Bacterial Pathogens And Disease 2- Endotoxins

Question 1

What are the components of a gram negative bacterial cell wall?

Answer 1

Lipopolysaccharide
Peptidoglycan
Cell membrane

Question 2

What are the components of the lipopolysaccharide part of the gram negative bacterial cell wall outer membrane?

Answer 2

O-polysaccharide
Core polysaccharide
Lipid A

Question 3

What are the features of the O-polysaccharide?

Answer 3

Highly variable between species

Hydrophilic

Question 4

What are the features of a core polysaccharide?

Answer 4

Relatively constant between species and hydrophilic

Question 5

What is a core polysaccharide made up of?

Answer 5

Ketodeoxyctenoic acid and heptose

Question 6

What is an O-polysaccharide made up of?

Answer 6

Repeat units of tri-, tetra- or pentosaccharide sugars

Question 7

What is lipid A made up of?

Answer 7

Phosphatidyl glucosamines attached to long chain fatty acids

Question 8

What are the features of lipid A?

Answer 8

Number and type of fatty acid varies by species

Hydrophobic

Question 9

What are lipoproteins made up of?

Answer 9

Porin

Protein

Question 10

What is peptidoglycan made up of?

Answer 10

Periplasm

Question 11

What is the cell membrane made up of?

Answer 11

Phospholipid

Proteins

Question 12

What are the features of an endotoxin?

Answer 12

Heat stable

Not converted to toxoids

Question 13

What are endotoxins a major initiator of?

Answer 13

The sepsis pathway

Question 14

What are the only types of bacteria endotoxins are found in?

Answer 14

Gram -ve bacteria

Question 15

Which is the active component of endotoxin?

Answer 15

Lipid A

Question 16

What is sepsis primarily driven by?

Answer 16

Innate immune system response

Question 17

What cells does the innate immune response involve?

Answer 17

Macrophages
Monocytes
Granulocytes
Natural killer cells
Dendritic cells

Question 18

What do the innate immune system cells detect?

Answer 18

PAMPs and DAMPs

Question 19

What is an example of a PAMP?

Answer 19

Endotoxin

Question 20

Where do DAMPs come from?

Answer 20

Damaged host cells

Question 21

What is PAMP and DAMP detection mediated by in sepsis?

Answer 21

Cell membrane receptors: TLR and C-type lectin receptors

Cytosol receptors: NOD and RIG-I-like receptors

Question 22

What are the effects of PAMPs and DAMPs in sepsis?

Answer 22

Production of pro-inflammatory cytokines TNFalpha, IL-1 and IL-6

Question 23

What are the effects of pro-inflammatory cytokines such as IL-1?

Answer 23

Increase number, lifespan and activation state of innate immune cells
Increase adhesion molecule and chemokine expression by endothelial cells
Increase acute phase protein such as complement, fibrinogen and CRP
Cause fever
Causes NETS
Release of microparticles by activated platelets
Increase tissue factor expression by blood monocytes

Question 24

What are NETs?

Answer 24

Neutrophil extracellular traps

Question 25

What are NETs made of?

Answer 25

DNA and antimicrobial proteins

Question 26

What do NETs form?

Answer 26

A scaffold for platelet activation

Question 27

What happens in dysregulation in sepsis?

Answer 27

Production of reactive oxygen species Complement activation Widespread immunothrombosis Mitochondrial damage

Question 28

What does the production of reactive oxygen species cause?

Answer 28

Damages cellular proteins, DNA and lipids and impairs mitochondria

Question 29

What does complement activation cause?

Answer 29

Increase ROS, granulocyte enzyme release, endothelial permeability and tissue factor expression

Question 30

What does mitochondrial damage lead to?

Answer 30

Decreased intracellular ATP and cells enter a state of hibernation that exacerbates organ dysfunction

Question 31

How is sepsis resolved?

Answer 31

IL-10 production Autophagy and removal of PAMPs and DAMPs Damaged cells undergo apoptosis and engulfment by macrophages

Question 32

What does IL-10 do in sepsis resolution?

Answer 32

Suppresses production of IL-6 and gamma interferon | Stimulates production of soluble TNF receptor and IL-1 receptor antagonist

Question 33

What is meningococcal sepsis caused by?

Answer 33

Neisseria meningitidis

Question 34

What are the meningococcal sepsis serotypes?

Answer 34

A, B, C, Y, W, 135

Question 35

What is serotype A associated with?

Answer 35

Large outbreaks in the Sahel region of africa

Question 36

How is meningococcal sepsis so effective?

Answer 36

Releases blebs full of LPS