Week 11 - Immune System Inflammatory Response

The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Click to edit Master title style Click to edit Master subtitle style * * * Immune System Innate (Non-specific) Adaptive (Specific) Cellular Components Humoral Components Cellular Components Humoral Components The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins Phagocytosis The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins Phagocytosis The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins Phagocytosis Phagocytosis Innate Host Defenses The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins Phagocytosis Neutrophils and macrophages are both phagocytic cells They have a variety of receptors on their cell membranes through which the infectious agents bind to the cells; they then respond by engulfing the infective agents Respiratory burst occurs which kills the bacteria Other Immune Responses Nitric oxide dependent killing – production of TNF-? induces the expression of the gene that produces nitric oxide which is toxic and can kill a microorganism near the macrophage Non-specific killer cells Phagocytosis Phagocytosis The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins Phagocytosis Neutrophils and macrophages are both phagocytic cells They have a variety of receptors on their cell membranes through which the infectious agents bind to the cells; they then respond by engulfing the infective agents Respiratory burst occurs which kills the bacteria Other Immune Responses Nitric oxide dependent killing – production of TNF-? induces the expression of the gene that produces nitric oxide which is toxic and can kill a microorganism near the macrophage Non-specific killer cells Phagocytosis Phagocytosis Specific Immunity Antibodies are effective against extracellular pathogens and carry out their tasks in three ways: Neutralization – bind to bacterial toxins or to molecules that viruses and bacteria need to gain entry into cells Opsonization – facilitates uptake by phagocytes Complement activation Specific Immunity T cell-mediated responses are effective against intracellular pathogens; the pathogen’s location mainly determines which type of T cells respond Cytotoxic T cells – express CD8 molecules and when activated kill pathogens found in cytosol Helper T cells – express CD4 molecules Inflammatory Th1 cells that eliminate pathogens residing in the vesicular system Helper Th2 cells required for antibody production by B cells against T-dependent aantigens on pathogens residing extracellularly Specific Immunity Pathogens may elicit both an antibody (humoral) and a cell-mediated response A humoral or cell-mediated response alone may not be sufficient to kill pathogens Every T cell receptor on an individual T cell has one specificity for an antigen Every B cell receptor that binds antigen is a membrane-bound immunoglobulin which has one specificity Signals are required for specific activation, and there is a lag time in specific (adaptive) immune responses The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins Phagocytosis Neutrophils and macrophages are both phagocytic cells They have a variety of receptors on their cell membranes through which the infectious agents bind to the cells; they then respond by engulfing the infective agents Respiratory burst occurs which kills the bacteria Other Immune Responses Nitric oxide dependent killing – production of TNF-? induces the expression of the gene that produces nitric oxide which is toxic and can kill a microorganism near the macrophage Non-specific killer cells Phagocytosis Phagocytosis Specific Immunity Antibodies are effective against extracellular pathogens and carry out their tasks in three ways: Neutralization – bind to bacterial toxins or to molecules that viruses and bacteria need to gain entry into cells Opsonization – facilitates uptake by phagocytes Complement activation Specific Immunity T cell-mediated responses are effective against intracellular pathogens; the pathogen’s location mainly determines which type of T cells respond Cytotoxic T cells – express CD8 molecules and when activated kill pathogens found in cytosol Helper T cells – express CD4 molecules Inflammatory Th1 cells that eliminate pathogens residing in the vesicular system Helper Th2 cells required for antibody production by B cells against T-dependent aantigens on pathogens residing extracellularly Specific Immunity Pathogens may elicit both an antibody (humoral) and a cell-mediated response A humoral or cell-mediated response alone may not be sufficient to kill pathogens Every T cell receptor on an individual T cell has one specificity for an antigen Every B cell receptor that binds antigen is a membrane-bound immunoglobulin which has one specificity Signals are required for specific activation, and there is a lag time in specific (adaptive) immune responses The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells And a few more details… Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism in which a biochemical cascade attacks the surfaces of foreign cells, helping antibodies kill pathogens; the complement system contains over 20 different proteins Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins Phagocytosis Neutrophils and macrophages are both phagocytic cells They have a variety of receptors on their cell membranes through which the infectious agents bind to the cells; they then respond by engulfing the infective agents Respiratory burst occurs which kills the bacteria Other Immune Responses