Innate 1


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Innate 1

  1. 1. INNATE ( NON-SPECIFIC ) IMMUNITY Abdul Ghaffar Microbiology and Immunology
  2. 2. macrophages, neutrophils complement, interferon, TNF etc. T cells; other effectors cells antibodies Components of the Immune System
  3. 3. Balance between Infection and Immunity infection immunity
  4. 4. Response to Infection adaptive immunity infection x disease Innate immunity no disease recovery re-infection no disease x
  5. 5. Significance of the Immune System <ul><ul><ul><li>Beneficial: </li></ul></ul></ul><ul><ul><ul><ul><li>Protection from Invaders </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Elimination of Altered Self </li></ul></ul></ul></ul><ul><ul><ul><li>Detrimental: </li></ul></ul></ul><ul><ul><ul><ul><li>Discomfort (inflammation) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Damage to self (autoimmunity) </li></ul></ul></ul></ul>
  6. 6. Characteristics of Innate and Adaptive Immunity <ul><li>No Immunologic </li></ul><ul><ul><li>memory </li></ul></ul><ul><li>Antigen independent </li></ul><ul><li>No time lag </li></ul><ul><li>Not antigen specific </li></ul><ul><li>Antigen dependent </li></ul><ul><li>A lag period </li></ul><ul><li>Antigen specific </li></ul><ul><li>Development </li></ul><ul><ul><li>of memory </li></ul></ul>Innate Immunity Adaptive Immunity
  7. 7. Components of Innate and Adaptive Immunity Innate Immunity Adaptive Immunity skin, gut Villi, lung cilia,etc many protein and non-protein secretions phagocytes , NK cell eosinophils, K cells physical barriers soluble factors cells none Immunoglobulins (antibody) T and B lymphocytes
  8. 8. Effector mechanisms in Innate Immunity -1 Site Component Functions Peristalsis, low pH bile salts, fatty acids columnar cells GI tract Skin squamous cells sweat desquamation flushing, fatty acids tracheal cilia Lung mucociliary elevator surfactants
  9. 9. Effector mechanisms in Innate Immunity -2 Site Component Functions Nasopharynx and eye mucus, saliva, tears flushing, lysozyme Phagocytes, K, NK & LAK cells Blood and Lymphiod organs phagocytosis and intracellular killing direct and antibody dependent cytolysis
  10. 10. Effector mechanisms in Innate Immunity -3 Site Component s Functions Serum and other serous fluids lactoferrin,transferrin iron deprivation interferons,TNF-  antiviral proteins phagocyte activation lysozyme peptidoglycan hydrolysis fibronectin complement opsonization, enhanced phagocytosis, inflammation
  11. 11. Phagocytes are the Most Important Cells Influenced by the work of Eli Metchnikoff, 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…”
  12. 12. All phagocytes eat, digest and extrude
  13. 13. Phagocytes: Neutrophils phagocytosis, intracellular killing, inflammation and tissue damage characteristic nucleus, cytoplasm granules and CD67 membrane marker.
