"SLE334 Medical Microbiology and Immunology, T2, 2017Topic 3: The War – Infection and Transmission of DiseaseIntroduction & Transmission of Disease(Mims’ Chapters 12 & 13)Lecture 9Friday 28 July 2017LT12 (X2.05), 11-12 pm(date, time and venue different for Geelong students)Dr Sharon La [email protected] Medical Microbiology and Immunology, T2, 2017Topic 3: The War – Infectionand Transmission of Disease SLE334 Medical Microbiology and Immunology, T2, 2017This lecture will cover……•? Host-Parasite relationships•? Entry of microorganisms•? Exit and transmission of microorganismsSLE334 Medical Microbiology and Immunology, T2, 2017Introduction•? Hosts developed highly efficient methods forrecognition of parasites•? Growth and spread of foreign invadersrestrained by effective inflammatory and immuneresponses•? However, microbes rapidly evolve characteristicsto overcome host defences:–? Microbes evolve with extraordinary speed (i.e. 1h generationtime for bacterium vs. 20 yrs for human host)–? Antibiotic resistance genes in bacteria (via plasmids)–? Microbes exploit weak points of host’s defences–? The host responds by slowly improving defencesSLE334 Medical Microbiology and Immunology, T2, 2017Host - parasite relationshipsEvery infection = race between the capacity of themicrobe to multiply, spread and cause disease and theability of the host to control and finally terminate theinfection.•? The speed of adaptive response mobilisation iscrucial•? Host - parasite adaptation leads to balancedrelationship•? Four types of infections:–? Microbial attachment/penetration mechanism–? Biting arthropod–? Skin wound/animal bite–? Antimicrobial defences impaired SLE334 Medical Microbiology and Immunology, T2, 2017Four types of microbial infection SLE334 Medical Microbiology and Immunology, T2, 2017Immuneresponse toinfectionFigure 12.1. Everyinfection is a race. Delaysin mobilizing host adaptivedefenses can lead todisease or death.SLE334 Medical Microbiology and Immunology, T2, 2017Myxomatosis•? a well-studied classic example of the evolution of an infectious disease unleashedon a highly susceptible population.SLE334 Medical Microbiology and Immunology, T2, 2017Causes of infectious diseases•? Commonly, more than 100 microbes causeinfection•? Koch’s ‘postulates’ to identify the microbialcauses of diseases•? Now, enlightened common sense used to reachconclusions regarding causationSLE334 Medical Microbiology and Immunology, T2, 2017‘Postulates’ of Robert Koch (1843-1910)•? Microbe present in everycase of disease•? Microbe must beisolated from host andgrown•? Disease must bereproduced in non- diseased host•? Microbe recoverablefrom experimentallyinfected hostCausation and Disease:The Henle-Koch Postulates RevisitedALFRED S. EVANS, THE YALE JOURNAL OF BIOLOGYAND MEDICINE 49, 175-195 (1976)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2595276/pdf/ yjbm00143-0072.pdf SLE334 Medical Microbiology and Immunology, T2, 2017Entry, exit and transmission SLE334 Medical Microbiology and Immunology, T2, 2017Introduction•? Microbes must attach to, or penetrate, the host’sbody surfaces•? Often, specific molecules on microbes bind toreceptor molecules on host cells •? Microbes must also exit from the body if they areto be transmitted to a fresh host SLE334 Medical Microbiology and Immunology, T2, 2017Body surfacesfor microbialinfection andshedding•? Microorganisms mustalso exit from the bodyif they are to betransmitted to a freshhost.•? Either shed in largenumbers in secretionsand excretions or areavailable in the bloodfor up-take, forexample by blood- sucking arthropods orneedles.SLE334 Medical Microbiology and Immunology, T2, 2017Sites of entry•? Skin (skin infection or infection elsewhere)–? Biting arthropods–? The conjunctiva•? Respiratory tract–? Interfering with cleansing mechanisms–? Avoiding destruction by alveolar macrophages•? Gastrointestinal tract–? Crude mechanical devices for attachment–? Mechanisms to resist mucus, acids, enzymes and bile–? Microbial exotoxin, endotoxin and protein absorption•? Urinogenital tract–? Vaginal defences (pH)–? Urethral and bladder defenses–? Mechanism of urinary tract invasion•? Oropharynx–? Oropharyngeal defenses–? Mechanisms of oropharyngeal invasion SLE334 Medical Microbiology and Immunology, T2, 2017Attachment of Influenza virus to ciliated epithelium tointerfere with cleansing mechanismsLeads to Ciliated celldysfunction or destruction byinfluenzaSLE334 Medical Microbiology and Immunology, T2, 2017Attachment of Vibrio cholerae to rabbit villus•? Infecting bacteria must attach themselves to the intestinal epithelium to establish themselves and multiply inlarge numbers. •? This avoids them being carried straight down the alimentary canal to be excreted.