MENINGITIS Flashcards
What are the leading causes of bacterial meningitis and the vaccines availsble for each
Meningococcus- Neisseria meningitis
Streptococcus pneumoniae
Group B strep
niesseria - MenB (men need to be nicer)
pneumoniae is PCV13
How does meningococcus evade the immune system
polysaccharise capsule
factor H binding protein
superoxide dismutase inactivates ROS
How does strep pneumoniae avoid the immune system
polysaccharide capsule
neuraminidase
IgA protease
pneumolysin
How does strep b avoid the immune system
polysaccharide capsule
ScpB (C5a peptidase)
IgA protease
Sod a
Nuclease A (degrades NETs)
How are reverse vaccines made
genome based approach
antigens (including humoura antibody responses) are located in extracellular or outer membranes of the pathogen
Describe how S.pyogenes aka step A
Asymptomatic carriage by 20-40% of schoolchildren.
Non-invasive infection manifests as pharyngitis or strep throat.
Can in some individuals progress to scarlet fever (systemic complications) where it produces Streptococcal pyrogenic exotoxins A, B, and C(Spe) aka superantigens which can induce inflammation.
If unchecked, can result in immune sequelae where responses against toxins such as result in autoimmune responses resulting in rheumatic heart disease and glomerular nephritis. E.g. streptococcal M protein structurally mimics cardiac myosin
Also the potential for invasive infection such as necrotising fasciitis seen in an estimated 650.000 cases yr worldwide.
AYMPTOMATCI CARRIAGE
NON INVASIVE INFECTION PHARYNGITIS, STEP THROAT
SYSTEMATIC COMPLICATION SCARLET FEVER
IMMUNE SEQUELAE - RHEMUATIC HEART DISEASE GLOMERULONEPHRITIS
INVASIVE INFECTION- NECROTISING FACIITIS
What does necrotising faciitis do
Infection destroying deep soft tissues
SUrgical debridement of necrotic tissue and borad spectrum ABs
24-34% die
How can you assay for levels of interleukin
ELISA
western blot
ihc
Assess the effects of a protease
SDS-PAGE analysis of the IL digested with the strain
Mass spectromotry
What gene encoding SpyCEp is upregulated in strains associated with necrotising faciitis
cepA encoding SpyCEP
(serine protease similar to S8, D151, H279, S617
LPXTG is the cell wall anchoring
How can you tell SpyCEP is responsible for necrotising disease
knock in and knock out strains of GAS
Invasive strains of what group of steptococcus produce SpyCEP and how does SpyCEP work
Gropu A step
cleaves CXCL8, stops neutrophil recruitment
Targeting what gene that affects SpyCEP is beneficial to impair GAS survival and stop spread to regional lymph nodes
cepA
What is Km. Kcat and Vmax
Km- conc of a substrate at which a particular enzymes works at half it max velocuty. is half Vmax
Kcat= number of substrate molecules processed per min
low Km vs high Km means what for enzyme substrate bidning
low= tight
high = loose