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INNATE (NON-SPECIFIC) IMMUNITY

Significance of the immune system Innate versus adaptive immunity Prevention from infection Non-specific killing of pathogens Humoral and cellular components of non-specific immunity. INNATE (NON-SPECIFIC) IMMUNITY. Objectives. Prevention from Infection. Significance of the Immune System.

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INNATE (NON-SPECIFIC) IMMUNITY

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  1. Significance of the immune system Innate versus adaptive immunity Prevention from infection Non-specific killing of pathogens Humoral and cellular components of non-specific immunity INNATE (NON-SPECIFIC)IMMUNITY Objectives

  2. Prevention from Infection

  3. Significance of the Immune System • Beneficial: • Protection from Invaders • Elimination of Altered Self • Detrimental: • Discomfort (inflammation) • Damage to self (autoimmunity)

  4. No Immunologic memory Characteristicsof Innate and Adaptive Immunity Innate Immunity Adaptive Immunity Antigen independent Antigen dependent No time lag A lag period Not antigen specific Antigen specific • Development of memory

  5. Componentsof Innate and Adaptive Immunity Innate Immunity Adaptive Immunity physical barriers skin, gut Villi, lung cilia,etc none soluble factors many protein and non-protein secretions Immunoglobulins (antibody) cells phagocytes, NK cell eosinophils, K cells T and B lymphocytes

  6. Skin squamous cells sweat desquamation flushing, fatty acids GI tract columnar cells Peristalsis, low pH bile salts, fatty acids Lung tracheal cilia mucociliary elevator surfactants Effector mechanisms in Innate Immunity -1 Site Component Mechanisms

  7. Nasopharynx and eye squamous cells sweat desquamation flushing, fatty acids phagocytosis and intracellular killing direct and antibody dependent cytolysis Blood and Lymphiod organs Phagocytes, K, NK & LAK cells Effector mechanisms in Innate Immunity -2 Site Component Mechanisms

  8. lactoferrin, transferrin interferons, TNF- lysozyme fibronectin complement iron deprivation antiviral proteins phagocyte activation peptidoglycan hydrolysis opsonization, enhanced phagocytosis, inflammation Serum Effector mechanisms in Innate Immunity -3 Site Component Mechanisms

  9. George Bernard Shaw wrote: “There is at bottom only one genuine treatment for all diseases,…to stimulate the phagocytes. Drugs are a delusion. …(when) the phagocytes are stimulated; they devour the disease…” Influenced by the work of Eli Metchnikoff, Phagocytes are the Most Important Cells

  10. All phagocytes eat, digest and extrude

  11. The two PhagocytesNeutrophils phagocytosis, intracellular killing, inflammation and tissue damage characteristic nucleus, cytoplasm granules and CD67 membrane marker.

  12. The two PhagocytesMacrophages phagocytosis, intracellular and extra-cellular killing, tissue repair, antigen presentation for specific immune response characteristic nucleus and CD14 membrane marker.

  13. Characteristics of Neutrophil Granules Primary granules Secondary granules azurophilic; characteristic of young neutrophils; specific for mature neutrophils contain cationic proteins, lysozyme, defensins, proteases and myeloperoxidase contain lysozyme, NADPH oxidase, lactoferrinand B12-binding protein

  14. Phagocyte Response to Infection • The SOS Signals • N-formyl methionine • Clotting system peptides • Complement products • Phagocyte response • Vascular adherence • Diapedesis • Chemotaxis • Activation • Phagocytosis and killing

  15. ScavengerR IgG FcR CR Initiation of Phagocytosis Attachment via

  16. Glucose +NADP+ G-6-P-dehydrogenase Pentose-P + NADPH NADPH + O2 Cytochrome b558 NADP+ + O2- 2O2- + 2H+ Superoxide dismutase H2O2 + 1O2 2O2- + H2O2 .OH + OH- + 1O2 Respiratory Burst Oxygen Dependent Myeloperoxidase Independent Reactions

  17. H2 O2 + Cl- myeloperoxidase OCl- + H2O 2O2- + 2H+ Superoxide dismutase 1O2 + Cl- + H2O OCL- + H2O H2O2 + 1O2 2 H2 O2 catalase H2O + O2 Respiratory Burst Oxygen Dependent Myeloperoxidase dependent reactions

  18. Pathways of Intracellular Killing

  19. Mediators of Oxygen Independent Killing in the Phago-lysosomes

  20. IFN( TNF TNF Nitric Oxide Nitric Oxide Dependent Killing

  21. NK and LAK cells K cell Activated macrophages Eosinophils They all kill foreign and altered self targets Non-specific Killer Cells

  22. also known as large granular lymphocytes (LGL) kill infected and malignant cells are identified by the presence of CD56 & CD16 and absence of CD3 activated by IL2 and IFN- to become LAK cells Natural Killer (NK) cells

  23. kills malignant cells kills transformed and malignant cells Lymphokine Activated Killer (LAK) cell IFN IFN IL2 IL2

  24. K Cells • morphologically undefined • have IgG Fc receptor • recognize antibody coated targets • could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG)

  25. Macrophages • phagocytose & kill intracellularly • identified by CD14 • adherent of plastic and glass surfaces • activated by cytokines • kill both intracellular organisms • kill malignant and altered self targets

  26. Elements of Nonspecific Immunity • Physical Barriers • skin, muco-ciliary escalator, secretions, peristaltic movement, etc. • Cells • pagocytes • Oxygen-independent killing • O2-dependent-MPO independent killing • O2-dependent-MPO dependent killing • Nitric Oxide mediated killing • cytotoxic cells • NK, LAK, K (ADCC)

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