Nitric oxide dependent killing – production of TNF-? induces the expression of the gene that produces nitric oxide which is toxic and can kill a microorganism near the macrophage Non-specific killer cells Phagocytosis Phagocytosis Specific Immunity B lymphocytes or B cells produce antibodies. Antibodies bind to antigens and are effective against extracellular pathogens, carrying out their tasks in three ways: Neutralization – bind to bacterial toxins or to molecules that viruses and bacteria need to gain entry into cells Opsonization – facilitates uptake by phagocytes Complement activation Specific Immunity T lymphocytes or Tcells attack antigens directly; T cell-mediated responses are effective against intracellular pathogens; the pathogen’s location mainly determines which type of T cells respond Cytotoxic T cells – express CD8 molecules and when activated kill pathogens found in cytosol Helper T cells – express CD4 molecules Inflammatory Th1 cells that eliminate pathogens residing in the vesicular system Helper Th2 cells required for antibody production by B cells against T-dependent aantigens on pathogens residing extracellularly Specific Immunity Pathogens may elicit both an antibody (humoral) and a cell-mediated response A humoral or cell-mediated response alone may not be sufficient to kill pathogens Every T cell receptor on an individual T cell has one specificity for an antigen Every B cell receptor that binds antigen is a membrane-bound immunoglobulin which has one specificity Signals are required for specific activation, and there is a lag time in specific (adaptive) immune responses Immune System Disorders and Allergies Allergies involve an immune response to a substance that the body usually perceives as harmless Autoimmune disorders occur when the immune system acts to destroy normal body tissues Hypersensitivity – an immune response that damages the body’s own tissues (allergies, autoimmune and infectious diseases) Immunodeficiency disorders occur when there is a near system-wide failure The Inflammatory Response When an invading organism is first recognized, the immune system launches the immune cascade: Mobilization of leukocytes (white blood cells) Increased blood flow Thinning of capillary endothelial cell walls to allow leukocytes to squeeze through Increased temperature which has an antibiotic effect Immune system signalling molecules (chemokines) released by leukocytes to coordinate immune response The Inflammatory Response Once the invader has been dealt with, the body ends the response by killing off the leukocytes (apoptosis): Cytokines are special cellular messenger molecules that tell leukocytes to die Helper T cells, a type of leukocyte, will release cytokines that keep other leukocytes alive until the presence of the pathogen can no longer be detected; once T helper cells no longer detect pathogen, the leukocytes can then die The Inflammatory Response Symptoms Swelling Redness Heat, Fever Pain Organ dysfunction Results Resolution Connective tissue scarring Abscess formation Chronic inflammation The Inflammatory Response Systemic inflammation Sepsis – inflammation overwhelms the entire organism due to infection Low-grade systemic inflammation – inflammation markers, such as interleukins, are associated with obesity, insulin resistance and atherosclerosis The Inflammatory Response Mediators Cell derived mediators Arachidonic acid derivatives (prostaglandins and leukotrines) Cytokines, lymphokines and monokines (interleukin) Platelet activating factor Histamine Kinin system (bradykinin) Plasma derived mediators Complement interferons The Immune System & the Inflammatory Response Milly Ryan-Harshman, PhD, RD Overview of the Immune System Overview of the Immune System The immune system has two major subdivisions, the innate and the adaptive immune systems. The innate immune system is the first line of defense against invaders. The adaptive immune system is the second line of defense, protecting against re-exposure to the same pathogen. Although each has distinct functions, they do influence one another. Overview of the Immune System The innate immune system defenses are ready to be mobilized at the moment of infection, whereas the adaptive immune system needs time to react to an invading organism. The adaptive immune system is antigen specific and reacts only with the organism that induced the response. Immunological memory allows it to react more quickly with subsequent exposure to the same organism. All cells of the immune system originate in bone marrow. Overview of the Immune System Myeloid progenitor (stem) cells Neutrophils* Basophils* Eosinophils* Macrophages** Dendritic cells** * Granulocytic ** Monocytic Lymphoid progenitor (stem) cells T cells B cells Natural Killer (NK) cells And a few more details… Overview of the Immune System Disease occurs when the bolus of infection is high, when the virulence of the pathogen is great, or when immunity is compromised. Inflammation is the response to an invading organism, and sometimes collateral damage can occur. Sometimes the immune response can be directed toward itself, resulting in autoimmune disease. Innate Host Defenses Anatomical barriers to infection Mechanical factors – skin, cilia, peristalsis, tears, saliva, mucous Chemical factors – fatty acids in sweat, lysozyme and phospholipase in tears, saliva and nasal secretions, low pH of sweat, gastric secretions, proteins with antimicrobial activity, surfactants in the lungs Biological factors – normal flora of the skin and GI tract