Sepsis Flashcards

(56 cards)

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
What PAMP can be present on both gram pos and neg bacteria, and what is its PRR?
``` PAMP = Peptidoglycans PRR = toll like receptor 2 ```
26
What does PRR activation lead to?
NFkB signalling
27
Which immune cells have PRRs?
Macrophages Neutrophils NK cells
28
What is NFkB signalling?
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
What initiates activation of the IKK?
PRR activation JAK/STAT receptors Cytokine receptors
30
What 4 things initiate the arachidonic acid pathway by activation of phospholipase A?
Kinin C5a Thrombin Cell damage
31
What are the products of NFkB signalling?
``` Proinflammatory cytokines Pro-oxidants Antioxidants Adhesion proteins (ICAM-1) Coagulation factors (e.g. tissue factor) ```
32
An example of an antioxidant and how it works
SOD - Superoxide Dismutases | Catalyses conversion of the superoxide ion (O2-) into hydrogen peroxide (H2O2)
33
Examples of pro-oxidants
iNOS, NADPH Oxidase, COX-2
34
How is NFkB signalling regulated?
NFkB transcription factors transcribes gene for IkB inhibitor, for negative feedback
35
How do phagocytes kill pathogens using ROS?
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
What are APPs?
Acute phase proteins Produced by liver Plasma concentration increases in response to inflammation
37
Examples of APPs
``` C-reactive protein Fibrinogen Complement protein C3 Serum Amyloid protein (opsonin) Mannose binding lectin (opsonin) Haptoglobulin ```
38
What is c-reactive protein and what does it do?
Non-specific biomarker of inflammation | Binds to phosphorylcholine on bacteria to fix complement and promote phagocytosis
39
Challenges of vaccine production
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
What are the 5 groups of cytokines?
``` Interleukins Interferons TNF (tumour necrosis factors) Lymphokines Chemokines ```
41
What are monokines?
Cytokines released from mononucleus cells, such as macrophages and monocytes
42
What are defensins?
Cationic (positively charged) proteins that can form ion pores in cell membranes
43
What is the difference between COX-1 and COX-2?
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
Where is MHC I and MHC II present?
MHC I on cell surface of all nucleated cells | MHC II on APC
45
Which is the only anti-inflammatory cytokine?
IL-10
46
What is the missing self hypothesis?
NK cells kills cells that aren't expressing MHC I | Kill cells using perforin and granzymes
47
How does NO kill pathogens?
Inhibits viral replication | Binds to iron, preventing bacteria from using it
48
What are alarmins?
Endogenous molecules released after tissue damage Perpetuate non-infectious inflammatory responses Also known as DAMPs (Damage associated molecular patterns)
49
What are commensal microorganisms?
Doesn't cause harm to health or benefit | Cover epithelial surfaces such as respiratory tract and GI tract
50
Which commensal microorganism can be the cause of bacterial meningitis?
Neisseria Meningitidis Gram negative Diplococcus (round, forms pairs) Causes meningitus B and C, and septicaemia Also staphylococcus aureus Gram positive
51
Through which G-protein subunit do prostaglandins signal through?
Gq
52
What is an attenuated vaccine? And example
Pathogen is alive but attenuated so not as pathogenic | e.g. MMR
53
What is a conjugate vaccine? And example
Bacterial polysaccharide conjugated to a toxoid | e.g. Men C, HPV
54
What is a subunit vaccine? And example and a disadvantage
Just contains antigen subunits e.g. Men B Can be time consuming and expensive to identify best subunits to use
55
What is a disadvantage of an inactivated vaccine? And example
Tend to require boosters | e.g. Polio
56
What is a toxoid vaccine? | Give an example of one and a disadvantage
Contains toxins that have been detoxified e.g. Tetanus Only useful when toxins are cause of the disease