HOST - MICROBE INTERACTIONS

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HOST - MICROBE INTERACTIONS EPIDEMIOLOGY
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RESOURCES

• http//dustman.net/wendy/mibo2500/mibo2500ch19.pdf
  
• http//www.hhmi.org/biointeractive/disease/animati
  ons.htmlecoli
• http//www.cook.rutgers.edu/dbm/lecture04HumanMic
  robeInteraction.pdf

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SYMBIOSIS

• MUTUALISM
• COMMENSALISM
• PARASITISM

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MUTUALISM

• BOTH BENEFIT FROM RELATIONSHIP
• DEEP OCEAN FISH LUMINESCENT BACTERIA
• BACTERIA IN HUMAN LARGE INTESTINE

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USE OF PROBIOTICS TO INCREASE MUTUALISTIC BACTERIA

• LIVE BACTERIAL CULTURES
• TAKEN TO INCREASE BENEFICIAL BACTERIA IN BODY
• I.E. LACTIC ACID BACTERIA

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COMMENSALISM

• ONE BENEFITS OTHER NEITHER BENEFITS OR IS
  HARMED
• SKIN NATURAL FLORA
• COMPETITIVE EXCLUSION

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PARASITISM

• ONE BENEFITS AND THE OTHER IS HARMED
• RANGES FROM SLIGHT DAMAGE TO DEATH

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CONTAMINATION

• MICROBES ARE ARE PRESENT

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INFECTION

• MULTIPLICATION WITHIN OR UPON THE BODY
• DOES NOT MEAN DISEASEBOOK IS WRONG

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TERMS

• A SYSTEMIC INFECTION SPREADS THROUGHOUT THE BODY
• A PRIMARY INFECTION IS CAUSED BY ONE TYPE OF
  MICROBE
• A SECONDARY INFECTION IS CAUSED BY ANOTHER
  MICROBE AFTER THE PRIMARY INFECTION
• A MIXED INFECTION IS CASED BY TWO OR MORE
  MICROBES
• A SUBCLINICAL INFECTION DOES NOT DISPLAY ANY
  SYMPTOMS

• BACTEREMIA IS A BACTERIAL INFECTION IN THE BLOOD
• SEPTICEMIA IS THE PRESENCE OF BACTERIA AND THEIR
  GROWTH PRODUCTS IN THE BLOOD
• VIREMIA--VIRUS IN BLOOD
• AN OPPORTUNISTIC INFECTION IS CAUSED BY A MICROBE
  THAT DOES NOT USUALLY CAUSE INFECTION
• NOSOCOMIAL INFECTIONS--ACQUIRED IN HOSPITAL OR
  CLINICAL SITUATIONS

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INFESTATION
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INFECTION DISEASE
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PATHOGENS, PATHOGENICITY, AND VIRULENCE
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PATHOGENICITY

• CAPACITY TO CAUSE DISEASE
• MUST INVADE, MULTIPLY AND EVADE IMMUNE SYSTEM

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VIRULENCE

• MEASURES INTENSITY OF DISEASE

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NORMAL FLORA

• INDIGENOUS FLORA
• FETUS IN WOMB IN STERILE ENVIRONMENT
• ACQUIRE NATURAL FLORA AFTER PARTURITION

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RESIDENT FLORA

• ALWAYS PRESENT
• SKIN, MOUTH, NOSE, CONJUNCTIVA, GI TRACT,
  GENITOURINARY TRACT, UPPER RESPRIATORY TRACT

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TRANSIENT FLORA

• PERSIST FOR HOURS TO MONTHS
• PATHOGENS CAN SOMETIMES BE TRANSIENT FLORA
• DO NOT REPRODUCE IN HOST

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MICROBIAL ANTAGONISM

• ALSO CALLED COMPETITIVE EXCLUSION
• INTERFERE WITH GROWTH OF PATHOGENS
• DEPLETING NUTRIENTS THE PATHOGENS CANNOT GROW
• ALSO SECRETE BACITROCINS AND OTHER ALLELOPATHIC
  PRODUCTS THAT SLOW OR KILL OTHER COMPETITORS
• PREVENT THEIR ESTABLISHMENT
• PARTICULARLY OF PATHOGENS

