Kuliah Mikropangan 2010 Food Borne Host Microbe Interactions 1

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    Host Microbe InteractionsHost Microbe Interactions

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    Host Microbe InteractionsHost Microbe Interactions

    daily wedaily we

     – ingest thousands of microorganisms on the food weingest thousands of microorganisms on the food we

    eateat

     – inhale hundreds of thousands of microorganisms ininhale hundreds of thousands of microorganisms inthe air we breaththe air we breath

     – have microorganisms stick to us wherever we gohave microorganisms stick to us wherever we go

    most of these invaders have no ill effect on us as wemost of these invaders have no ill effect on us as we

    slough, cough, gag, urinate and defecate them awayslough, cough, gag, urinate and defecate them awaywe are also protected by the “friendly” residentwe are also protected by the “friendly” resident

    microorganisms found throughout our bodymicroorganisms found throughout our body

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    Host Microbe InteractionsHost Microbe Interactions

    microorganisms very easily colonize the warm, moist,microorganisms very easily colonize the warm, moist,

    nutrient rich environment we call the human bodynutrient rich environment we call the human body

     – usually they live as normal florausually they live as normal flora

     – in some cases, they are able to overcome the bodiesin some cases, they are able to overcome the bodies

    defenses, and cause diseasedefenses, and cause disease

     – organisms that can cause any noticeable damage,organisms that can cause any noticeable damage,invade tissue, or produce toins are called pathogensinvade tissue, or produce toins are called pathogens

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    !igestive "ystem Infections!igestive "ystem Infections

    "ometimes referred to"ometimes referred toas theas the gastrointestinalgastrointestinaltracttract

    #assageway running#assageway runningfrom mouth to anusfrom mouth to anus

    Ma$or route of microbialMa$or route of microbialinvasioninvasion

    !ivided into upper and!ivided into upper andlower tractslower tracts

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    • The intestinal tract is slightly acidic to neutral and supportsa diverse population of microorganisms in a variety ofnutritional and environmental conditions.

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    %ormal &lora%ormal &lora

    Important in protecting body from invasionImportant in protecting body from invasion

    &lora of digestive tract mainly found in the oral cavity&lora of digestive tract mainly found in the oral cavity

    and intestinesand intestines

     – 'sophagus has very little flora'sophagus has very little flora – %ormal stomach is devoid of microorganisms%ormal stomach is devoid of microorganisms

    (illed by stomach acid(illed by stomach acid

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    ) *he presence of a population of normal*he presence of a population of normal

    nonpathogenic microorganisms in thenonpathogenic microorganisms in the

    respiratory tract and urogenital tract is essentialrespiratory tract and urogenital tract is essential

    for normal organ function and often preventsfor normal organ function and often preventsthe colonization of pathogens+the colonization of pathogens+

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    ) In theIn the upper respiratory tractupper respiratory tract nasopharyn,nasopharyn,

    oral cavity, and throat-, microorganisms live inoral cavity, and throat-, microorganisms live in

    areas bathed with the secretions of the mucousareas bathed with the secretions of the mucousmembranes+membranes+

    )*he normal lower respiratory tract trachea,

    bronchi, and lungs- has no resident microflora,

    despite the large numbers of organisms

    potentially able to reach this region during

    breathing+

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    %ormal &lora%ormal &lora

    MouthMouth

     – .elatively few species colonize oral cavity.elatively few species colonize oral cavity

    "treptococcal"treptococcal species most commonspecies most common

     – Host limits number of bacteria on mucus membranesHost limits number of bacteria on mucus membranesMembrane cells constantly sheddingMembrane cells constantly shedding

     – *eeth are nonshedding surface*eeth are nonshedding surface

    /arge numbers of bacteria can collect and form/arge numbers of bacteria can collect and form biofilmbiofilm

     – Masses of bacteria termed dental pla0ueMasses of bacteria termed dental pla0ue

    122 billion bacteria per gram of pla0ue122 billion bacteria per gram of pla0ue

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    IntestinesIntestines

     – "mall number of bacteria colonize upper small intestine"mall number of bacteria colonize upper small intestine#redominant organisms are aerobic and facultative 3ram#redominant organisms are aerobic and facultative 3ramnegative bacilli and some streptococcinegative bacilli and some streptococci

     – /arge intestine contains very high numbers of organisms/arge intestine contains very high numbers of organisms 4pproimately 4pproimately 12121111 bacteria per gram of fecesbacteria per gram of feces

     – *hat is 122 billion bacteria55555*hat is 122 billion bacteria55555

    High population is due to abundance of nutrients in fecesHigh population is due to abundance of nutrients in feces) Escherichia coli Escherichia coli  and other enterobacteriaand other enterobacteria predominate bacterialpredominate bacterial

    populationpopulation – Important source of opportunistic infectionsImportant source of opportunistic infections

    'specially of the urinary tract'specially of the urinary tract

     – %ormal intestinal flora prevent pathogenic colonization of%ormal intestinal flora prevent pathogenic colonization oflarge intestinelarge intestine

    %ormal &lora%ormal &lora

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     4natomical 6arriers 4natomical 6arriers

    in addition to providing barriers to the microbial world,in addition to providing barriers to the microbial world,skin and mucous membranes also create anskin and mucous membranes also create an

    environment for interacting microorganisms and theenvironment for interacting microorganisms and thehuman bodyhuman body

    these interactions are referred to as symbiosis, whichthese interactions are referred to as symbiosis, whichmeans living together means living together 

     – the players in symbiosis are referred to as symbiontsthe players in symbiosis are referred to as symbionts

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     4natomical 6arriers 4natomical 6arriers

    symbiotic relationships between microorganisms and asymbiotic relationships between microorganisms and ahost includehost include

