Block C - immunology of pregnancy 2 Flashcards
effect of progesterone on immune cells ?
Macrophages & dendritic cells accumulate after implantation around the decidua & in the uterus throughout pregnancy. This could be detrimental to pregnancy if they were to present foetal Ag to T cells, so current view is that they are suppressed, or tolerogenic. Pro-inflammatory functions are down-modulated by oestrogen & progesterone.
progesterone on IL-12 ?
Progesterone decrease Il-12 as it is associated with Th1 response which is associated with spontaneous abortion , P40 production in both macrophages and dendritic cells.
progesterone on T cells ?
Progesterone and oestrogen both favour the production of Th2 associated cytokines by T cells and inhibit the production of Th1 associated cytokines.
oestrogen on B cells ?
Oestrogen causes a reduction in pre-B cells and IL-7 responsive cells in the bone marrow. Progesterone (via Progesterone Induced Blocking Factor, PIBF) stimulates production of asymmetric antibodies. These are IgG molecules with altered structures which are ineffective at activating effector functions typically associated with antibodies (e.g., opsonization for phagocytosis and complement fixation). This protects foetus by acting as blocking antibodies. Higher levels of asymmetric antibodies exist in healthy pregnancy women than recurrent spontaneous abortions.
progesterone effect on decidual lymphocytes and NK cells?
Progesterone stimulates decidual lymphocytes to produce progesterone induced blocking factor(PIBF), this acts on Th2 cells to induce the production of Th2 associated cytokines such as IL-4, this can act on other cells with the receptor.
PIBF can also affect NK cells, is causes a reduction in the production of arachidonic acid, inhibition of IL-12 and reduced NK cell activity.
role of NK cells ?
NK cells are part of the innate immune system and are important in the early response to viruses. NK cells possess a range of activating & inhibitory receptors on their surface. Within the blood, two main types of NK cells have been characterised based on expression of CD56.
NK cells that are CD56+ dim ?
90% of blood NK cells are CD56+ dim which contain high lytic activity.
NK cells that are CD56+ bright ?
10% of blood NK cells are CD56+ bright which contain low lytic activity.
NK cells and pregnancy ?
NK cells are found in large numbers in the endometrium and decidua. Uterine NK cells have a unique phenotype compared to blood NK cells, due to the specific tissue environment in which they reside.
uterine NK cells comprise endometril leukocytes ?
Uterine NK cells (uNK ) comprise over 70% of the endometrial leukocytes in first trimester decidua, but are undetectable by term pregnancy.
function of uNK cells ?
They protect trophoblasts bearing paternal antigens from maternal immune system, protect mother from trophoblast invasion and limit trophoblast expansion. They regulate restructuring of maternal spiral arteries and protect the uterus against infection.
Women with recurrent pregnancy losses, infertility and assisted reproductive failure have significantly increased activated peripheral blood NK cells compared to normal fertile controls. Dosiou & Giudice (2005)
progesterone on nK cells?
In pregnancy, progesterone causes a decrease in peripheral NK cell numbers, activation and cytotoxicity via direct action on NK cells and/or through promoting Th2 cytokine and PIBF production by T cells. It also facilitates NK cell homing to the endometrium, via inducing expression of homing receptors and addressins on peripheral NK cells and the endometrium, respectively, and possibly through induction of VEGF and MIP-1b expression by the endometrium.
endometrial stromal cells and progesterone?
Endometrial stromal cells, under the influence of progesterone, produce IL-15, prolactin, and likely other unidentified factors, which may regulate uNK cell proliferation, differentiation and production of cytokines and other molecules that support placental and trophoblast development and promote local immunomodulation.
HLA?
he HLA region spans 4 X 106 nucleotides on chromosome 6p21.1 to p21.3, with class II, class III and class I genes located from the centromeric (Cen) to the telomeric (Tel) end. HLA class I molecules restrict CD8+ cytotoxic T lymphocyte function and mediate immune responses against ‘endogenous’ antigens and virally infected targets
normally in an immune response MHC class I and II
MHC class II to be presenting exogenous antigens to CD4+ cells. While MHC class I in presenting endogenous antigens to CD8+ cells.
