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π“œπ‘’π’Ήπ’Ύπ’Έπ’Άπ“ π“œπ’Ύπ’Έπ“‡π‘œπ’·π’Ύπ‘œπ“π‘œπ‘”π“Ž > Bacterial Pathogens and Disease II - Endotoxins > Flashcards

Bacterial Pathogens and Disease II - Endotoxins Flashcards

1
Q

What is the difference in the peptidoglycan layer in gram + and - bacteria?

A

β†’ gram - have very thin peptidoglycan cell walls compared to gram +

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2
Q

What are the three components of lipopolysaccharide?

A

β†’ Lipid A
β†’ polysaccharide core
β†’ O- side chain

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3
Q

What is Lipid A made from?

A

β†’ Phosphorylated glucosamines attached to long chain fatty acids and is hydrophobic

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4
Q

What is the polysaccharide core made from?

A

β†’ Ketodeoxyoctanoid acid (KDO) and heptose

β†’ relatively constant between species - hydrophilic

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5
Q

What is the O side chain made from?

A

β†’ Repeat units of tri tetra or pentasaccharide sugars

β†’ hydrophilic

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6
Q

What is endotoxin?

A

β†’ lipopolysaccharide

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7
Q

What is the active component of endotoxin?

A

β†’ Lipid A is the active component that is not immunogenic

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8
Q

Why does a vaccine for all O antigens not work?

A

β†’ each type of O antigen elicits a specific response

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9
Q

What 3 things are in the membrane of gram -ve bacteria?

A

β†’ Proteins
β†’ Porins
β†’ lipopolysaccharide

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10
Q

What is a major initiator of the sepsis pathway?

A

β†’ lipopolysaccharide

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11
Q

What is a structural property of lipopolysaccharide?

A

β†’ Heat stable

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12
Q

Why can’t you make a vaccine against lipid A?

A

β†’ not immunogenic

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13
Q

What is the definition of sepsis?

A

β†’ Life threatening organ dysfunction caused by dysregulated host response to infection

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14
Q

What 5 components of the immune system drive the sepsis response?

A 
β†’ Macrophages
β†’ monocytes
β†’ granulocytes
β†’ natural killer cells
β†’ dendritic cells
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15
Q

What does the immune system detect during sepsis?

A

β†’ Pathogen associated molecular patterns (PAMPs) such as endotoxins
β†’ damage associated molecular patterns (DAMPs) from damaged host cells

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16
Q

What two categories of receptor are used to detect PAMPs and DAMPs?

A

β†’ Cell membrane receptors and cytosol receptors

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17
Q

Give 2 examples of cell membrane receptors that are used to detect PAMPs and DAMPs?

A

β†’ Toll like receptors

β†’C-type lectin receptors

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18
Q

Give 2 examples of cytosol receptors used to detect PAMPs and DAMPs?

A

β†’ NOD-like receptors

β†’ RIG-I like receptors

19
Q

What is the effect of detecting PAMPs and DAMPs and how is this mediated?

A

β†’ Production of pro-inflammatory cytokines : TNFa, IL-1, IL-6
β†’ via inflammasomes to produce IL-1beta and IL-18 that cause rapid programmed cell death

20
Q

Describe how cytokines are produced as a result of LPS binding?

A

β†’ LPS binds to a macrophage (CD14 receptor)
β†’ after it is bound by CD14 it gets passed to the toll-like receptor (TLR4) by MD2
β†’ The TLR4 dimerizes
β†’ causes myddosome formation intracellularly
β†’ Activation of NF-Kb
β†’ Production of TNF alpha and other cytokines occur

21
Q

What are the 7 effects of pro-inflammatory cytokines?

A

1) increase number,lifespan and activation state of innate immune cells
2) increase adhesion molecule and chemokines expression by endothelial cells
3) increases acute phase protein such as complement , fibrinogen and CRP
4) cause fever
5) causes neutrophils to release extracellular traps (NETs) made of DNA and antimicrobial proteins that form a scaffold for platelet activation
6) cause release of microparticles by activated platelets
7) increase tissue factor expression by blood monocytes

22
Q

What 3 things lead to the formation of an immunothrombosis?

