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endotoxins |- |correct |answer |✔a |toxic |integral |component |of |the |outer |membrane |of |certain |gram-negative |bacteria |that |is |released |into |the |host |environment |only |when |the |bacteria |die
- |lipopolysaccharide |(LPS), |lipotechoic |acid |(LTA), |and |phosphatidylglycerol |(PG) |and |peptidoglycan
structure |of |LPS |- |correct |answer |✔O |antigen, |core, |and |Lipid |A
structure |of |lipid |A |- |correct |answer |✔GlcN |attached |together |containing |fatty |acids
gram-negative |envelope |- |correct |answer |✔- |outer |Membrane, |periplasmic |space |with |peptidoglycan |and |plasma |membrane
- |thin |peptidoglycan |wall |between |an |outer |membrane |and |a |cytoplasmic |membrane
- |covered |by |an |outer |membrane, |which |confers |defensive |abilities |and |toxigenic |properties |on |many |pathogens
- |inward-facing |leaflet |includes |lipoprotein
-outward-facing |leaflet |contains |lipopolysaccharides
porins
phospholipid |structure |- |correct |answer |✔glycerol, | 2 |fatty |acids, |phosphate |group
sepsis |- |correct |answer |✔toxic |inflammatory |condition |arising |from |the |spread |of |microbes, |especially |bacteria |or |their |toxins, |from |a |focus |of |infection; |DANGEROUS |INFECTION |OF |BLOOD
septicemia |- |correct |answer |✔systemic |disease |in |which |bacteria |multiply |in |the |blood |or |are |continuously |seeded |into |the |blood |stream
- |the |release |of |endotoxins |from |circulating |bacteria |triggers |the |systemic |immune |response |that |leads |to |sepsis |(SIRS, |sepsis, |severe |sepsis, |septic |shock)
stages |of |sepsis |- |correct |answer |✔1. |infection |(fever)
- |SIRS |- |system |inflammatory |response |syndrome |(increased |HR/RR |and |an |altered |Temp)
- |sepsis |(altered |WBC)
- |severe |sepsis |- |sepsis |with |organ |dysfunction |(oliguria, |altered |MS)
- |septic |shock |- |(hypoxia, |end |organ |dys, |hypotension) |(fluid |resuscitation |does |not |help)
- |MODS |(renal |failure, |ARDS, |DIC)
innate |immune |system |- |correct |answer |✔a |collection |of |nonspecific |barriers |and |cellular |responses |that |serve |as |an |inborn |first |and |second |line |of |defense |against |pathogens |and |foreign |invaders
- |always |present |and |ready |to |respond
- |SPECIFICALLY |STUDYING |CELLS |AND |PROTEINS
phagocytes |- |correct |answer |✔a |type |of |white |blood |cell |that |ingests |and |kill |invading |microbes |and |bacteria
cytokines |- |correct |answer |✔proteins |secreted |by |cytotoxic |T |cells |to |aid |in |antigen |destruction
- |glycoproteins |(8-30 |kDal) |produced |by |a |number |of |cell |types |including |macrophages
- |examples |include |tumor |necrosis |factor-alpha |(TNF-a), |interleukin-1 |(IL-1), |gamma |interferon |(IFN-y)
- |cytokines |and |chemokines |bind |to |specific |receptors |on |the |surface |of |target |immune |cells
- |this |binding |initiates |a |signal |transduction |cascade |that |modifies |the |function |of |these |cells
chemokines |- |correct |answer |✔smaller |peptides |produced |by |the |same |type |of |cells; |induce |migration |of |leukocytes
- |ex: |interleukin-8 |(IL-8)
- |cytokines |and |chemokines |bind |to |specific |receptors |on |the |surface |of |target |immune |cells
- |this |binding |initiates |a |signal |transduction |cascade |that |modifies |the |function |of |these |cells
