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The Immune System Chapter 21. Immune System functional system rather than organ system  Hematopoetic  Vasculature  Lymphatic Fig 21.1

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Text of The Immune System Chapter 21. Immune System functional system rather than organ system ...

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  • The Immune System Chapter 21
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  • Immune System functional system rather than organ system Hematopoetic Vasculature Lymphatic Fig 21.1
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  • Innate vs. Adaptive Immune System Introduction Innate: structural defenses; responds to nonspecific foreign substances First line: external surface epithelium & membranes Second line: inflammatory processes antimicrobial proteins, phagocytes, etc. Fig 21.1
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  • Innate vs. Adaptive Immune System Introduction Adaptive: responds to specific foreign substances Innate & adaptive mechanisms work together Fig 21.1
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  • Innate, Surface Defenses Skin physical barrier to microbes Keratin resistant to most bacterial enzymes & toxins secretions are acidic pH 3-5 Mucosa physical barrier & produces a variety of protective chemicals Gastric mucosa very acidic & produces proteolytic enzymes Saliva & lacrimal fluid contain lysozyme Mucous traps bacteria & moves them away from epithelial surface
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  • Innate, Internal Defenses Based on recognition of surface carbohydrates (glycocalyx) Glycocalyx is recognized as self or non-self Figure 3.3
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  • Innate, Internal Defenses Phagocytes Macrophages: derived from monocytes Free Macrophages: roam through tissues Fixed Macrophages: Kupffer cells (liver) & microglia (brain) Ingest cellular debris, foreign material, bacteria, fungi Neutrophils: ingest pathogens Eosinophils: weakly phagocytic of pathogens. Attack parasites (degranulation) Mast Cells: phagocytic of various bacteria
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  • Innate, Internal Defenses Phagocytic mechanisms: Adherence: cell binds to invader Aided by opsonization (a chemical process that enhances binding via complement & antibodies) Ingestion: formation of phagolysosomes Respiratory Bursts: merge phagosome with lysosome & flood phagolysosome with free radicals (macrophage) Defensins: proteins that crystallize out of solution & pierce pathogen membranes (neutrophils)
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  • Mechanism of Phagocytosis Figure 21.2
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  • Innate, Internal Defenses Natural Killer Cells: Small population of large granular lymphocytes Non specific for non-self Not phagocytic: attack is by release of perforins that perforate the target cell plasma membrane. Shortly after perforation the target nucleus disintegrates. Release chemicals that enhance the inflammatory response
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  • Innate, Internal Defenses: Inflammation tissue response to injury Triggered by injury trauma, heat, chemical irritation, infection, etc. Beneficial effects Prevents spread of injury Disposes of cellular debris & pathogens Promotes repair
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  • Innate, Internal Defenses: Inflammation cardinal signs of inflammation Redness Heat Swelling Pain (functional impairment Rigor) Weapons of the Spanish Inquisition Weapons of the Spanish Inquisition
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  • Innate, Internal Defenses: Inflammation Inflammatory response: signs are associated with vasodilation & increased vascular permeability Dilation: redness, heat Permeability: edema, (increased pressure) pain Pain also associated with bacterial toxins & some mediators (kinins, PGs)
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  • Innate, Internal Defenses: Inflammatory Response Mechanisms causing vasodilation & vascular permeability Injured cells release inflammatory mediators Histamines Kinins Prostaglandins Complement Cytokines (also activated by receptors on macrophages in response to microbial glycocalyx)
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  • Innate, Internal Defenses: Inflammatory Response Edema Dilutes harmful substances Provides nutrients (& O 2 ) for repair Enhances entry of clotting protein Epithelial breaches also stimulate -defensin release from epithelial cells
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  • Events in Inflammation Figure 21.3
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  • Innate, Internal Defenses: Inflammatory Response Phagocyte mobilization: infiltration of damaged area by neutrophils & macrophages
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  • Innate, Internal Defenses: Inflammatory Response Leukocytosis: leukocytosis inducing factors released by injured cells promote rapid release of WBCs from marrow Margination: increased vascular permeability causes decreased fluid in vessels; blood flow slows & neutrophils are able to move to vessel margins. Here endothelial markers (CAMs) allow neutrophils to cling to vessel walls (pavementing).