•? Vibrio cholerae and the rotaviruses both establish specific binding to receptors on the surface of intestinalepithelial cells. •? For V. cholerae, establishment in surface mucus may be sufficient for infection and pathogenicity. SLE334 Medical Microbiology and Immunology, T2, 2017Attachment of Vibrio cholerae to human M cells•? Infection sometimes involves more than mere adhesion to the luminal surface of intestinalepithelial cells.•? Initial entry occurs after up-take by M cells, and the bacteria then invade local macrophages. •? Gives rise to an inflammatory response, which in turn causes disruption of the epithelialbarrier. •? Bacteria enhance their entry by exploiting the host's inflammatory response. SLE334 Medical Microbiology and Immunology, T2, 2017Attachment of gonococci to human urethral epithelial cell•?The regular flushing actionof urine is a major urethraldefense, and urine in thebladder is normally sterile.•?Urinary tract is nearlyalways invaded from theexterior via the urethra,and an invadingmicroorganism must avoidbeing washed out duringurination. •?Specialized attachmentmechanisms have beendeveloped by successfulinvaders (e.g. gonococci)•? peptide on the bacterial pili binds to a syndecan-like proteoglycan on theurethral cell, and the cell is then induced to engulf the bacterium. •? referred to as parasite-directed endocytosis and also occurs with chlamydia.SLE334 Medical Microbiology and Immunology, T2, 2017Mechanism of urinary tract invasion Figure 13.6. Sexual anatomy is amajor determinant of infection.•? The female urinogenital tract isparticularly vulnerable to infectionwith fecal bacteria, mainlybecause the urethra is shorter andnearer to the anus.•? Intestinal bacteria (mainly E. coli)are common invaders of theurinary tract, causing cystitis.•? Spread to the bladder is no easytask in the male, where the urethrais 20 cm long.•? Urinary infections are rare inmales unless organisms areintroduced by catheters or whenthe flushing activity of urine isimpaired.SLE334 Medical Microbiology and Immunology, T2, 2017Exit and transmission•? Microbes possess a number of mechanisms toensure exit from host and transmission•? Nearly all microbes are shed from bodysurfaces, the route of exit to the outside world•? Transmission depends on several factors:–? Number of microbes shed–? Stability in environment–? Number of microbes required for infection–? Other factors (genetic factors of microbes; coughing/ sneezing by infected host) SLE334 Medical Microbiology and Immunology, T2, 2017Types of transmission and their control SLE334 Medical Microbiology and Immunology, T2, 2017Types of transmission and their control(refers to previous slide) •? Microorganisms can be transmitted to humans by humans,vertebrates and biting arthropods. •? Transmission is most effective when it takes place directly fromhuman to human. •? Commonest worldwide infections are spread by the respiratory,fecal-oral or venereal routes. •? A separate set of infections are acquired from animals, eitherdirectly from vertebrates (the zoonoses) or from biting arthropods.•? Arthropod-borne infections and zoonoses: controlled by controllingvectors or by controlling animal infection- virtually no person to person transmission of these infections (except forpneumonic plague) •? Infections acquired from other species are either not transmitted ortransmit very poorly from human to human.SLE334 Medical Microbiology and Immunology, T2, 2017Types of transmission between humans•? Transmission from respiratory tract (rapid spread inindoor crowds)•? Transmission from gastrointestinal tract (easy spreadwith poor public health & hygiene)•? Transmission from urinogenital tract–? Sexually transmitted diseases (STDs)–? Semen as a source of infection–? Perinatal transmission•? Transmission from oropharynx (i.e. saliva)•? Transmission from skin (i.e. shedding or direct contact)–? Transmission in milk•? Transmission from blood (via arthropods or needles)•? Vertical (from parents to offspring) and horizontal(person to person) transmissionSLE334 Medical Microbiology and Immunology, T2, 2017Droplet dispersal from a sneeze Most of the 20 000 particles seen are coming from the mouth. "