complement |- |correct |answer |✔a |set |of |proteins |produced |by |the |liver |that |circulate |in |blood |and |have |the |capability |to |enter |tissue
- |become |active |through |proteolytic |cleavage |and |are |then |involved |in |various |functions
functions |that |involve |complement |proteins |- |correct |answer |✔1. |enhancing |phagocytosis |of |invaders
- |chemotaxis |of |macrophages |and |neutrophils
- |rupturing |membranes |of |invaders
- |vasodilation
pathways |involved |in |complement |activation |- |correct |answer |✔1. |mannose- binding |lectin |pathway
- |classical |pathway
- |alternative |pathway
mannose-binding |lectin |pathway |- |correct |answer |✔mannose-binding |lectins |are |produced |in |the |liver |and |bind |specifically |to |mannose |residues |on |the |surface |of |bacteria
classical |pathway |- |correct |answer |✔activated |by |antibodies |bound |to |antigen, |which |interact |with |complement |system
alternative |pathway |- |correct |answer |✔involves |binding |of |bacterial |surface |components, |such |as |lipopolysaccharide |(LPS), |lipoteichoic |acid |(LTA), |peptidoglycan |(PG) |by |complement |component |C3b
opsonization |- |correct |answer |✔coating |antigen |with |antibody |enhances |phagocytosis
steps |of |ingestion |- |correct |answer |✔1. |bacteria |is |engulfed
Toll-like |receptors |- |correct |answer |✔each |recognize |a |specific |"danger" |molecule |AND |are |embedded |in |cellular |membranes
- |toll |was |first |identified |as |a |transmembrane |receptor |protein |required |for |development |and |immune |function |in |Drosophila |melanogaster
- |now |known |that |humans |have |a |number |of |TLR |(10 |in |human |genome, | 9 |in |mouse)
LPS |binding |protein |- |correct |answer |✔binds |LPS |and |brings |it |to |CD |14; |binds |complex |with |TLR4 |(and |other |proteins) |to |signal |gene |transcription |for |inflammatory |response
lipid |A |(endotoxin) |receptor, |TLR-4 |- |correct |answer |✔- |includes |direct |binding |and |activation |and |LBP-mediated |LPS |transfer |CD
- |induction |of |inflammatory |and |immune |response |genes
- |from |previous, |cytokines |(IL-1, |TNF-alpha)
NF-kB |- |correct |answer |✔a |"rapid-acting" |primary |transcription |factor
- |transcription |factors |arre |present |in |cells |in |an |inactive |state |and |do |not |require |new |protein |synthesis |to |be |activated
RECALL |- |cytokines |and |chemokins |- |correct |answer |✔bind |to |specific |receptors |on |the |surface |of |target |immune |cells
- |this |initiates |a |signal |transduction |cascade |that |modifies |the |function |of |these |cells
- |cytokines |and |chemokines |modify |the |function |of |circulating |neutrophils |and |monocytes
- |both |fully |activate |killing |capacity |of |PMNs |upon |entrance |into |tissue |and |cause |monocytes |to |differentiate |into |macrophages
inflammation |- |correct |answer |✔a |localized |response |to |an |injury |or |to |the |destruction |of |tissues
- |part |of |the |innate |immune |response |to |infection |by |a |bacterium |or |other |foreign |invader
- |characterized |by |redness, |swelling, |pain, |and |heat
inflammation |and |neutrophils |and |monocytes |- |correct |answer |✔- |neutrophils |and |monocytes |(macrophages) |recruited |from |blood |vessels |by |pro- inflammatory |cytokines |and |chemokinies
- |include |TNF-alpha, |IL-1, |IL-8, |PAF, |and |IL-6; |produced |by |phagocytes |at |site |of |infection |as |well |as |from |other |sources |there |as |well
