems. • In the latter case, the complement cascade is initiated by binding of a complement protein to an antibody on the surface of the invading cell.
Concept 39.2 Innate Defenses Are Nonspecific • Cytokines: signaling proteins produced in response to PRR activation • Includes interferons, which help increase resistance of neighboring cells to infection. They bind to uninfected cells and trigger pathways that prevent viral reproduction, and they stimulate breakdown of bacterial and viral proteins. • Interferons can be induced by molecules such as double-stranded viral RNA.
Concept 39.2 Innate Defenses Are Nonspecific • Inflammation is a coordinated response to infection or injury; it results in redness, swelling, heat, and pain at the damaged site. • It isolates damage, recruits defense cells and molecules to the site, and promotes healing. • Mast cells are the first responders, and they release chemical signals: • Tumor necrosis factor—cytokine that kills target cells and activates immune cells
Concept 39.2 Innate Defenses Are Nonspecific • Prostaglandins—initiate inflammation in nearby tissues; many other roles • Histamine—amino acid derivative that increases permeability of blood vessels to white blood cells and proteins so they can act on nearby tissues
Concept 39.2 Innate Defenses Are Nonspecific • Redness and heat result from dilation of blood vessels in the area. • Phagocytes enter the area and engulf pathogens and dead cells. • Phagocytes produce cytokines—some can signal the brain to produce fever. • Increased body temperature accelerates lymphocyte production and phagocytosis, thus speeding the immune response. Fever inhibits growth of some pathogens.
Figure 39.4 Interactions of Cells and Chemical Signals Result in Inflammation
Concept 39.2 Innate Defenses Are Nonspecific • Pain of inflammation is from pressure due to swelling, action of leaked enzymes on nerve endings, and prostaglandins, which increase sensitivity of nerve endings to pain. • Pus is a mixture of leaked fluid and dead cells. It gets consumed by macrophages. • Platelets (blood cell fragments) appear near a wound to promote healing. They produce growth factors that stimulate skin cells to divide.
Concept 39.2 Innate Defenses Are Nonspecific • The inflammation response can be too strong: • Allergic reaction: a nonself molecule that is normally harmless binds to mast cells, causing the release of histamine and subsequent inflammation. • Autoimmune diseases: the immune system fails to distinguish between self and nonself and attacks tissues in the organism’s own body.
Concept 39.2 Innate Defenses Are Nonspecific • Sepsis: inflammation due to a bacterial infection does not remain local. • Dilation of blood vessels throughout the body can result in a dangerous drop in blood pressure.
Concept 39.3 The Adaptive Immune Response Is Specific • Early experiments showed that factors in the blood were important in adaptive immunity. • These factors were later identified as antibody proteins. • Development of immunity from antibodies received from another individual is called passive immunity.
Concept 39.3 The Adaptive Immune Response Is Specific • Adaptive immunity has four key features: • Specificity • Distinguishing self from nonself • Diversity • Immunological memory
Concept 39.3 The Adaptive Immune Response Is Specific • Specificity • Lymphocytes play the crucial role. • Nonself substances are called antigens. • T cell receptors and antibodies made by B cells bind to specific antigens. • Each T cell and each antibody-producing B cell is specific for a single antigen.
Concept 39.3 The Adaptive Immune Response Is Specific • Sites on the antigens recognized by the immune system are called antigenic determinants, or epitopes.
Concept 39.3 The Adaptive Immune Response Is Specific • Antigens are usually proteins or polysaccharides, and there can be multiple antigens on a single bacterium. • A single antigenic molecule can have multiple, different antigenic determinants. • Antigenic determinants are often referred to as antigens.
Concept 39.3 The Adaptive Immune Response Is Specific • Distinguishing self from nonself • An individual’s immune system must be able to recognize the body’s own antigens and not attack them. • When B and T cells encounter antigens during their early development, any cells that show potential to mount an immune response to self antigens undergo apoptosis (clonal deletion).
Concept 39.3 The Adaptive Immune Response Is Specific • Failure of clonal deletion can lead to autoimmunity. • In diseases such as systemic lupus erythematosis (SLE) or Hashimoto’s thyroiditis, immune cells mount a response against normal tissues.
Concept 39.3 The Adaptive Immune Response Is Specific • Diversity • The immune system must respond to a wide variety of pathogens and a variety of genetic strains of those pathogens. • Humans can respond specifically to about 10 million different antigens. • The body generates a pool of lymphocytes from which specific cells are selected when needed.
Concept 39.3 The Adaptive Immune Response Is Specific • Diversity is generated primarily by DNA changes that occur just after B and T cells are formed. • The adaptive immune system is “predeveloped”—all of the machinery available to respond to an immense diversity of antigens is already there, even before the antigens are encountered.
Concept 39.3 The Adaptive Immune Response Is Specific • Antigen binding “selects” a particular B or T cell for proliferation. • Clonal selection: a particular lymphocyte is selected via binding and activation, and then it proliferates to generate a clone