reproductive immunology Flashcards

- Define the maternal foetal interface. - Describe the role of maternal immune system in regulation of key events in pregnancy. - Understand the cellular and humoral immune mechanisms allowing for the maternal tolerance of foetal tissues.

1
Q

what does the success of pregnancy depend on?

A

depends on ability of maternal immune system to change and adapt in each developmental stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Immune system activation during the journey of pregnancy

what are the three developmental stages?

A
  1. Periovulation stage
  2. after coitus (intercourse)
  3. during pregnancy (first, second and third trimesters)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Immune system activation during the journey of pregnancy - Periovulation

what uterus layer contains the greatest abundance of immune cells and what parts of the menstrual cycle does this increase and why?

for why, think cytokine and chemokines

A
  • endometrial layer
  • increases in proliferative and periovulatory phases
  • due to influx of leukocytes in response to ovarian hormone regulated chemokine + cytokine expression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Immune system activation during the journey of pregnancy - after coitus

after coitus, what induces a proinflammartory response in the ectocervix?

think seminal fluid and antigens

A

seminal fluid containing:
* paternal alloantigens
* soluble and sperm-associated immune regulatory factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Immune system activation during the journey of pregnancy - after coitus

what does local release of cytokines and chemokines do?

think WBCs

A

causes:

  • recruitment of immune cells into local environment
  • primes treg cells and other Leukocytes into the uterine endometrium from the ectocervix
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Immune system activation during the journey of pregnancy - during Preg.

what type of stages are the 1st-3rd trimester in terms of inflammation

1st = implantatoin and placentation
2nd = fetal growth
3rd = labour

A

1st: pro-inflammatory stage
2nd: anti-inflammatory stage
3rd: pro-inflammatory stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Immune system activation during the journey of pregnancy - during preg.

what 3 ways can implantation be divided into

A

apposition
adhesion/attachment
invasion/penetration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

First trimester immunology

what happens in apposition phase in implantation

think blastocyst

A
  • blastocyst expresses L-selectins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

First trimester immunology

what happens in adhesion phase in implantation

think blastocyst and ensuring successful attachment

A

blastocyst promotes cleavage of MUC-1 at the implantation site to ensure successful attachment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

First trimester immunology

what supports the embryo-endometrial interactions?

think cytokines

A

Leukemia inhibitory factor (LIF)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

First trimester immunology

what happens in invasion/penetration phase of implantation

think trophoblast cells and epitheliums

A

trophoblast cells from blastocyst penetrate endometrial epithelium into stroma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

First trimester immunology

what happens once embryo breaches the luminal epithelium?

think stromal cells

A

stromal cells surrounding the embryo transform into decidualized cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

First trimester immunology

why are immune cells recruited to the decidua in implantation

A

specifically recruited to facilitate proper implantation and promote successful pregnancy (NOT due to foreign bodies)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

THE MATERNAL-FETAL INTERFACE

what is the materal fetal interface composed of

A
  • maternal decidua
  • placental trophoblasts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

THE MATERNAL-FETAL INTERFACE

what is the unique, time-limited function

think development and protection from injury

A

to nourish and suppport developlment of semi allogeneic fetus and protect from inflammatory or immune-mediated injury

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Decidua formation

what happens during decidualization and why?

for what happens, think arteries
for why, think gaseous exchange

A
  • fetal and maternal mediated remodeling of spiral arteries
  • this is so placenta becomes bathed in maternal blood to facilitate exchange of nutrients, gases and waste
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Decidua formation

what do maternal leukocytes do in the remodelling process in tandem with fetal trophoblasts?

think arteries and placenta

A

dilation of spiral arteries to decrease force and maximum volume of maternal blood bathing placenta

18
Q

Uterine Natural killer cells (UNK)

what do the unique phenotypes CD56bright and CD16-neg of uNKs mean for the uNK?

A

means they have low cytotoxicity and induce Treg generation

19
Q

Uterine Natural killer cells (UNK)

what are uNK cells a potent source of?

