GBS

Question 1

Intra-uterin infection scenarios?

Answer 1

Ascending (lower genital tract microbiota to the uterine cavity)
Hematogenous route

Question 2

GBS progression

Answer 2

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!)

Question 3

What other bacteria isolated in choriaomnionitis?

Answer 3

mycoplasmas Ureaplasma urealyticum and Mycoplasma hominis - 67%
Gram-positive GBS (15%) and the Gram-negative E. coli (8%)

Question 4

Why not study mycoplasmas then?

Answer 4

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

Question 5

Factors associated with GBS colonisation

Answer 5

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

Question 6

Is GBS more asymptomatic during pregnancy?

Answer 6

Yes

Question 7

How does GBS invade and become part of the vaginal microbiota?

Answer 7

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

Question 8

how many variants of GBS?

Answer 8

10 serotypes
Ia and Ib most freq detected in pregnancy

Question 9

What is GBS neonatal early-onset infection vs late-onset infection?

Answer 9

Early: within 6 days, pneumonia/respiratory distress
Late: 7-90 days, bacteremia, high risk of meningitis

Question 10

Explain tx for GBS

Answer 10

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

Question 11

What is clinical chorio

Answer 11

Present of clinical symptons like maternal fever, tachycardia, preterm rupture of membranes

Question 12

What is histologic chorio

Answer 12

infiltration of PMN into chorioamniotic membranes, most abundant leukocyte present in amnionitic cavity during infection

Question 13

PMN fetal or maternal origin?

Answer 13

maternal will migrate from decidua to chorion and amnion (First responder)
placental chorionic plate/umbilical cord - fetal origin

Question 14

GBS recognised by immune system how?

Answer 14

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)

Question 15

What is FIRS?

Answer 15

Inflammatory molecules (fetal/maternal) transfer to developing fetus via bloodstream –> cardiac/renal dysfunction, pulmonary injury, dematitis, gut injury, neuroinflamm

Question 16

GBS acts through which TLR

Answer 16

TLR 2 and 6

Question 17

Examples of PAMPs on GBS surface

Answer 17

lipoteichoic acid, lipoproteins, peptidoglycan, and β-hemolysin

Question 18

PAMPS can interact with what?

Answer 18

TLR, integrins (CD11b/CD18), NOD-liek receptors

Question 19

What happens after cascades?

Answer 19

Robust release of proinflammatory ctyokines, chemokines attracting PMN, PMN infiltration and activation, prostaglandin and MMP synthesis

Question 20

What is IL1b amplification loop?

Answer 20

PMN can release it directly too

Question 21

What are NETs?

Answer 21

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.

Question 22

Composition of NETs?

Answer 22

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.

Question 23

What are the alarmins?

Answer 23

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).

Question 24

Example of antiinflammatory cytokine

Answer 24

IL-10
inhibits the production of cehmokine, PMNs

Question 25

what are MMPs?

Answer 25

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.

Question 26

which phagocytes msotely producing IL1b

Answer 26

82% PMN
7% mac

Question 27

Explain once GBS binds to TLR

Answer 27

Activate intracellular signaling pathway, requiring adaptor protein MyD88, leads to nuclear translocation of NF-kb –> transcription of a number of proinflammatory genes

Question 28

are cytokines mostly autocrine, paracrine or endocrine?

Answer 28

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.

Question 29

purpose of chemokines

Answer 29

process called chemotaxis, speed and direction controlled by concentration gradient of signaling molecules
clearing of infection, amplifies the responst

Question 30

how does GBS invade

Answer 30

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 antimicrobial peptide

Question 31

causes of chorioamnionitis?

Answer 31

• 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