"SLE334 Medical Microbiology and Immunology, T2, 2017Topic 3: The War – Infection and Transmission of DiseaseSpread and replication(Mims’ Chapter 15)Lecture 11Friday 4 August 2017LT12 (X2.05), 10-11 am(date, time and venue different for Geelong students)Dr Sharon La [email protected] Medical Microbiology and Immunology, T2, 2017This lecture will cover……•? Surface and systemic infections- features- measles- typhoid fever•? Mechanisms of spread of infection through body•? Routes of invasion•? Genetic determinants of spread and replication SLE334 Medical Microbiology and Immunology, T2, 2017Introduction•? An infection may be surface or systemic•? Many microbes multiply in epithelial cellsat site of entry on body surface•? However, microorganisms fail to spread todeeper structures or through the body•? Local spread on fluid-covered mucosalsurface, aided by ciliary action•? Large-scale movement of fluid spreadinfection to distant areas of surface SLE334 Medical Microbiology and Immunology, T2, 2017Surface andsystemicinfections•?Rapid replication is essential for surfaceinfections•?Many microorganisms are obliged to spreadsystemically because they fail to spread andmultiply at the site of initial infection, the bodysurface (Eg. measles or typhoid).SLE334 Medical Microbiology and Immunology, T2, 2017Features of surface andsystemic infections•? Variety of factors determine surface or systemicinfections –? Temperature–? Site of budding–? Many microbes fail to spread and multiply on bodysurface, thus obliged to spread systematically•? Rapid replication crucial for surface infections•? In systemic infections, stepwise invasion ofdifferent tissues of bodySLE334 Medical Microbiology and Immunology, T2, 2017Pattern of infection determined by topographyof virus release from epithelial surfaces SLE334 Medical Microbiology and Immunology, T2, 2017Spread of infectionthroughout thebody•? In dengue, malaria and typhus,multiplication occurs in blood cells orvascular endothelium.•? ††Poliovirus invades the brain and spinalcord from the blood, but is not shed fromthese sites, whereas rabies invades andlater travels from brain to salivary glandsvia peripheral nerves.SLE334 Medical Microbiology and Immunology, T2, 2017Pathogenesis of measleshttp:// colonialdiseasedigitaltextbook.wikispaces.co Virus invades body surfaces from the blood, reaches surfacem/3.+Measlesepithelium first in the respiratory tract and then in mucosae (Koplik'sspots) and finally in the skin (rash). SLE334 Medical Microbiology and Immunology, T2, 2017Pathogenesis of typhoid feverSLE334 Medical Microbiology and Immunology, T2, 2017Mechanism of spread through the body•? Invading microbes encounter defences on enteringthe body–? Tissue fluids containing antimicrobial substances (Ab, C)–? Local macrophages–? Physical barrier of tissue structure–? Lymphatic system (macrophages)•? Fate of microbes in blood depends if free orassociated with circulating cells•? Circulating microbes invade characteristic targetorgans and tissues•? Some viruses spread via peripheral nerves to CNSand vice versa•? Once blood-cerebrospinal barrier crossed, microbesspread rapidly in cerebrospinal fluid spaces SLE334 Medical Microbiology and Immunology, T2, 2017Microbial invasion and spread tolymph and blood •?Microbes beneath surface epithelium readily enter local lymphatics.•?Invading microbes face the following defenses:- tissue fluids containing antimicrobial substances (antibody, complement)- local macrophages (histiocytes); subcutaneous and submucosal macrophages are a threat to microbialsurvival- the physical barrier of local tissue structure.SLE334 Medical Microbiology and Immunology, T2, 2017Routes of microbial invasion of CNS •? Certain viruses spread via peripheral nerves from peripheral parts of the body to the central nervous systemand vice versa.•? Eg. Rabies, herpes simplex virus (HSV) and varicella-zoster virus (VZV) travel in axons.•? Rabies reaches CNS largely by peripheral nerves, and takes the same route from the CNS when it invadesthe salivary glands.SLE334 Medical Microbiology and Immunology, T2, 2017Genetic determinants of spreadand replication•? Pathogenicity of a microbe determined byinterplay of variety of factors•? Ability of a microbe to infect and cause diseaseinfluenced by genetic constitution of the host•? Susceptibility usually operates at the level ofimmune response (i.e. Lubeck disaster, yellowfever vaccine, tuberculosis in identical twins)•? Virulence coded by more than one microbialgene •? Other factors (brain/stress)SLE334 Medical Microbiology and Immunology, T2, 2017Summary•? Infections restricted to body surface have shortincubation periods (I.e. common cold) than systemicinfections (i.e. measles) and adaptive (immune) hostresponses•? Microbes with slow growth evolve slowly•? Spread through body occurs via lymph and blood•? Up-take by reticuloendothelial cells in liver and spleenfocuses infection to these organs•? Viruses spread in either direction along nerve axons•? Pathogenicity and virulence determined by geneticfactors of host (i.e tuberculosis in identical twins) andgenetic factors of microbe•? Advances in molecular biology help our understanding ofvirulence SLE334 Medical Microbiology and Immunology, T2, 2017RemindersClass Test: Thursday 10 August 2017, 1-2 pm(normal lecture time), LT13 (HC2.005)PC2 Biosafety Training Quiz – ALL studentsto complete and pass before first prac classSLE334 Medical Microbiology and Immunology, T2, 2017Class Test 1•? Covers Lectures 1-12 •? CLOSED book•? Multiple choice questions•? Venue and time:–?WHEN: Thursday 10 August 2017, 1-2 pm(normal lecture time)–?VENUE: LT13 (HC2.005) SLE334 Medical Microbiology and Immunology, T2, 2017PC2 Biosafety Training •? Compulsory hurdle requirement for pracs•? Review a pre-recorded 1 hour PC2 training movie onCloudDeakin in your own time•? Complete on-line quiz prior to your first prac and hand incompleted quiz to your prac demonstrator at first pracattendance•? Important for your safety and containment of Risk Group 2microorganisms•? Great knowledge/skill/attribute to have for work placement•? You must complete this training regardless of previous PC2training and certificationSLE334 Medical Microbiology and Immunology, T2, 2017Next:Topic 3: The War – Infection andTransmission of Disease•? Parasite survivalstrategies andpersistentinfections "