Micro-N (Corynebacteria And Diptheria)

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morphology of corynebacteria

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pleomorphic {varying size and shape} gram positive rods
aerobes
do not form spores
often club shaped
arrangement in gram stain resembles chinese characters

Front 2

2 groups of corynebacteria

Back 2

Corynebacterium diptheriae (the cause of diptheria)

all others, generally called diptheroids (normal inhabitants of skin and throat)

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the only natural hosts for corynebacterium diptheriae (cause of diptheria)

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humans

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transmission of corynebacterium diptheriae (cause of diptheria)

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usually by respiratory droplets

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incubation period of corynebacterium diptheriae (cause of diptheria)

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2-5 days (short) of bacterial growth in the throat, results in a local inflammatory response

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early symptoms of diptheria

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local inflammatory response to bacterial growth in throat:
fever, cough, sore throat, that progresses to form a gray PSEUDOMEMBRANE (of fibrin, necrotic epithelium, and white cells)

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other than throat, where might diptheria infections be seen

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in the tropics, also seen as necrotizing skin infections spread by contact

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how does diptheria cause systemic disease?

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bacteria (confined to pharynx) produce an EXOTOXIN that damages eukaryotic cells (including those in heart, kidney, nervous system, etc..)

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characteristics of EXOTOXIN-
chemical composition:
bacterial origin:
coded by bacteriophage or plasmid:
stable to boiling:
highly antigenic and easily induces protective Ab:

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chemical composition: PROTEIN
bacterial origin: GRAM (+) or (-)
Coded by phage or plasmid: USUALLY
stable to boiling: USUALLY NOT
highly antigenic and easily induces protective Ab: YES

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characteristics of ENDOTOXIN-
chemical composition:
bacterial origin:
coded by phage or plasmid:
stable to boiling:
highly antigenic and easily induces protective Ab:

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chemical composition: LPS
bacterial origin: Gram (-) OM
coded by phage or plasmid: NEVER
stable to boiling: YES
highly antigenic and easily induces protective Ab: NO

Front 11

ENTEROTOXINS are the same as...

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EXOTOXINS

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All toxogenic strains of C. diptheriae are lysogenic for a specific temperate bacteriophage called:

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BETA

Front 13

The gene for the diptheria toxin is part of what genome?

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a specific temperate bacteriophage called beta,

capable of lysogenizing bacteria.. to integrate their genome into (and be replicated with) host chromosome

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What are the two ways by which a temperate bacteriophage can alter the phenotype of bacteria?

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TRANSDUCTION (by transferring bacterial genes from their previous bacterial host)

CONVERSION (via the expression of their own bacteriophage genes)

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What are the 2 domains of Diptheria Exotoxin?

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B DOMAIN: binds to a specific cell surface receptor, causes endocytosis of EXOTOXIN

A DOMAIN= "toxic domain" separates from B domain, leaves vesicle to enter cytoplasm, BLOCKS EUKARYOTIC PROTEIN SYNTHESIS {by inactivating EF2}

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What is the role of the "A DOMAIN" of Diptheria Exotoxin

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"TOXIC DOMAIN" enters cytoplasm of infected cell, acts as enzyme

blocks EUCARYOTIC PROTEIN SYNTHESIS by INACTIVATING EF2 (elongation factor 2) mechanisms involves: adenosine diphosphate ribosylation

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immunity to Diptheria depends on what?

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presence of Ab against the toxin {ANTITOXIN)

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describe the vaccine used for immunity to Diptheria

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formaldehyde treated diptheria toxin = TOXOID
{formaldehyde destroys the toxic activity, but immunogenicity of toxin is maintained}
protection lasts 10 years

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How is Diptheria Dx made?

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-IN VITRO TEST (suspected bacteria grown as single streaked line, at right angle to strip of antitoxin-soaked paper) in agar (diagonal precipitates form)
also..
-characteristic growth on tellurite and Leoffler media
-staining characteristics (metachromatic granules)
-demonstration of toxin production via indradermal injection of animals (to produce local necrosis)

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how is diptheria treated?

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must be treated immediately

treated with HORSE or HUMAN ANTITOXIN (to neutralize free toxin)

Penicillin is used to eliminate bacteria that would continue to produce toxin

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prevention of diptheria in those exposed

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those in contact with infected patients should be reimmunized and treated with penicillin

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Diptheria epidemiology

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before immunization (many carriers of Corynebacterium diptheriae)

epidemics are now seen in poorly immunized populations with inadequate medical care. (major problem in developing countries with inadequate immunization)

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ALL SKIN TESTS involve what?

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intradermal injection of small volume of a BIOLOGICAL REAGENT

results:
NEGATIVE (if nothing happens)
POSITIVE (if somethign happens)

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If skin test reagent is a TOXIN, a positive response means what?

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NO IMMUNITY (no toxin-neutralizing Abs)

{whereas a negative response means immunity resulting from previous infection or immunization}

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If skin test reagent is a delayed-hypersensitivity-inducing Ag, a POSITIVE response means what?

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IMMUNITY (cell mediated immunity, induced by previous infection or immunization)

{whereas a NEGATIVE response means no previous infection)

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What is the SHICK TEST?
(what is the potential complication?)

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intradermal injection of a small amount of toxin

persons lacking antibody dvp local necrotic-inflammatory response that develops slowly and is maximal at 5 days

potential COMPLICATION: delayed hypersensitivity against other proteins

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How can Shick Test be used to determine if reaction is a true positive, a pseudopositive or a combined positive?

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Inject TOXIN in one arm and TOXOID in other arm

TRUE POSITIVE: (toxin injected arm will be (-) @ 1.5 days, (+) @ 5 days)

PSEUDOPOSITIVE: (both toxin arm and toxoid arm with be (+) @ 1.5 days and (+/-) @ 5 days)

COMBINED: toxin arm (+) @ 1.5 & 5 days, toxoid arm: + @ 1.5 days, (+/-) @ 5 days

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What do the following Shick Tests Results indicate regarding: IMMUNITY & HYPERSENSITIVITY

Negative Rxn
Positive Rxn
Pseudo Positive
Combined Poisitive

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Negative: IMMUNE but not hypersensitive
Positive: not immune, not hypersensitive
Pseudo: IMMUNE & HYPERSENSITIVE
Comb: not immune, yes HYPERSENSITIVE