L2: Bacterial pathogens & disease- ENDOTOXINS Flashcards
What are LPS detected by?
→ TLRs
→ innate immune response
What are LPS?
→ major outer surface membrane components present in almost all Gram-negative bacteria
Name the components of gram negative bacterial cell wall
→ lipopolysaccharide → outer membrane → lipoprotein → peptidoglycan → cell membrane
Describe the structure of LPS
→ LIPID A
→ POLYSACCHARIDE CORE
→ O – SIDE CHAIN
What is lipid A in LPS?
→ Phosphorylated glucosamines attached to long chain fatty acids.
→ Number and type of fatty acid vary by species.
→ Hydrophobic
Describe the polysaccharide core of LPS
→Ketodeoxyoctanoic acid (KDO) and heptose.
→ Relatively constant between species
→ Hydrophilic
Describe the O-side chain of LPS
→ Repeat units of tri, tetra or penta-saccharide sugars.
→ Highly variable between species
→ Hydrophilic
What is the active component of LPS?
→ Lipid A
→ not immunogenic
What is the immunogenic component of LPS?
→ O-antigen
What is the major initiator of sepsis pathway?
→ LPS
Describe endotoxins
→ Heat stable
→ Not converted to toxoids.
→ Major initiator of the sepsis pathway
How are LPS molecules cross bridged and what does this allow?
→ non covalently cross bridged by Ca and Magnesium ions
→ barrier to hydrophobic molecules including bile salts
What is sepsis?
→ Life threatening organ dysfunction caused by a dysregulated host response to infection
What are the immune cells involved in sepsis?
→ macrophages, → monocytes, → granulocytes, → natural killer cells → dendritic cells
What do innate immune cells detect?
→ pathogen associated molecular patterns (PAMP’s) such as endotoxin,
→ damage associated molecular patterns (DAMP’s) from damaged host cells