can prevent colonization of pathogenic bacteria or compete with them for survival Innate Host Defenses Cellular barriers to infection Neutrophils – recruited to the infection site where they kill invading organisms intracellularly Macrophages – kill microorganisms both intracellularly and extracellularly; kill both infected cells and altered self target cells; also contribute to tissue repair and are required for the induction of specific immune responses Natural killer (NK) – not part of the inflammatory response but are important re: immunity to viral infections and tumour surveillance Eosinophils – granular proteins kill certain parasites Innate Host Defenses Humoral barriers to infection Complement system – the major humoral nonspecific defense mechanism in which a biochemical cascade attacks the surfaces of foreign cells, helping antibodies kill pathogens; the complement system contains over 20 different proteins Coagulation system Lactoferrin and transferrin – prevent bacteria from obtaining iron, an essential nutrient Interferons – limit virus replication Lysozyme – breaks down cell walls of bacteria Interleukin 1 – induces fever and production of antimicrobial proteins Phagocytosis Neutrophils and macrophages are both phagocytic cells They have a variety of receptors on their cell membranes through which the infectious agents bind to the cells; they then respond by engulfing the infective agents Respiratory burst occurs which kills the bacteria Other Immune Responses Nitric oxide dependent killing – production of TNF-? induces the expression of the gene that produces nitric oxide which is toxic and can kill a microorganism near the macrophage Non-specific killer cells Phagocytosis Phagocytosis Specific Immunity B lymphocytes or B cells produce antibodies. Antibodies bind to antigens and are effective against extracellular pathogens, carrying out their tasks in three ways: Neutralization – bind to bacterial toxins or to molecules that viruses and bacteria need to gain entry into cells Opsonization – facilitates uptake by phagocytes Complement activation Specific Immunity T lymphocytes or T cells attack antigens directly; T cell-mediated responses are effective against intracellular pathogens; the pathogen’s location mainly determines which type of T cells respond Cytotoxic T cells – express CD8 molecules and when activated kill pathogens found in cytosol Helper T cells – express CD4 molecules Inflammatory Th1 cells that eliminate pathogens residing in the vesicular system Helper Th2 cells required for antibody production by B cells against T-dependent aantigens on pathogens residing extracellularly Specific Immunity Pathogens may elicit both an antibody (humoral) and a cell-mediated response A humoral or cell-mediated response alone may not be sufficient to kill pathogens Every T cell receptor on an individual T cell has one specificity for an antigen Every B cell receptor that binds antigen is a membrane-bound immunoglobulin which has one specificity Signals are required for specific activation, and there is a lag time in specific (adaptive) immune responses Immune System Disorders and Allergies Allergies involve an immune response to a substance that the body usually perceives as harmless Autoimmune disorders occur when the immune system acts to destroy normal body tissues Hypersensitivity – an immune response that damages the body’s own tissues (allergies, autoimmune and infectious diseases) Immunodeficiency disorders occur when there is a near system-wide failure The Inflammatory Response When an invading organism is first recognized, the immune system launches the immune cascade: Mobilization of leukocytes (white blood cells) Increased blood flow Thinning of capillary endothelial cell walls to allow leukocytes to squeeze through Increased temperature which has an antibiotic effect Immune system signalling molecules (chemokines) released by leukocytes to coordinate immune response The Inflammatory Response Once the invader has been dealt with, the body ends the response by killing off the leukocytes (apoptosis): Cytokines are special cellular messenger molecules that tell leukocytes to die Helper T cells, a type of leukocyte, will release cytokines that keep other leukocytes alive until the presence of the pathogen can no longer be detected; once T helper cells no longer detect pathogen, the leukocytes can then die The Inflammatory Response Symptoms Swelling Redness Heat, Fever Pain Organ dysfunction Results Resolution Connective tissue scarring Abscess formation Chronic inflammation The Inflammatory Response Mediators Cell derived mediators Arachidonic acid derivatives (prostaglandins and leukotrines) Cytokines, lymphokines and monokines (interleukin) Platelet activating factor Histamine Kinin system (bradykinin) Plasma derived mediators Complement interferons The Inflammatory Response Systemic inflammation Sepsis – inflammation overwhelms the entire organism due to infection Low-grade systemic inflammation – inflammation markers, such as interleukins, are associated with obesity, insulin resistance and atherosclerosis Inflammatory/Autoimmune Conditions/Diseases Tendinitis Bursitis Myocarditis Nephritis Vasculitis Emphysema Psoriasis Atherosclerosis Ulcerative colitis Crohn’s disease Multiple sclerosis Type 2 diabetes Lupus Rheumatoid arthritis Inflammatory/Autoimmune Conditions/Diseases Appendicitis Gastritis Laryngitis Meningitis Otitis Pancreatitis Dermatitis Asthma Pneumonia Tuberculosis Chronic cholesystitis Thyroiditis Silicosis Rheumatic fever