     – mutualismmutualism

     – commensalismcommensalism

     – parasitismparasitism

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    MutualismMutualism

    in this type of relationship, both partners benefitin this type of relationship, both partners benefit

     – E. coli E. coli  synthesizes vitamin ( in the intestinesynthesizes vitamin ( in the intestine

     – in echange the large intestine provides nutrientsin echange the large intestine provides nutrients

    necessary for survival of the microorganismsnecessary for survival of the microorganisms

    E. coli E. coli 

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    7ommensalism7ommensalism

    one organism is benefited and the other is unaffected byone organism is benefited and the other is unaffected by

    this type of relationshipthis type of relationship

     – many of the microorganisms that make up our normalmany of the microorganisms that make up our normal

    flora inhabit places like the eyes, ears, and eternalflora inhabit places like the eyes, ears, and eternal

    genitaliagenitalia

    these bacteria live on secretions and sloughed offthese bacteria live on secretions and sloughed off

    cellscells

    they bring no benefit to the host and yet thethey bring no benefit to the host and yet the

    microorganisms benefit greatly from themicroorganisms benefit greatly from the

    environment they inhabitenvironment they inhabit

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    #arasitism#arasitism

    one organism benefits at the epense of the other one organism benefits at the epense of the other 

     – all pathogens are parasitesall pathogens are parasites

    parasitic microorganisms

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    %ormal &lora%ormal &lora

    the presence of normal florathe presence of normal flora

     – cover potential adherence sites for invadingcover potential adherence sites for invading

    microorganismsmicroorganisms

     – consume the available nutrientsconsume the available nutrients – produce compounds toic to other microorganismsproduce compounds toic to other microorganisms

    bacteria found on skin

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    %ormal &lora%ormal &lora

    when the balance between normal flora andwhen the balance between normal flora and

    pathogens is upset, disease can resultpathogens is upset, disease can result

     – the normal bacterial microorganisms of the adultthe normal bacterial microorganisms of the adult

    human vagina maintain the pH at about 8+9 – 9+:human vagina maintain the pH at about 8+9 – 9+:

     – the presence of this normal flora inhibits thethe presence of this normal flora inhibits the

    overgrowth ofovergrowth of Candida albicansCandida albicans, yeast, yeast

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    %ormal &lora%ormal &lora

     – if the presence of the normal flora is eliminated byif the presence of the normal flora is eliminated by

    antibiotics, or ecessive douching, the pH of theantibiotics, or ecessive douching, the pH of the

    vagina becomes nearly neutral, creating anvagina becomes nearly neutral, creating an

    environment very conducive to the growth ofenvironment very conducive to the growth of C.C.

    albicansalbicans

    C. albicans

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     &oodborne pathogens

    It can be classified into three forms;

    foodborne intoxication

    foodborne infection

    foodborne toxicoinfection

    &ood

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    &ood #athogens&ood #athogenswww.textbookofbacteriology.netwww.textbookofbacteriology.net

    Todar's Online Textbook of BacteriologyTodar's Online Textbook of BacteriologyMicrorganisms that cause food borne infection orMicrorganisms that cause food borne infection or

    intoication;intoication;

    SalmonellaBotulinum

    E.coli

    ListeriaCampylobacter 

    Stapylococci

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    &oodborne Intoication&oodborne Intoication

    illness from microbial eotoinillness from microbial eotoin

     – microorganism does not cause the illness, the toinmicroorganism does not cause the illness, the toin

    released by the microorganism doesreleased by the microorganism does

    common eotoin producing microorganismscommon eotoin producing microorganisms

     – Staphylococcus aureusStaphylococcus aureus

     – Clostridium botulinumClostridium botulinum

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    Toxic bacterial food poisoning

    some bacteria grow in food and produce atoin within the food which is then consumed

    e+g+ Bacillus cereus and Staphylococcus

    aureus+ ?hen the food is consumed viable

    cells of the bacteria do not need to be

    present+

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    &ollowing ingestion, *oins are absorbed through

    the gastrointestinal epithelial lining and cause

    local tissue damage and may induce inflammationresulting in diarrhea or vomiting+

    In some cases, toins are translocated to distant

    organs or tissues such as liver, kidney, peripheral,or central nervous system where they can cause

    damage+

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    *oins*oins

      Some bacteria release poisons known astoxins which cause food poisoning.

      Some toxins, known as exotoxins multiply in

    food. These toxins are not easily destroyedby cooking and may remain in food oncethey have developed.

    Other bacteria produce toxins inside thehuman body only after the food has beeneaten. These are called endotoxins 

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    *oins

    "ubstances that contribute to pathogenicity

    Exotoxins are secreted out of the cell during cell life+

    Endotoxins from inside the cell+ .eleased upon

    cell lysis+

    *oemia #resence of toin the host@s blood

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    'otoins'otoins

    eotoins are soluble in body fluids which makes themeotoins are soluble in body fluids which makes them

    easily diffused into blood and then are rapidlyeasily diffused into blood and then are rapidly

    transported throughout the bodytransported throughout the body

    eotoins work by destroying particular parts of the hosteotoins work by destroying particular parts of the host

    cells or by inhibiting certain metabolic functionscells or by inhibiting certain metabolic functions

    soluble protein, thus readily carried throughbody by lymphatics or blood

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    'otoins'otoinseotoins are highly specificeotoins are highly specific

    eotoins are among the most lethal substances knowneotoins are among the most lethal substances known

    to manto man

     – 1 gram of the eotoin produced from1 gram of the eotoin produced from ClostridiumClostridium

    botulinumbotulinum

     is capable of killing the entire population ofis capable of killing the entire population of

    the Anited "tates, close to 822 million peoplethe Anited "tates, close to 822 million people

    the danger with eotoinsthe danger with eotoins is notis not the ingestion of thethe ingestion of the

    bacterium, but the ingestion of the toinbacterium, but the ingestion of the toin

    Clostricium botulinum

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    'otoins'otoins

    most eotoins are grouped according to the tissuesmost eotoins are grouped according to the tissues

    they adversely impactthey adversely impact

     – neurotoins damage the nervous systemneurotoins damage the nervous system

     –entereotoins upset the intestinal systementereotoins upset the intestinal system

