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Chapter 36 Defenses Against Disease Lecture Outlines by Gregory Ahearn, University of North Florida Copyright © 2011 Pearson Education Inc. Chapter 36 At a Glance 36.1 What Are the Mechanisms of Defense Against Disease? 36.2 How Do Nonspecific Defenses Function? 36.3 What Are the Key Components of the Adaptive Immune Response? 36.4 How Does the Adaptive Immune System Recognize Invaders? 36.5 How Does the Adaptive Immune System Launch an Attack? Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Chapter 36 At a Glance (continued) 36.6 How Does the Adaptive Immune System Remember Its Past Victories? 36.7 How Does Medical Care Assist the Immune Response? 36.8 What Happens When the Immune System Malfunctions? 36.9 How Does the Immune System Combat Cancer? Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.1 What Are the Mechanisms of Defense Against Disease? The world is teeming with microscopic living organisms called microbes, which include bacteria, protists, and fungi; and viruses, which are not considered to be alive – Most microbes live in water or the soil; most that live in animal bodies do not harm them and may be beneficial – When microbes cause disease, they are called pathogens – Most microbial diseases, such as cholera, measles, plague, tetanus, and chicken pox, have been with humans for thousands of years – New, more deadly strains of familiar pathogens are called emerging infectious diseases Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.1 What Are the Mechanisms of Defense Against Disease? Emerging infectious diseases – Since the early 1980s, several viruses have emerged as serious threats to human health, including HIV, Ebola virus, West Nile virus, SARS, swine flu, and bird flu – One strain of the common intestinal bacterium E. coli, which is normally harmless, can cause food poisoning – Some Staphylococcus bacteria that normally cannot penetrate the skin will cause severe infections or fatal toxic shock syndrome when they enter the body Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.1 What Are the Mechanisms of Defense Against Disease? Vertebrate animals have three major lines of defense against disease – Nonspecific external barriers – Nonspecific internal defenses – Specific internal defenses Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Levels of Defense Against Disease Nonspecific External Barriers skin, mucous membranes If these barriers are penetrated, the body responds with Innate Immune Response phagocytic and natural killer cells, inflammation, fever If the innate immune response is insufficient, the body responds with Adaptive Immune Response cell-mediated immunity, humoral immunity Biology: Life on Earth, 9e Fig. 36-1 Copyright © 2011 Pearson Education Inc. 36.1 What Are the Mechanisms of Defense Against Disease? Vertebrate animals have three major lines of defense against disease (continued) – Nonspecific external barriers – These barriers prevent most disease-causing microbes from entering the body – They are primarily anatomical structures, such as skin and cilia, and secretions such as tears, saliva, and mucus – These barriers cover the external surfaces of the body and line the body cavities that come in contact with the external environment such as the surfaces of the respiratory, digestive, and urogenital tracts Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.1 What Are the Mechanisms of Defense Against Disease? Vertebrate animals have three major lines of defense against disease (continued) – Nonspecific internal defenses – If the external barriers are breached, a variety of nonspecific internal defenses, collectively called the innate immune response, swing into action – Components of this response include: – White blood cells, which engulf foreign particles or destroy infected cells – Chemicals released by damaged cells and proteins released by white blood cells that trigger inflammation and fever – These responses operate regardless of the exact nature of the invader, neutralizing the threat Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.1 What Are the Mechanisms of Defense Against Disease? Vertebrate animals have three major lines of defense against disease (continued) – Specific internal defenses – The final line of defense is the adaptive immune response, in which immune cells selectively destroy specific invading microbes and toxins and then remember the invader – This allows for a rapid response to the invader if it reappears in the future Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Table 36-1 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Table 36-2 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.1 What Are the Mechanisms of Defense Against Disease? Invertebrate animals possess the first two lines of defense – Invertebrates lack adaptive immune responses and must rely on the two nonspecific defenses that include: – External skeletons – Slimy secretions – White blood cells that attack pathogens and secrete proteins to neutralize the invaders or the toxins they release – Defensive proteins, such as lysosome, are similar in vertebrates and invertebrates, suggesting a common ancestor among most of today’s animal species Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? The ideal defenses are barriers that prevent invaders from entering the body in the first place If these barriers are breached, however, the body has several nonspecific methods of killing a wide variety of invading microbes Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? The skin and mucous membranes form external barriers to invasion – The first line of defense consists of two surfaces with direct exposure to the environment –The skin –The mucous membranes of the digestive, respiratory, and urogenital tracts Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? The skin and its secretions block entry and provide an inhospitable environment for microbial growth – The skin is a barrier to microbes – The outer surface of the skin consists of dry, dead cells filled with tough proteins that do not allow the