- |PAF |induces |mast |cells |to |produce |vasoactive |compounds |(e.g., |histamine |at |site |of |infection)
- |these |compounds |increases |vascular |permeability |of |blood |vessels |which |promote |neutrophil |and |monocyte |transmigration
inflammation |and |permeability |- |correct |answer |✔- |results |in |increased |blood |flow |(redness) |and |increased |temperature |in |the |infected |area
- |causes |blood |fluids |to |leak |out |into |the |tissue
RECALL |sepsis |- |correct |answer |✔sepsis |results |from |septicemia |(systemic |disease |in |which |bacteria |multiply |in |the |blood |or |are |continuously |seeded |into |the |bloodstream)
RECALL |endotoxins |and |immune |response |- |correct |answer |✔the |release |of |endotoxins |from |circulating |bacteria |triggers |the |systemic |immune |response |that |leads |to |sepsis |(SIRS, |sepsis, |severe |sepsis, |septic |shock)
exotoxins |- |correct |answer |✔protein |toxins |produced |by |bacteria |that |are |usually |released |into |host |environment |during |growth
effector |proteins |(exoenzymes) |- |correct |answer |✔bacterial |toxins |delivered |directly |into |host |cells |by |bacterial |secretion |systems
superantigens |(type |I |toxins) |- |correct |answer |✔peptide |toxins |that |cause |T |cells |(part |of |adaptive |immune |response) |to |become |overstimulated |and |release |large |amounts |of |cytokines
membrane-disrupting |toxins |(type |II |toxins) |- |correct |answer |✔lyse |host |cells |(or |compartment |within |host |cells |by |disrupting |the |integrity |of |their |plasma |membranes
two |types |of |type |II |toxins |- |correct |answer |✔1. |proteins |that |form |channels |(pores) |in |the |plasma |membrane
- |enzymes |that |compromise |the |integrity |of |the |plasma |membrane |phospholipids
A-B |toxins |(type |III |toxins) |- |correct |answer |✔- |consist |of |two |functional |subunits
- |the |A |subunit |has |enzymatic |(toxin) |function
- |B |subunit |binds |to |a |receptor |on |host |cells
- |single |chain |A-B |toxins |have |one |A |subunit |and |one |B
Diptheria |toxin |from |Corynebacterium |diptheriae |(single |chain |A-B |toxin
|example) |- |correct |answer |✔- |upper |respiratory |illness |characterized |by |sore |throat, |low |fever, |and |an |adherent |membrane |(pseudomembrane) |on |tonsils, |pharynx, |and/or |nasal |activity
- |first |known |epidemic |occurred |in |Spain |in | 1613 |- |"El |Ano |de |Los |Garotillos"
- |206,000 |cases |recorded |in |U.S. |in | 1921
- |led |to |the |"Great |Race |of |Mercy" |in | 1925
notes |in |action |of |diphtheria |toxin |- |correct |answer |✔- |includes |Heparin-binding |epidermal |growth |factor |receptor
- |B |subunit |for |diphtheria |toxin |consists |of |a |B |domain |and |a |T |domain
- |SH |connects |to |subunit |and |then |cell |death |occurs
diphtheria |toxin |(ADP |ribosylating |toxin) |- |correct |answer |✔for |ADP |ribosylating |toxins, |the |A |protein |subunit |catalyzes |the |formation |of |ADP-ribose |from |NAD+ |and |transfers |it |to |a |target |protein
- |in |dummy |terms, |NAD |and |target |by |toxin |>> |target |and |ADP-ribose |and |product
persistent |activation |of |adenylyl |cyclase |- |correct |answer |✔leads |to |constant |efflux |of |electrolytes |(Na+ |and |C- |ions) |into |lumen |of |intestines |followed |by |efflux |of |water
anthrax |toxin |from |Bacillus |anthracis |(multi-subunit |A-B |toxin |example) |-
|correct |answer |✔- |humans |and |animals |are |susceptible |upon |infection |by |B. |anthracis |spores