     – cytotoins afflict their damage on many different typescytotoins afflict their damage on many different types

    of cells by disrupting cellular function of by lysing theof cells by disrupting cellular function of by lysing the

    cellcell

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    'otoins

    Figure 15.4a

    Mostly seen in Gram (+

    !acteria

    Most gene that code for

    e"oto"ins are located on

     plasmids or phages

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    'otoin

    'otoin

    "ource Mostly 3ram B

    Metabolic product 6y

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    1+ Cytotoxins

     – kill cellsF+ "eurotoxins

     – interfere with normal nerveimpulses

    8+ Enterotoxins

     – effect cells lining the 3+I+ *ract

    Many toins have 4

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    'otoins'otoins

    'otoins'otoins < soluble, heat

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    Membrane

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    6 t li t i i t f

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    )  6otulinum toin consists of seven

    related toins that are the most potent

    biological toins known igure ().(*-+

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    EnterotoxinsEnterotoxins) EnterotoxinsEnterotoxins are eotoins that specificallyare eotoins that specificallyaffect the small intestine, causing changes inaffect the small intestine, causing changes in

    intestinal permeability that lead to diarrhea+intestinal permeability that lead to diarrhea+

    ) Many enteric pathogens colonize thesmall intestine and produce 4

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    ) *he action of cholera enterotoin isshown in igure ().((+

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    & db I f ti& db I f ti

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    &oodborne Infection&oodborne Infection

    re0uires consumption of microorganismre0uires consumption of microorganism

    symptomatic about 1 day following ingestion ofsymptomatic about 1 day following ingestion ofcontaminated foodcontaminated food

    common foodborne infecting microorganismscommon foodborne infecting microorganisms

     – SalmonellaSalmonella andand Campylobacter Campylobacter 

    poultry product infectionspoultry product infections

     – Escherichia coli Escherichia coli  21:;H21:;H

    undercooked hamburger undercooked hamburger 

    7ampylobacter "almonella

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    !nfecti+e bacterial food poisoning

    infections occur when pathogens are ingestedvia contaminated food and the bacteria is

    established in the body, usually growing inside

    the intestinal tract and irritating intestines e+g+

    Salmonella spp+ and Campylobacter jejuni +

    *he infection may involve subse0uent growth

    in other tissues

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    #rinciples of Infectious !isease#rinciples of Infectious !isease

    a parasitic relationship between a microorganism and aa parasitic relationship between a microorganism and a

    host is called an infectionhost is called an infection

     – infections can be subclinical or inapparent; meaninginfections can be subclinical or inapparent; meaning

    no symptoms or the symptoms are so mild as to beno symptoms or the symptoms are so mild as to be

    noticednoticed

    infection that causes impairment of body function isinfection that causes impairment of body function is

    called diseasecalled disease

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    #rinciples of Infectious !isease#rinciples of Infectious !isease

    patogenicitypatogenicity is the ability of a microorganism to causeis the ability of a microorganism to cause

    disease by overcoming the host defensesdisease by overcoming the host defenses

    )#athogen invasion starts at the site of adherence andmay spread throughout the host via the circulatory

    systems+

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    &actors Impacting =utcome of&actors Impacting =utcome of

    Host

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    ) #athogens gain access to host#athogens gain access to host

    tissues by adherence to mucosaltissues by adherence to mucosal

    surfaces through interactionssurfaces through interactionsbetween pathogen and hostbetween pathogen and host

    macromolecules+macromolecules+

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    Coloni,ation and -rowtColoni,ation and -rowt

    )  4 pathogen must gain access to nutrients and 4 pathogen must gain access to nutrients and

    appropriate growth conditions beforeappropriate growth conditions before

    coloni,ationcoloni,ation and growth in substantialand growth in substantialnumbers in host tissue can occur+ =rganismsnumbers in host tissue can occur+ =rganisms

    may grow locally at the site of invasion or maymay grow locally at the site of invasion or may

    spread through the body+spread through the body+

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    ) If etensive bacterial growth in tissues occurs,If etensive bacterial growth in tissues occurs,

    some of the organisms are usually shed into thesome of the organisms are usually shed into the

    bloodstream in large numbers, a conditionbloodstream in large numbers, a condition

    calledcalled bacteremiabacteremia++

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    "higellosis"higellosis

    #athogenesis#athogenesis

     – S. dysenteriaeS. dysenteriae

    .arely encountered.arely encountered

    in Anited "tatesin Anited "tates

    #roduces potent#roduces potent 4

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    Helicobacter pyloriHelicobacter pylori 3astritis3astritis

    #athogenesis#athogenesis

     – 6acteria6acteria survivesurvive

    etreme acidityetreme acidity ofof

    the stomachthe stomach

     4ble to neutralize 4ble to neutralize

    environmentenvironment

     – =rganism uses=rganism uses

    flagella to corkscrewflagella to corkscrew

    through mucosalthrough mucosallininglining

     – InflammatoryInflammatory

    response beginsresponse begins

     – Mucus production

    decreases

    ) ?ithout mucus stomach liningnot protected from acidic

    environment

     – Infection persists for years) #ossibly for a life time

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    irulenceirulence

    ) irulenceirulence is determined byis determined by in+asi+enessin+asi+eness,,

    toxicitytoxicity, and other factors produced by a, and other factors produced by a

    pathogen+ Earious pathogens produce proteinspathogen+ Earious pathogens produce proteinsthat damage the host cytoplasmic membrane,that damage the host cytoplasmic membrane,

    causing cell lysis and death+causing cell lysis and death+

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    Major virulence determinantsMajor virulence determinants::

    toxinstoxins - destroy, damage, inactivate- destroy, damage, inactivate

    natural defense mechanism of hostnatural defense mechanism of host– exotoxinsexotoxins