microbes to obtain the water and nutrients they need to survive – The secretions from sweat and sebaceous glands contain natural antibiotics, such as lactic acid, that inhibit the growth of many bacteria and fungi Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? Antimicrobial secretions, mucus, and ciliary action defend the mucous membranes against microbes – Mucous membrane secretions trap microbes entering the nose or mouth – They contain antibacterial proteins, including lysozyme, which kills bacteria by digesting their cell walls, and defensin, which makes holes in bacterial plasma membranes – Cilia on the membranes sweep up the mucus, so it is swallowed or coughed or sneezed out of the body Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. The Protective Function of Mucus Bacteria trapped by mucus and cilia Fig. 36-2 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? – If the microbes are swallowed, they enter the stomach, where protein-digesting enzymes and extreme acidity is lethal to them – The intestines contain bacteria that, while harmless to humans, secrete substances that destroy invading bacteria or fungi – In the urinary tract, the slight acidity of urine inhibits bacterial growth – In females, acidic secretions and mucus help protect the vagina – Tears, urination, diarrhea, and vomiting all help to expel invaders – Despite these defenses, many disease-causing microbes enter the body through the mucous membranes or through cuts in the skin Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? The innate immune response combats invading microbes – Microbes that penetrate the skin or mucous membranes encounter an array of internal defenses, collectively called innate immunity – Innate immune responses are nonspecific—that is, they attack many different types of microbes rather than targeting particular invaders Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? Innate immune responses fall into three categories: – White blood cells, which are also called leukocytes, attack and destroy invading cells or the body’s own cells if they have been infected by viruses – The inflammatory response recruits leukocytes to the site of a wound and walls off the injured area, isolating the infected tissue from the rest of the body – Fever is produced when microbes start a major infection in the body, which both slows down microbial reproduction and enhances the body’s own fighting abilities Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? Phagocytic leukocytes and natural killer cells destroy invading microbes – The body has several types of leukocytes, collectively known as phagocytes, which ingest foreign invaders and cellular debris by phagocytosis – Three important types of phagocytes are: – Macrophages – Neutrophils – Dendritic cells – These cells travel within the bloodstream, ooze through capillary walls, and patrol the body’s tissues, where they consume bacteria and other foreign elements Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. The Attack of the Macrophages Fig. 36-3 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? Phagocytic leukocytes and natural killer cells destroy invading microbes (continued) – Natural killer cells are another type of leukocyte, which strike primarily at the body’s own cells that have become cancerous or have been invaded by viruses – The surfaces of normal body cells display proteins of the major histocompatibility complex (MHC), identifying the cell as “self” – Natural killer cells kill any “nonself” cells they encounter by releasing proteins that bore holes in the infected or cancerous cell’s membranes and then secrete enzymes through the holes that kill the infected cell Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? The inflammatory response attracts phagocytes to injured or infected tissue – The inflammatory response causes tissues to become warm, red, swollen, and painful – This defense mechanism has several functions: –It attracts phagocytes to infected or injured tissue –It promotes blood clotting –It initiates protective behavior by causing pain Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? The inflammatory response begins when damaged cells release chemicals that cause certain cells in the connective tissue, called mast cells, to release histamine – Histamine relaxes the smooth muscle surrounding arterioles, increasing blood flow and causing capillary walls to become leaky –Extra blood flowing through leaky capillaries drives fluid from the blood and into the wounded area, causing redness, warmth, and swelling Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? The inflammatory response (continued) – Other chemicals released by the wounded cells, mast cells, and by the microbes themselves attract macrophages, neutrophils, and dendritic cells – These cells consume bacteria, dirt, and cellular debris – In some cases pus, a thick, whitish mixture of dead bacteria, tissue debris, and white blood cells, may accumulate – Other chemicals released by injured cells initiate blood clotting to reduce blood loss and prevent more microbes from entering the blood stream Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Author Animation: The Inflammatory Response Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. The Inflammatory Response dead cell layer 1 Tissue damage carries bacteria into the wound epidermis 2 Wounded cells release chemicals (red) that stimulate mast cells 3 Mast cells release histamine (blue) dermis 4 Histamine increases capillary blood flow and permeability 5 Phagocytes leave the capillaries and ingest bacteria and dead cells Fig. 36-4 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? Fever combats large-scale infections – If invaders breach these defenses and mount a full-blown infection, they may trigger a fever, which is an important part of the body’s defense against infection – The human thermostat, located in the hypothalamus of the brain, is set at 97–99ºF – During an infection, macrophages release a protein called endogenous pyrogen that travels to the hypothalamus and raises the thermostat’s set point – Elevated body temperature increases phagocytic activity and slows bacterial reproduction Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.2 How Do Nonspecific Defenses Function? Fever combats large-scale infections (continued) – Fever also stimulates cells infected by viruses to produce a protein called interferon, which travels to other cells and increases their resistance to viral attack; interferon also stimulates natural killer cells that destroy virusinfected body cells – In an experiment, volunteers were infected with a virus and given aspirin (to reduce fever) or a placebo – Those with aspirin had more viruses in their noses and coughed out more viruses than the controls because fevers in the controls helped reduce the viral infection Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.3 What Are the Key Components of the Adaptive Immune System? External barriers and the nonspecific defenses— phagocytic cells, natural killer cells, the inflammatory response, and fever—may be penetrated by specific microbes – When these mechanisms are breached, the body mounts a highly specific and coordinated adaptive immune response directed against the particular organism that successfully colonized the body – The adaptive immune response attacks one specific type of microbe, overcomes it, and provides future protection against that microbe but no others Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.3 What Are the Key Components of the Adaptive Immune System? The adaptive immune system consists of cells and molecules dispersed throughout the body – The adaptive immune system (or simply the immune system) is distributed throughout the body, with concentrations of cells in certain locations – It consists of three major components: immune cells, tissues and organs, and secreted proteins Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.3 What Are the Key Components of the Adaptive Immune System? Immune cells – The adaptive immune response is produced by interactions among several types of white blood cells, such as macrophages, dendritic cells, and lymphocytes – Macrophages and dendritic cells play a role in both the innate and adaptive immune responses – The key cellular players in the adaptive immune response are B cells and T cells, which arise from stem cells in the bone marrow – Some of the stem cells complete their development in the bone marrow, becoming B (for bone) cells – Others migrate from the marrow to the thymus, where they develop into T (for thymus) cells Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.3 What Are the Key Components of the Adaptive Immune System? Tissues and organs – The cells of the immune system are produced and reside in a variety of locations, including the vessels of the lymphatic system, the lymph nodes, the thymus, the spleen, and patches of specialized connective tissue such as the tonsils Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.3 What Are the Key Components of the Adaptive Immune System? Tissues and organs (continued) – Lymph flows through the lymph nodes, which contain masses of macrophages and specialized white blood cells called lymphocytes – The thymus is located beneath the breastbone, slightly above the heart, and is essential for development of some immune cells Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.3 What Are the Key Components of the Adaptive Immune System? Tissues and organs (continued) – The spleen, located in the abdominal cavity, is a fist-sized organ that filters blood, exposing it to white blood cells that destroy foreign particles and aged red blood cells – The tonsils are located in the throat and contain macrophages and other white blood cells that sample microbes entering the body through the mouth, destroying many of them and often starting an adaptive immune response Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. The Lymphatic System Contains Much of the Immune System thymus thoracic duct bone marrow spleen lymph vessels lymph nodes valve prevents backflow lymph node chambers packed with white blood cells Biology: Life on Earth, 9e Fig. 36-5 Copyright © 2011 Pearson Education Inc. 36.3 What Are the Key Components of the Adaptive Immune System? Secreted proteins – Leukocytes and some other cells secrete many different proteins, collectively called cytokines, that are used for communication between cells – A large number of proteins in the blood, collectively called complement, assist the immune system in killing invading microbes – Some cytokines and complement proteins are involved in both the innate and adaptive responses – A subset of leukocytes, called B cells, produce antibodies that help the immune system recognize invading microbes and destroy them Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.3 What Are the Key Components of the Adaptive Immune System? All adaptive immune responses include the same three steps: 1. Lymphocytes recognize an invading microbe and distinguish the invader from self 2. They launch an attack 3. They retain a memory of the invader that allows them to ward off future infections by the same type of microbe Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? To understand how the immune system recognizes invaders and initiates a response, we must answer three related questions: – How do lymphocytes recognize foreign cells and molecules? – How can lymphocytes produce specific responses to so many different types of cells and molecules? – How do they avoid mistaking the body’s own cells and molecules for invaders? Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? The adaptive immune system recognizes invaders’ complex molecules – Bacteria and humans differ from one another because each contains specific, complex molecules that the other does not have – These large, complex molecules are called antigens, because they are “antibody generating” molecules that can provoke an immune response, including the production of antibodies Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? The adaptive immune system recognizes invaders’ complex molecules (continued) – Antigens are often located on the surfaces of invading microbes – Many viral antigens become incorporated into the plasma membranes of infected body cells – Viral or bacterial antigens are also “displayed” on the plasma membranes of dendritic cells and macrophages that engulf them – Other antigens, such as toxins released by bacteria, may be toxins in the blood plasma, lymph, or other extracellular fluids Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibodies and T-cell receptors recognize and bind to foreign antigens – Lymphocytes generate two types of proteins that recognize, bind, and help to destroy specific antigens: –Antibody proteins, produced by B cells and their offspring –T-cell receptor proteins, produced by T cells Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibodies recognize and help destroy invaders – Antibodies are Y-shaped proteins composed of two pairs of peptide chains: one pair of identical large (heavy) chains and one pair of identical small (light) chains – Both heavy and light chains consist of a constant region, which is similar in all antibodies of the same type, and a variable region that differs among individual antibodies – Antibodies have two functional parts: the “arms” of the Y and the “stem” of the Y Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibodies recognize and help destroy invaders (continued) – The variable regions at the arm tips form sites that bind antigens – Each binding site has a particular size, shape, and electrical charge so that only certain molecules can fit in and bind to the antibody – The sites are so specific that each antibody can bind only a few, very similar, types of antigen molecules Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Antibody Structure antigen light chain heavy chain Variable regions form antigen binding sites Constant regions are the same in all antibodies of a given type Fig. 36-6 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibodies recognize and help destroy invaders (continued) – Antibodies may function as receptors, binding to specific antigens and eliciting a response to them, or as effectors, helping them destroy cells or molecules that bear the antigen –As a receptor, the stem of the antibody anchors the antibody in the plasma membrane of the B cell that produced it, while its two arms stick out from the B cell, sampling the blood and lymph for antigen molecules Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? – Antibodies (continued) –When the arm of the antibody encounters an antigen with a compatible chemical structure, it binds to it and initiates a response in the B cell –As effectors, many antibodies are secreted into the bloodstream, where they neutralize poisonous antigens, destroy microbes that bear antigens, or attract macrophages that engulf the antigen-bearing microbes Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Antibodies Can Serve as Receptors or Effectors macrophage B cell antibody antigen antibody antigen (a) Antibody receptor function (b) Antibody effector function Fig. 36-7 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? T-cell receptors recognize invaders and help trigger an immune response – T-cell receptors are found only on the surfaces of T cells – Like antibodies, they consist of peptide chains that form highly specific binding sites for antigens – Unlike antibodies, T-cell receptors are never released into the bloodstream, and they do not directly contribute to the destruction of invading microbes or toxic molecules – A T-cell receptor triggers a response in its T cell when the receptor binds an antigen on a cell that has ingested an invading microbe Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? The immune system can recognize millions of different antigens – The adaptive immune system recognizes and responds to virtually all of the harmful antigens that may be encountered, because B and T cells produce millions of different antibodies and T-cell receptors – How can the body produce so many? Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibody genes are assembled from segments of DNA – There are no genes for entire antibodies – Instead, B cells have genes that code for parts of antibodies—constant regions (C), variable regions (V), and “joining” (J) or “diversity” (D) regions that connect the two – The constant region in each chain is the same for any antibody of a particular type – Humans have about 200 genes for the variable region of heavy chains, and 50 and 6 genes, respectively, for the diversity and joining regions Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibody genes are assembled from segments of DNA (continued) – There are 150 genes for the variable region of the light chain, and 5 genes for the joining region – As each B cell develops, it randomly cuts out and discards all but one gene of each type, and assembles two unique antibody genes from the genes it keeps – A heavy-chain gene, consisting of one variable, one diversity, one joining, and one constant region – A light-chain gene, consisting of one variable, one joining, and one constant region – Antibodies are produced from these composite genes Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Recombination Produces Antibody Genes heavy chain V2 V1 V3 light chain V4 V200 V2 V1 V3 D1 D2 V4 D50 J1 J1 V150 J2 J2 J3 J4 J6 CM CD CG CE CA J5 CK (a) Genes for parts of the heavy chain (top) and light chain (bottom) of antibodies heavy chain V2 D11 J4 CG light chain V80 J2 V87 D8 CK J1 V101 J5 Cell 1 CG V111 D40 J1 CK J1 V6 Cell 2 CG CK Cell 3 (b) Complete antibody genes in three different B cells V2 D11 J4 V80 J2 CK CG V80 J2 CK CG Cell 1 V87 D8 J1 V101 J5 CK V101 J5 CK CG CG Cell 2 (c) Antibodies synthesized by these three B cells Biology: Life on Earth, 9e V111 D40 J1 V6 J1 CK CG V6 J1 CK CG Cell 3 Fig. 36-8 Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibody genes are assembled from segments of DNA (continued) – The random assembly of composite antibody genes yields about 3 million unique combinations – Further diversity arises because only part of each joining region is actually used in any given antibody – Immunologists estimate that 15 to 20 billion unique antibodies are possible – The result is that each B cell produces an antibody that is different from the one produced by every other B cell, except its own daughter cells Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibody genes are assembled from segments of DNA (continued) – T-cell receptors are made from different genes, but the process is similar – There are more parts available for constructing T-cell receptor genes, so there may be as many as a quadrillion different possible T-cell receptors! Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? Antibodies and T-cell receptors are not tailormade for antigens – B and T cells do not design antibodies and T-cell receptors to fit invading antigens – Instead, the immune system randomly synthesizes millions of different antibodies and Tcell receptors – Antigens almost always encounter antibodies or T-cell receptors that will bind them Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? The immune system distinguishes self from non-self – The surface of body cells bear large proteins and polysaccharides that are collectively called the major histocompatibility complex (MHC), which are unique to each person – If the cells of the immune system bind to the antigens of the MHC, they undergo apoptosis, or “programmed cell death” – Therefore, the immune system distinguishes self from non-self by retaining only those immune cells that do not respond to the body’s own molecules Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.4 How Does the Adaptive Immune System Recognize Invaders? The immune system distinguishes self from non-self (continued) – Not all self-reactive B and T cells are eliminated in this way – Although no one understands the mechanism, regulatory T cells prevent these remaining selfreacting lymphocytes from attacking the body and causing an autoimmune disease – A person’s MHC proteins act as foreign antigens in other people’s bodies during organ transplants; a donor must be found whose MHC proteins are similar to the recipient in order to reduce effects of the immune system on the transplanted organ Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? The adaptive immune system simultaneously launches two types of attack against microbial invaders: – Humoral immunity is provided by B cells and the antibodies that they secrete into the blood that attack pathogens outside the body’s cells – Cell-mediated immunity is produced by a type of T cell called the cytotoxic T cell that attacks infected body cells, killing both the cell and any pathogens inside it Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? An immune response takes time to develop – While a person may have millions of different antibodies and T-cell receptors, there is only one, or a few, cells bearing each type of antibody or Tcell receptor – The immune system requires time to be effective because cells recognizing the invader must multiply and differentiate – It takes 1 or 2 weeks to mount a strong immune response after the first exposure to an invading microbe Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. An Effective Immune Response Takes Time to Develop Fig. 36-9 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Humoral immunity is produced by antibodies dissolved in the blood – Each B cell bears its own unique antibodies on its surface – When an infection occurs, the antibodies borne by a few B cells can bind to antigens on the invader – Antigen–antibody binding causes these B cells, but no others, to divide rapidly by the process of clonal selection, producing a population of “clones” of the original cell that was selected after responding to a particular invading antigen Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Humoral immunity is produced by antibodies dissolved in the blood (continued) – The daughter cells differentiate into two cell types: – Memory B cells, which do not release antibodies but play an important role in future immunity to the invader that stimulated their production – Plasma cells, which become enlarged and produce a huge quantity of specific antibodies that are released into the bloodstream – Clonal selection, multiplication of activated B cells, differentiation into memory and plasma cells, and antibody secretion by plasma cells all take time to overcome an infection Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Author Animation: B Cell Activation and Differentiation Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Clonal Selection Among B Cells by Invading Antigens antigens antibodies 1 Invading antigens bind to antibodies on one B cell (dark blue) 2 The B cell “selected” by the antigen multiplies rapidly 3 A large clone of genetically identical B cells is produced 4 These B cells differentiate into plasma cells and memory B cells plasma cell 5 Plasma cells release antibodies into the blood Biology: Life on Earth, 9e endoplasmic reticulum memory B cell antibodies Fig. 36-10 Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Humoral antibodies have multiple modes of action – Antibodies in the blood combat invading molecules or microbes in three ways: 1. The circulating antibodies may bind to a foreign molecule, virus, or cell and render it harmless by a process called neutralization – An example of neutralization is an antibody covering the active site of a toxic enzyme in snake venom Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Antibodies Neutralize Toxic Molecules snake venom enzyme active site antibody Antibodies block the active site of the toxic enzymes in snake venom Biology: Life on Earth, 9e Fig. 36-11 Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Antibodies in the blood combat invading molecules or microbes in three ways (continued) 2. Antibodies may coat the surface of invading molecules, viruses, or cells and make it easier for phagocytic cells to destroy them – Macrophages recognize the antibody stems sticking out into the blood, then engulf the antibody-coated invaders and digest them Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Antibodies