A

β†’ neutrophils releasing NETs
β†’ microparticles released by activated platelets
β†’ tissue factor expression increase by blood monocytes

23
Q

What is the reason for the pro-inflammatory cytokine effects?

A

β†’ Rapid control of localised and minor infections

24
Q

What is the effect of TNF in the liver and why?

A

β†’ cause a decrease in iron

β†’ liver tries to collate the iron because bacteria need it to grow

25
Q

What is septicaemia driven by?

A

β†’ Endotoxin

26
Q

What are 5 things that occur during sepsis?

A 
β†’ increased vascular permeability 
β†’ hypotension leading to hypovolaemic shock
β†’ fever
β†’ DIC
β†’ multiple organ failure
27
Q

What are 4 things that occur as a result of dysregulation?

A

β†’ production of reactive oxygen species
β†’ complement activation
β†’ Widspread immunothrombosis leading to DIC
β†’ Mitochondrial damage

28
Q

What are two reactive oxygen species?

A

β†’ Hydroxyl and nitric oxide

29
Q

What is the function of reactive oxygen species?

A

β†’ damages cellular proteins
β†’ Damages DNA and lipids
β†’ impairs mitochondria

30
Q

What happens during complement activation?

A

β†’ granulocyte enzyme release
β†’ endothelial permeability
β†’ tissue factor expression
β†’ C5a increase ROS

31
Q

What is DIC?

A

β†’ clots are formed everywhere but they start bleeding because all the clotting factors are used up

32
Q

What does mitochondrial damage lead to?

A

β†’ decreased intracellular ATP

β†’ cells enter a state of hibernation and exacerbates organ dysfunction

33
Q

What kind of a process is sepsis resolution?

A

β†’ Active not passive

34
Q

What are the three things that occur in the resolution of sepsis?

A

β†’ Anti-inflammatory IL-10 is produced early in the process
β†’ Autophagy of PAMPs and DAMPs
β†’ Damaged cells undergo apoptosis and engulfment by macrophages

35
Q

What is the effect of IL-10 being produced during sepsis resolution?

A

β†’ Suppresses production of IL-6 and gamma interferon

β†’ Stimulates the production of a soluble TNF receptor and IL-1 receptor antagonist

36
Q

Why are there TNF receptors in the blood in sepsis resolution?

A

β†’ TNF binds to the receptor instead of being taken up by cells

37
Q

What is the function of IL-1 antagonist in sepsis resolution?

A

β†’ IL-1 antagonist competes for binding so less IL-1 can bind to the receptor

38
Q

What types of cytokines are IL-6 and gamma interferon?

A

β†’ Pro inflammatory

39
Q

What bacteria is meningococcal sepsis caused by?

A

β†’ Neisseria meningitidis

40
Q

What kind of bacteria is neisseria meningitidis?

A

β†’ Gram negative diplococcus

41
Q

What are the 5 serotypes of meningococcal sepsis?

A 
β†’ A
β†’ B
β†’ C
β†’ Y
β†’ W135
42
Q

What serotype is associated with outbreaks in the Sahel region of Africa?

A

β†’ A

43
Q

What serotypes of meningitidis are found in the UK?

A

β†’ B
β†’ C
β†’ W135

44
Q

What are the 5 things that make meningococcus so effective in sepsis?

A

β†’ It has a different lipid A and polysaccharide to all gram -ve bacteria
β†’ 6 fatty acid chains
β†’ Similar carbohydrates to the ones in humans so the immune response is not very effective
β†’ blebs are pieces of outer cell membrane which are shedded all the time - shedding endotoxins into the environment

π“œπ‘’π’Ήπ’Ύπ’Έπ’Άπ“ π“œπ’Ύπ’Έπ“‡π‘œπ’·π’Ύπ‘œπ“π‘œπ‘”π“Ž (17 decks)

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