A

immunoregulatory cytokines which help in angiogenesis

20
Q

Uterine Natural killer cells (UNK)

why don’t uNK cells not reject the fetus?

think cytolytic acton and MHC I interaction with trophoblast cells

A
  • uNK cytolytic action is at baseline
  • non-classical MHC I molecule interaction on trophoblast cell
21
Q

decidual macrophages

what do decidual macrophages help with

think spiral artery and producing factors

A
  • early spiral artery remodelling by producing factors associated with:
    -tissue remodelling
    -matrix metalloproteinases and
    angiogenesis
22
Q

decidual macrophages

what do decidual macrophages phagocytose?

think cells in vascular wall

A
  • phagocytose apopototic cells in remodeled vascular wall and apoptotic trophoblasts
23
Q

decidual macrophages

what is responsible for inhibition of human uNK cell-mediated lysis of invasive cytotrophoblast?

think growth factor secretion

A

secretion of transforming growth factor-beta-1 (TGF-B1) by decidual macrophages

24
Q

Dendritic cells (DCs)

what is the 2 roles of dendritic cells in blastocyt implantation?

think: secretion of factors and faciliating attachment of embryo

for 2, think tolerance

A
  1. DCs secrete factors that remove mucin layer of surface epithelium of uterus, exposing adhesion molecules that can facilitate attachment of embryo
  2. promotes tolerance to paternal antigens
25
Q

Regulatory T cells (Treg cells)

what is the function of Treg cells

then paternal antigens and maternal immune system

A

to protect fetal cells that express paternal antigens from rejection by maternal immune system

26
Q

Regulatory T cells (Treg cells)

why do Treg cells indicate memory-type regulatory response?

A

this is because Treg cells persist after delivery adn rapidly accumulate during subsequent pregnancies

27
Q

2nd trim : anti-inflammatory stage : TH2-type tissue environment

how do Th2 cells play role in anti-inflammatory process?

A

they secret IL-4, IL-5 and IL-10

28
Q

2nd trim : anti-inflammatory stage : TH2-type tissue environment

what do Th17 cells do?

A

help to protect maternal-fetal interface from microbial infection

(TH17 cell function regulated by Treg)

29
Q

3rd trimester : A pro-inflammatory switch necessary for labour

what signalling pathway is initates labour/delivery

A

the NF-kB pathway

30
Q

3rd trimester : A pro-inflammatory switch necessary for labour

what receptor activates the NF-kB pathway?

A

Toll-like receptor 4 (TLR4)

31
Q

Hypotheses/concepts to explain maternal tolerance of the fetus

what are 4 concepts that could explain why there is maternal tolerance of the fetus

think HLA, Th1, T regulatory cells and other factors

A
  1. HLA/HLA-G expression by trophoblast
  2. The Th1/Th2 balance
  3. Regulatory CD4+/CD25+ T cells
  4. other factors like LIF, suppressor macrophages and hormones
32
Q

HLA expression by the trophoblast

what actually expresses HLA/HLA-G

A

extravillous trophoblasts

NOTE, does NOT express HLA-A, HLA-B or MHC class II molecules

33
Q

HLA expression by the trophoblast

what does HLA-E on trophoblast do?

think CD94 on uNK

A
  • binds to receptor CD94/NKG2A on uNK cells to prevent lysis of tissue cells
34
Q

HLA expression by the trophoblast

what does HLA-G do on trophoblasts

think secretion and different factors

A

binds to ILT2 expressed by uNK and increases secretion of inflammatory and proangiogenic factors

35
Q

HLA expression by the trophoblast

what does KIR do?

think HLA-G

A

binds to HLA-G to reduce cytotoxic function of uNK cell

36
Q

Other tolerance factors

how do APCs play a role in vascular remodelling

APCs = antigen presenting cells

think inhibitory receptors and induction of molecules

A

express inhibitory receptors like ILT2 and ILT4 for HLA-G on trophoblasts, and once they bind together it leads to the induction of anti-inflammatory cytokines & tolerance to trophoblast

37
Q

Other tolerance factors

how do APCs play role in interaction of NK and T cells in decidua

think differentiation of cells and IL-15

A

APCs induce differentiation of endometrial NK cells into activated dNK cells via production of IL-15

dNK = decidua natural killer cells

38
Q

Other tolerance factors

how do APCs interact with dNK cells?

think DC-sign, IFNy and IDO production

A

via DC-sign/ICAM-3, leading to dNK to release IFNy which upregulates IDO production in APCs, leading to immune supression

39
Q

Toll Like Receptors (TLRs)

what percentage of preterm birth cases is caused by bacterial infection

A

40%

40
Q

Viral infection abolishes beneficial effects of commensal microbiota

what can viral infection do leading to preterm labour?

think IFNB

A

can abolish IFNB signalling pathway and it immunomodulatory effects