  14. 14. Phagocytes: Macrophages <ul><li>phagocytosis, intracellular and extra-cellular killing, tissue repair, antigen presentation for specific immune response </li></ul><ul><li>characteristic nucleus and CD14 membrane marker. </li></ul>
  15. 15. Characteristics of Neutrophil Granules primary granules contain cationic proteins, lysozyme, defensins, proteases and myeloperoxidase secondary granules contain lysozyme, NADPH oxidase, lactoferrin and B12-binding protein azurophilic; characteristic of young neutrophils; specific for mature neutrophils
  16. 16. Phagocyte Response to Infection <ul><li>The SOS Signals </li></ul><ul><ul><li>N-formyl methionine </li></ul></ul><ul><ul><li>Clotting system peptides </li></ul></ul><ul><ul><li>Complement products </li></ul></ul><ul><li>Phagocyte response </li></ul><ul><ul><li>Vascular adherence </li></ul></ul><ul><ul><li>Diapedesis </li></ul></ul><ul><ul><li>Chemotaxis </li></ul></ul><ul><ul><li>Activation </li></ul></ul><ul><ul><li>Phagocytosis and killing </li></ul></ul>
  17. 17. Initiation of Phagocytosis Attachment via IgG FcR ScavengerR CR
  18. 18. Respiratory Burst Oxygen Dependent Myeloperoxidase Independent Reactions 2O 2 - + H 2 O 2 .OH + OH - + 1 O 2 Glucose +NADP + G-6-P-dehydrogenase Pentose-P + NADPH NADPH + O 2 Cytochrome b558 NADP + + O 2 - 2O 2 - + 2H + Superoxide dismutase H 2 O 2 + 1 O 2
  19. 19. Respiratory Burst Oxygen Dependent Myeloperoxidase dependent reactions H 2 O 2 + 1 O 2 2O 2 - + 2H + Superoxide dismutase H 2 O 2 + Cl - myeloperoxidase OCl - + H 2 O H 2 O + O 2 2 H 2 O 2 catalase OCL - + H 2 O 1 O 2 + Cl - + H 2 O
  20. 20. Pathways of Intracellular Killing
  21. 21. Mediators of Oxygen Independent Killing in the Phago-lysosome Effector Molecule Function Cationic proteins (cathepsin) Damage to microbial membranes Lysozyme Hydrolyses mucopeptides in the cell wall Lactoferrin Deprives pathogens of iron Hydrolytic enzymes (proteases) Digests killed organisms
  22. 22. Nitric Oxide Dependent Killing IFN  TNF TNF Nitric Oxide
  23. 23. Non-specific Killer Cells <ul><li>NK and LAK cells </li></ul><ul><li>K cell </li></ul><ul><li>Activated </li></ul><ul><li>macrophages </li></ul><ul><li>Eosinophils </li></ul><ul><li>They all kill foreign and altered self targets </li></ul>
  24. 24. Natural Killer (NK) cells <ul><li>also known as large granular lymphocytes (LGL) </li></ul><ul><li>kill infected and malignant cells </li></ul><ul><li>are identified by the presence of CD56 & CD16 and absence of CD3 </li></ul><ul><li>activated by IL2 and IFN-  to become LAK cells </li></ul>
  25. 25. Lymphokine Activated Killer (LAK) cell IL2 IFN IFN IL2 kills malignant cells kills transformed and malignant cells
  26. 26. Regulation of NK Cell Function
  27. 27. K Cells <ul><li>morphologically undefined </li></ul><ul><li>have IgG Fc receptor </li></ul><ul><li>recognize antibody coated targets </li></ul><ul><li>could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG) </li></ul>
  28. 28. Macrophages <ul><li>phagocytose & kill intracellularly </li></ul><ul><li>identified by CD14 </li></ul><ul><li>adherent of plastic and glass surfaces </li></ul><ul><li>activated by cytokines </li></ul><ul><li>kill both intracellular organisms </li></ul><ul><li>kill malignant and altered self targets </li></ul>
  29. 29. Elements of Nonspecific Immunity Summary <ul><li>Physical Barriers </li></ul><ul><ul><li>skin, muco-ciliary escalator, secretions, peristaltic movement, etc. </li></ul></ul><ul><li>Cells </li></ul><ul><ul><li>pagocytes </li></ul></ul><ul><ul><ul><li>Oxygen-independent killing </li></ul></ul></ul><ul><ul><ul><li>O2-dependent-MPO independent killing </li></ul></ul></ul><ul><ul><ul><li>O2-dependent-MPO dependent killing </li></ul></ul></ul><ul><ul><ul><li>Nitric Oxide mediated killing </li></ul></ul></ul><ul><ul><li>cytotoxic cells </li></ul></ul><ul><ul><ul><li>NK, LAK, K (ADCC) </li></ul></ul></ul>