Maternal Immune Activation

Question 1

is there a pro or antiinflammatory response in the first few weeks of pregnancy?

Answer 1

proinflammatory response

Question 2

do innate or adaptive immune cells dominate the uterus in early pregnancy?

Answer 2

innate

Question 3

is there typically a pro or anti inflammatory response between late 1st and early 3rd trimester?

Answer 3

anti inflammatory response

Question 4

what effect does a heightened immune response have during the late 1st trimester to early 3rd trimester?

Answer 4

this can be detrimental to mother and fetus, can lead to placental disorders and miscarriage

Question 5

what is the role of the proinflammatory response towards the end of pregnancy?

Answer 5

it is key in preparing the body for labour and childbirth

Question 6

what cytokine is particularly important for triggering childbirth

Answer 6

IL-6

Question 7

Why is there an increased risk of schizophrenia if you are born in Spring?

Answer 7

this is because there is a higher risk of the mother contracting a seasonal flu/common cold virus during her pregnancy which can interfere with the dampened immune response optimal for late 1st to early 3rd trimester, particularly if infection occurs in second trimester

Question 8

what increases the risk of ASD

Answer 8

maternal hospitalisation due to infection increases the risk of ASD for the fetus

Question 9

what is vertical transmission of pathogens?

Answer 9

pathogens that can be transmitted directly from the mother to the fetus

Question 10

what is meant by the acronym TORCH

Answer 10

Vertically transmitted viruses: Toxoplasma gondii, other, rubella, CMV, HSV

Question 11

name viruses that have a high degree of neurotropism

Answer 11

HSV and Zika virus affect neurodevelopment directly

Question 12

what is maternal immune activation?

Answer 12

stimulation of a proinflammatory state by the mother’s immune system during pregnancy, occurs in response to infection and other stimuli, and certain maternall or gestational disorder

Question 13

name ways to induce MIA in animals

Answer 13

LPS (to mimic gram -ve infection like e. coli)
Poly IC (dsDNA to mimic viral infection like influenza)
Enterotoxins (mimic gram +ve bacteria like s. aureus)
transgenic animals (with receptors expressed in humans to mimic pathogens that are human-specific)

Question 14

what does early prenatal LPS exposure do in rats?

Answer 14

it alters reward seeking behaviour

Question 15

what does late prenatal exposure to LPS do in rats?

Answer 15

causes motor defects

Question 16

what effect does poly IC exposure in mice have?

Answer 16

causes dopamine and serotonin imbalances, similar to what is seen in schizophrenia

Question 17

MIA increases ___ ___ and affects ___ ___ and ___ activity in the brain of a prenatal mouse

Answer 17

MIA increases microglial activity and affects cortical cytoarchitechture and neural activity

Question 18

what is the cytokine hypothesis of Neurodevelopmental Disorders

Answer 18

that the increased risk of neurodevelopmental disorders caused by maternal infection is not due to the specific pathogen itself, but the MIA it induces and as a result, high levels of cytokines reaching the fetal brain

Question 19

what characteristics must cytokines produced in response to maternal infection have to cause neurodevelopmental disorders

Answer 19

cytokines must cross the placenta and the BBB
have been found in elevated conc in brains of offspring of MIA animal models
have potent effects on neurons in vitro

Question 20

other factors linked to neurodevelopmental changes in offspring in humans

Answer 20

high fat diet, pesticide exposure, air pollution
gestational disorders like pre-eclampsia and GDM
pre-existing autoimmune conditions like asthma and allergies
maternal cytokine CRP levels

Question 21

what does IL-6 promote

Answer 21

IL-6 promotes neuronal differentiation, growth, and survival, induces death in serotonin neurons, activates microglia

Question 22

what is elevated levels of maternal IL-6 associated with

Answer 22

elevated maternal IL-6 levels is associated with altered structural and functional connectivity in offspring

Question 23

describe IL-6 signalling

Answer 23

A JAK1/2-bound gp130 co-receptor is recruited to heterodimerise with IL-6Ralpha
JAK1 and JAK2 transphosphorylate
p-JAK1 and p-JAK2 phosphorylate their respective gp130 proteins
cytosolic STAT3 is recruited to each gp130
STAT3 is phosphorylated on tyr705 by pJAK1/2
p-STAT3 dissociates from receptor complex, dimerizes and translocates to nucleus
p-STAT3 dimer acts as a transcription factor, enhancing the expression of target genes

Question 24

name another cytokine that is seen in increased levels in MIA in maternal circulation and fetal brains

Answer 24

IL-17

Question 25

What does IL-17 injection do in mice?

Answer 25

it increases sociability in mice

Question 26

what is circulating elevated IL-17 associated with in humans?

Answer 26

ASD

Question 27

Describe IL-17 signalling

Answer 27

Uses adapter protein Act1
Act1 ubiquitinates Traf6
this activates NF-kB