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The Immune System Chapter 43 A macrophage engulfing bacteria The Body’s Defenses Smallpox virus The Body’s Defenses Anthrax bacteria The Body’s Defenses Protozoan Trypanosoma (African sleeping sickness) The Body’s Defenses Sac fungus Candida albicans (yeast infections) The Body’s Defenses Heartworm nematodes... How does the human body defend against invaders? INNATE IMMUNITY Rapid responses to a broad range of microbes External defenses Invading microbes (pathogens) ACQUIRED IMMUNITY Slower responses to specific microbes Internal defenses Skin Phagocytic cells Mucous membranes Antimicrobial proteins Secretions Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Figure 43.2 Skin is an inhospitable barrier of dead, dry cells, & secretions containing oil & lactic acid Mucous membranes in respiratory, digestive & urogenital tracts secrete mucus & antibiotic chemicals (e.g., lysozyme, which digests bacterial cell walls) How does the human body defend against invaders? INNATE IMMUNITY Rapid responses to a broad range of microbes External defenses Invading microbes (pathogens) ACQUIRED IMMUNITY Slower responses to specific microbes Internal defenses Skin Phagocytic cells Mucous membranes Antimicrobial proteins Secretions Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Figure 43.2 If external defenses are not effective – nonspecific, innate response Four types of phagocytic leucocytes (WBCs) engulf invaders E.g., macrophages, dendritic cells If external defenses are not effective – nonspecific, innate response Microbes Macrophage Vacuole Lysosome Figure 43.4 If external defenses are not effective – nonspecific, innate response Natural killer cells (WBCs) – destroy infected cells & cancer cells by inducing apoptosis (programmed cell death) If external defenses are not effective – nonspecific, innate response Antimicrobial proteins – (e.g., lysozyme) produced by many cells of the body, often in response to infection; actively destroy microbes If external defenses are not effective – nonspecific, innate response Local inflammatory response – injury or pathogens can cause mast cells of connective tissues to release histamine, triggering dilation and increased permeability of capillaries Fever – systemic (widespread) response that increases the body’s thermostat How does the human body defend against invaders? INNATE IMMUNITY Rapid responses to a broad range of microbes External defenses Invading microbes (pathogens) ACQUIRED IMMUNITY Slower responses to specific microbes Internal defenses Skin Phagocytic cells Mucous membranes Antimicrobial proteins Secretions Inflammatory response Natural killer cells Humoral response (antibodies) Cell-mediated response (cytotoxic lymphocytes) Figure 43.2 Immune system – mounts attack on specific disease agents Circulatory System Immune System Lymphatic System Immune system – mounts attack on specific disease agents 2 main types of lymphocytes (WBCs): B cells – produced in bone marrow differentiate in bone marrow T cells – produced in bone marrow differentiate in thymus Mature B and T cells are found throughout the body in lymph and blood Immune system – mounts attack on specific disease agents 2 main types of lymphocytes (WBCs): Lymphoid stem cell Bone marrow Thymus B cell T cell Blood, lymph, and lymphoid tissues Figure 43.10 RECOGNITION Lymphocytes recognize and respond to particular microbes and foreign molecules, i.e., they display specificity A foreign molecule that induces an immune response is known as an antigen RECOGNITION Multiple antibodies may recognize the same antigen by different epitopes (small accessible portions of the larger molecule) Fig. 43.7 RECOGNITION B cells produce antibodies, that are either secreted out of the cells or remain embedded in the B cell membranes, and that bind to antigens RECOGNITION B cells produce antibodies, that are either secreted out of the cells or remain embedded in the B cell membranes, and that bind to antigens T cells have T-cell receptors, embedded in their cell membranes, that bind to antigens RECOGNITION Even though many receptors (antibodies or T-cell receptors) encounter a given type of antigen, only the receptors that are compatible will bind to them Illustrated here for B cells, but the process for T cells is similar Fig. 43.12 This process is known as clonal selection RECOGNITION Secreted antibodies constitute a group of proteins called immunoglobulins Antibodies have 2 heavy chain and 2 light chain subunits Each subunit has a constant region and a variable region The variable region can bind to an antigen Fig. 43.8 RECOGNITION of non-self molecules Construction of antibodies (and T-cell receptors) Millions of antigens are recognized by randomly combining the protein products of hundreds of genes Card analogy: although there are only 52 cards in the deck, random combinations can produce an enormous number of different hands Construction of antibodies B Construction of antibodies B B Construction of antibodies B B B RECOGNITION of self molecules In a healthy immune system, as B and T cells mature they are destroyed by apoptosis if they attack self molecules Healthy, mature B and T cells then have the capacity to distinguish self from non-self molecules RECOGNITION of self molecules Almost all cells in an individual human’s body have major histocompatibility complex (MHC) glycoproteins embedded in their cell membranes Class I MHC molecules are found on almost every nucleated cell Class II MHC molecules are restricted to a few specialized cells, including macrophages, dendritic cells, B cells, etc. RECOGNITION of self molecules MHC glycoproteins migrate to the cell membrane after they are produced MHC glycoproteins pick up molecules from the cytosol that are presented at the cell’s surface T cells bind to MHC glycoproteins and the molecules they present An individual’s own MHC glycoproteins, and molecules of its own body that the MHC glycoproteins present, are treated as self RECOGNITION of non-self molecules However, T cells treat foreign molecules presented by MHC glycoproteins as antigens Fig. 43.9 RECOGNITION of non-self molecules Cytotoxic T cells bind to cells that carry Class I MHC glycoproteins Fig. 43.9 RECOGNITION of non-self molecules Helper T cells bind to cells that carry Class II MHC glycoproteins Fig. 43.9 ATTACK & MEMORY The B and T cells that recognize a given