Bacterial Pathogens and Disease 2 (endotoxins) Flashcards
Describe the structure of a gram negative bacterial cell wall?
Lipopolysaccharide is outer membrane
Peptidoglycan
Cell membrane made of phospholipids
Where are lipopolysaccharides found?
Outer membrane of only GRAM -VE BACTERIA CELL WALLS
Where are endotoxins in bacterial cells?
Lipopolysacchrides in outer membrane of cell wall are where the endotoxins are located
Which type of bacteria have endotoxins?
Gram negative
What is a lipopoylsaccharide?
Layer in outer membrane of gram negative bacterial cell wall
What are the 3 components of a lipopolysacchride?
Lipid A
Polysaccharide core
O - side chain
What is lipid A?
Active component and hydrophobic
Phosphorylated glucosamines attached to long chain fatty acids
What is a polysaccharide core?
Ketodeoxyoctanoid acid and heptose
- hydrophilic
What is a O-side chain?
Repeat units of sugards
Which region of gram negative cell wall is highly variable and which region in constant across species?
Polysaccharide core is constant
O side chain is highly variable
Which region of gram negative cell wall is immunogenic? and what does it do?
O-side chain
- ellicits formation of antibodies specific to lipid A
What is an endotoxin?
Lipopolysaccharide (LPS)
Where are LPS found?
Only in gram negative bacteria cell walls
Which region of the endotoxin is not immunogenic and which region is immunogenic?
Lipid A is not immunogenic
O-side chain is highly immunogenic and immune specific
What is advantageous about endotoxins?
Heat stable
What is the use of endotoxins? for the bacteria itself
Major initiator of sepsis pathway
Which toxin can be converted into toxoids and which cant?
Exotoxins can be converted into toxoids
Endotoxins can not be converted into toxoids
Define sepsis
Life threatening organ dysfunction cause by dyregulated host response to infection
- depends on Lipopolysacchrides (endotoxins mechanism)
Which part of immune system and which cells drive sepsis?
Innate immune system
Cells
- macrophages, monocytes, granulocytes, natural killer cells, dendritic cells
What do cells in the innate immune system detect during sepsis?
PAMPs e.g. endotoxins
DAMPs
What are PAMPs and DAMPs?
PAMP - pathogen associated molecular patterns
DAMP - damage associated molecular patterns
How do innate immune cells detect PAMPs and DAMPs during sepsis?
Cell membrane receptors (TLR)
Cytosol receptors (NOD like receptors)
What is the effect of of innate immune cells detecting DAMPs and PAMPs through TLRs and NOD like receptors?
Production of inflammatory cytokines OR
INFLAMMASOME activation causes rapid programmed cell death
What are the effects of pro-inflammatory cytokines? (7)
1) increase number, lifespan and activation of innate immuen cells
2) increase adhesion molecule and chemokine expression by endothelial cells
3) Cause fever
4) neutrophils release extra cellular traps made of DNA and antimicrobial proteins to form scaffold for platelet activation
5) release of microparticles by activated platelets
6) increase tissue factor expression by blood monocytes
7) formation of thrombus, so microbes trapped inside to attract further leucocytes
What is the reason the process before dysregulation into sepsis occurs?
To achieve rapid control of localised and minor infections
What are the main effects of sepsis?
1) production of reactive oxygen species (ROS) - damages cellular proteins, DNA and mitochondria
2) Complement activation - which also increases ROS, endothelial permeability and granulocyte enzyme release
3) Widespread immunothrombosis - causes impaired microvasculature function and organ dysfunction
4) mitochondrial damage - decreased intracellular ATP so organ dysfunction
How is sepsis resolved?
Active process
- autophagy of DAMPs and PAMPs
- damaged cells go through apoptosis + engulfment by macrophages
- anti-inflammatory IL-10
What is meningococcal sepsis caused by?
Neisseria meningitidis
What type of bacteria is neisseria meningitidis?
Gram negative diplococcus
Why is meningococcus so effective in sepsis?