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PSEUDOMEMBRANOUS ENTEROCOLITIS
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OPPORTUNISTIC PATHOGENS

• GENERALLY DO NOT CAUSE DISEASE
• MAY GAIN ACCESS TO THE BODY WHEN THE IMMUNE
  SYSTEM IS COMPROMISED
• I.E CRYPTOCOCCUS NEOFORMANS AND PNEUMOCYSTIS
  CARNII
• OR IF NATURAL FLORA MAY ENTER OTHER BODY
  COMPARTMENTS
• I. E. ECOLI IN BLADDER OR VAGINA

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ETIOLOGY

• THE STUDY OF THE CAUSES OF DISEASE
• MAY BE CLEARLY APPARENT
• COLDS, FLU, MEASLES, E.TC.
• MAY BE VERY UNCLEAR OR UNKNOWN
• CANCER, ALZHEIMERS, E.T.C.

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KOCHS POSTULATE

• MUST OBSERVE IN EVERY CASE OF A DISEASE
• AGENT MUST BE ISOLATED FROM HOST WITH DISEASE AND
  GROWN IN PURE CULTURE
• AGENT FROM PURE CULTURE IS INOCULATED INTO
  SUSCEPTIBLE HOSTS--AND MUST CAUSE DISEASE
• AGENT MUST BE REISOLATED AND IDENTIFIED

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EXCEPTIONS TO KOCHS POSTULATES

• ORGANISMS WITH UNIQUE CULTURE REQUIREMENTS
• TREPONEMA PALLIDUM, LEGIONELLA PNEUMOPHILA,
  MYCOBACTERIA LEPRAE
• DISEASES THAT CAN BE CAUSED BY A VARIETY OF
  PATHOGENS
• NEPHRITIS, PNEUMONIA, MENINGITIS
• PATHOGENS THAT CAN CAUSE A VARIETY OF DIFFERENT
  DISEASES
• MYCOBACTERIUM TUBERCULOSIS, STREPTOCOCCUS
  PYROGENES

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DISEASES THAT AFFECT ONLY HUMANS POSE AN ETHICAL
CONCERN

• IT IS ILLEGAL TO INTENTIONALLY EXPOSE HUMANS TO
  DISEASE ORGANISMS

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THE DISEASE PROCESS
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WHAT IS A DISEASE

• SIGNS, SYMPTOMS AND SYNDROMES

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SIGNS

• OBSERVABLE
• OBJECTIVE
• RASH
• DIARRHEA
• PEELING SKIN
• LESIONS
• CHANCRE
• CHICKEN POX

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CHICKEN POX IN NEWBORN
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SYMPTOMS

• CHANGE IN BODY STRUCTURE OR FUNCTION
• SUBJECTIVE
• CAN NOT BE QUANTITATED BY OBSERVATION
• SHORTNESS OF BREATH
• PAIN
• GENERAL WEAKNESS

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ASYMPTOMATIC

• NO SYMPTOMS
• OFTEN IN EARLY STAGES

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SYNDROMES

• SIGNS AND SYMPTOMS
• TYPICAL PATTERN
• DOWNS SYNDROME

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FACTORS THAT AFFECT DISEASE OUTCOME

