Bacterial Pathogens And Disease 2- Endotoxins Flashcards
What are the components of a gram negative bacterial cell wall?
Lipopolysaccharide
Peptidoglycan
Cell membrane
What are the components of the lipopolysaccharide part of the gram negative bacterial cell wall outer membrane?
O-polysaccharide
Core polysaccharide
Lipid A
What are the features of the O-polysaccharide?
Highly variable between species
Hydrophilic
What are the features of a core polysaccharide?
Relatively constant between species and hydrophilic
What is a core polysaccharide made up of?
Ketodeoxyctenoic acid and heptose
What is an O-polysaccharide made up of?
Repeat units of tri-, tetra- or pentosaccharide sugars
What is lipid A made up of?
Phosphatidyl glucosamines attached to long chain fatty acids
What are the features of lipid A?
Number and type of fatty acid varies by species
Hydrophobic
What are lipoproteins made up of?
Porin
Protein
What is peptidoglycan made up of?
Periplasm
What is the cell membrane made up of?
Phospholipid
Proteins
What are the features of an endotoxin?
Heat stable
Not converted to toxoids
What are endotoxins a major initiator of?
The sepsis pathway
What are the only types of bacteria endotoxins are found in?
Gram -ve bacteria
Which is the active component of endotoxin?
Lipid A
What is sepsis primarily driven by?
Innate immune system response
What cells does the innate immune response involve?
Macrophages Monocytes Granulocytes Natural killer cells Dendritic cells
What do the innate immune system cells detect?
PAMPs and DAMPs
What is an example of a PAMP?
Endotoxin
Where do DAMPs come from?
Damaged host cells
What is PAMP and DAMP detection mediated by in sepsis?
Cell membrane receptors: TLR and C-type lectin receptors
Cytosol receptors: NOD and RIG-I-like receptors
What are the effects of PAMPs and DAMPs in sepsis?
Production of pro-inflammatory cytokines TNFalpha, IL-1 and IL-6
What are the effects of pro-inflammatory cytokines such as IL-1?
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
What are NETs?
Neutrophil extracellular traps
What are NETs made of?
DNA and antimicrobial proteins
What do NETs form?
A scaffold for platelet activation
What happens in dysregulation in sepsis?
Production of reactive oxygen species
Complement activation
Widespread immunothrombosis
Mitochondrial damage
What does the production of reactive oxygen species cause?
Damages cellular proteins, DNA and lipids and impairs mitochondria
What does complement activation cause?
Increase ROS, granulocyte enzyme release, endothelial permeability and tissue factor expression
What does mitochondrial damage lead to?
Decreased intracellular ATP and cells enter a state of hibernation that exacerbates organ dysfunction
How is sepsis resolved?
IL-10 production
Autophagy and removal of PAMPs and DAMPs
Damaged cells undergo apoptosis and engulfment by macrophages
What does IL-10 do in sepsis resolution?
Suppresses production of IL-6 and gamma interferon
Stimulates production of soluble TNF receptor and IL-1 receptor antagonist
What is meningococcal sepsis caused by?
Neisseria meningitidis
What are the meningococcal sepsis serotypes?
A, B, C, Y, W, 135
What is serotype A associated with?
Large outbreaks in the Sahel region of africa
How is meningococcal sepsis so effective?
Releases blebs full of LPS