- |three |forms |of |infections |depending |on |route |of |infection: |subcutaneous, |gastrointestinal, |and |inhalation |anthrax
- |first |vaccine |developed |in |Louis |Pasteur |in | 1881
inhaled |anthrax |- |correct |answer |✔- |particularly |deadly
- |although |the |spores |are |dormant |when |breathed |in, |they |germinate |when |exposed |to |a |warm, |moist |environment, |such |as |lungs
- |not |all |particles |are |small |enough |to |pass |into |the |alveoli |(air |sacs) |but |those |that |do |begin |to |multiply |and |may |spread |to |the |lymphatic |system
- |when |the |spores |germinate |ini |the |lymph |nodes, |several |toxins |are |released
anthrax |toxin |- |correct |answer |✔- |has |two |A |subunits |called |edema |factor |(EF) |and |lethal |factor |(LF)
- |B |subunit |is |called |protective |antigen |(PA)
- |LF |is |a |protease |that |inactivates |MAP |kinase |kinases
- |EF |is |a |calmodulin-dependent |adenylate |cyclase
- |anthrax |toxin |= | 2 |LF |+ | 1 |EF |+ | 7 |PA
botulism |toxin |from |Clostridium |botulism |(exotoxin |example) |- |correct |answer
|✔- |typically |not |caused |by |infection |but |by |intoxication |(2 |exceptions)
- |caused |by |seven |serologically |and |antigenically |distinct |types |of |botulism |(BoNT); |serotypes |A |through |G
- |serotype |A |is |the |most |potent |toxin |for |humans |(lethal |dose |of |~1-5 |ng/kg |body |weight)
- |toxin |produced |>> |toxin |in |bloodstream |>> |attacks |neurons |(flaccid |paralysis)
botulism |- |correct |answer |✔- |structures |of |BoNTs |are |similar |to |single |chain |A-B |toxins |but |involve |"heavy |chain" |and |"light |chain" |protein |and |fragments |joined |by |a |disulphide |bridge
- |BoNTs |cleave |SNARE |proteins |(syntaxin, |SNAP-25 |and |VAMP |[synaptobrevin]) |proteins |involved |in |synaptic |vesicle |fusion |and |acetylcholine |release |in |peripheral |nerves |>> |results |in |flaccid |paralysis
Tetanus |toxin |from |Clostridium |tetani |(exotoxin |example) |- |correct |answer |✔- |C. |tetani |spores |present |in |a |deep |puncture |wound |germinate |and |the |bacterium |grows |in |this |anoxic |environment
- |tetanus |toxin |is |produced |and |diffuses |to |central |nervous |system
- |structure |of |TeNT |is |very |similar |to |BoNTs
- |TeNT |cleaves |VAMP |(synaptobrevin) |proteins |involved |in |synaptic |vesicle |fusion |and |acetylcholine |release |in |CNS |neurons |that |normally |signal |relaxation |after |muscle |contraction
common |secretory |systems |- |correct |answer |✔1. |sec |system |(general |secretory |system)
- |twin-arginine |transport |(TAT)
- |includes |type | 2 |and |type | 5 |secretion |systems
type | 2 |secretion |system |- |correct |answer |✔- |proteins |are |secreted |across |the |outer |membrane |through |a |pore
- |there |are |12-14 |proteins |involved |in |a |T2SS
- |T2SS |proteins |in |outer |membrane |(OM) |form |a |pore
- |T2SS |proteins |in |inner |membrane |form |a |pseudopilus |that |extends |(pushes) |secreted |proteins |through |channels |in |OM
type | 5 |secretion |system |- |correct |answer |✔- |the |protein |to |be |exported |(auto- transporter) |secretes |a |portion |of |itself |across |the |outer |membrane
- |autotransporter |consists |of |multiple |domains: |an |N-terminal |Sec |signal |sequence, |a |passenger |(P) |domain |(a |portion |of |which |may |also |have |protease |function), |a |linker |(L) |regions |and |C-terminal |B |pore-forming |domain