• GENETICS
• AGE
• NUTRITIONAL STATUS
• PRIOR EXPOSURE
• LEVEL OF IMMUNITY
• SANITATION
• SOCIOECONOMIC FACTORS

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SEQUELAE

• AFTER EFFECTS OF DISEASE
• HEPATITIS--LIVER DAMAGE
• SYPHILIS--TABES DORSALIS

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PROGNOSIS

• PROJECTED COURSE AND OUTCOME OF DISEASE

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INFECTIOUS DISEASES

• PRESENCE OF MICROORGANISMS IN BODY
• DISRUPTSBODY FUNCTION

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CONTAGIOUS NONCONTAGIOUS

• COMMUNICABLE
• FLU
• MEASLES
• SYPHILIS
• GONORRHEA

• NONCOMMUNICABLE
• TETANUS
• FOOD POISONING

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EXOGENOUS DISEASES

• CAUSED BY MICROBES OUTSIDE THE BODY

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ENDOGENOUS DISEASES

• CAUSED BY ORGANISMS ALREADY PRESENT ON SKIN OR IN
  HOST

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PREDISPOSING FACTORS AND THEIR EFFECT ON DISEASES

• MAY MAKE ONE MORE SUSCEPTIBLE
• HLAS
• GENDER
• GENETICS
• AGE
• LIFE STYLE
• SOCIOECONOMIC STATUS

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COURSE OF AN INFECTIOUS DISEASE

• MOST DISEASES GO THROUGH STANDARD PHASES

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INCUBATION PERIOD

• MULTIPLICATION OF PATHOGEN

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PRODROMAL PERIOD

• EARLY PHASE
• NONSPECIFIC SYMPTOMS
• HEADACHE
• GENERAL WEAKNESS

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INVASIVE PERIOD/PERIOD OR ILLNESS

• PATHOGEN INVADE AND CAUSE TISSUE DAMAGE
• SIGNS AND SYMPTOMS APPEAR

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ACME

• CRITICAL STAGE
• PERIOD OF MOST INTENSE SYMPTOMS
• BATTLE IS GREATEST HERE

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DECLINE PHASE

• HOST DEFENSES FINALLY WIN BATTLE
• CRISIS VS LYSIS

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CONVALESCENCE PERIOD

• RECOVERY PERIOD
• HEALING
• REGAIN STRENGTH
• SYMPTOMS DISAPPEAR
• CAN STILL BE CONTAGIOUS IN SOME DISEASES

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ACUTE VS CHRONIC
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ACUTE DISEASE

• OCCURS RAPIDLY
• SOMETIMES INTENSE SYMPTOMS
• I.E. BACTERIAL ENDOCARDITIS

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SUBACUTE

• SOMEWHERE BETWEEN ACUTE AND CHRONIC
• SUBACUTE LUPUS

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CHRONIC DISEASE

• DEVELOPS SLOWLY
• LASTS LONGER
• OFTEN FOR INDEFINITE PERIOD
• I.E. CHRONIC BRONCHITIS

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LATENT DISEASES

• PATHOGEN IS PRESENT IN BODY BUT IS INACTIVE BUT
  MAY BECOME ACTIVE AGAIN AND CAUSE DISEASE
• I.E. HERPES ZOESTER
• CAUSES CHICKEN POX
• HIDES IN GANGLIA OF THE NERVOUS SYSTEM IN
  INACTIVE STATE
• BECOMES ACTIVE TO CAUSE SHINGLES AND PERHAPS
  BELLS PALSY

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HOW MICROBES CAUSE DISEASE
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DIRECT BACTERIAL ACTION

• PENETRATE THE SKIN
• INGESTED WITH FOOD
• INHALED
• TRANSMISSION ON FOMITE

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ADHERANCE

• ADHESINS--HELP BACTERIA ATTACH
• ALLOW ADHERANCE TO CERTAIN TISSUES

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ADHERANCE IS THE MAJOR FACTOR FOR DISEASE
CAUSATION
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COLONIZATION

• GROWTH ON EPITHELIAL TISSUES
• PATHOGENS MUST SURVIVE AND REPRODUCE
• DEGREE OF INVASIVENESS
• INVASINS

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INVASINS

• ACTIVATE PHAGOCYTOSIS
• EVEN IN CELLS THAT DO NOT NORMALLY DO ENDOCYTOSIS

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CHLAMYDIA IN EPITHELIAL CELLS
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BORDETELLA PERTUSSIS COLONIZING RESPIRATORY TRACT
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BACTERIAL PRODUCTS THAT INCREASE PATHOGENICITY
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HEMOLYSINS

