Bacterial Pathogens and Disease 2 (endotoxins)

Question 1

Describe the structure of a gram negative bacterial cell wall?

Answer 1

Lipopolysaccharide is outer membrane
Peptidoglycan
Cell membrane made of phospholipids

Question 2

Where are lipopolysaccharides found?

Answer 2

Outer membrane of only GRAM -VE BACTERIA CELL WALLS

Question 3

Where are endotoxins in bacterial cells?

Answer 3

Lipopolysacchrides in outer membrane of cell wall are where the endotoxins are located

Question 4

Which type of bacteria have endotoxins?

Answer 4

Gram negative

Question 5

What is a lipopoylsaccharide?

Answer 5

Layer in outer membrane of gram negative bacterial cell wall

Question 6

What are the 3 components of a lipopolysacchride?

Answer 6

Lipid A
Polysaccharide core
O - side chain

Question 7

What is lipid A?

Answer 7

Active component and hydrophobic

Phosphorylated glucosamines attached to long chain fatty acids

Question 8

What is a polysaccharide core?

Answer 8

Ketodeoxyoctanoid acid and heptose

- hydrophilic

Question 9

What is a O-side chain?

Answer 9

Repeat units of sugards

Question 10

Which region of gram negative cell wall is highly variable and which region in constant across species?

Answer 10

Polysaccharide core is constant

O side chain is highly variable

Question 11

Which region of gram negative cell wall is immunogenic? and what does it do?

Answer 11

O-side chain

- ellicits formation of antibodies specific to lipid A

Question 12

What is an endotoxin?

Answer 12

Lipopolysaccharide (LPS)

Question 13

Where are LPS found?

Answer 13

Only in gram negative bacteria cell walls

Question 14

Which region of the endotoxin is not immunogenic and which region is immunogenic?

Answer 14

Lipid A is not immunogenic

O-side chain is highly immunogenic and immune specific

Question 15

What is advantageous about endotoxins?

Answer 15

Heat stable

Question 16

What is the use of endotoxins? for the bacteria itself

Answer 16

Major initiator of sepsis pathway

Question 17

Which toxin can be converted into toxoids and which cant?

Answer 17

Exotoxins can be converted into toxoids

Endotoxins can not be converted into toxoids

Question 18

Define sepsis

Answer 18

Life threatening organ dysfunction cause by dyregulated host response to infection

• depends on Lipopolysacchrides (endotoxins mechanism)

Question 19

Which part of immune system and which cells drive sepsis?

Answer 19

Innate immune system

Cells
- macrophages, monocytes, granulocytes, natural killer cells, dendritic cells

Question 20

What do cells in the innate immune system detect during sepsis?

Answer 20

PAMPs e.g. endotoxins

DAMPs

Question 21

What are PAMPs and DAMPs?

Answer 21

PAMP - pathogen associated molecular patterns

DAMP - damage associated molecular patterns

Question 22

How do innate immune cells detect PAMPs and DAMPs during sepsis?

Answer 22

Cell membrane receptors (TLR)

Cytosol receptors (NOD like receptors)

Question 23

What is the effect of of innate immune cells detecting DAMPs and PAMPs through TLRs and NOD like receptors?

Answer 23

Production of inflammatory cytokines OR

INFLAMMASOME activation causes rapid programmed cell death

Question 24

What are the effects of pro-inflammatory cytokines? (7)

Answer 24

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

Question 25

What is the reason the process before dysregulation into sepsis occurs?

Answer 25

To achieve rapid control of localised and minor infections

Question 26

What are the main effects of sepsis?

Answer 26

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

Question 27

How is sepsis resolved?

Answer 27

Active process

• autophagy of DAMPs and PAMPs
• damaged cells go through apoptosis + engulfment by macrophages
• anti-inflammatory IL-10

Question 28

What is meningococcal sepsis caused by?

Answer 28

Neisseria meningitidis

Question 29

What type of bacteria is neisseria meningitidis?

Answer 29

Gram negative diplococcus

Question 30

Why is meningococcus so effective in sepsis?