Maternal Immune Activation Flashcards

1
Q

Which immune cells dominate the uterus in early pregnancy?

A

Innate

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2
Q

What type of inflammatory response is there in the first few weeks of pregnancy?

A

Pro-inflammatory

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3
Q

Describe a healthy maternal immune system during pregnancy

A

Pregnancy involves complex changes to the maternal immune system that can be categorised into 3 stages
1. Initially pro inflammatory for the first few weeks
2. For the longest part of gestation (the late 1st to early 3rd trimester), in general, there is an anti-inflammatory phenotype
3. Towards the end of a healthy pregnancy, there is another pro-inflammatory response

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4
Q

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

A

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

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5
Q

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

A

it is key in preparing the body for labour and childbirth

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6
Q

what cytokine is particularly important for triggering childbirth

A

IL-6

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7
Q

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

A

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

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8
Q

what increases the risk of ASD

A

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

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9
Q

vertical transmission of pathogens?

A

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

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10
Q

acronym TORCH

A

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

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11
Q

viruses that have a high degree of neurotropism

A

HSV and Zika virus affect neurodevelopment directly

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12
Q

maternal immune activation?

A

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

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13
Q

How to to induce MIA in animals

A

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)

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14
Q

what does early prenatal LPS exposure do in rats?

A

It alters reward seeking behaviour

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15
Q

what does late prenatal exposure to LPS do in rats?

A

Motor defects

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16
Q

what effect does poly IC exposure in mice have?

A

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

17
Q

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

A

MIA increases microglial activity and affects cortical cytoarchitechture and neural activity

18
Q

what is the cytokine hypothesis of Neurodevelopmental Disorders

A

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

19
Q

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

A

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

20
Q

What does IL-6 promote?

A

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

21
Q

What is elevated levels of maternal IL-6 associated with?

A

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

22
Q

Describe IL-6 signaling

A

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

23
Q

Another cytokine observed in increased levels in MIA in maternal circulation and the fetal brain?

A

IL-17

24
Q

Describe IL-17 signalling

A

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

25
Q

Risk factors for maternal obesity

A

Chronic stress
Genetics
High caloric diets
Lack of physical activity