Immunology of Pregnancy III Flashcards
What contributes to increased inflammation in Pre-eclampsia ?
- Reduced [T reg]
- Circulating syncytiotrophoblast microfragments (STBMs) are
increased - STBMs from preeclamptic women increase superoxide anion in leukocytes
- STBMs linked to endothelial dysfunction and maternal symptoms of preeclampsia
What characterizes Pre-eclampsia ?
Hypertension, proteinuria, end organ damage
Factors contributing to Pre-eclampsia
- Anti-angiogenic response
- Abnormal trophoblast invasion = poor spiral artery remodelling
- Oxygen disruption = increased placental oxidative stress
- Altered immune response
How does an altered immune response contribute to Pre-eclampsia ?
- increased inflammatory (IL-6, TNF-a) and decreased (IL-10) cytokines
- reduced T regs
- increased Circulating syncytiotrophoblast microfragments (STBMs) = increased superoxides in leukocytes
Rheumatoid arthritis
- Autoimmune disease involving Th1 and Th2
- Initiated by CD4+ T cells
= Systemic inflammatory disease
= Chronic inflammation of joints and surrounding tissues
2 pathways of rheumatoid arthritis
Self-antigen presented by APC via MHC II
- Cell-mediated:
- activated CD4+ T cell = IFNy
- macrophage = TNFa, IL-1, IL-6 - Humoral mediated
- activated CD4+ T cell = IL-4 and IL-10
- B cell = rheumatoid factor
= immune complexes activate macrophages
= Complement activation
NOTE: both result in cartilage and bone damage
Rheumatoid arthritis in pregnancy
- Affects specific immunity: extent of improvement correlates to HLA incompatibility
- Increased numbers of Tregs and levels of IL-10 in third trimester were associated with amelioration of symptoms
- Postpartum flares
APS + Treatment
Anti-phospholipid syndrome:
- caused by an autoimmune response to phospholipids
(aPL) such as cardiolipin
= increased blood clots especially in high risk populations
= recurrent miscarriages in 2nd and 3rd trimesters
Preventative Treatment:
blood thinners, heparin or low-dose aspirin
Pathogenesis of APS and recurrent miscarriages
- aPL may interact with platelets and cause microvascular thrombosis
— APS is reduced by anticoagulant therapy (low-dose aspirin and
heparin) - aPLs bind to cytotrophoblasts
— Inhibit release of human chorionic gonadotropin
— Inhibit trophoblast proliferation
— Reduce integrin expression by trophoblasts – prevents
trophoblast invasion into uterine wall
aPL = Anti-phospholipid
What kind of immune response is needed against viruses ?
Cell-mediated
- viruses have to be inside cells to replicate
Influenza and pregnancy
- pregnancy increases risk for disease, hospitalization and death
- increased preterm birth, intrauterine growth restriction and fetal death
COVID-19 and Pregnancy
- increased ICU admission, gestational diabetes, pre-eclampsia, C-sections, preterm birth and increased CRP
- rarely transmitted through BUT does cause damage to placenta
Importance of IFNs for a balanced anti-viral response
- Infected cell produces IFN-B = anti-viral state in surrounding cells
- IFN-B increases CCL2 = inflammatory monocyte and NK cell recruitment
- Monocytes make IL-18 = NK produce IFNy
- IFNy = increased IFNa and B
- All IFNs increase APC Ag presentation = stimulates Th1 adaptive response
- IFNs control inflammatory responses by ILC2 immune cells
What happens when IFNs are reduced/ non-functional during a COVID-19 infection ?
- uncontrolled virus replication and inflammatory response
= hyper inflammation = cytokine storm
Should pregnant mothers be vaccinated for influenza and COVID ?
YES; yearly influenza vaccine reduced risk of stillbirths and prematurity