• LYSE RED BLOOD CELLS
• ALPHA HEMOLYSINS--PARTIALLY HEMOLYZE BLOOD CELLS
  -LEAVE GREEN RING AROUND COLONIES
• BETA HEMOLYSIS--COMPLETELY HEMOLYZE BLOOD CELLS
  --LEAVE A CLEAR RING AROUND COLONIES
• STREP AND STAPH

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LEUKOCIDINS

• STREPTOCOCCI AND STAPHYLOCOCCI
• DAMAGE OR DESTROY WHITE BLOOD CELLS --
  NEUTROPHILS MACROPHAGES

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LEUKOSTATIN

• INTERFERES WITH THE ABILITY OF WHITE BLOOD CELLS
  TO PHAGOCYTIZE PATHOGENS

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HYALURONIDASES

• DIGEST HYALURONIC ACID
• COMPONENT OF LOOSE CONNECTIVE TISSUES
• NECROTIZING FASCIITIS
• GAS GANGRENE

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COLLAGENASE

• DIGEST COLLAGEN
• A MAJOR COMPONENT OF CONNECTIVE TISSUES THROUGH
  OUT THE BODY
• NECROTIZING FASCIITIS
• GAS GANGRENE

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LIPASES

• DISRUPT MEMBRANES OF THE BODY
• PHOSPHOLIPASE
• GAS GRANGRENE
• NECROTIZING FASCIITIS

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NECROTIZING FASCIITIS

• HYALURONIDASE
• COLLAGENASES
• STREPTOKINASE
• LIPASE

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IgA PROTEASES

• DESTROY IMMUNOGLOBULIN A MOLECULES
• WHICH WOULD PREVENT ADHERANCE OF ANTIBODIES TO
  ANTIGEN
• NESSERIA GONORRHEA
• NESSERIA MENINGITIDIS

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COAGULASE

• ACCELERATES COAGULATION OF BLOOD

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KINASES

• STEPTOKINASE OR FIBROLYSIN
• DIGEST FIBRIN--DISSOLVES CLOTS

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IMPORTANCE OF CAPSULES IN AVOIDING PHAGOCYTOSIS
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COMPONENTS OF CELL WALLS

• STREPTOCOCCUS PYROGENES
• NESSERIA GONORRHEA
• MYCOBACTERIAL SPECIES

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M PROTEIN OF STREPTOCOCCUS PYROGENES

• INCREASES VIRULENCE
• HELPS RESIST PHAGOCYTOSIS
• HELPS ATTACH BACTERIA TO EPITHELIAL CELLS

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NESSERIA GONORRHEA

• USES FIMBRIAE
• USES OPA
• OUTER MEMBRANE PROTEIN
• COMBINATION OF FIMBRIAE AND OPA CAUSES HOST CELL
  TO PHAGOCYTIZE BACTERIA

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MYCOLIC ACID OF MYOCBACTERIA

• MYCOLIC ACID
• WAXY LIPID IN CELL WALL
• ALLOWS CELLS TO BE RESISTANT TO DIGESTIONS BY
  PHAGOCYTIC VESSICLES CALLED PHAGOLYSOSOMES
• ALSO ALLOWS RESISTANCE TO MANY TYPES OF
  ANTIBIOTICS

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TOXINS

• POISONOUS SUBSTANCE PRODUCED BY BACTERIA,
  PROTOZOA, FUNGI, AND HELMINTHS
• VIRUS DO NOT PRODUCE TOXINS

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BACTERIAL TOXINS

• EXOTOXINS AND ENDOTOXINS

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ENDOTOXIN

• ALMOST ALL GRAM NEGATIVE
• BOUND WITHIN BACTERIAL CELL WALL
• LIPOPOLYSACCHARIDE COMPLEX
• RELATIVELY STABLE
• WEAKLY TOXIC BUT CAN BE FATAL
• CAUSES RAPID RISE IN TEMPERATURE

