Topic 1: Maternal Immune Activation

Question 1

describe the first few weeks’ of pregnancy proinflammatory immune response

Answer 1

around Day 6: the blastocyst attaches to the endometrium to commence implantation. maternal tissue, the endometrium is transformed into a specialised tissue called decidua, which is the infiltrated by maternal immune cells. here, the uterus is populated predominantly by innate immune cells.
the syncytiotrophoblast is the outermost layer of the placenta in direct contact with the maternal decidua, expresses no HLA (this would facillitate its rejection). it also secretes cytokines to communicate with the immune cells in the decidua. the placental-decidua crosstalk via immune molecules is crucial for implantation, placentation, and uterine remodeling

Question 2

describe the immune response during pregnancy

Answer 2

for the longest part of gestation (late first to early third trimester) there is an anti-inflammatory phenotype. there is increased activity of the complement system and monocytes, and a reduction in T and B cells (adaptive immunity), a heightened immune response in this period can be detrimental to the mother and fetus and is associated with placental disorders and miscarriage

Question 3

describe the immune response during late pregnancy and labour

Answer 3

towards the end of a healthy pregnancy there is another surge of pro-inflammatory response. his increased immune activity is important for labour and childbirth, cytokines including IL-6 are crucial for initiating childbirth

Question 4

list the effects of IL-6 in vitro on neurons

Answer 4

promotes neuronal diferentiation, growth, and survival
induces death in 5-HT neurons
actvates microglia

Question 5

describe the IL-6 signalling pathway

Answer 5

IL-6 binds to its receptor, forming a homodimer.
gp130 coreceptors are recruited and are bound to JAK1/JAK2.
JAK1 and JAK2 transphosphorylate each other
pJAK1/pJAK2 will phosphorylate their respective gp130 proteins.
this recruits STAT3 to p-gp130.
STAT3 is phosphorylated at Tyr705 by pJAK1/2
pSTAT3 dissociates from the receptor complex and dimerizes, translocating to the nucelus. pSTAT3 acts as a transcription facotr and enhances the expression of target genes

Question 6

what did IL-17 injection promote in mice

Answer 6

sociability

Question 7

Which cytokine is elevated in circulation of people with ASD?

Answer 7

IL-17

Question 8

Describe the IL-17 pathway

Answer 8

IL-17 is produced upstream of IL-6.
IL-17 binds to its receptor
corecetpor Act1 will ubiquitinate Traf6
ub+Traf6 will ubiquitinate NF-kB inducing expression of target genes