in the blood combat invading molecules or microbes in three ways (continued) 3. When antibodies bind to antigens on the surface of a microbe, the antibodies interact with complement proteins that are always present in the blood – Some of the complement proteins punch holes in the plasma membranes of the microbe, killing it – Other complement proteins promote phagocytosis of the invaders Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Humoral immunity fights invaders that are outside cells – Antibodies are large proteins that cannot enter cells; therefore, the humoral response is effective only against bacteria, bacterial toxins, or fungi when they are outside of cells, in the blood or extracellular fluid – Viruses are vulnerable when they are outside of body cells, but after they enter a body cell, they are safe from antibody attack – Cell-mediated immune reactions are required to fight viruses once they have entered body cells Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Cell-mediated immunity is produced by cytotoxic T cells – Cell-mediated immunity, produced by cytotoxic T cells, is the body’s primary defense against cells that are cancerous or that have been infected by viruses – Cytotoxic T cells in the blood may bump into an infected body cell that is displaying a viral protein on its surface – The cytotoxic T cell receptor will bind to the viral protein and squirt proteins onto the surface of the infected cell, punching holes in the cell and killing it, sparing new body cells a future infection – Cancerous cells also display unusual proteins that the cytotoxic T cells recognize as foreign, and are killed as a result Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Cell-mediated Immunity in Action Fig. 36-12 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Helper T cells enhance both humoral and cell-mediated immune responses – B cells and cytotoxic T cells are ineffective without assistance from helper T cells – Helper T cells bear receptors that bind to antigens displayed on the surfaces of dendritic cells or macrophages that have engulfed and digested invading microbes – When its receptor binds an antigen, a helper T cell multiplies rapidly, and its daughter cells differentiate and release cytokinins that stimulate cell division and differentiation in both B cells and cytotoxic T cells Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.5 How Does the Adaptive Immune System Launch an Attack? Helper T cells enhance both humoral and cellmediated immune responses (continued) – Both B cells and cytotoxic T cells are most effective against infection when they receive stimulation by cytokinins from helper T cells – Human immunodeficiency virus (HIV), which causes AIDS, kills off helper T cells, and without these cells, the immune system cannot fight off diseases that would otherwise be trivial Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. A Summary of Humoral and Cell-Mediated Immune Responses HUMORAL IMMUNITY Targets invaders outside cells (e.g., viruses, bacteria, fungi, protists, and toxins) HELPER T CELLS CELL-MEDIATED IMMUNITY Stimulate both humoral and cell-mediated Targets defective body cells (e.g., infected cells and cancer cells), transplants immunity by releasing cytokines virus viral antigen Viral antigens presented on the surfaces of dendritic cells or macrophages, and infected cells dendritic cell or macrophage infected cell B-cell antibodies bind to viral antigens and stimulate the B cells to divide and differentiate T-cell receptors bind to viral antigens antibody cytokines B cell helper T cell cytotoxic T cell Cytokines released by helper T cells stimulate B cells and cytotoxic T cells Fig. 36-13, 1 of 2 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. A Summary of Humoral and Cell-Mediated Immune Responses HUMORAL IMMUNITY Targets invaders outside cells (e.g., viruses, bacteria, fungi, protists, and toxins) HELPER T CELLS CELL-MEDIATED IMMUNITY Stimulate both humoral and cell-mediated immunity by releasing cytokines Targets defective body cells (e.g., infected cells and cancer cells), transplants antibody cytokines helper T cell B cell cytotoxic T cell Cytokines released by helper T cells stimulate B cells and cytotoxic T cells plasma cell memory B cell memory helper T cell memory cytotoxic T cell cytotoxic T cell infected cell Plasma cells secrete antibodies into the blood and extracellular fluid Memory cells confer future immunity to this virus Cytotoxic T cells release pore-forming proteins that destroy infected cells Fig. 36-13, 2 of 2 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.6 How Does the Adaptive Immune System Remember Its Past Victories? After recovering from a disease, you remain immune to that particular microbe for many years, perhaps a lifetime – Some of the daughter cells of the original B cells, cytotoxic T cells, and helper T cells that responded to the original infection differentiate into memory B cells and memory T cells that survive for many years – If the body is reinvaded by the same type of microbe, the memory cells recognize the invader and mount an immune response Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Author Animation: Humoral Versus Cell-Mediated Immunity Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.6 How Does the Adaptive Immune System Remember Its Past Victories? – Memory B cells rapidly produce a clone of plasma cells, secreting antibodies that combat this second invasion – Memory T cells produce clones of either helper T cells or cytotoxic T cells specific for the “remembered” invader – Each memory cell responds so fast and so largely in a second infection, the body fends off the attack before the person suffers any symptoms—they have become immune – Acquired immunity confers long-lasting protection against many diseases such as small pox, measles, mumps, and chicken pox Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Author Animation: Memory B Cells Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Acquired Immunity Fig. 36-14 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.7 How Does Medical Care