Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

140 Cards in this Set

  • Front
  • Back
head-resistant, non-secreted, cell associated toxin

first described from a cell-free lysate of Vibrio cholerae (causing toxic shock in animals)
how can endotoxic shock be induced? what type of bacteria are involved?
if sufficient numbers of gram negative bacteria (which slough off endotoxin) or sufficient amount of endotoxin in cell-free suspensions are introd into the bloodstream of an individual
mortality rates caused by endotoxic shock:
depending on the patient's condition and the gram negative organism
estimated fatalities of gram-negative sepsis in the US each year
20,000 / year
What is endotoxin and where is it found?

found in the outer leaflet of the outer cell membrane of all Gram-NEGATIVE bacteria
"toxic" portion of LPS (lipopolysaccharide)
the "antigenic" portion of LPS
the "O-antigen"
what molecular elements are necessary to induce endotoxic shock?
pure lipid A can induce endotoxic shock

but the polysaccharide influences its activity (partially explains diffferent mortality rates of different gram negative organisms, because endotoxin must be released from the cell surface (often by lysis) to have its full effect
who is at risk of endotoxic shock?
an individual who has a gram-negative infection, who also exhibits an impaired host defense against bacterial infection (most likely to have high #s of bacteria in bloodstream)
usually transient presence of bacteria in blood

could be due to a wound, a trip to the dentist, surgery, or other causes
bacterial growth or infection of the blood stream (more serious than bacteremia)
associated with septicemia or bacteremia

bacteria are in the blood
caused by toxin that is circulating in the blood

bacteria do NOT need to be in the bloodstream.

a patient can still go into shock AFTER the bacteria are cleared, either because the TOXIN REMAINS or the CASCADE of events has already been INITIATED in the host
what must be done if gram-negative bacteremia or septicemia is suspected?
3 blood cultures, taken over time interval (i.e. 3 hours to days)

cultured aerobically and anaerobically

though transient nature of bacteremias can make detection difficult
other than blood, what else can be cultured in order to id the organism causing bacteriemia?
the ecythma gangrenosum (most commonly associated with a pseudomonas aeruginosa bacteremia)
LPS is resistant to

can cause infection without living bacteria
primary symptoms of endotoxic shock
change in mental status
clinical signs and complications associated with endotoxic shock syndrom
warm hypotension
leukopenia (reduced WBCs)
thrombocytopenia (reduced platelets)
Skin lesions (ecthyma gangrenosum, particularly with pseudomonas infections)

lung (cyanosis, acidosis), kidney (oliguria, anuria, acidosis), liver (jaundice), heart (congestive heart failure)
molecular factor responsible for disseminated intravascular coagulation, fever and hypotension associated with endotoxic shock
major mediators of LPS induced endotoxic shock appear to be:
(especially lethal in combination)
How does LPS trigger production of TNF-alpha?
1. LPS-Binding Protein (LBP) removes LPS from OM
2. LPS-LBP complex interacts with soluble CD14
3. LPS-LBP-sCD14 delivers LPS to either directly or via membrane bound CD14 to the TLR4 receptor.
4. Oligomerization of the LPS-TLR4/MD-2 complex leads to signaling events that activate both innate and acquired responses. Immediate responses include activation of pro-inflammatory cascades.
how do we get rid of LPS?
transferred to HDL and neutralized, then secreted from liver
effect of endotoxin on Macrophages:
stimulate M0s to produce 3 groups of powerful mediators:
PROTEINS: TNF-alpha, IL-1,6 and 9
prostaglandin E2
sometimes produced by M0s stimulated by endotoxin

inhibits synthesis of other mediators
TNFalpha produced by M0s stimulated by endotoxins
amplified mediate synthesis
pathway of FEVER induced by endotoxin
(Lipid A) --> Mediator (i.e. TNFa) --> Endogenous pyrogen (IL-1 produced by leukocytes) --> prostaglandin synthesis --> increased metabolic rate and decreased heat loss (peripheral vasoconstriction)
pathway of HYPOTENSION induced by endotoxin
Mediator (i.e. TNFa, NO, Bradykinin)
--> Systemic Vasodilation
-> Fxnl Hypovolemia
-> Tissue Hypoxia
-->Increased K (cap leakage)
-> actual hypovolemia
disseminated intravascular coagulation:
generalized activation of clotting mechanisms throughout the body, depleted platelets (then not available at actual injury sites), eventually clot dissolving systems are activated (i.e. plasmin release) and causes clot dissolution and local bleeding
consequences of DIC
localized necrosis (kidney, adrenals, lung, bowel, skin) as well as generalized bleeding
DIC pathway
see D-5
what complement pathway(s) can be activated by LPS or whole microorganisms
how do microorganisms activate the alternative complement pathway?
this Ab-dept pathway is directly activated by bacterial pathogens
how do microorganisms activate the Lectin complement pathway?
MBL (mannos-binding lectin) proteins and ficolin bind carb moieties associated with bacteria