    – endotoxinsendotoxins

    enzymesenzymes - assist bacteria in establishing- assist bacteria in establishing

    infection and producing diseaseinfection and producing disease

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    ) 6ecause the activity of these toins is most6ecause the activity of these toins is most

    easily detected with red blood cellseasily detected with red blood cells

    erythrocytes-, they are callederythrocytes-, they are called emolysinsemolysins 

    Table ()./Table ()./-+ In most pathogens, a number of-+ In most pathogens, a number offactors contribute to virulence+factors contribute to virulence+

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    ) Salmonella displays a wide variety of

    traits that enhance virulence igure

    ().)0-+

    irulence actors andirulence actors and

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    u e ce acto s a du e ce acto s a d

    ToxinsToxins

    irulence actorsirulence actors) #athogens produce a variety of enzymes that#athogens produce a variety of enzymes thatenhance virulence by breaking down or alteringenhance virulence by breaking down or altering

    host tissue to provide access and nutrients+host tissue to provide access and nutrients+) "till other pathogen

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    ) *he presence of endotoin detected by the*he presence of endotoin detected by the

    /imulus amebocyte lysate assay indicates/imulus amebocyte lysate assay indicates

    contamination of a substance by gram

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    2ost actors in !nfection2ost actors in !nfection 

    2ost 3isk actors for2ost 3isk actors for

    !nfection!nfection

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    ) 7onditions of age, stress, diet, general health,7onditions of age, stress, diet, general health,

    lifestyle, prior or concurrent disease, andlifestyle, prior or concurrent disease, and

    genetic makeup may compromise the host@sgenetic makeup may compromise the host@s

    ability to resist infection+ability to resist infection+

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    !nnate 3esistance to!nnate 3esistance to

    !nfection!nfection) %onspecific physical, anatomical, and%onspecific physical, anatomical, and

    chemical barriers prevent colonization of thechemical barriers prevent colonization of the

    host by most pathogens host by most pathogens igure ().(/igure ().(/-+ /ack-+ /ackof these defenses results in susceptibility toof these defenses results in susceptibility to

    infection and colonization by a pathogen+infection and colonization by a pathogen+

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    ) Table ().4 shows tissue specificity ininfectious disease+

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    ToxinsToxins

    endotoxinsendotoxins

    – produced only by gram negative bacteriaproduced only by gram negative bacteria

    – part of the outer cell wall (lipopolysaccharidepart of the outer cell wall (lipopolysaccharide

    coat)coat)

    lipid component is toxiclipid component is toxic

    side chains (!, " antigen) are immunogenicside chains (!, " antigen) are immunogenic– released in large amounts at cell deathreleased in large amounts at cell death

    – heat stable, not destroyed by autoclavingheat stable, not destroyed by autoclaving

    – less potent and less speci#c than exotoxinsless potent and less speci#c than exotoxins

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    ToxinsToxins

    endotoxinsendotoxins– pyrogenicpyrogenic

    – toxic to most animals, producing similar rangetoxic to most animals, producing similar range

    of biological e$ects regardless of sourceof biological e$ects regardless of source

    feverfever

    increased %&'increased %&'

    ' (disseminate intravascular coagulopathy)' (disseminate intravascular coagulopathy)

    hypotensionhypotension

    shoc* shoc* 

    deathdeath

    – degraded by oxidizing agentsdegraded by oxidizing agents

    – examples+examples+ E. coli, Salmonella, ShigellaE. coli, Salmonella, Shigella

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    nzymesnzymes

    spreading factorsspreading factors– hyaluronidasehyaluronidase (gram ) - attac*s interstitial(gram ) - attac*s interstitial

    cement of connective tissuecement of connective tissue

    – collagenasecollagenase ('lostridium) - brea* down('lostridium) - brea* down

    collagen, facilitating invasion of muscle andcollagen, facilitating invasion of muscle and

    gas gangrene formationgas gangrene formation

    – neuraminidaseneuraminidase (.ibrio and /higella) - brea*(.ibrio and /higella) - brea*

    down intercellular cement of intestinaldown intercellular cement of intestinal

    epithelial cellsepithelial cells

    – *inase*inase (/trep and /taph) - digests #brin,(/trep and /taph) - digests #brin,

    preventing clotting and allowing rapidpreventing clotting and allowing rapid

    di$usiondi$usion

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    #rinciples of Infectious !isease#rinciples of Infectious !isease

    the more virulent a pathogen is the more diseasethe more virulent a pathogen is the more diseasepromoting attributes it possessespromoting attributes it possesses

     – virulence factors are substances or features of avirulence factors are substances or features of a

    microorganism that help it infect and cause diseasemicroorganism that help it infect and cause disease

     – they may includethey may include

    ability to adhereability to adhere

    ability to overcome host defenseability to overcome host defense

    ability to evade host defenseability to evade host defense

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    Coloni,ation and -rowt

      4 pathogen must gain access to nutrients and

    appropriate growth conditions before coloni,ation and

    growth in substantial numbers in host tissue can occur+

    =rganisms may grow locally at the site of invasion or

    may spread through the body+

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     If etensive bacterial growth in tissues occurs, some

    of the organisms are usually shed into the bloodstream

    in large numbers, a condition called bacteremia+

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    &lagellar &unction&lagellar &unction

