3 Gram-Negative Bacterial Structure & Endotoxin in Human Diseases Flashcards
What symptoms would Schlievert’s story of a boy with Neisseria meningitidis gram-negative shock have?
VERY low B.P. (blood pressure), petechia (red spots), 24 hrs of nausea, vomiting, stiff neck, fever
[exteremely severe and rapid, can also have Purpura Fulminans]
What’s petechia?
tiny red spots (minor hemorrhage) that is often associated with increased pressure/trauma or even clotting disorders.
What are the 3 common causes of meningitis in non-babies
- Streptococcus pneumoniae (all ages)
- Neisseria meningitidis (all ages)
- Haemophilus influenzae type b (3 mo. to 7 yrs)
[1st 2 are the majority of cases]
What are the 3 common causes of meningitis in neonates?
- Streptococcus aggalactiae (group B) [40%]
- Escherichia coli [40%]
- Listeria monocytogenes [10%]
Which capsule groups of Neisseria meningitidis are common in the U.S.? Which one is not immunogenic?
- A, B, C, Y, W135
- B (no vaccine)
How is gram-neg. shock due to N. Meningitidis treated?
- “Supportive therapy” (fluid & electrolytes for B.P., blood pressure)
- Coricosteroids prevent inflammation
- 3rd generation cephalosporin
Describe the look a Neisseria meningitidis bacteria? (2 things)
encapsulated diplococcus
What characteristics are important for N. meningitidis damage to host and virulence? (3)
- Encapsulated
- Gram-neg. (endotoxin)
- Antiphagocytic capsule
Which antibiotic is for prophylactic treatment of N. meningitids? Why?
Rifampin. Penetrates mucosal membranes where n. meningitidis lives
How is N. meningitids transmitted?
saliva, intimate contact more commonly than just a cough
T/F n. meningitids causes pus around the meninges of the CNS?
T.
In what 4 ways are gram negative cell walls different than gram positives?
- Thinner, less cross-linked (25 vs 75%) peptidoglycan layer
- Outer membrane (Phospholipid) atop peptidoglycan.
- LPS layer atop outer membrane.
- Periplasm zone between inner and outer membranes(includes the peptidoglycan layer)
What are 4 key gram-negative structures?
- Outer Membrane Proteins (OMP’s)
- Pili
- Spheroplasts
- Flagella
Porins are an example of what? What is the structure of a porin?
OMP’s (porins are trimers)
Pili are made of? Have what function?
- Pilin
- sex w/ bacteria & attachment to host
T/F All OMP’s are immunogenic, since they are proteins.
F.
OMP’s attach to what part of the cell wall?
covalent link to peptidoglycan layer!
[NOT to outer layer of cell like you might think]
What is the structure of LPS (lipopolysaccharide A)?
- O side chain sugars
- Core polysaccharide
- Lipid A
Enterobacteriaceae share what common feature?
Core polysaccharide of LPS
How is LPS identified in lab med?
Find KDO (ketodeoxyoctonate) sugar (or heptose)
What is the toxic part of endotoxin (a.k.a. LPS)?
Lipid A
What provide the antigen specificity of LPS?
O antigen.
“emia” (suffix) means?
in the blood
What is the cause of multiorgan dysfunction syndrome?
host immune response
How are LPS and LOS different?
-Incomplete O side chain in the LPS means it is LOS.
[Our key example is Neisseria]
T/F gram negative bacteria have exotoxin?
T, some do.
[Note: when secreted, if large it gets caught in the periplasm before reaching host]
T/F the toxic portion of endotoxin is part of the gram negative cell wall facing the host?
F. (faces inside of the bacteria)
T/F gram pos. bacteria have exotoxin?
T, some do.
T/F endotoxin & exotoxin are enzymatic?
F, many exotoxins are but not endotoxin.
Put in order of most to least potent: LTA-peptidoglycan(lipotechoic acid), superantigen exotoxin, LPS? What type of bacteria secretes each?
- Superantigen exotoxin (.1 ug) [Toxic shock syndrome bacteria types]
- LPS (1 ug) [gram neg]
- LTA-peptigoglycan (1 mg) [gram pos]
enterotoxins are?
exotoxins that act on the enteron (gut)
[NOT endotoxins!]
Exotoxins are made of what molecule type?
protein
[unlike LPS a lipid]
Which type of bacterial toxin are variable traits genetically?
exotoxins.
[endotoxin doesn’t vary]
Describe the immune cascade activated by LTA:
Macrophage
TLR2/6 ->
IL-1B, IL-6, (both=fever) , TNF-alpha=hypotension
Describe the immune cascade activated by LPS?
Macrophage
TLR-4 ->
IL-1B, IL-6, (both=fever) , TNF-alpha=hypotension
Describe the immune cascade activated by superantigen?
Macrophage presents to T-cell & gets crosslinked especially to Beta chain of TCR ->
Macrophage releases: IL-1B, IL-6, TNF-alpha
AND
T-cell releases: IFNgamma & IL-2 (rash) + TNF-Beta (hypotension)
