Sepsis Flashcards

1
Q

What are the possible causes of meningitus?

Also comment on how common and severity

A

Viral (most common, least severe)
Bacterial (least common, most severe)
Parasitic
Fungal

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2
Q

What is meningitus?

A

Inflammation of the meninges as the result of an infection that has spread into the subarachnoid space

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3
Q

Which two meninges is the subarachnoid space in between?

A

Arachnoid and pia mater

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4
Q

Mechanism of bacterial meningitus

A

Bacterial infection spreads into the bloodstream through a mucous surface e.g. nasal cavity
Infection enters the subarachnoid space
The immune response is triggered - astrocytes and microglia release cytokines
The BBB becomes permeable allowing WBCs into the CSF
Entry of WBCs triggers large scale inflammation and cerebral oedema
Increased intracranial pressure makes it harder for blood to enter the brain, cells apoptose

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5
Q

Which type of cells cause initial T cell activation and how?

A

Dendritic cells

Phagocytose pathogen and migrate to lymph node

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6
Q

3 things needed for T cell activation

A
  1. APC cell presents antigen on MHC II, binds to toll-like receptor
  2. Co activation by B7 (or CD80/86) binding to CD28 receptor
  3. Presence of IL-2 for proliferation
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7
Q

What do activated CD4+ T helper cells do?

A

Release more IL-2 and other cytokines to help proliferation of CD8 cytotoxic T cells

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8
Q

What do activated CD8+ cytotoxic T cells do?

A

Kill cells expressing the antigen on MHC I

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9
Q

What general things would you expect to see in CSF of a patient with meningitus?

A

Decreased glucose
Cloudy (due to leukocytes)
Increased intracranial pressure

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10
Q

What would you expect to see in a CSF sample taken from a patient with bacterial meningitus?

A

High neutrophils

High protein

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11
Q

What would you expect to see in a CSF sample taken from a patient with viral meningitus?

A
High lymphocytes (T and B cells)
Low protein
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12
Q

What would you expect to see in a CSF sample taken from a patient with parasitic meningitus?

A

High eosinophils

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13
Q

If viral meningitus is suspected, what further tests could be done?

A

PCR

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14
Q

If bacterial meningitus is suspected, what further tests could be done?

A

Gram stain
Purple = gram pos bacteria
Pink = gram neg bacteria

Or a blood culture to see if any bacterial cultures grow

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15
Q

What are the ligands of JAK/STAT receptors?

A
Cytokines (IFNy, IFN-a, IFN-b, IL-2)
EPO
Growth hormone
Prolactin
Leptin
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16
Q

What does JAK/STAT signalling initate?

A

Processes such as immunity (iNOS, APPs)
Cell division
Cell death
Tumour formation (Myc)

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17
Q

Process of JAK/STAT receptor signalling

A

Ligand binds to receptor
Two receptors dimerise which activates JAK
JAK phosphorylates tyrosine residues on receptors
Phosphorylated receptors attract SH2 domain on STAT
JAK phosphorylates STAT
Two STATs dimerise
Translocate to nucleus to transcribe genes

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18
Q

How is JAK/STAT signalling regulated?

A

STAT transcribes gene for SOCS
‘Suppressor of cytokine signalling’
Inactivates JAK
Causes negative feedback

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19
Q

What is sepsis?

A

An infection triggers the body’s immune response, which starts to damage the body’s own tissues

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20
Q

What is septic shock?

A

Sepsis causes extremely low blood pressure, that does not improve with IV fluids

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21
Q

What is severe sepsis?

A

Insufficient blood supply to organs, which can lead to organ failure

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22
Q

What are PAMPs?

A

Pathogen Associated Molecular Patterns
Exogenous molecules present on all pathogens
Recognised by PRRs (Pathogen recognition receptors)

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23
Q

What is the PAMP/PRR combination for gram negative bacteria?

A
PAMP = lipopolysaccharides
PRR = toll like receptor 4
24
Q

What is the PAMP/PRR combination for gram positive bacteria?

A
PAMP = lipoteichoic acid (LTA)
PRR = toll like receptor 2
25
Q

What PAMP can be present on both gram pos and neg bacteria, and what is its PRR?

A
PAMP = Peptidoglycans
PRR = toll like receptor 2
26
Q

What does PRR activation lead to?

A

NFkB signalling

27
Q

Which immune cells have PRRs?

A

Macrophages
Neutrophils
NK cells

28
Q

What is NFkB signalling?

