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5/30/2011 Innate Immune Response Chapter 15 How does the body protect itself from infection? • Protective barriers • Sensing mechanisms to sound the alarm • Specialized cells and mechanisms to kill invaders • Adaptive responses (next time) What are the first-line of defenses? 1 5/30/2011 What are the first-line defenses? Physical Barriers Skin Mucous membranes Physical Barriers Skin •Sheets of tightly packed cells •Outermost layers are dead, embedded with keratin (dry) •Cells continually slough off •Perspiration (salty) 2 5/30/2011 Physical Barriers Skin Physical Barriers Skin Physical Barriers Skin New Scientist 1/30/93 Mudlarks’ marks ….the case of seven students who attended the health clinic at the Universityy of Washington at Seattle last spring covered in hundreds of red, pus-filled spots… 3 5/30/2011 Physical Barriers Mucous Membranes •Often a single layer of cells •Layer of mucus (traps particles, including microbes) •Often a mechanism to propel the mucus toward an “exit” •(ex. mucociliary escalator, peristalsis) Question From a protection standpoint, which is a more effective barrier? 1. Skin 2. Mucous membrane Antimicrobial Chemicals •Lysozyme •Transferrin, lactoferrin •Gastric acid 4 5/30/2011 Normal Microbiota (aka normal flora) Nanamio News Bulletin, July 20, 2010 C. diff continues to bug patients at Nanaimo hospital Two more patients at Nanaimo Regional General Hospital have acquired Clostridium difficile in the hospital in the last week, but no new deaths were reported. The Cells of the Immune System The Cells of the Immune System 5 5/30/2011 The Cells of the Immune System Cell Communication Surface receptors - “eyes, ears” Cytokines - chemical messengers; proteins released by cells that effect the behavior of other cells; “voice” 6 5/30/2011 Cell Communication Surface receptors - “eyes, ears” Cytokines - chemical messengers; proteins released by cells that effect the behavior of other cells; “voice” Adhesion molecules - “hands” Sensor Systems Surface receptors - “eyes, ears” Sensor Systems Toll-like receptors (TLRs) - surface receptors that allow cells to “see” molecules that signify the presence of microorganisms or viruses pattern recognition pathogen-associated molecular patterns (PAMPs) 7 5/30/2011 Inside cells: NLRs (NOD proteins) Sensor Systems Toll-like receptors (TLRs) - surface receptors that allow cells to “see” molecules that signify the presence of microorganisms or viruses pattern recognition pathogen-associated molecular patterns (PAMPs) Sensor Systems The complement system - series of proteins that, when activated, result in destruction/removal of foreign material; cascade reaction C3 → C3a + C3b C5 → C5a + C5b Sensor Systems The complement system - series of proteins that, when activated, result in destruction/removal of foreign material; cascade reaction C3 → C3a + C3b C5 → C5a + C5b “prepare for eating” 8 5/30/2011 Sensor Systems The complement system - series of proteins that, when activated, result in destruction/removal of foreign material; cascade reaction C3 → C3a + C3b C5 → C5a + C5b Sensor Systems Sensor Systems The complement system - series of proteins that, when activated, result in destruction/removal of foreign material; cascade reaction C3 → C3a + C3b C5 → C5a C5 + C5b 9 5/30/2011 Sensor Systems Recognition of long double-stranded RNA Signifies to a cell that it is infected with a virus infected cell produces interferon Apoptosis = programmed cell death Phagocytosis Macrophages Neutrophils (polymorphonuclear leukocytes, PMNs, polys) Process of phagocytosis Chemotaxis Recognition and attachment opsonins •opsonins Engulfment (ingestion) •phagosome Fusion of the phagosome with lysosomes (forms a phagolysosome) Destruction and digestion Exocytosis http://www.youtube.com/watch?v=VAhM9OxZDkU&feature=related 10 5/30/2011 •Specialized attributes of macrophages Fixed in tissue or routinely wander Clean up infection Long-lived (months) Can become activated •Specialized attributes of neutrophils First to migrate to site of infection Short-lived (days) Always have tremendous killing power •Specialized attributes of macrophages Fixed in tissue or routinely wander Clean up infection Long-lived (months) Can become activated •Specialized attributes of neutrophils First to migrate to site of infection Short-lived (days) Always have tremendous killing power Inflammation a coordinated response to invasion Redness, pain, swelling, heat Purpose: Contain a site of damage Localize the response Restore tissue function Factors that initiate the inflammatory response Microbial cell products detected by toll-like receptors Microbial surfaces (trigger the complement cascade) Tissue damage 11 5/30/2011 The Inflammatory Process •Pro-inflammatory cytokines released •Dilation of small blood vessels → increased blood flow to the area •Leakage of fluids from vessels •Adherence of phagocytic cells to endothelial cells •Diapedesis Apoptosis - programmed cell death; does not trigger inflammation 12