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Outline of Lecture 06

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BIOL 1010U

Outline of Lecture 06 Phagocytic Cells, Innate Immunity, and Host Defense *** Innate Immunity: Definition, Activation, Receptors I. Innate versus Adaptive Immunity Rehash from previous lectures II. Activation of Innate Immune Response: PAMPs and PRRs - General invariant features of pathogen surfaces are recognized (Pathogen Assoc. Molecular Patterns, PAMPs) by a limited set of fixed receptors (Pattern Recognition Receptors, PRRs) III. Toll Like Receptors - TLRs are PRRs, originally discovered as dToll and 18-Wheeler in Drosophila - In humans, 9 types of TLRs recognize PAMPs and activate innate immune response *** Cells of Innate Immunity: Differentiation, Activation, Migration IV. There are 3 Effector Cells of the Innate Immune System 1) Neutrophils: short lived phagocytes, kill 2) Macrophages: long lived phagocytes, kill, involved in inflammation, remodeling 3) Natural Killer (NK): Kill viral infected cells that lack MHC I - Metchnikoff first observed phagocytic cells in late 1800’s V. Differentation of Neutrophils and Macrophages A) Pluripotent hematopoietic stem cell gives rise to: 1) neurons, 2) endothelium, 3) erythroids, 4) megakaryocytes, 5) myeloids, 6) lymphoids B) Neutrophils PHSC  myeloblast  promyelocyte  myelocyte  metamyelocyte  neutrophil Two types of granules: primary/azurophil and secondary/specific Signals (IL-1, TNF-α, G-CSF, GM-CSF) stimulate neutrophil production Increased immature neutrophils in circulation is sign of infection/inflammation C) Macrophages Promonocytes  monocytes  macrophages Signals (IL-3, M-CSF, GM-CSF) stimulate monocyte production Monocytes in circulation enter tissues and differentation into macrophages VI. Macrophage Activation A) Macrophages may be activated through PRRs; activated cells phagocytose pathogens and actively kill them (e.g. ROS, NO) B) Adaptive and innate immune system interact - macrophages are APCs that can activate T cells
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