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ENDOTOXIN

• WEAKLY ANTIGENIC
• CANNOT BE CONVERTED TO TOXOIDS--CAN NOT BE USED
  FOR VACCINES

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EFFECTS OF ENDOTOXIN

• LPS, ESPECIALLY WHEN IN THE BLOOD, CAN CAUSE A
  NUMBER OF PATHOPHYSIOLOGICAL CHANGES SUCH AS
• FEVER PRODUCTION INFLAMMATION TISSUE
  DESTRUCTION RESPIRATORY DISTRESS CAPILLARY
  DAMAGE
• INTRAVASCULAR COAGULATION
• SHOCK
• HYPOTENSION
• DECREASED CARDIAC OUTPUT IRREVERSIBLE
  SHOCK WASTING OF THE BODY DIARRHEA (FROM
  ENDOTOXIN IN INTESTINES)

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IMPORTANCE OF ENDOTOXINS IN CLINICAL SETITING

• ENDOTOXIN CAN BE INTRODUCED INTO BODY THROUGH
  IVs, DRUGS, MEDICAL DEVICES, E.T.C.
• IF CONTAMINATED WITH ENDOTOXIN
• LIMULUS AMOEBOCYTE ASSAY
• DETECTS EVEN MINUTE AMOUNTS OF ENDOTOXIN
• POSITIVE TEST SHOW PRECIPTIATION

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HORSESHOE CRAB

• LIMULUS SPECIES

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EXOTOXINS

• SOLUBLE SUBSTANCES OFTEN SECRETED INTO HOST
  TISSUES
• USUALLY GRAM POSITIVE
• SOME GRAM NEGATIVE
• EXTRACELLULAR
• MOSTLY POLYPEPTIDES
• UNSTABLE, DENATURED ABOVE 60 DEGREES CELCIUS

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EXOTOXINS

• SOME OF MOST POWERFUL TOXINS KNOWN
• HIGHLY SPECIFIC
• LITTLE OR NO FEVER
• STRONGLY ANTIGENIC
• TOXOIDS CAN INDUCE IMMUNITY

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TYPES OF TOXINS

• A-B TOXINS
• MEMBRANE DISRUPTING TOXINS
• SUPERANTIGENS
• ERYTHROGENIC TOXINS

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A-B TOXIN

• B PORTION BINDS TO CELL MEMBRANE
• FACILITATES ENTRY INTO CELL
• A PORTION IS RESPONSIBLE FOR TOXIC EFFECTS

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MEMBRANE DISRUPTING TOXINS

• LEUKOCIDINS
• HEMOLYISINS
• PHOSPHOLIPASES
• STREPTOLYSINS

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SUPERANTIGENS
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EXAMPLE OF TOXINS
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BOTULISM TOXIN

• http//www.neuro.wustl.edu/neuromuscular/nother/bo
  t.htm
• http//www.cdc.gov/ncidod/dbmd/diseaseinfo/botulis
  m_g.htm
• http//www.healthatoz.com/healthatoz/Atoz/common/s
  tandard/transform.jsp?requestURI/healthatoz/Atoz/
  ency/botulism.jsp

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GAS GANGRENE

• CLOSTRIDIUM PERFINGENS
• TOXINS CAUSE GAS GANGRENE
• ALPHA TOXIN

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• http//www.emedicine.com/MED/topic843.htm
• http//www.merck.com/mmhe/sec17/ch190/ch190g.html
• http//www.umm.edu/ency/article/000620.htm

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FOOD POISONING

• CLOSTRIDIUM PERFINGENS
• INGESTION OF TOXINS
• APPEARS 10 - 24 HOURS AFTER INGESTION

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DIPHTHERIA

• CORYNEBACTERIUM DIPHTHERIAE
• TEMPORATE PHAGE INVOLVED
• A/B TOXIN
• INHIBITS PROTEIN SYNTHESIS

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BULLNECK DIPHTHERIA
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PSEUDOMEMBRANE
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SPREAD BY RESPIRATORY DROPLETS
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TETANUS TOXIN
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NEONATAL TETANUS
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OPISTHOTONOS
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TOXIC SHOCK SYNDROME

