Sepsis Flashcards
What are the possible causes of meningitus?
Also comment on how common and severity
Viral (most common, least severe)
Bacterial (least common, most severe)
Parasitic
Fungal
What is meningitus?
Inflammation of the meninges as the result of an infection that has spread into the subarachnoid space
Which two meninges is the subarachnoid space in between?
Arachnoid and pia mater
Mechanism of bacterial meningitus
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
Which type of cells cause initial T cell activation and how?
Dendritic cells
Phagocytose pathogen and migrate to lymph node
3 things needed for T cell activation
- APC cell presents antigen on MHC II, binds to toll-like receptor
- Co activation by B7 (or CD80/86) binding to CD28 receptor
- Presence of IL-2 for proliferation
What do activated CD4+ T helper cells do?
Release more IL-2 and other cytokines to help proliferation of CD8 cytotoxic T cells
What do activated CD8+ cytotoxic T cells do?
Kill cells expressing the antigen on MHC I
What general things would you expect to see in CSF of a patient with meningitus?
Decreased glucose
Cloudy (due to leukocytes)
Increased intracranial pressure
What would you expect to see in a CSF sample taken from a patient with bacterial meningitus?
High neutrophils
High protein
What would you expect to see in a CSF sample taken from a patient with viral meningitus?
High lymphocytes (T and B cells) Low protein
What would you expect to see in a CSF sample taken from a patient with parasitic meningitus?
High eosinophils
If viral meningitus is suspected, what further tests could be done?
PCR
If bacterial meningitus is suspected, what further tests could be done?
Gram stain
Purple = gram pos bacteria
Pink = gram neg bacteria
Or a blood culture to see if any bacterial cultures grow
What are the ligands of JAK/STAT receptors?
Cytokines (IFNy, IFN-a, IFN-b, IL-2) EPO Growth hormone Prolactin Leptin
What does JAK/STAT signalling initate?
Processes such as immunity (iNOS, APPs)
Cell division
Cell death
Tumour formation (Myc)
Process of JAK/STAT receptor signalling
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
How is JAK/STAT signalling regulated?
STAT transcribes gene for SOCS
‘Suppressor of cytokine signalling’
Inactivates JAK
Causes negative feedback
What is sepsis?
An infection triggers the body’s immune response, which starts to damage the body’s own tissues
What is septic shock?
Sepsis causes extremely low blood pressure, that does not improve with IV fluids
What is severe sepsis?
Insufficient blood supply to organs, which can lead to organ failure
What are PAMPs?
Pathogen Associated Molecular Patterns
Exogenous molecules present on all pathogens
Recognised by PRRs (Pathogen recognition receptors)