    • 3uide bacteria in a direction in response to eternal3uide bacteria in a direction in response to eternalstimulus;stimulus;

    1- chemical stimuli –1- chemical stimuli – cemotaxiscemotaxis positive and negative positive and negative

    F- light stimuli –F- light stimuli – pototaxispototaxis• "ignal sets flagella into rotary motion clockwise or"ignal sets flagella into rotary motion clockwise or

    counterclockwisecounterclockwise

    4 i l &il t4ial &ilaments

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     4ial &ilaments 4ial &ilaments

    #eriplasmic, internal flagella, enclosed between cell#eriplasmic, internal flagella, enclosed between cell

    wall and cell membrane of spirocheteswall and cell membrane of spirochetes#roduce cellular motility by contracting and imparting#roduce cellular motility by contracting and imparting

    twisting or fleing motiontwisting or fleing motion

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    &imbriae&imbriae

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    &imbriae&imbriae&ine, proteinaceous, hairlike bristles from the cell&ine, proteinaceous, hairlike bristles from the cell

    surfacesurface&unction in adhesion to other cells and surfaces&unction in adhesion to other cells and surfaces

    #ili#ili

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    #ili#ili

    .igid tubular structure made of.igid tubular structure made of pilinpilin proteinprotein

    &ound only in 3ram negative cells&ound only in 3ram negative cells

    &unction to $oin bacterial cells for partial !%4 transfer called&unction to $oin bacterial cells for partial !%4 transfer called

    con5ugationcon5ugation

    3lycocaly3lycocaly

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    3lycocaly3lycocaly

    7oating of molecules eternal to the cell wall,7oating of molecules eternal to the cell wall,

    made of sugars andJor proteinsmade of sugars andJor proteins

    *wo types;*wo types;

    1+1+ slime layer < loosely organized and attachedslime layer < loosely organized and attached

    F+F+ capsule < highly organized, tightly attachedcapsule < highly organized, tightly attached

    &unctions;&unctions; – protect cells from dehydration and nutrient lossprotect cells from dehydration and nutrient loss

     – inhibit killing by white blood cells by phagocytosisinhibit killing by white blood cells by phagocytosis

    contributing to pathogenicitycontributing to pathogenicity

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    Bacterial %iliBacterial %ili

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    Bacterial %iliBacterial %ili

    CapsulesCa

    psules

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    $ttacment$ttacment

    • %athogen gro&th on the surface of a host'often on the mucous membranes may result

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    often on the mucous membranes' may resultin infection and disease 

    Mechanisms of #athogenesisMechanisms of #athogenesis

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    Mechanisms of #athogenesisMechanisms of #athogenesis

    pathogenesis is the manner in which a disease developspathogenesis is the manner in which a disease develops – patterns that disease

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    Mechanisms of #athogenesisMechanisms of #athogenesis

    colonization of host surface, then toin productioncolonization of host surface, then toin production

     – invading pathogen is able to grow to highinvading pathogen is able to grow to high

    numbers on host surfaces such as thenumbers on host surfaces such as the

    respiratory and intestinal tractrespiratory and intestinal tract

     – they then produce a toin that is damaging tothey then produce a toin that is damaging tothe cellsthe cells

     – organisms that use this mechanism includeorganisms that use this mechanism include

    VibrioVibrio choleraecholerae, which causes cholera or, which causes cholera or

    Corynebacterium diphtheriaeCorynebacterium diphtheriae, which causes, which causesdiphtheriadiphtheria

    M h i f # th iM h i f # th i

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    Mechanisms of #athogenesisMechanisms of #athogenesis

    invasion of host tissueinvasion of host tissue

     – breaching bodyGs barriers then multiplies in thebreaching bodyGs barriers then multiplies in the

    bodyGs tissuesbodyGs tissues

     – these organisms have mechanisms that allowthese organisms have mechanisms that allow

    them to avoid macrophage destructionthem to avoid macrophage destruction

     – some are also capable of avoiding detection bysome are also capable of avoiding detection by

    antibodiesantibodies

     – organisms that use this mechanism includeorganisms that use this mechanism include

    Mycobacterium tuberculosisMycobacterium tuberculosis, causative agent, causative agentfor tuberculosis, andfor tuberculosis, and Yersinia pestisYersinia pestis, causative, causative

    agent for pla0ueagent for pla0ue

    M h i f # th iMechanisms of #athogenesis

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    Mechanisms of #athogenesisMechanisms of #athogenesis

    invasion of tissue, then toin productioninvasion of tissue, then toin production

     – breach the bodyGs barriers, then make toinsbreach the bodyGs barriers, then make toins

     – in addition to invasion, these organisms alsoin addition to invasion, these organisms also

    make toinsmake toins

     – organisms that use this mechanism includeorganisms that use this mechanism include

    ShigellaShigella dysenteriaedysenteriae andand StreptococcusStreptococcus

     pyogenes pyogenes

    M h i f # th iMechanisms of #athogenesis

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    Mechanisms of #athogenesisMechanisms of #athogenesis

    in order to cause disease microorganisms need to bein order to cause disease microorganisms need to beable toable to

