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Transcript
Principles of Immunology Prince Agri-Products & Phibro Animal Health Training Seminar – Atlanta, Georgia July 17-18, 2006 Immunity: security against a particular disease; nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or the toxic effect of antigenic substances. Innate Immune System: consists of physical, chemical, enzymatic barriers and activity of phagocytic cells (neutrophils) which are associated w/ a signaling system Adaptive (antibodymediated) Immune System: consists of two components Humoral (antibody production in response to antigen, medicated by B-lymphocytes) Cell-mediated (production of specific killer cells in response to an antigen, mediated by Tlymphocytes) Innate Immune Response Neutrophils, first line of defense Phagocytes: first to arrive at the site of infection Function to contain infections, provide time for adaptive system to develop 200 billion in adult cow, 50% in circulation, remainder in bone or attached to vessel walls Life span of 1-2 days Contain a protein component: L-Selectin, index of innate immunity Neutrophil recognition of pathogen Receptors on surface of neutrophil Neutrophil Pathogen Pathogen-associated molecular Patterns: PAMPs) Phagocytosis Bacterium Recognition Production of NETS by neutrophils Inactive neutrophils Activated neutrophils with NETs + interleukin-8 (IL-8) Source: Brinkmann et al., 2004 Association of neutrophil “NETs” with bacteria S. aureus (gram +) Salmonella (gram -) Shigella (gram -) Neutrophils: a first line of defense - tethering via L-selectin (A) -shedding L-selectin (B) - Interleukin-1- proinflammatory (C) -migration toward “signals” (D) -phagocytosis (F) Source: Burton and Erskine, 2003 -pathogens Example of relationship between stress and immunity Cortisol - Adrenal hormone • released in response to a stressful event • needed by uterus at time of calving • aids in intiating milk secretion by the mammary gland • elevated blood Cortisol cause neutrophils to lose their ability to migrate from blood into tissue by interfering with Lselectin synthesis Source: Burton and Erskine, 2003 Cortisol Response Relative to Parturition Cortisol (ug/dL) TRANSITION COW TRIAL - CORTISOL 16 14 12 10 8 6 4 2 0 Hospital Cows All Cows -7 -6 -5 -4 -3 -2 -1 0 1 7 14 Puntenney & French 2003 Effect of stress on neutrophils Normal L-selectin and interleukin Stress Proliferation and invasion of pathogens Take home on neutrophils First line of defense against bacteria and molds L-selectin (tethering/rolling/ “surveillance”) (A/B) IL-8 (signal from infection site) (D) IL-1β (access infection site/ “diapedesis”) (C) Free-flowing blood neutrophil (E) Killing mechanisms (digestion and NETs) (F) Pluripotent hematopoeitic stem cell (Self-renewing, white blood cell producing) Common lymphoid Progenitor (lymph tissue) B cells T cells NK cells Common myeloid Progenitor (bone marrow) White blood cells Red blood cells Megakaryocytes Platelets Monocyte Neutrophil Eosinophil Basophil Dendritic cell -Adaptive Macrophage Janeway et al., 2005 -Innate Phases of an infection Innate Acquired 1. Entry of pathogen 2. encounter a macrophage/dendritic cell 3. macrophage recruits neutrophils via IL-8 4. macrophage (phagocytic cell) and dendritic cells (antigen-presenting cells) migrate to lymph tissue where they encounter naïve B and T lymphocyte 5. B and T lymphocytes clonally expand and differentiate and make antibodies Linkage of innate and adaptive immunity 1. Activated macrophages and dendritic cells with ingested pathogen present antigen to Tlymphocytes 2. Chemokines, secreted by macrophages, enhance tissue permeability and influx of Tlymphocytes into an infection site (IL-1B) 3. Macrophages and neutrophils produce activating molecules (e.g., IL1β and IL-6) Janeway et al., 2005 Activated neutrophil IL-1β + B and T lymphocytes 4. Activated T-cells, in turn, activate macrophages Review Terms Pathogen: disease-causing infectious agent Antigen: any molecule that stimulates the immune response (pathogen proteins or carbohydrates) Phagocytes: cells attracted to site of infection to destroy pathogens (not antigen-specific, part of innate system) Neutrophils Eosinophils Monocytes/macrophages Natural Killer Cells (virus-infected and cancer cells) Review Terms Leukocytes: white blood cells Adaptive Immunity: response to repeat infection Synthesis of antibody to bind antigen and promote elimination T cell killing of virus-infected cells T cell activation of macrophages to destroy phagocytosed pathogens that are resistant to destruction Review Terms Innate Immunity: defense system that can recognize “generic danger” and responds by walling off and engulfing foreign organisms Barriers - skin, mucous membranes Mechanical – cilia, blinking, sneezing, coughing, vomiting Chemical – HCl in stomach, digestive enzymes in tears, mucus Phagocytes – Neutrophils, eosinophils, macrophages, M cells, monocytes Natural Killer Cells – kill virus/cancer cells Review Terms Apoptosis: programmed cell death Macrophages: innate immune cell, binds pathogens, produce cytokines to attract other phagocytic cells and make blood vessels leaky, may present antigen to stimulate T cell activation (adaptive) Dendritic cells: innate immune cell, may be phagocytic and may present antigen to simulate T cell activation (adaptive immune system) Lymphocytes: antigen-specific white blood cells responsible for adaptive immunity Review Terms Natural Killer (NK) Cells: large lymphocytes that lack specific antigen receptors but respond to altered tissue typing in virus-infected and cancer cells Cytokines: small proteins produced by macrophages in response to bacterial antigens; signal other white blood cells; act by binding to specific membrane receptors to signal the cell to alter its behavior (gene expression) Lymphokine (lymphocytes), monokine (monocytes), chemokine (chemotactic activity), interleukin (made by one leukocyte and acting on others) Review Terms Antibody: antigen receptor on B cells and is also secreted to bind and remove antigen from the body Immunoglobulins: antibodies that are antigen-binding proteins (IgG, IgM, IgD, IgA, IgE) Interleukin-1: cytokines produced by macrophages which activate nearby vascular endothelium to promote leukocyte movement into the tissue (extravasation) Interlukin – 8: chemokines which recruit leukocytes and attract them to site of infection L-selectin: neutrophil-adhesion molecule that initiates binding between leukocytes and endothelium