Assist the Immune Response? Antibiotics slow down microbial reproduction – Antibiotics are chemicals that help to combat infection by slowing down the multiplication of bacteria, fungi, or protists – The occasional mutant microbe that is resistant to an antibiotic will pass on the genes for resistance to its offspring, which results in many antibiotics becoming ineffective in treating diseases – Antibiotics are not effective against viruses – Drugs are available that target different stages of the viral cycle of infection, and are used to treat HIV, severe herpes, and in some cases, the flu virus Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.7 How Does Medical Care Assist the Immune Response? Vaccinations stimulate the development of memory cells and future immunity against disease – A vaccine stimulates an immune response by exposing a person to antigens produced by a pathogen – Vaccines often consist of weakened or killed microbes, or some of the pathogen’s antigens – Exposure to these antigens results in the body producing an army of memory cells that confer immunity against living microbes of the same type Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? Allergies are misdirected immune responses – Allergies are immune reactions to harmless substances that are treated as if they were pathogens –Common allergies include those to pollen, mold spores, bee or wasp venoms, and some foods such as milk, eggs, fish, wheat, tree nuts, and peanuts Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? An allergic reaction – All allergic reaction begins when allergy-causing antigens, called allergens, enter the body and bind to “allergy antibodies” on a special type of B cell – This B cell proliferates, producing plasma cells that pour out allergy antibodies into the plasma – The antibodies attach to mast cells, mostly in the respiratory and digestive tracts Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? An allergic reaction (continued) – If allergens later bind to these attached antibodies, they trigger the release of histamine, which causes leaky capillaries and other symptoms of inflammation – In the respiratory tract, histamine increases mucous secretions and results in symptoms such as a runny nose, sneezing, and congestion typical of “hay fever” – Food allergies may cause intestinal cramps and diarrhea; some reactions are so strong that the airways may completely close, causing death by suffocation Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. An Allergic Reaction to Pollen 1 First exposure to pollen (yellow) stimulates B cells to produce “allergy” plasma cells 2 Plasma cells produce allergy antibodies mast cell plasma cell 3 Allergy antibodies bind to mast cells 4 Reexposure to pollen results in pollen binding to allergy antibodies on mast cells 5 Binding of pollen stimulates mast cells to release histamine (blue), triggering the inflammatory response Biology: Life on Earth, 9e Fig. 36-15 Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? An autoimmune disease is an immune response against the body’s own molecules – Occasionally, our immune system produces “anti-self” antibodies – The result is an autoimmune disease in which the immune system attacks a component of one’s own body, such as a type of anemia where antibodies destroy a person’s red blood cells – Type 1 diabetes may begin when the immune system attacks the insulin-secreting cells of the pancreas – Other autoimmune diseases include rheumatoid arthritis, multiple sclerosis, and systemic lupus Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? An autoimmune disease is an immune response against the body’s own molecules (continued) – There are no known cures for autoimmune diseases – Replacement therapy can alleviate the symptoms—for instance, by giving insulin to diabetics or blood transfusions to anemia victims – The autoimmune response can be reduced with drugs that suppress the immune response – This course of action also reduces responses to the everyday assaults of disease microbes, so the therapy has major drawbacks Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? Immune deficiency diseases occur when the body cannot mount an effective immune response – There are two very different disorders in which the immune system cannot combat routine infections: – Severe combined immune deficiency (SCID), a group of genetic defects in which few or no immune cells are formed – Acquired immune deficiency syndrome (AIDS), where a viral infection destroys a formerly functional immune system Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. HIV Causes AIDS Fig. 36-16 Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? Severe combined immune deficiency is an inherited disorder – A child with severe combined immune deficiency (SCID) may survive the first few months of postnatal life, protected by antibodies acquired from the mother during pregnancy – Once these antibodies are lost, common infections can prove fatal because the child lacking an immune system cannot generate an effective immune response – A form of therapy is to transplant bone marrow from a healthy donor into the child to provide enough immune cells to confer normal immune responses Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? AIDS is an acquired immune deficiency disease – The most common immune deficiency disease is acquired immune deficiency syndrome (AIDS) – AIDS is caused by human immunodeficiency viruses (HIV) that undermine the immune system by infecting and destroying helper T cells, stimulating both the cell-mediated and humoral immune responses – AIDS does not kill people directly, but AIDS victims become increasingly susceptible to other diseases as their helper T-cell populations decline Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? AIDS is an acquired immune deficiency disease (continued) – Because HIV cannot survive for long outside the body, it is transmitted only by the direct contact of broken skin or mucous membranes with virus-laden body fluids, including blood, semen, vaginal secretions, and breast milk – HIV can spread by sexual