leads to generation of same C3 convertase produced in the classical pathway
complement activation results in:
a. triggering inflammation
b. chemotactically attract phagocytes to the infection site
c. promote the attachment of antigens to phagocytes (enhanced attachment)
d. cause lysis of bacterial cells
e. cause lysis of human cells displaying foreign epitopes
acquired immunity to endotoxin?
activation through CD14/TOLL receptors allows eventual development of acquired immunity
Lipid A is recognized by the immune response via what mechanism?
Lipid A is a PAMP (pathogen-associated molecular pattern) recognized by PRRs (pattern recognition receptors) that are part of the host's innate immune system
4 major host responses to endotoxin
Hageman Factor's role in endotoxic shock
activated by endotoxin to initiate the coaculation cascade resulting in DIC
complement components involved in neutrophil chemotaxis
complement component involved in Hypotension and Edema
compounds associated with endotoxin induced hypotension
NO (produced by Macrophages)
C3a (produced via complement cascade)
Treatment and prevention of endotoxic shock
1. Rapid Dx and Rx of dangerous gram negative infection
2. supportive therapy for hypotension, bleeding, and loss of homeostatic mechanisms
3. Antibiotic Rx (though risk of bacteria release to bloodstream!)
4. Drain abscesses or remove obvious infectious source
5. Management of fluid and electrolyte balance
strategies to prevent endotoxic shock (not particularly successful)
a. neutralization of TNF-a or LPS w/ neutralizing Ab
b. use of competitive inhibitors of LPS binding (to LPS-binding site or M0 LPS receptor site)
c. Inhibition of LPS syntehsis by gram negative organism
Endotoxin-like molecules in Gram-positive
teichoic acid or peptidoglycan

can cause an endotoxin-like reaction

these molecules likely also utilize Toll receptors to trigger these events
what test is used to id endotoxin?
Limulus polyphoemus (horshoe crab) amoebocyte aggultination test
endotoxin vs. exotoxin
chemical nature
endotoxin: LPS (lippopolysaccharide, mw=10kDa)
exotoxin: Protein (mw=50-1000kDa)
endotoxin vs. exotoxin
relationship to cell
endotoxin: part of Outer Membrane
exotoxin: extracellular, diffusable
endotoxin vs. exotoxin
denatured by boiling?
endotoxin: NO
exotoxin: usually
endotoxin vs. exotoxin
endotoxin: YES
exotoxin: YES
endotoxin vs. exotoxin
Form Toxoid?
endotoxin: NO
exotoxin: YES
endotoxin vs. exotoxin
endotoxin: relatively low (>100micrograms)
exotoxin: relatively high (1 microgram)
endotoxin vs. exotoxin
endotoxin: low degree
exotoxin: high degree
endotoxin vs. exotoxin
enzymatic activity
endotoxin: no
endotoxin vs. exotoxin
endotoxin: yes
exotoxin: occasionally
Toll-like Receptor 4
receptor that binds LPS, lipoteichoic acid

involved in kicking off immune response to microbes bearing these ligands
LPS-TLR4 binding complex also involves
LPS Binding Protein (bound to LPS)
and CD14, associated with TLR4 of host cell
Hageman Factor

involved in mediating coagulation cascade triggered by Lipid A

leads to activation of thrombin, fibrin and the eventual clotting response
due to hemorrhaging
membrane attack complex of complement protein

forms pres in biological membranes
interaction of LPS and LPS-bp with CD14 on phagocytic WBCs (neutrophils) can lead to the release of:
toxic oxygen radicals
NO (a vasodilator)
harmful effects of endotoxin are basically..
due to high levels of normal mediators, that modulate beneficial effects at low levels, but harmful effects at high levels
appearance of red or purple discolorations on the skin, caused by bleeding underneath the skin.
a eukaryotic, unicellular to filamentous, achrolophyllous organism having an absorptive nutrition.
reproduction of fungi
can be:
or both
study of fungi
disease caused by fungi
disease caused by a fungal toxin
cephalasporins and penicillin are produced by
fungi are primarily pathogens of