     – adhere and colonize host tissueadhere and colonize host tissue

     – avoid the innate defensesavoid the innate defenses

     – avoid the adapted defensesavoid the adapted defenses

     – cause damage related to the diseasecause damage related to the disease

    4dherence4dherence

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     4dherence 4dherence

    to establish disease the causative agent needs toto establish disease the causative agent needs to – adhereadhere

    difficult to overcome our first

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    "higellosis

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    "higellosis

    #athogenesis

     – S. dysenteriae

    .arely encountered inAnited "tates

    #roduces potent 4

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    7olonization7olonization

    causative agent needs tocausative agent needs to – multiply in order to colonizemultiply in order to colonize

    to multiply, they must compete successfully withto multiply, they must compete successfully with

    the normal flora for space and nutrientsthe normal flora for space and nutrients

     – toins that may be produced by the normal floratoins that may be produced by the normal flora

    must be overcomemust be overcome

    4voiding Innate "ystem4voiding Innate "ystem

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     4voiding Innate "ystem 4voiding Innate "ystemwhile some bacteria are able to cause disease whilewhile some bacteria are able to cause disease while

    remaining on the surface of the skin or mucosa,remaining on the surface of the skin or mucosa,many need to penetrate that barrier many need to penetrate that barrier 

    once this is done, those pathogens have it on easyonce this is done, those pathogens have it on easy

    street, eclusive rights to rich nutrition andstreet, eclusive rights to rich nutrition and

    multiplying without any competitionmultiplying without any competitionpenetrating the skin is etremely difficultpenetrating the skin is etremely difficult

     – bacteria take advantage of trauma to provide abacteria take advantage of trauma to provide a

    break in the skinbreak in the skin

     – ?est %ile Eirus is transmitted to the host through?est %ile Eirus is transmitted to the host througha mos0uito bite, a penetration of the skina mos0uito bite, a penetration of the skin

    4voiding Innate "ystem4voiding Innate "ystem

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     4voiding Innate "ystem 4voiding Innate "ystem

    mucous membranes penetration is the most commonmucous membranes penetration is the most commonentry for most microorganismsentry for most microorganisms

     – one method that is used is referred to as rufflingone method that is used is referred to as ruffling

    once the microorganism attaches to theonce the microorganism attaches to the

    membrane, it can direct the that cell to engulf themembrane, it can direct the that cell to engulf thebacterium;bacterium; this is referred to as rufflingthis is referred to as ruffling

    ruffling on the surface of

    mucous membrane

    4voiding Innate and 4daptive "ystem4voiding Innate and 4daptive "ystem

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     4voiding Innate and 4daptive "ystem 4voiding Innate and 4daptive "ystem

    several mechanisms can be used by microorganisms toseveral mechanisms can be used by microorganisms to

    avoid the potentially lethal effects of our immune systemavoid the potentially lethal effects of our immune system

     – hide inside a host cellhide inside a host cell

    phagocytes, complement and antibodies canGt findphagocytes, complement and antibodies canGt findthem; remember self and non

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     4voiding Innate and 4daptive "ystem 4voiding Innate and 4daptive "ystem

    avoid destruction by phagocytes by simply preventingavoid destruction by phagocytes by simply preventingencounters with phagocytesencounters with phagocytes

     – 7:a peptides are an enzyme that is made by some7:a peptides are an enzyme that is made by some

    bacteriabacteria

     – 7:a peptide7:a peptide destroys te complement componentdestroys te complement component

    if the complement is not activated, neither are theif the complement is not activated, neither are the

    phagocytesphagocytes

     – some bacteria produce membrane

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     4voiding Innate and 4daptive "ystem 4voiding Innate and 4daptive "ystem

    avoid recognition and attachment to phagocytes byavoid recognition and attachment to phagocytes by – producing capsules to prevent phagocytosisproducing capsules to prevent phagocytosis

    Streprococcus pneumoniaeStreprococcus pneumoniae procduces capsulesprocduces capsules

    survive in the phagocytesurvive in the phagocyte – they donGt worry about being engulfed, simply en$oythey donGt worry about being engulfed, simply en$oy

    the “free ride”the “free ride”

    some microorganisms can escape from thesome microorganisms can escape from the

    phagosome before being fused with the enzymephagosome before being fused with the enzymelysosomelysosome

    4voiding Innate and 4daptive "ystem 4voiding Innate and 4daptive "ystem

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     4voiding Innate and 4daptive "ystemo d g ate a d dapt e "yste

    survive in the phagocytesurvive in the phagocyte

     – some microorganisms can block the fusion of thesome microorganisms can block the fusion of the

    phagosome and lysosomephagosome and lysosome

     – a few organisms can actually survive the lysosomea few organisms can actually survive the lysosome

    environmentenvironment

     4voiding the 4daptive "ystem 4voiding the 4daptive "ystem

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    g yavoiding antibodies which integral to the adaptiveavoiding antibodies which integral to the adaptive

    system this can be accomplished several ways includingsystem this can be accomplished several ways including

     – Ig4 proteaseIg4 protease

    cleaves Ig4 class of antibodies found in mucus andcleaves Ig4 class of antibodies found in mucus and

    other secretionsother secretions

     – antigenic variationantigenic variationalter structure of antigensalter structure of antigens

    stay ahead of antibody production and destructionstay ahead of antibody production and destruction

    by altering the structure the antibodies areby altering the structure the antibodies are

    searching for searching for  – mimic host moleculesmimic host molecules

    some microorganisms have the ability to coversome microorganisms have the ability to cover

    themselves with molecules similar to “self”themselves with molecules similar to “self”

    Host !amageHost !amage

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    Host !amageHost !amage

    in order for disease to happen damage of some sortin order for disease to happen damage of some sortmust happen to the hostmust happen to the host

     – in most cases damage to the host facilitates dispersalin most cases damage to the host facilitates dispersal

    of the pathogenof the pathogen

    damage to the host can occur either damage to the host can occur either  – directlydirectly

