GBS Flashcards
Intra-uterin infection scenarios?
Ascending (lower genital tract microbiota to the uterine cavity)
Hematogenous route
GBS progression
bacteria can migrate from the urogenital tract to the uterus (cervical breach)
colonise the uterine mucosa or decidua (deciduitis)
chorion and the amnion (chorioamnionitis)
umbilical cord (funisitis), the amniotic fluid and the developing fetus (more extreme!)
What other bacteria isolated in choriaomnionitis?
mycoplasmas Ureaplasma urealyticum and Mycoplasma hominis - 67%
Gram-positive GBS (15%) and the Gram-negative E. coli (8%)
Why not study mycoplasmas then?
Although both GBS and E. coli are the most frequent bacteria isolated from neonates with sepsis, e coli more for preterm birth
GBS is leading cause of neonatal infection
Factors associated with GBS colonisation
premature rupture of the membranes, gastrointestinal colonisation, the age of the mother (higher colonisation rate in women older than 40 years old), and neonatal sepsis
Is GBS more asymptomatic during pregnancy?
Yes
How does GBS invade and become part of the vaginal microbiota?
GBS interacts with other microorganisms in the vaginal tract, likely via niche competition and production of antimicrobial peptides.
GBS can adhere to luminal epithelial cells and surface proteins to establish a local niche and invade tissues. This process is facilitated by metallopeptidases cleaving the extracellular matrix proteins, surface adherence proteins of particular GBS serotypes, and the β-hemolysin/cytolysin toxin
how many variants of GBS?
10 serotypes
Ia and Ib most freq detected in pregnancy
What is GBS neonatal early-onset infection vs late-onset infection?
Early: within 6 days, pneumonia/respiratory distress
Late: 7-90 days, bacteremia, high risk of meningitis
Explain tx for GBS
swab bw 35-37 weeks pregnancy
nature of serotype not detected
+ve screen = intrapartum phrophylaxis / clindamycin at labour to protect vertical transmission during delivery, successful prevent early-onset BGS by 80%
BUT 60% early onset happened with a neg test result (could be diff routes, transient infection)
this tx does NOT treat placental inflammation
What is clinical chorio
Present of clinical symptons like maternal fever, tachycardia, preterm rupture of membranes
What is histologic chorio
infiltration of PMN into chorioamniotic membranes, most abundant leukocyte present in amnionitic cavity during infection
PMN fetal or maternal origin?
maternal will migrate from decidua to chorion and amnion (First responder)
placental chorionic plate/umbilical cord - fetal origin
GBS recognised by immune system how?
PAMPS recognized by TLR - leading to production of transcription factors like NF-kb –> release of pri inflammation cytokines, chemokines, MMPS –> inc cellular recruitment/activation (PMNs, macrophages)
What is FIRS?
Inflammatory molecules (fetal/maternal) transfer to developing fetus via bloodstream –> cardiac/renal dysfunction, pulmonary injury, dematitis, gut injury, neuroinflamm
GBS acts through which TLR
TLR 2 and 6
Examples of PAMPs on GBS surface
lipoteichoic acid, lipoproteins, peptidoglycan, and β-hemolysin
PAMPS can interact with what?
TLR, integrins (CD11b/CD18), NOD-liek receptors
What happens after cascades?
Robust release of proinflammatory ctyokines, chemokines attracting PMN, PMN infiltration and activation, prostaglandin and MMP synthesis
What is IL1b amplification loop?
PMN can release it directly too
What are NETs?
NETs are web-like structures formed by neutrophils during a process called NETosis.
Involves disassembly of the nuclear membrane, release of DNA, and expulsion of chromatin.
Composition of NETs?
PMNs DNA studded with:
Antimicrobial Proteins
elastase: Degrades bacterial proteins.
Myeloperoxidase: Produces reactive oxygen species (ROS) and hypochlorous acid.
Elastin: Supports tissue repair and antimicrobial activity.
Calprotectin heterodimer (S100A8/S100A9):
Lactoferrin: Binds iron, inhibiting bacterial growth.
What are the alarmins?
DAMPs, released by stressed or damaged cells
Calprotectin regulates the activation and antibacterial action of circulating polymorphonuclear neutrophils (PMNs) and monocytes.
Controls the adhesion of these myeloid cells to the endothelium (blood vessel lining) and extracellular matrix (supportive tissue structures).
Example of antiinflammatory cytokine
IL-10
inhibits the production of cehmokine, PMNs
what are MMPs?
matrix metalloproteinase
enzymes responsible for the degradation and remodeling of the extracellular matrix (ECM).ECM Remodeling: Facilitate tissue remodeling and repair.
Cell Migration: Allow cells to move during healing and development.
which phagocytes msotely producing IL1b
82% PMN
7% mac
Explain once GBS binds to TLR
Activate intracellular signaling pathway, requiring adaptor protein MyD88, leads to nuclear translocation of NF-kb –> transcription of a number of proinflammatory genes
are cytokines mostly autocrine, paracrine or endocrine?
mostly auto and paracrine
Autocrine: Neutrophils can produce and respond to their own cytokines, such as IL-8, which enhances their own activation and chemotaxis.
Paracrine: They release cytokines like IL-1 and TNF-α that act on nearby immune cells, recruiting more neutrophils and activating macrophages.
purpose of chemokines
process called chemotaxis, speed and direction controlled by concentration gradient of signaling molecules
clearing of infection, amplifies the responst
how does GBS invade
GBS can adhere to luminal epithelial cells and surface proteins to establish a local niche and invade tissues.
It interacts with vaginal epithelium and other bacteria colonising the genital tract by niche competitie and production of virulence factors like b hemolysin, surface proteins and enzymes that help it evade the host immune system
causes of chorioamnionitis?
- primary causes is upward transmission of bacteria , colonization of decidua, then chorion/amnion, rarely can be caused by invasive medical procedures/hematogenous transmission
- healthy vaginal microbiota has lactobacillus - dysbiosis develops when healthy amount of lactobasillus declines - so variety increases - can result in pregnancy issues
why use lewis rats in this study?
they are more susceptible to inlfammation, so allows us to study smaller changes in inflammation
for example an arthritis rat model compared effects on sprague dawley vs lewis and the lewis rats,
heat-killed Mycobacterium tuberculosis
inbred LEW rats developed much more severe and less variable AIA, at an incidence of 92% affliction with secondary polyarthritic signs, than the outbred Sprague–Dawley (SD) rats, which showed only a 60% incidence
why only screen at 35-7 week?
Transient - GBS colonization in the maternal genital and rectal tracts can change throughout pregnancy. A woman who tests positive earlier in pregnancy may no longer be colonized at delivery, and vice versa
Testing close to delivery (35–37 weeks) provides the most accurate prediction of GBS status during labor