less frequent pathogens of humans and animals
fungi are part of what domain?
-true nucleus, bounded by a nuclear membrane
why is it hard to treat fungal infections?
because they are eukaryotic, difficult to find agents that will selectively inhibit fungal growth, without harming mammalian hosts
perfect form (of fungi)
the sexual form
the imperfect form (of fungi)
the asexual form
the genus of a fungi is determined by
whether or not it is the sexual (perfect) or asexual (imperfect) form
How are crytococcus neoformans and Filobasidiella neoformans related?
SAME organism, different forms
cryptococcus neoformans (imperfect) and filobasidiella neoformans (perfect)
all fungal genera of medical importance can be placed into one of 5 sexual groups
(do we need to know these??)
describe the motility of medically important fungi
what membrane component is found in most fungi, but absent in most bacteria?
sterols, specifically ERGOSTEROL
special sterol, found (in place of cholesterol) in cytoplasmic membrane of most fungi (except Pneumocystis)
proteins are anchored to cytoplasmic membrane of fungi by what 2 different mechanisms?
a) via a GPI (glycosylphosphatidylinositol) anchor
b) via proteins with hydrophobic transmembrane domains
the cell wall in fungi
-makes up large proportion of the cell mass
-found in all medically important fungi
-biochemically UNrelated to bacterial cell walls
composition of fungal cell wall
-inner layer of glucose and chitin polymers
-outer layer of glycoproteins
(inner glucan polymers allow wall to expand/contract- preventing lysis, chitin confers rigidity, crosslinking of glucose and chitin via glycosidic bonds give rise to strength and rigidity)
cross-linking in fungal cell wall
glycosidic bonds between chitin and glucose polymers in inner layer of cell wall

gives strength, rigiditiy, and osmotic stability to the cell.
rigidity of fungal cell wall, due to what type of linkages?
beta 1,3 glucan
cross-linking of glycoproteins to the fungal cell wall occurs via
the carbohydrate remnant of a GPI anchor to beta1,6 glucan (this transglycosylation rxn is carried out by an unknown enzyme)
fungal cell wall glycoproteins are often:
high mannose type (or may contain other complex carbohydrates)

-N-linked to asparagines
-O-linked to hydroxy amino acids
Glycoprotein maturation
typical of eukaryotic secreted proteins

enter ER via a signal sequence
transported through Golgi and secretory vessels to fuse with plasma membrane
fungal cell wall components (from outside to inside)
Glycoproteins (cross-linked to..)
Glucan polymers (crosslinked to..)
Periplasmic proteins
Cytoplasmic Membrane (containing Glucan synthase, Ergosterol, and other transmembrane proteins)
electron dense layer of fungal cell wall is which layer, made up of what?
outermost layer
a glycoprotein layer
inner layer of fungal cell wall is between what? what is it made of?
inner glucan layer
between outer electron dense glycoprotein layer and cytoplasmic membrane
fungal capsule is found...
only in one fungus (crypotococcus neoformans)

loose mucoid layer on the cell surface, composed of polymers of glucuronoxylomannan (GXM)

campsular polysaccharides are shed into blood, CSF, urine and other body fluids
distribution of fungi
ubiquitous, but geographic preferences
major sources of fungi
bird droppings
plant surfaces
exogenous fungi
free-living fungi that are medical pathogens (ecological niche is in nature, outside of the host)
endogenous fungi
have adapted to humans and animals (most important fungal pathogen in this group is Candida albicans ~ normal flora of GI tract)
Candida albican
most important endogenous fungal pathogen (part of normal GI flora in warm-blooded animals)
Fungi grow in two basic forms
Fungi are absorptive heterotrophs?