activity, by sharing needles among intravenous drug users, or through blood transfusions – HIV enters a helper T cell and hijacks the cell’s metabolic machinery, forcing it to make more viruses which then emerge, taking an outer coating of T-cell membrane with them Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? AIDS is an acquired immune deficiency disease (continued) – Early in the infection, as the immune system fights the virus, the victim may develop a fever, rash, muscle aches, headaches, and enlarged lymph nodes – Over time, the helper T cell levels drop, severely weakening the immune response – As HIV levels increase, they kill more helper T cells and the person becomes prey to other infections Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. Author Animation: HIV: The AIDS Virus Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? AIDS is an acquired immune deficiency disease (continued) – Several drugs can slow down the replication of HIV and thereby slow the progress of AIDS; unfortunately, HIV can mutate into forms that are resistant to the drugs – However, some HIV-positive individuals receiving the best medical care might now live out a normal life span Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.8 What Happens When the Immune System Malfunctions? AIDS is an acquired immune deficiency disease (continued) – The best solution would be to develop a vaccine against HIV – This is a challenge because HIV disables the immune response that a vaccine depends on – Furthermore, HIV has an incredibly high mutation rate, perhaps a thousand times faster than that of flu viruses – Lone infected individuals may harbor different strains of HIV in their blood and semen because of mutations that occurred within their bodies after they were first infected – Despite billions of dollars spent to develop a vaccine, none have proven effective Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.9 How Does the Immune System Combat Cancer? Cancer will kill more than 500,000 people in the United States this year – Approximately 40% of U.S. citizens will eventually contract some form of cancer – Cancers may be triggered by many causes, including environmental factors such as UV radiation or smoking, faulty genes, mistakes during cell division, and viruses – All these triggers produce cancer by sabotaging the mechanisms that normally control the growth of the body’s own cells Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.9 How Does the Immune System Combat Cancer? The immune system recognizes most cancerous cells as foreign – Cancer cells are self and the immune response usually does not respond to self – However, the process that causes a cell to become cancerous leads to slightly different proteins appearing on their surfaces – Natural killer cells and cytotoxic T cells encounter these new proteins, recognize them as non-self antigens, and destroy the cancer cells – Some cancer cells do not bear antigens that allow the immune system to recognize them as foreign or, as in leukemia, suppress the immune system Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.9 How Does the Immune System Combat Cancer? Vaccination can prevent some cancers – Some cancers are caused by viruses, including some cancers of the liver, mouth, throat, and penis; some types of leukemia; and probably all cervical cancers – In the United States, two vaccines are available that help prevent certain cancers: – A vaccine against hepatitis B, which reduces the risk of liver cancer – A vaccine against two human papilloma viruses, which cause most cases of cervical cancer Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.9 How Does the Immune System Combat Cancer? Vaccines may someday help to cure cancer (continued) – Some “treatment vaccines” may cure certain cancers by providing a patient with antigens commonly found on cells of the type of cancer that the patient has, often enhanced in various ways to boost the patient’s immune response against the cancer – Current trials of this type of vaccine against prostate cancer and melanoma (a type of skin cancer) are in progress – Other treatment vaccines consist of antigens from a patient’s own tumor cells, often enhanced to stimulate a stronger immune response Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.9 How Does the Immune System Combat Cancer? Vaccines may someday help to cure cancer (continued) – Still another approach is to take antigenpresenting dendritic cells from a patient, expose them to antigens from cancer cells, and force them to multiply rapidly in culture – The resulting daughter cells are then injected back into the patient – This large number of activated dendritic cells should stimulate the patient’s own anticancer immune response Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.9 How Does the Immune System Combat Cancer? Most medical treatments for cancer depend on selectively killing cancerous cells – Attempts to eliminate cancer mostly focus on surgery, radiation, and chemotherapy – Surgically removing the tumor is the first step in treating many cancers, but it can be difficult to remove all the cancerous tissue – Tumors can be treated with radiation, which can destroy even microscopic clusters of cancer cells by disrupting their DNA, thus preventing their cell division – Neither surgery nor radiation is effective against cancer that has spread throughout the body Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc. 36.9 How Does the Immune System Combat Cancer? Most medical treatments for cancer depend on selectively killing cancerous cells (continued) – Chemotherapy is commonly used to supplement surgery or radiation – Chemotherapy drugs attack the machinery of cell division, so they are somewhat selective for cancer cells, which divide more frequently than normal cells do – Chemotherapy also kills some healthy, dividing cells – Damage to dividing cells in patient’s hair follicles and intestinal lining by chemotherapy produces its wellknown side effects of hair loss, nausea, and vomiting Biology: Life on Earth, 9e Copyright © 2011 Pearson Education Inc.