immune function in fetuses and pregnancy

Question 1

overproduction of which cytokine drives allergies and asthma?

Answer 1

IL-4

Question 2

what are the 2 qualities of MHC genes?

Answer 2

o Polygenic – different types of the MHC molecules

o Polymorphic – different versions of the genes in the population

Question 3

bc MHC genes are polymorphic, what does this mean for individuals?

Answer 3

they’ll;
o Express different MHC molecules
o Be heterozygous

we have a good chance of being able to present different types of antigens

Question 4

what is an allograft?

Answer 4

transplant between 2 genetically different individuals

Question 5

why is an allograft usually rejected?

Answer 5

normally rejected bc of immune recognition of MHC antigens present in donor but not in recipient.

Question 6

why is a fetus not rejected?

Answer 6

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

Question 7

what are the protective features of the trophoblast?

Answer 7

• 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.

Question 8

how does the site of haematopoiesis change throughout development?

Answer 8

• 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)

Question 9

what immune cells do children have when theyre born/

Answer 9

• 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

Question 10

when does T cell production begin?

Answer 10

8 weeks into gestation

Question 11

why is it okay to remove the thymus of a baby?

Answer 11

• enough T cells produced to get them through adult life

Question 12

when may the thymus need to be removed?

Answer 12

during heart surgery

Question 13

how is the innate response different in early life?

Answer 13

lower responses to PAMPs, reduced DC numbers, hypo-responsive NK cells, lower complement activity.

Question 14

how is the adaptive response different in early life?

Answer 14

skewing to Th2 responses, poor antibody responses (poor response to T cell helpers and reduced plasma cell survival).

Question 15

when is there a risk of infection in babies?

Answer 15

• As maternal antibodies decay away there’s a window before the child’s own IgG production starts – risk of infection

Question 16

which maternal antibodies can cross the placenta?

Answer 16

IgG

Question 17

how is maternal IgG transported across the palcenta?

Answer 17

actively transported across the placenta by neonatal FcR

Question 18

how is FcR involved in preventing IgG degradation in adults?

Answer 18

sequesters IgG from degradation in endothelial cells and prolongs antibody half life

Question 19

explain how the Rhesus factor can cause problems in pregnancy?

Answer 19

• 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

Question 20

what is the treatment of rhesus?

Answer 20

• Disease prevented if mother is passively transfused with anti-D antibodies during first and subsequent pregnancies

Question 21

how do anti-D antibodies work?

Answer 21

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

Question 22

which antibodies protect mucosal surfaces?

Answer 22

IgA

Question 23

what does IgA do?

Answer 23

limits access of pathogens without risking inflammatory damage

exclude and agglutinate pathogens

Question 24

what does IgA not do?

Answer 24

activate complement, recruit inflammatory cells, opsonise for phagocytosis

Question 25

how does a baby acquire IgA?

Answer 25

• 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

Question 26

how can breast feeding protect against allergies later in life?

Answer 26

• 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)

Question 27

what are the consequences of neonatal immune responses?

Answer 27

• 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