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  • Innate, Internal Defenses: Inflammatory Response Diapedesis: neutrophils migrate through capillary walls Chemotaxis inflammatory chemicals attract neutrophils to move up the chemical concentration gradient (neutrophils respond first) As the process continues, monocytes diapedes into the area & become macrophages. With chronic inflammation, macrophages predominate
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  • Inflammatory Response: Phagocytic Mobilization Figure 21.4
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  • Innate, Internal Defenses: Inflammatory Response Macrophages clean up cellular debris & pathogens If pathogens were associated with the injury, activation of the complement cascade occurs & elements of adaptive immunity join the process
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  • Innate, Internal Defenses Viral replication (viruses lack metabolic processes) Viruses release nucleic acid (RNA or DNA) into cytoplasm. The information on the nucleic acid is incorporated into the cells DNA. Normal cellular mechanisms then produce viral structural components. Multiple new viral particles are produced & released from the cell (sometimes killing the cell)
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  • Innate, Internal Defenses Antiviral proteins: interferon & complement Interferon: some cells produce & release interferons (IFNs) when invaded by virus Released interferons stimulate nearby cells to produce proteins (PKR) that interfere with viral replication by disrupting protein synthesis & the ribosome Not virus specific.
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  • Interferon (IFN) Figure 21.5
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  • Innate, Internal Defenses Complement a group of plasma proteins (20) that are activated in the presence of foreign substances Complement activation enhances & amplifies inflammation Bacteria & some other cell types are lysed by complement activation Complement activation enhances both innate & adaptive defenses
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  • Innate, Internal Defenses Complement activation pathways Classical pathway: requires antibodies Antibodies bind to target (antigen) Complement protein C1 binds to the antibody- antigen complex (complement fixation) Alternative pathway: complement factors interact with microorganism glycocalyx Both pathways lead to a cascade of protein activation, leading to activation of C3
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  • Innate, Internal Defenses C3 is the start of the; Final Common Pathway C3 cleaves to form C3a & C3b C3a (& C5a) enhance inflammation by increasing histamine release, increasing vascular permeability & stimulating chemotaxis C3b coats bacterial membrane supplying adhesion points (opsonization) C3b initiates the cascade forming the membrane attack complex (MAC) The MAC forms a hole in the cell membrane & enhances Ca 2+ influx cell lysis
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  • Innate, Internal Defenses; Complement Figure 21.6
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  • Innate, Internal Defenses C-reactive proteins (CRP) produced by the liver in response to inflammatory molecules can activate the classical pathway by binding to membrane & activating C1. Also participates in opsonization. Fever a systemic response to infection. Leukocytes & macrophages release pyrogens that raise the hypothalamic set point for temperature
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  • ADAPTIVE DEFENSES Innate & adaptive mechanisms work together in a cohesive fashion
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  • Adaptive Defenses: Characteristics Specificity: directed at specific targets Systemic: not restricted to initial site of infection / invasion Memory: after initial exposure & activation, a more rapid & more vigorous response is made to subsequent exposures to pathogens (secondary response)
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  • Adaptive Defenses: Components Humoral Immunity: (antibody mediated immunity) provided by antibodies floating free in body fluids Cell mediated immunity: lymphocytes directly attack specific invaders by lysis or indirect attack by initiating inflammation and/or activating other lymphocytes & macrophages
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  • Adaptive, Humoral Immunity Antigen = any substance that can mobilize the immune system & provoke an immune response* *Humoral and/or cell mediated
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  • Adaptive, Humoral Immunity Complete antigens (proteins, nucleic acids, lipids, polysaccharides): Immunogenicity: the ability to stimulate specific lymphocytes & specific antibodies Reactivity: the ability to react with activated lymphocytes & antibodies Hapten (an incomplete antigen): a smaller molecule that is not immunogenic until attached to proteins
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  • Adaptive, Humoral Immunity Antigenic determinants: sites on an antigenic molecule that are immunogenic Epitope Major Hist