Transcript Cells
Abdul Ghaffar Microbiology and Immunology "When the mind is ready,a teacher appears.“ Chinese Proverb Development of the Immune System ery pl neu mφ CD8+ nk CTL CD4+ TH1 thy TH2 mye lym Cells of the Immune System Myeloid cells lymphoid cells Granulocytic Monocytic T-cells B-cells Neutrophils Basophils Eosinophils Macrophages Langerhans & Kupffer cells Dendritic cells? Helper Cytotoxic Suppressor Plasma cells Dendritic cells? Components of the Immune System Nonspecific Humoral complement, interferon, TNF etc. Cellular macrophages, neutrophils Specific Humoral antibodies Cellular T cells; other effectors cells Balance between Infection and Immunity infection Disease = immunity Bolus of infection x virulence immunity Response to Infection infection Innate immunity x disease no disease adaptive immunity Significance of the Immune System Beneficial: Protection from Invaders Elimination of Altered Self Detrimental: Discomfort (inflammation) Damage to self (autoimmunity) Characteristics of Innate and Adaptive Immunity Innate Immunity Adaptive Immunity Antigen independent Antigen dependent No time lag A lag period Not antigen specific Antigen specific No Immunologic memory Development of memory Components of Innate and Adaptive Immunity Innate Immunity Adaptive Immunity physical barriers skin, gut Villi, lung cilia,etc soluble factors many protein and non-protein secretions cells phagocytes, NK cell eosinophils, K cells non e Immunoglobulins (antibody) T and B lymphocytes Physical Barriers to Resistance Effector mechanisms in Innate Immunity -1 Site Skin GI tract Lung Component Functions squamous cells sweat desquamation flushing, fatty acids columnar cells Peristalsis, low pH bile salts, fatty acids tracheal cilia mucociliary elevator surfactants Effector mechanisms in Innate Immunity -2 Site Component Functions Nasopharynx and eye mucus, saliva, tears flushing, lysozyme Blood and Lymphiod organs Phagocytes phagocytosis and intracellular killing K, NK & LAK cells direct and antibody dependent cytolysis Effector mechanisms in Innate Immunity -3 Site Serum and other serous fluids Component Functions lactoferrin, transferrin iron deprivation interferons, TNF- antiviral proteins phagocyte activation lysozyme Fibronectin & complement peptidoglycan hydrolysis opsonization, enhanced phagocytosis, inflammation Phagocytes are the Most Important Cells George Bernard Shaw wrote: “There is at bottom only one genuine treatment for all diseases,…to stimulate Influenced by the work of phagocytes.theDrugs are a Eli Metchnikoff, delusion. …(when) the phagocytes are stimulated; they devour the disease…” Phagocytes: Macrophages phagocytosis, intracellular and extracellular killing, tissue repair, antigen presentation for specific immune response characteristic nucleus and CD14 membrane marker. 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, lactoferrin and B12binding protein 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 Initiation of Phagocytosis Attachment via ScavengerR IgG FcR CR Toll-like R Respiratory Burst Oxygen Dependent Myeloperoxidase Independent Reactions Glucose +NADP+ G-6-P-dehydrogenase NADPH + O2 Cytochrome b558 Pentose-P + NADPH + NADP + O2 - - 2O2 + 2H+ Superoxide dismutase - 2O2 + H2O2 H2O2 + 1O2 .OH + OH- + 1O2 Respiratory Burst Oxygen Dependent Myeloperoxidase dependent reactions - H2 O2 + Cl myeloperoxidase - 2OCL + H2O OCl- + H2O 1O -+ Cl-+ 2 H2O - 2O2 + 2H+ Superoxide dismutase 2 H2 O2 catalase H2O2 + O2 H2O + O2- - Pathways of Intracellular Killing Intracellular Killing oxygen-depenedent myloperoxidase-independent oxygen-independent myeloperoxidase-dependent 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 Nitric Oxide Dependent Killing TNF TNF Nitric Oxide Nitric Oxide Non-specific Killer Cells NK and LAK cells ADCC (K) cell Activated macrophages Eosinophils They all kill foreign and altered self targets Natural Killer (NK) cells 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-γ to become LAK cells Lymphokine Activated Killer (LAK) cell kills kills transformed malignant and malignant cells cells Regulation of NK Cell Function MHC I KIR No Killing KAR KAL Killing 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)