• TOXIC SHOCK SYNDROME TOXIN 1
• STAPHYLOCOCCUS AUREUS
• HIGH FEVER
• NAUSEA
• VOMITING
• MAY CAUSE DEATH

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ACTION OF TOXIN

• ATTACHES TO MONONUCULEAR CELLS
• STIMULATES PRODUCTION OF INTERLEUKINS

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VIRUSES AND DISEASE
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SOME EXAMPLES OF CYTPATHIC EFFECTS

• VISUAL EFFECTS OF THE VIRUS ON THE CELLS

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CYTOCIDAL

• KILL CELLS BY CAUSING ENZYMES FROM LYSOSOMES TO
  BE RELEASED
• DIVERTING SYNTHETIC PROCESS OF CELL TO VIRAL
  SYNTHESIS

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INCLUSION BODIES

• GRANULES IN CELL
• NUCLEUS OR CYTOPLASM
• MAY VARY IN APPEARANCE
• NEGRI BODIES MOST FAMOUS
• DIAGNOSTIC FOR RABIES

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SYNCYTIUMS
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HOW VIRUSES AVOID THE IMMUNE SYSTEM

• FUSION OF HOST CELLS
• INHIBITION OF IMMUNE CELLS
• PRODUCTION OF LARGE AMOUNTS OF FALSE ANTIGEN
• ANTIGENIC DRIFT

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VIROKINES

• ALTER BODYS IMMUNE RESPONSE
• MIMICK NORMAL HUMAN MOLECULES
• SOME ARE ANALOGS OF CYTOKINES

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IMPORTANCE OF ONCOGENIC VIRUSES

• MAY CAUSE TRANSFORMATIONS OF CELLS

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FUNGI AND DISEASES

• RELEASE EXTRACELLULAR ENZYMES
• PROGRESSIVELY DIGESTS CELLS OF TISSUE
• SOME PRODUCE TOXINS--ERGOT OF RYE AFLATOXIN

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ERGOTISM

• CLAVICEPS PURPUREA

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AFLATOXIN

• ASPERGILLUS FLAVUS
• GRAINS
• PEANUTS
• PEANUT BUTTER
• CARCINOGEN
• LINKED TO CANCERS IN ANIMALS
• PEOPLE IN THIRD WORLD
• ONLY CARCINOGEN IN US WITH ALLOWABLE LIMIT IN FOOD

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FUNGAL PATHOGENS THAT CAUSE DISEASE

• CANDIDA ALBICANS
• TRICHOPHYTON
• CRYPTOCOCCUS NEOFORMANS

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CANDIDA ALBICANS

• SECRETES PROTEASES
• SEEM TO HELP WITH ATTACHMENT BY CHANGING CELL
  MEMBRANES OF HOST
• THRUSH
• MUCOCUTANEOUS CANDIDIASIS
• VAGINAL INFECTIONS

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TRICHOPHYTON

• DERMATOMYCOSES
• SECRETES PROTEASES THAT HELP IT TO ATTACH

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CRYPTOCOCUS NEOFORMANS

• OPPORTUNISTIC PATHOGEN
• IMMUNE SYSTEM MUST BE COMPROMISED
• CAPSULE ALLOWS IT TO RESIST PHAGOCYTOSIS

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MYCOTOXINS

• EXTREMELY DEADLY FROM AMANITA PHALLOIDES
• PHALLOIDIN
• AMANTIN
• ONE SMALL BITE CAN KILL YOU
• LESS DEADLYJUST MAKE YOU THINK YOUR GOING TO DIE
• GASTROINTESTINAL TOXINS
• DIARRHEA AND VOMITING

120
PROTOZOA, HELMINTHS AND DISEASE

• ATTACH TO TISSUES AND INGEST CELLS AND FLUIDS
• ADHESIVE DISCS
• MANY PROTOTOA AND HELMINTHS RELEASE WASTES THAT
  MAY TRIGGER IMMUNE RESPONSE

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ALGAL TOXINS