A

NFkB is a transcription factor
Normally inhibited by the IkB inhibitor
IkB inhibitor can be removed by the IkB Kinase (IKK)
IKK phosphorylates IkB, marking it for ubiquitylation

29
Q

What initiates activation of the IKK?

A

PRR activation
JAK/STAT receptors
Cytokine receptors

30
Q

What 4 things initiate the arachidonic acid pathway by activation of phospholipase A?

A

Kinin
C5a
Thrombin
Cell damage

31
Q

What are the products of NFkB signalling?

A
Proinflammatory cytokines
Pro-oxidants
Antioxidants
Adhesion proteins (ICAM-1)
Coagulation factors (e.g. tissue factor)
32
Q

An example of an antioxidant and how it works

A

SOD - Superoxide Dismutases

Catalyses conversion of the superoxide ion (O2-) into hydrogen peroxide (H2O2)

33
Q

Examples of pro-oxidants

A

iNOS, NADPH Oxidase, COX-2

34
Q

How is NFkB signalling regulated?

A

NFkB transcription factors transcribes gene for IkB inhibitor, for negative feedback

35
Q

How do phagocytes kill pathogens using ROS?

A

Phagocytosis of pathogen into phagosome
Phagosome fuses with lyososome
Fusion activates myeloperoxidase (MPO)
MPO catalyses formation of hypochlorus acid (HOCl) from hydrogen peroxide (H2O2) and chloride ions

36
Q

What are APPs?

A

Acute phase proteins
Produced by liver
Plasma concentration increases in response to inflammation

37
Q

Examples of APPs

A
C-reactive protein
Fibrinogen
Complement protein C3
Serum Amyloid protein (opsonin)
Mannose binding lectin (opsonin)
Haptoglobulin
38
Q

What is c-reactive protein and what does it do?

A

Non-specific biomarker of inflammation

Binds to phosphorylcholine on bacteria to fix complement and promote phagocytosis

39
Q

Challenges of vaccine production

A

Pathogens can frequently mutate and become resistant to the vaccine
Animal models cannot be used to develop vaccines for diseases that only occur in humans

40
Q

What are the 5 groups of cytokines?

A
Interleukins
Interferons 
TNF (tumour necrosis factors)
Lymphokines
Chemokines
41
Q

What are monokines?

A

Cytokines released from mononucleus cells, such as macrophages and monocytes

42
Q

What are defensins?

A

Cationic (positively charged) proteins that can form ion pores in cell membranes

43
Q

What is the difference between COX-1 and COX-2?

A

COX-2 is specifically produced during inflammation
COX-1 is constitutively produced, causes production of gastric mucous
Specific COX-2 inhibits have fewer GI effects

44
Q

Where is MHC I and MHC II present?

A

MHC I on cell surface of all nucleated cells

MHC II on APC

45
Q

Which is the only anti-inflammatory cytokine?

A

IL-10

46
Q

What is the missing self hypothesis?

A

NK cells kills cells that aren’t expressing MHC I

Kill cells using perforin and granzymes

47
Q

How does NO kill pathogens?

A

Inhibits viral replication

Binds to iron, preventing bacteria from using it

48
Q

What are alarmins?

A

Endogenous molecules released after tissue damage
Perpetuate non-infectious inflammatory responses
Also known as DAMPs (Damage associated molecular patterns)

49
Q

What are commensal microorganisms?

A

Doesn’t cause harm to health or benefit

Cover epithelial surfaces such as respiratory tract and GI tract

50
Q

Which commensal microorganism can be the cause of bacterial meningitis?

A

Neisseria Meningitidis
Gram negative
Diplococcus (round, forms pairs)
Causes meningitus B and C, and septicaemia

Also staphylococcus aureus
Gram positive

51
Q

Through which G-protein subunit do prostaglandins signal through?

A

Gq

52
Q

What is an attenuated vaccine? And example

A

Pathogen is alive but attenuated so not as pathogenic

e.g. MMR

53
Q

What is a conjugate vaccine? And example

A

Bacterial polysaccharide conjugated to a toxoid

e.g. Men C, HPV

54
Q

What is a subunit vaccine? And example and a disadvantage

A

Just contains antigen subunits
e.g. Men B
Can be time consuming and expensive to identify best subunits to use

55
Q

What is a disadvantage of an inactivated vaccine? And example

A

Tend to require boosters

e.g. Polio

56
Q

What is a toxoid vaccine?

Give an example of one and a disadvantage

A

Contains toxins that have been detoxified
e.g. Tetanus
Only useful when toxins are cause of the disease