"SLE334 Medical Microbiology and Immunology, T2, 2017Topic 3: The War – Infection and Transmission of DiseaseParasite survival strategies and persistent infections(Mims’ Chapter 16)Lecture 12Friday 4 August 2017LT12 (X2.05), 11-12 pm(date, time and venue different for Geelong students)Dr Sharon La [email protected] Medical Microbiology and Immunology, T2, 2017This lecture will cover……•? Strategies to avoid innate mechanisms•? Strategies to avoid adaptive mechanisms•? Parasite survival strategies•? Antigenic variation•? Immunosuppression•? Persistent infections SLE334 Medical Microbiology and Immunology, T2, 2017Introduction•? Battery of mechanisms available to thehost, both natural and adaptive, to keepout and destroy parasite•? Powerful but not 100% effective•? Most infectious organisms developed‘answers’ to host defences•? Microbes are of major concern as theydeveloped strategies for evading oractively interfering with host defencesSLE334 Medical Microbiology and Immunology, T2, 2017Strategies to evade natural non- adaptive defences like phagocyte•? Killing or avoiding being killed byphagocytes•? Interfering with ciliary action•? Interfering with complement’s alternativepathway•? Producing iron-binding molecules•? Blocking interferonsSLE334 Medical Microbiology and Immunology, T2, 2017Various mechanisms adopted by microorganisms toavoid phagocytosisSLE334 Medical Microbiology and Immunology, T2, 2017Bacterial strategiesto avoid complement- mediated damage(1)? Outer capsule / coat preventscomplement activation. (2) Complement receptors on phagocytescannot obtain access to fixed C3b. (3) Surface structures expressed that divertattachment of the lytic complex (MAC)from the cell membrane. (4) Membrane-bound enzyme can degradefixed complement or cause it to be shed. (5) Outer membrane can resist the insertionof the lytic complex. (6) Secreted decoy proteins can causecomplement to be deposited on themand not on the bacterium itself.SLE334 Medical Microbiology and Immunology, T2, 2017Strategies to evade adaptive defences are more sophisticated than those for evading innate defencesSLE334 Medical Microbiology and Immunology, T2, 2017Parasite survival strategies•? Viruses are good at thwarting immunedefences•? Some microbes able to persist in the host•? Strategies for evading host defencesinclude a rapid ‘hit-and-run’ infection•? Otherwise main strategies to eludelymphocyte include:–?Concealment of Ags–?Antigenic variation–?Immunosuppression SLE334 Medical Microbiology and Immunology, T2, 2017Concealment of Ags•? Remaining inside cells without Ags displayed onthe surface prevents recognition•? Colonizing privileged sites keeps microbe out ofreach of circulating lymphocytes•? Mimicking host Ags (does not stop host makingantimicrobial response)•? Microbes conceal themselves by taking up hostmolecules to cover their surface (i.e. productionof Fc receptors)SLE334 Medical Microbiology and Immunology, T2, 2017Viral infection of cell surfacesAllows direct shedding of thevirus to the exterior, as wellas avoidance of host immunedefenses SLE334 Medical Microbiology and Immunology, T2, 2017Wart virus replication in epidermis•? Cell differentiation such askeratinization controls virusreplication•? Virus matures whenphysically removed fromimmune defenses – eg.during keratinization ofepidermisSLE334 Medical Microbiology and Immunology, T2, 2017Hydatid cysts•? Hydatid cysts: Multiple, thin-walled, fluid-filled cysts in a surgical specimen; the lungis a common site.•? Worms can survive inside the cysts even though the blood of the host containsprotective levels of antibody. SLE334 Medical Microbiology and Immunology, T2, 2017Molecular mimicry by microbe caninduce host cell damage•? Eg. rheumatic heart disease following streptococcal infection is caused by antibodies reactingwith meromyosin, the cross-reacting determinant.•? In this case mimicry does not protect the bacteria•? Occurs by accident and does not necessarily prevent the host from making an antimicrobial andautoimmune response. SLE334 Medical Microbiology and Immunology, T2, 2017Production of Fc receptors by microbes•? A number of virusesand bacteria produceFc receptors, whichare displayed on theirsurface and bindimmunoglobulinmolecules in a uselessupside-down position.•? Prevents the access ofspecific antibodies or Tcells to the microbe orthe infected cell.SLE334 Medical Microbiology and Immunology, T2, 2017Antigenic variation•? Antigenic variation can occur:–? During the course of infection in a given individual–? During spread of microbe through the host community•? At the molecular level, 3 main mechanisms ofantigenic variation:–? Mutation (i.e. influenza virus)–? Recombination (i.e. influenza A virus)–? Gene switching (i.e. African trypanosomes)SLE334 Medical Microbiology and Immunology, T2, 2017Antigenic variation as a microbial strategyChange in antigens may take place in the originally infected individual, somicrobe can undergo renewed growth (e.g. trypanosomiasis, relapsing fever)- or it may take place as the microbe passes through the host population,enabling it to re-infect a given individual (e.g. influenza). SLE334 Medical Microbiology and Immunology, T2, 2017Hemagglutinin and neuraminidase are themajor surface antigens of influenza virus•?The influenza virus canchange its antigenicproperties slightly (antigenicdrift) or radically (antigenicshift). •?Alterations in the structure ofthe hemagglutinin antigenrender earlier antibodiesineffective and new virusepidemics therefore breakout. •?The diagram shows strainsthat have emerged byantigenic shift since 1933. For information and updates onInfluenza see:http://www.who.int/csr/disease/ avian_influenza/en/SLE334 Medical Microbiology and Immunology, T2, 2017Immunosuppression•? Many virus infections cause a general temporaryimmunosuppression•? Different microbes have different immunosuppressive effects•? Immunosuppression by microbes often involves infection of immunecells:–? T cells (HIV, measles)–? B cells (EBV)–? Macrophages (HIV)–? Dendritic cells (HIV)•? Certain microbe toxins are immunomodulators (B and T cellmitogens)•? Successful microbes interfere with signaling between immune cells,with cytotoxic T cell recognition or with host apoptotic responses•? Some microbes interfere with local expression of immune responsein tissues SLE334 Medical Microbiology and Immunology, T2, 2017Microbial interference with the immune systemby production of T and B cell mitogensSLE334 Medical Microbiology and Immunology, T2, 2017Persistent infections•? Persistent infections represent a failure of hostdefences•? Latent infections can become reactivated•? Reactivation is clinically important inimmunosuppressed individuals (AIDS, tumours,transplantation)•? There are two stages in reactivation (stages Aand B) SLE334 Medical Microbiology and Immunology, T2, 2017Patterns of acute and persistent infectionsSLE334 Medical Microbiology and Immunology, T2, 2017Patterns of acute and persistent infections SLE334 Medical Microbiology and Immunology, T2, 2017Patterns of acute and persistent infectionsSLE334 Medical Microbiology and Immunology, T2, 2017Persistenceis amicrobialsurvivalstrategy•? Survival advantages if the microbe is shed,either continuously or intermittently.•? Especially when the host species consists ofsmall isolated groups of individuals "