     – indirectlyindirectly

    !irect Host !amage!irect Host !amage

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    !irect Host !amage!irect Host !amage

    toins produced by the invading pathogen cause directtoins produced by the invading pathogen cause directdamage to the host which results in diseasedamage to the host which results in disease

    toins capable of causing damage includetoins capable of causing damage include

     – eotoinseotoins

    a protein toin released from a living cella protein toin released from a living cell

    mostly found in 3ram B cellsmostly found in 3ram B cells

    Bacillus anthraxis 

    produces an eotoin

    Immune .esponse !amageImmune .esponse !amage

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    Immune .esponse !amageImmune .esponse !amage

    inflammatory response can destroy tissueinflammatory response can destroy tissue

     – antibody

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    (ey traits to a pathogen

    *he ability to;1+ $derence

     – *o host surfaces and not be washed off 

    F+ $+oid pagocytosis

     – #revent host defenses from destroying

    8+ %enetrate

     – 3et into host and spread

    9+ #roduce En,ymes

     – "pread, prevent host defenses and cause

    damage at or near site of infection:+ #roduce Toxins

     – 7ause damage at distant site

    4dherence

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     4dhesionsJligands bind to receptors on host cells so

    wonGt get flushed off+

    Mechanisms to adhere and avoid host defenses;

     – 3lycocaly Streptococcus mutans 

    !etran pla0ue-

     – ?aes Mycobacteria

     – &imbriae Escherichia coli 

     – M protein Streptococcus pyogenes

     – *apered end wJ hooks reponema pallidum

     4dherence

    QuickTime™ and a TIFF (LZ! decompressor

    are needed to see this picture"QuickTime™ and a TIFF (LZ! decompressor

    are needed to see this picture"

    7apsules

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    7apsules#revent pagocytosis

     and help with attacment adherence-

    Streptococcus pneumoniae

    !lebsiella pneumoniae

    Haemophilus influen"aeBacillus anthracis

    Streptococcus mutans

    Yersinia pestis

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    Hemolysins

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    Hemolysinslpha ,emolytic -treptococci

    $ secrete hemolysins that cause the incomplete lysis

    or !#Gs

    !eta ,emolytic -treptococci 

    $ secrete hemolysins that cause the complete lysis of !#Gs

    /eukocidins

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    /eukocidins

    'nzymes that attack certain types of ?67Gs

    1+ (ills ?67Gs which prevents phagocytosisF+ .eleases K ruptures lysosomes

     – lysosomes < contain powerful hydrolytic enzymes which

    then cause more tissue damage

    'nzymes; %ecrotizing &actor 

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    “Flesh /ating !acteria”

     0ecrotiing fasciitiscauses death (necrosis to tissue cells

    "ummary of How 6acterial #athogens#enetrate Host !efenses

    1 4dh

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    1+ 4dherence

    F+ 7apsule

    8+ 'nzymes

     – leukocidins

     – Hemolysins

     –7oagulase

     – (inases

     – Hyaluronidase

     – 7ollagenase

     – %ecrotizing &actor 

    #enetration into the Host 7ell

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    #enetration into the Host 7ell

    Figure 15.

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    Endotoxins

     Endotoxins are lipopolysaccharides derived from

    the outer membrane of gram

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    endotoins are lioopolysaccharides /#"- found inendotoins are lioopolysaccharides /#"- found inthe lipid portion of the outer wall of 3ram – bacteriathe lipid portion of the outer wall of 3ram – bacteria

     – endotoins are released when 3ram – bacteria dieendotoins are released when 3ram – bacteria die

    and the cell wall undergoes lysisand the cell wall undergoes lysis

    antibiotics that are used to treat 3ram –antibiotics that are used to treat 3ram –diseases can lyse the bacterial cells, releasingdiseases can lyse the bacterial cells, releasing

    the endotointhe endotoin

     – this can lead to an immediate worsening ofthis can lead to an immediate worsening of

    the symptomsthe symptoms

     – these symptoms usually improve as thethese symptoms usually improve as the

    endotoins break downendotoins break down

    'ndotoins < part of the 3ram

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    6acterial cell wall/#" /ipopolysaccharides-

     – = 4ntigen

     – /ipid 4

    Heat "table eotoins are typically heat liable-

    /ipid 4 < *oin portion of the /#"

     – responsible for &ever that is associated with

    many 3ram

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    e"oto"ins (Table 21.5.

    'ndotoin

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    Figure 15.4)

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    'ndotoins

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    Figure 15.2

    Mechanisms of #athogenicity

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    g y

    Figure 15.3

    'ndotoins'ndotoins

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    endotoins can also activate blood

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    viral pathogenesis is very dependent onviral pathogenesis is very dependent on

     – gaining access to the hostgaining access to the host

     – evading the hostGs defensesevading the hostGs defenses

     – causing damage to or death of the host cell whilecausing damage to or death of the host cell while

    continuing to reproduce themselvescontinuing to reproduce themselves

    viral access to the host was discussed in the virusviral access to the host was discussed in the virus

    lecture remember viral attraction is specific to the hostlecture remember viral attraction is specific to the host

     – viruses bind more successfully to organisms found inviruses bind more successfully to organisms found inmucous membranesmucous membranes

    Eiral 'vasion of HostEiral 'vasion of Host

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    interferons play a role in limiting the ability of virusesinterferons play a role in limiting the ability of virusesmoving from neighbor cell to neighbor cellmoving from neighbor cell to neighbor cell

     – once infected cells are capable of producing a proteinonce infected cells are capable of producing a protein

    that can regulate and limit viral replicationthat can regulate and limit viral replication

    some viruses are able to encode proteins to shutsome viruses are able to encode proteins to shutdown this cellular protective devicedown this cellular protective device

