Cells and Effectors II

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Western University
Microbiology and Immunology
Microbiology and Immunology 3300B
Rodney Dekoter

LECTURE 3: CELLS AND EFFECTORS II Lecture 3 Objectives 1. Learn the mechanisms of innate self/non-self recognition a. Self-recognition receptors b. Examples of PAMPs 2. Learn the origin, circulation, morphology and function of myeloid immune cells Innate Immunity – Detection of Self  Other mechanisms of innate self-recognition: o Sialic acid o Glycosaminoglycans o MHC-binding receptors Innate Immunity – Detection of Non-Self  Pattern recognition receptor (PRRs) o Germ-line encoded receptors o Bind evolutionarily-conserved pathogen molecules Review: Innate Self-Non-Self  Regulated by germ-line encoded receptors which recognize: o Self – other germ-line encoded proteins, or carbohydrate moieties not found in pathogens o Non-self – evolutionarily conserved pathogen molecules  Common to many pathogens Myeloid (Innate) Cells  Initiated by bone marrow cells  Differentiate into common myeloid progenitor  Results in various immune cells Monocytes/Macrophages  Common immune cells  Begin as monocytes in the blood  In peripheral tissue, monocytes differentiate into macrophage  Monocytes – released from bone marrow and go into blood, and get recruited into tissues where they turn into tissue-specific macrophages  Equipped to very quickly respond to pathogens; once differentiated into macrophages, more like a vacuum cleaner in the body  Name varies by tissue: o Liver = Kupffer cells o Brain = Microgilia o Lungs = Alveolar Mφ Neutrophils  Most abundant immune cells in the blood (50-60%)  React first to an infection, purpose is to hold the infection until the other immune cells can respond  Multi-lobbed nucleus o Condensed DNA in order to make as much free cytoplasm as possible in order to contain granules  Granules – pre-formed clumps of proteins with anti-bacterial capacity  Granules strain with acidic and basic (neutral) dyes  Major component of anti-bacterial responses  Major component of pus – dead neutrophils  Short-lived cells (18-24 hours)  Neutrophilia: increased number of circulating neutrophils  Neutropenia: decreased number of circulating neutrophils o Often a sign of a prolonged infection, bone marrow’s ability to make neutrophils is depleted Dendritic Cells  Bridge between adaptive and immune systems  Named after their shape – star-like looking shape, extensions are called dendrites  Come in two forms: o Immature – out in tissue, and collecting antigens  Immature DCs (iDCs) reside in peripheral tissues where they accumulate antigens  Highly phagocytic  Poor presenters of Ags  When immune response is needed, they become mature and stop collecting antigens and start presenting antigens o Mature – iDCs mature, forming mature DCs (mDCs)  Poorly phagocytic  Best presenters of Ags in the immune system Phagocytes  Perform phagocytosis, capable of engulfing large particles such as bacteria, fungi, etc.  Phagocytosis – uptake of a large (greater than 0.1 μm) particle o Particle is internalized into a membrane-bound vesicle called a phagosome  Destroy phagocytized particles by fusing granules and lysosomes with the phagosome Large Particle Phagocytosis  Bead – mimic bacteria, same size as macrophage  Macrophage has no trouble taking up beads and destroying them  Can take up to three times their size Cellular Responses – Phagocytosis  Pre-formed granules – membrane bound vesicles  Defensins – pore-forming toxins  Proteases – enzymes that chew up proteins  NADPH oxidase and MPO – cause respiratory burst  Iron-binding proteins – prevent pathogens from growing inside the phagosome Cellular Responses – Respiratory Burst  Superoxide – O 2 o Catalyzed by NADPH oxidase complex o Extremely reactive o Membrane permeable – can get out of the phagos
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