Slide 222 – Pregnancy and the immune system
Pregnancy otherwise known as gestation consists of 3 trimesters:
3 trimesters: 1st – week 1-12 (high lipid accumulation + glucose tolerance)
2nd – week 13-26 (medium LP, GT, L and IR)
3rd – week 27- end (high lipolysis + insulin resistance)
There are 4 key immunological changes:
- Shift change to TH2 type immunity in the periphery
- Increase in Treg/ TH17 ratio
- Suppression of cytotoxic T (CD8+) and NK (natural killer) cells
- Increased innate immunity: more activated granulocytes and monocytes
Adverse pregnancy outcomes:
- Gestational diabetes mellitus (GDM)
- Obstetric cholestasis
- Preeclampsia
- Increased risk of severe diabetes with flu e.g., SARS-CoV-2
Monocyte RECAP:
-Originate from hematopoietic stem cells in bone marrow
-Account for 5-10% of circulating leukocytes (WBC)
-Have several roles: phagocytosis, antigen presentation, inflammation immunological
homeostasis and cytokine production.
-Half life of 1-2 days.
-3 subsets: Classical (CD14++ CD16-) 90-95% of monocytes, inflammatory effectors
Intermediate (CD14+ + CD16+) <1%, inflammatory effectors
Non-classical (CD14 + CD16+) 5-10%, CX3CR1 receptor, anti-viral function.
M1 Function: pro-inflammatory, microbicidal, tumoricidal
M2 Function: anti-inflammatory, phagocytosis, angiogenesis, tissue repair
Maternal foetal Interface:
- Fetal derived placenta
- Maternal derived decidua
- Connected by extra villous cytotrophoblasts
- Decidual macrophages (maternal)
- Placental macrophages (Hoffbauer; fetal)
Non pregnant uterine macrophages- heterogenous, diverse, adaptive
Pregnant decidual macrophages – peri-implantation period: M1, establishment of placentalfetal blood supply (M1+M2), source of IL-10
Roles of decidual macrophages:
-
EVT
Remodelling of the uterine muscles, glands and spiral arteries
Secrete immunomodulatory molecules (IL-10, PGE2, TGFβ, IDO)
Prevent maternal t cell activation
Slide 222 – Pregnancy and the immune system
Placental macrophages – observed before fetal circulation is established (18th day)
-Derived from mesenchymal cells
-pro-angiogenic
- reservoir for ZIKV and other viruses
-Last two trimesters – anti-inflammatory
-IL-18, TNFα, CCL2, CXCL10, IL-6 – decrease
-IL-1RA, sTNFR – increase
-More activated CD14, CD64, CD11b
-increased TNF⍺ and IL-1β can cause premature labour
-produce more oxygen free radicals
-Decreased phagocytosis
-Conflicting data on cytokine production
- Increased non-classical monocytes
Preeclampsia: complication in 2nd trimester
- Hypertention & proteinuria
- Early onset - poor placentation
Peripheral monocytes in preeclampsia – increase in CD11b, ICAM-1, CD14, TLR4
-increased reactive oxygen species
-increased intermediate monocytes
Increased soluble factors from fetal placenta
Increased M1, decreased M2
ZIKV
-
Mosquito borne
Outbreaks is suitable weather
Mild and non-harmful infection mostly
Sexually transmitted
More serious for pregnant women – microcephaly, brain defects
Mechanism is unclear – can cause placental insufficiency
ZIKV neurotropism observed – mice models
Changes CD14 to CD16