immune function in fetuses and pregnancy Flashcards
overproduction of which cytokine drives allergies and asthma?
IL-4
what are the 2 qualities of MHC genes?
o Polygenic – different types of the MHC molecules
o Polymorphic – different versions of the genes in the population
bc MHC genes are polymorphic, what does this mean for individuals?
they’ll;
o Express different MHC molecules
o Be heterozygous
we have a good chance of being able to present different types of antigens
what is an allograft?
transplant between 2 genetically different individuals
why is an allograft usually rejected?
normally rejected bc of immune recognition of MHC antigens present in donor but not in recipient.
why is a fetus not rejected?
o Immune recognition = IgM antibodies to father’s MHC molecules. Not a problem for the fetus because the IgM antibodies do not cross the placenta
o Trophoblast = has several protective features
what are the protective features of the trophoblast?
- No expression of classical MHC molecules on trophoblast surface (so not recognised by T cells).
- Expression of the enzyme IDO (degrades tryptophan inhibits T cell activation.
- Production of anti-inflammatory cytokines (e.g. TGFB, IL-10)
- HLA-G = engages inhibitory receptors on NK cells.
how does the site of haematopoiesis change throughout development?
- 0 to 3 months = Yolk Sac
- 1 to 7 months = Fetal and Spleen
- 4 months to rest of life = Bone Marrow (mainly in bone marrow of skull, ribs, sternum, spine, pelvis and femurs)
what immune cells do children have when theyre born/
- Few plasma cells and memory T cells due to little exposure to antigens in utero.
- Abundant naïve T cells and B cells in lymph nodes and spleen
when does T cell production begin?
8 weeks into gestation
why is it okay to remove the thymus of a baby?
- enough T cells produced to get them through adult life
when may the thymus need to be removed?
during heart surgery
how is the innate response different in early life?
lower responses to PAMPs, reduced DC numbers, hypo-responsive NK cells, lower complement activity.
how is the adaptive response different in early life?
skewing to Th2 responses, poor antibody responses (poor response to T cell helpers and reduced plasma cell survival).
when is there a risk of infection in babies?
• As maternal antibodies decay away there’s a window before the child’s own IgG production starts – risk of infection
which maternal antibodies can cross the placenta?
IgG
how is maternal IgG transported across the palcenta?
actively transported across the placenta by neonatal FcR
how is FcR involved in preventing IgG degradation in adults?
sequesters IgG from degradation in endothelial cells and prolongs antibody half life
explain how the Rhesus factor can cause problems in pregnancy?
- Potential problem when RhD+ (has antigen on cells) expressing fetus is developing in a RhD- mother mother makes anti-Rh antibodies
- Problem arises during second Rh+ pregnancy bc anti-Rh antibodies can cross the placenta and attack the fetus
what is the treatment of rhesus?
• Disease prevented if mother is passively transfused with anti-D antibodies during first and subsequent pregnancies
how do anti-D antibodies work?
o RBC destruction – RBC taken up and destroyed before it can be detected by mother’s immune cells
o Epitope masking
o Inhibition of signaling
prevents activation of B cells specific for RhD
which antibodies protect mucosal surfaces?
IgA
what does IgA do?
limits access of pathogens without risking inflammatory damage
exclude and agglutinate pathogens
what does IgA not do?
activate complement, recruit inflammatory cells, opsonise for phagocytosis
how does a baby acquire IgA?
- B-cells that recognise intestinal pathogens get activated in the mother
- IgA-producing B plasma cell migrate to breast and secrete IgA antibodies into milk.
- On feeding, the baby passively acquires antibodies to relevant pathogens – coat and protect the gut
how can breast feeding protect against allergies later in life?
• Idea is that an environmental antigen is passed from mother to baby through this protected environment and allow for tolerance in the child (Treg cells)
what are the consequences of neonatal immune responses?
- susceptibility to infection - when maternal antibodies decay in baby there’s increased chance of influenza
- responses to vaccination - may be poorly induced or short-lived
- development of allergies - Skewing of CD4 T cell responses towards Th2 may favour development of allergy