foreign antigen produce two types of clones: effector cells (attackers) and memory cells Illustrated here for B cells, but the process for T cells is similar Fig. 43.12 ATTACK & MEMORY The B and T cells that first recognize a given foreign antigen are short lived, whereas immune memory cells can have long lifetimes Illustrated here for B cells, but the process for T cells is similar Fig. 43.12 ATTACK & MEMORY Memory cells help produce a secondary immune response that is faster, of greater magnitude, and of longer duration than the primary immune response Fig. 43.13 ATTACK & MEMORY There are two types of immune response: Humoral response B cells and antibodies Attack antigens that have not yet infected cells (toxins, bacteria, and viruses in body fluids) Deactivate, coat, and clump antigens (which are then often engulfed and destroyed by macrophages) ATTACK & MEMORY There are two types of immune response: Cell-mediated response T cells Attack antigens after they have entered cells, as well as fungi, protozoa, and parasitic worms Activated T cells kill antigen-containing cells by creating pores in their cell membranes RECOGNITION, ATTACK, & MEMORY Cell-mediated response Humoral response Involves the activation and clonal selection of B cells First exposure to antigen Infected cells Dendritic cells MHC I MHC II Antigens Activate Results in the production of antibodies that circulate in the blood and lymph Activate B cell Helper T cell Cytokines activate Memory B cells Active and memory helper T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Cytotoxic T cell Gives rise to Gives rise to Gives rise to Plasma cells Activate Memory cytotoxic T cells Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues Figure 43.14 RECOGNITION, ATTACK, & MEMORY Cell-mediated response Humoral response First exposure to antigen Infected cells Dendritic cells MHC I MHC II Antigens Activate Activate B cell Helper T cell Plasma cells Activate Cytokines activate Memory B cells Active and memory helper T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Cytotoxic T cell Gives rise to Gives rise to Gives rise to Involves the activation and clonal selection of cytotoxic T cells Memory cytotoxic T cells Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues Figure 43.14 Cytotoxic T cells directly destroy certain target cells RECOGNITION, ATTACK, & MEMORY Cell-mediated response Humoral response First exposure to antigen A primary immune response begins with the first exposure to an antigen Infected cells Dendritic cells MHC I MHC II Antigens Activate Activate B cell Helper T cell Plasma cells Cytokines activate Memory B cells Active and memory helper T cells Secrete antibodies that defend against pathogens and toxins in extracellular fluid Cytotoxic T cell Gives rise to Gives rise to Gives rise to A secondary immune response begins with a re-exposure to an antigen, and stimulates memory cells Activate Memory cytotoxic T cells Active cytotoxic T cells Defend against infected cells, cancer cells, and transplanted tissues Figure 43.14 Medical practices can augment our immune response by inhibiting invaders or enhancing the immune response Antibiotics Inhibit microbial reproduction Potent agents of natural selection Vaccines (weakened or dead microbes, or their toxins) Stimulate development of memory cells = faster response to invasion Selectively effective The immune system and blood types antigen Table 43.1 antigen antigens What happens when the immune system malfunctions? Allergies Exaggerated immune responses to otherwise benign substances What happens when the immune system malfunctions? 1. Antibodies are produced Fig. 43.20 What happens when the immune system malfunctions? 1. Antibodies are produced 2. Stems of antibodies attach to mast cells, especially in the respiratory tract Fig. 43.20 What happens when the immune system malfunctions? 1. Antibodies are produced 2. Stems of antibodies attach to mast cells, especially in the respiratory tract Fig. 43.20 3. When antibodies attached to mast cells bind antigens, the mast cells release histamine, which causes inflammation What happens when the immune system malfunctions? Autoimmune diseases The immune system lacks or loses its ability to distinguish self vs. non-self molecules, i.e., it loses its self-tolerance and produces anti-self antibodies Rheumatoid arthritis (cartilage of joints) Multiple sclerosis (mylein sheaths of neurons) Insulin-dependent diabetes mellitus (insulinsecreting cells of the pancreas) What happens when the immune system malfunctions? Immunodeficiency diseases Inhibit effective immune response; either inherited or acquired Severe Combined Immunodeficiency (SCID) An inherited disorder Acquired Immunodeficiency Syndrome (AIDS) Caused by retroviruses (Human Immunodeficiency Viruses – HIV) that especially infect helper T cells What happens when the immune system malfunctions? Adults and children estimated to be living with HIV as of the end of 2001 North America 940,000 Caribbean 420,000 Latin America 1.4 million Eastern Europe Western Europe & Central Asia 560,000 1 millionEast Asia & Pacific North Africa 1 million & Middle East South Asia 440,000 & South-East 6.1 million Sub-Saharan Africa 28.1 million Total: 40 million Australia & New Zealand 15,000 What happens when the immune system malfunctions? Estimated number of deaths from AIDS during 2001 North America 20,000 Caribbean 30,000 Latin America 80,000 Eastern Europe & Western Europe Central Asia 6,800 North Africa & Middle East 23,000 East Asia & Pacific 35,000 South 30,000 & South-East Asia Sub-Saharan Africa 2.3 million Total: 3 million 400,000 Australia & New Zealand 120 What happens when the immune system malfunctions? The global AIDS epidemic HIV destroy helper T cells – Victims die from other diseases Transmission – Direct contact between broken skin, mucous membranes & body fluids No cure – Treatments = inhibitors of reverse-transcriptase and protease – Problem = virus evolves quickly How to reduce your risk – Practice safe sex – Avoid used needles What happens when the immune system malfunctions? Cancer Malfunction in cell production combined with a lack of recognition by the immune system of aberrant cells or too many of them Uncontrolled growth = tumor Causes Carcinogens, viruses, inheritance No guaranteed cure Most treatments also destroy healthy cells How to reduce your risk Reduce exposure to carcinogens