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Overview of the Immune System

Overview of the Immune System. Interactions between the two systems. No memory. Innate Immunity. Adaptive Immunity. Comparison of Innate and Adaptive Immunity. No time lag. A lag period. Not antigen specific. Antigen specific. Development of memory. Cells of the Immune System. m φ.

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Overview of the Immune System

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  1. Overview of the Immune System Interactions between the two systems

  2. No memory Innate Immunity Adaptive Immunity Comparisonof Innate and Adaptive Immunity • No time lag • A lag period • Not antigen specific • Antigen specific • Development of memory

  3. Cells of the Immune System

  4. mφ pl neu CD8+ CTL ery nk CD4+ TH1 thy TH2 mye lym Development of the Immune System

  5. Function of the Immune System(Self/Non-self Discrimination) • To protect from pathogens • Intracellular (e.g. viruses and some bacteria and parasites) • Extracellular (e.g. most bacteria, fungi and parasites) • To eliminate modified or altered self

  6. Disease = Bolus of infection x virulence immunity Infection and Immunity Balance infection immunity

  7. Effects of the Immune System • Beneficial: • Protection from Invaders • Elimination of Altered Self • Detrimental: • Discomfort and collateral damage (inflammation) • Damage to self (hypersensitivity or autoimmunity)

  8. Innate (Nonspecific) Immunity

  9. Overview of the Immune System

  10. Innate Host Defenses Against Infection • Anatomical barriers • Mechanical factors • Chemical factors • Biological factors • Humoral components • Complement • Coagulation system • Cytokines • Cellular components • Neutrophils • Monocytes and macrophages • NK cells • Eosinophils

  11. Anatomical Barriers - Mechanical Factors

  12. Anatomical Barriers - Chemical Factors

  13. Anatomical Barriers - Biological Factors

  14. Humoral Components

  15. Cellular Components

  16. PhagocytosisandIntracellular Killing

  17. Phagocytes - Neutrophils (PNMs) • Characteristic nucleus, cytoplasm • Granules • CD 66 membrane marker

  18. Characteristics of Neutrophil Granules primary granules secondary granules azurophilic; characteristic of young neutrophils; specific for mature neutrophils contain cationic proteins, lysozyme, defensins, elastase and myeloperoxidase contain lysozyme, NADPH oxidase components, lactoferrinand B12-binding protein

  19. Phagocytes - Macrophages • Characteristic nucleus • Lysosomes • CD14 membrane marker

  20. Phagocyte Response to Infection • The SOS Signals • N-formyl methionine-containing peptides • Clotting system peptides • Complement products • Cytokines released by tissue macrophages • Phagocyte response • Vascular adherence • Diapedesis • Chemotaxis • Activation • Phagocytosis and killing

  21. Initiation of Phagocytosis Attachment via Receptors: IgG FcR Complement R ScavengerR Toll-like R

  22. Phagocytosis • Attachment • Pseudopod extension • Phagosome formation • Granule fusion • Phagolysosome formation

  23. G-6-P-dehydrogenase Glucose +NADP+ Pentose-P + NADPH NADPH oxidase Cytochrome b558 NADPH + O2 NADP++ O2- Superoxide dismutase 2O2- + 2H+ H2O2 + 1O2 2O2- + H2O2 OH* + OH- + 1O2 Toxic compounds – Superoxide anion (O2-), Hydrogen peroxide (H2O2), Singlet oxygen (1O2) and Hydroxyl radical (OH*) Respiratory Burst Oxygen-Dependent Myeloperoxidase-Independent Reactions

  24. myeloperoxidase H2O2 + Cl- OCl- + H2O 1O2+Cl-+ H2O 2OCl- + H2O Toxic compounds – Hypochlorous acid (OCl-), and Singlet oxygen (1O2) Respiratory Burst Oxygen-Dependent Myeloperoxidase-Dependent Reactions

  25. Respiratory Burst Detoxification Reactions Superoxide dismutase 2O2- + 2H+ H2O2+O2 Catalase 2 H2O2 H2O + O2

  26. Oxygen-Independent Killing in the Phagolysosome 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

  27. Summary of Intracellular Killing Pathways

  28. IFNγ  TNF TNF Nitric Oxide Nitric Oxide Nitric Oxide Dependent Killing

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

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

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

  32. MHC I • KIR • KAR • KAL • No Killing • Killing Regulation of NK Cell Function

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

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