what are absorptive heterotrophs?
require that carbon be supplied in organic form, they grow in their food secreting digestive enzymes that break down complex molecules into simpler ones that they can absorb.
many fungi grow optimally at what pH?
<5.0 Acid tolerant (relative to bacteria)
secondary metabolites produced by fungi
-psychotropic agents
-aflatoxins (Aspergillus and Fusarium = toxic and carcinogenic)
diseases caused by toxic metabolites of fungi (e.g. aflatoxins)
structure of yeast
oval cell
yeast reproduces by
budding or fission
on agar plates, yeast cells form
smooth pasty colonies
structure of hypha
thread-like filament that may branch and may contain septa that divide the cytoplasm into segments, each segment having a nucleus
aseptate or coenocytic fungi
hypha that don' thave septa (crosswalls)
multinucleate bass of protoplasm resulting from repeated nuclear division unaccompanied by cell fission
why type of funghi produce easily spread spores
aerial hyphae (produce air born spores)
reproductive propagule that forms either following meiosis or asexually by a cleavage process (very common in fungi)
asexual spores classified either as: microconidia- small usually easily airborne and are often the infectious form of fungal pathogens)
or macroconidia (large and are useful for identification)
barrel shaped spore with hyphal filament
advantages of hyphal growth
1. apical grwoth enables fungust to extend into fresh zones of substrate
2. tip extension can be rapid
3. hyphal tips have penetrating power
4. polymer degrading enzymes allow fungi to breakdown complex organic molecules
5. hyphae produce spores of variable shapes
a colony of hyphae and spores may be described as
intermediate growth form of yeasts is called

primarily seen in what species?
(elongate under certain conditions)
primarily candida species
thermal dimorphism
two different forms occur at different temperatures:

eg some fungi grow in hyphal (mold) form in the soil at enviro temps, but as yeast forms in tissue at physiologic temperatures
increased frequency of severe fungal infections is a result of:
larger numbers of compromised (altered) hosts and
environmental factors that bring fungi into contact with humans
superficial mycoses
fungal infections that involve the outermost layers of skin, cuticle or hair shaft (fungi are not recognized by host defenses)
cutaneous mycoses
caused by dermatophytes (specialized saprophytes, can use keartin to establish transitory equilibrium with host)

among the most common infectious agents in humans

allergic rxn by the host to presence of fungi and byproducts
do not invade living tissue, but utilize only dead cornified appendages of host (eg hair, skin, and nails)
specialized saprophytes (colonize cornified structures)
subcutaneous mycoses
enter body by traumatic implantation, all soil saprophytes of regional habitat, require long time to adapt to tissue invironment and years may pass before noticeable disease occurs
systemic mycoses
traditionally either Primary or Opportunistic fungal pathogens
Primary fungal pathogens
those that are capable of causing infections in hosts that are not immunocompromised
Opportunistic fungal pathogens
cause diseases that are manifested almost exclusively in patients debilitated by some other underlying non-fungal cause
charateristics of primary fungal pathogens
grow in nature as soil saprophytes (usually filamentous forms that produce conidial spores and usually in defined geographic regions
adapt and grow in the host as yeasts rather than hyphal filaments) no person to person transmission, no production by infected hosts
characteristics of opportunistic fungal pathogens
diverse (candida albicans = most important, niche = GI tract of warm blooded animals, produces systemic, and severe mucosal infections)

others are ubiquitous in nature and commonly inhaled by humans and animals
cinical specimins useful in identification of fungi
skin scrapings, hair and nails, material from mucosal surfaces, blood, urine, CSF, biopsy
NaOH/KOH mount
useful for examination of fungal specimens (because they are often entwined/embedded in host material)

this dilute alki hydrolyzes the lipids in keratinocytes and other host materials, allowing the fungal elements to stand out
Saline wet mount may be useful for..
may be useful for determining if colonies on plates are composed of fungi or bacteria
India ink is useful for...
useful for demonstrating capsule surrounding cryptococcus neoformans
Histological stains for fungi react with what?
cell wall carbohydrate
PAS stain
Periodic Acid Shiff
glycol groups are converted to reactive aldehydes by action of acid

Shiff's reagent colors them a bright magenta

polysaccharides are strongly stained by this method
Gemori methanamine silver stain, useful for?
what stain does not usually work for fungi?
gram stain
Innate host defenses against fungi
normal innate mechanisms + natural Abs to fungal flora, cationic proteins in secretions (eg: histatins in saliva) inhibit fungal growth, DEFNESINS are also fungacidal
why are most fungal infections asymptomatic or quickly resolved?
because natural immunity to fungal diseases is very high
the infectiousness of a fungal invader depends on:
exposure to sufficient inoculum, size of organism, and general resistance of host
most important protective immune response against fungi is:
how can one demonstrate the CMI response against a given fungus?
DTH response following skin testing

or by the ability of lymphocytes isolated from blood to undergo blast transformation in the presence of fungal antigens)
accumulation of activated macrophages that coalesce and surround the fungi (one manifestation of the CMI response to fungal infection) result in walled-off lesions that may contain viable organisms
role of antibodies in immune defense against fungal infection
aid in phagocytosis by WBCs and clearance of shed capsule (**C. neoformans)

vary in ability to confer protection, CMI more important, but Abs still help