    Eiral 'vasion of HostEiral 'vasion of Host

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    though limited in the ability to control viruses, those fewthough limited in the ability to control viruses, those fewantibodies that are used can be circumvented by virusesantibodies that are used can be circumvented by viruses

    that have developed methods to transfer directly fromthat have developed methods to transfer directly from

    one cell to its immediate neighbor one cell to its immediate neighbor 

     – since antibodies control viruses by neutralizingsince antibodies control viruses by neutralizingetracellular viral particles, the above renders thisetracellular viral particles, the above renders this

    uselessuseless

    Eirus and Host !amageEirus and Host !amage

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    gg

    some viruses take

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    #athogenesis#athogenesis

    these mechanisms are not clearly understood, thoughthese mechanisms are not clearly understood, thoughthe mechanisms include colonization of the host, evasionthe mechanisms include colonization of the host, evasion

    of the host defenses and damage to the hostof the host defenses and damage to the host

    fungifungi

     – these organisms are generally opportunistic, takingthese organisms are generally opportunistic, takingadvantage of a weakening or change in our immuneadvantage of a weakening or change in our immune

    systemsystem

    ecessive growth ofecessive growth of Candida albicansCandida albicans is often ais often a

    result in immunocompormised hostsresult in immunocompormised hosts – C. albicansC. albicans is the causative agent of thrush, ais the causative agent of thrush, a

    common occurrence in 4I!" patientscommon occurrence in 4I!" patients

    Mechanisms of 'ukaryoticMechanisms of 'ukaryotic

    #athogenesis#athogenesis

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    #athogenesis#athogenesis

    eukaroytic parasiteseukaroytic parasites – are generally found in the intestinal tract or haveare generally found in the intestinal tract or have

    gained access through an insect bitegained access through an insect bite

     – attach with specific receptorsattach with specific receptors

     – are capable of hiding within the host cellare capable of hiding within the host cell

     – the damage they can inflict variesthe damage they can inflict varies

     some cause malnutrition by competing forsome cause malnutrition by competing for

    nutrientsnutrients

    some can cause direct damage by the enzymessome can cause direct damage by the enzymes

    they producethey produce

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    *erminology of Infectious !iseases*erminology of Infectious !iseases

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    gygy

    infectious doseinfectious dose

     – L of microbes needed to establish infectionL of microbes needed to establish infection

    some microorganisms are less contagious thansome microorganisms are less contagious than

    others and as a result re0uire a larger number ofothers and as a result re0uire a larger number ofpathogens present to establish diseasepathogens present to establish disease

    *erminology of Infectious !iseases*erminology of Infectious !iseases

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    gy

    signsign – ob$ective changes that are observable andob$ective changes that are observable and

    measurablemeasurable

     – eamples of signs include swelling, fever, paralysiseamples of signs include swelling, fever, paralysis

    symptomssymptoms

     – sub$ective effects eperienced by patientsub$ective effects eperienced by patient

     – eamples of symptoms include pain or nauseaeamples of symptoms include pain or nausea

    *erminology of Infectious !iseases*erminology of Infectious !iseases

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    gy

    disease stagesdisease stages – incubationincubation

    the time between the initial infection and the firstthe time between the initial infection and the firstappearance of any signs or symptomsappearance of any signs or symptoms

    this time can vary depending on the pathogen andthis time can vary depending on the pathogen andthe condition of the hostthe condition of the host

     – illnessillness

    signs and symptoms of the disease are eperiencedsigns and symptoms of the disease are eperienced

    if the disease is not successfully overcome orif the disease is not successfully overcome ortreated, the patient dies during this periodtreated, the patient dies during this period

     – convalescenceconvalescence

    person regains strength and the body returns to itsperson regains strength and the body returns to itspre

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    gy

    types of infectious diseasestypes of infectious diseases

     – acute diseaseacute disease

    rapid onset, short durationrapid onset, short duration

    influenza is an acute diseaseinfluenza is an acute disease

     – chronic diseasechronic disease

    develop slowly, last longer develop slowly, last longer 

    the bodyGs reaction may be less severethe bodyGs reaction may be less severe

    hepatitis 6 is a chronic disusehepatitis 6 is a chronic disuse

     – latent diseaselatent disease

    causative agent is never completely eliminatedcausative agent is never completely eliminated

    remains inactive, but can become reactivated andremains inactive, but can become reactivated andsymptomatic if immune response is diminishedsymptomatic if immune response is diminished

    shingles is a latent diseaseshingles is a latent disease

    *erminology of Infectious !iseases*erminology of Infectious !iseases

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    localized infectionslocalized infections – invading microorganisms are limited to a small areainvading microorganisms are limited to a small area

     – boils and abscesses are local infectionsboils and abscesses are local infections

    systemic infectionssystemic infections

     – infectious agent spread throughout body by blood orinfectious agent spread throughout body by blood or

    lymphlymph

     – measles is a systemic infectionmeasles is a systemic infection

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    Control of Microbial #ro$thControl of Microbial #ro$th

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    19F19F

    History; /ister and "emmelwiessHistory; /ister and "emmelwiess *erminology*erminology

    #hysical Methods#hysical Methods

    Heat; !ry, moist, with pressureHeat; !ry, moist, with pressure.adiation; Ionizing and non

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    Te $utocla+eTe $utocla+e

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    MetabolismMetabolism

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    Introductory 7onceptsIntroductory 7oncepts%utritional patterns, Metabolism, 4*#, 'nzymes,%utritional patterns, Metabolism, 4*#, 'nzymes,.e

    7atabolism7atabolism

    3lycolysis, *74 cycle, 'lectron transport chain3lycolysis, *74 cycle, 'lectron transport chain

    &ermentations&ermentations

    'thanol, /actic acid'thanol, /actic acid

     4nabolism 4nabolism6iosynthesis6iosynthesis