bacterial pathogens and disease II

Question 1

describe lipopolysaccharide

Answer 1

LIPID A.
- Phosphorylated glucosamines attached to long chain fatty acids.
- Number and type of fatty acid vary by species.
- Hydrophobic
POLYSACCHARIDE CORE
- Ketodeoxyoctanoic acid (KDO) and heptose.
- Relatively constant between species
- Hydrophilic

O – SIDE CHAIN

• Repeat units of tri, tetra or penta-saccharide sugars.
• Highly variable between species
• Hydrophilic

Question 2

endotoxin characteristics

Answer 2

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.

Question 3

what is sepsis

Answer 3

life threatening organ dysfunction caused by dysregulated host response to infection

Question 4

sepsis

Answer 4

driven by innate immune system response:
macrophage, monocytes, granulocytes, natural killer cells and dendritic cells

these cells detect:
pathogens associated molecular patterns e.g. endotoxin and damage associated molecular patterns from damaged host cells

detection mediated via:
cell membrane receptors: toll like receptors and c-type lectin receptor
cytosol receptor - NOD like receptor and RIG-I like receptor

effect =
production of pro inflammatory cytokines TNFalpha, IL-1, IL-6

via inflammasomes to produce IL-1beta and iL-18 that cause rapid programmed cell death

Question 5

effects of pro-inflammatory cytokines

Answer 5

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 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

5+6+7 → formation of a thrombus
(immunothrombosis)
Microbes trapped within this. → attracts and activate further leucocytes.

Question 6

sepsis - dysregulation

Answer 6

process described achieves rapid control of localised and minor infections

however, process may pass a threshold, systemic injury

Question 7

meningococcal sepsis

Answer 7

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.
Can cause disease ranging from meningitis to life threatening meningococcal sepsis.