Bacterial Pathogens And Disease 2 Flashcards
What is a endotoxin?
the main component of the outer membrane of the cell wall of Gram-negative bacteria.
What structures are present in the gram negative bacterial cell wall?
Proteins and porin and liposacharride - outer membrane
Lipoprotein
Peptidoglycan
What is the structure of the liposacharride?
Lipid A - associates with membrane
Core polysaccharide
O side chain
Describe the lipid A subsection of a liposacharride?
- phosphorylated glucosamines attached to long chain fatty acids
- number and type of fatty acid vary by species
- hydrophobic
Describe the polysaccharide core of the lipopolysachrride
KDO and heptose
Relatively constant between species
Hydrophilic
Describe the O side chain of lipopolysacharride
- Repeat units of tri, tetra, or Penta saccharide sugars
- highly variable between species
- hydrophilic
What are the characteristics of endotoxin?
- Endotoxin is lipopolysaccharide (LPS)
• Lipid A is the active component. – not immunogenic.
• O antigen is highly immunogenic and immune specific.
• Found only in gram negative bacteria.
• Heat stable
• Not converted to toxoids.
• Major initiator of the sepsis pathway.
What is sepsis?
Life threatening organ dysfunction caused by a dysregulated host response to infection
What innate immune system cells primarily drive sepsis?
•macrophages,
•monocytes,
•granulocytes,
•natural killer cells
•dendritic cells.
What do the innate immune cells detect in sepsis?
•pathogen associated molecular patterns (PAMP’s) such as endotoxin,
•damage associated molecular patterns (DAMP’s) from damaged host cells.
What is the detection of innate immune cells mediated by?
•cell membrane receptors
– toll-like receptors (TLR) and C-type lectin receptors.
•cytosol receptors
- NOD-like receptors, RIG-I-like receptors.
What is the effect of detection in sepsis?
•Production of pro-inflammatory cytokines TNFα, IL-1, IL-6
•via inflammasomes to produce IL-1β and IL-18 that cause rapid programmed cell death
Describe the signalling pathways of LPS
- LPS binds to MD2 and CD14 on the cel surface of a host
- This causes a cascade inside the cell causing mydosome formation
- TRAF6 forms
- Activation of NF-kb by TRAF6
- This causes production of TNF-alpha and other cytokines
Why are pro inflammatory cytokines important
• 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
What are the positive and negatives of dis regulation of sepsis?
Achieves rapid control of localised and minor infections
However, process may pass a threshold - systemic injury
What occurs during dysregulation of sepsis?
Production of reactive oxygen species (ROS) - damages cellular proteins, DNA and lipids + impared mitochondri
Complement activation —. Increase ROS, granulocyte enzyme release, endothelial permeability and tissue factor expression
Widespread immunothrobsis - disseminated intravascular coagulation (DIC) + impaired micro vascular function + organ dysfunction
Mitochondrial damage leads to decreased intracellular TP an cells enter sate of hibernation - exacerbates organ dysfunction
What is the resolution of sepsis?
What is Meningococcal Sepsis?
• Caused by Neisseria meningitidis
• Gram negative diplococcus
• Serotypes A,B,C, Y, W135
• Serotype A associated with large outbreaks in Sahel region of Africa – Meningitis belt.
• Serotype B,C and W135 found in UK – declined since introduction of MenC and now MenB vaccine.
What makes meningococcus so effective in sepsis?
It’s a active endotoxin and can go anywhere away from bacteria
What do pro flammitory cytokines cause?
Cause fever.
• Causes neutrophils to release extra-cellular traps (NETs) made of DNA and antimicrobial proteins that forms a scaffold for platelet activation.
• Cause release of microparticles by activated platelets
• Increase tissue factor expression by blood monocytes
