19. Immune Function in the Foetus and Infancy Flashcards
List some extracellular and intracellular immune mechanisms.
What type of T cell and interleukin drives allergies and asthma?
Why are allografts usually rejected?
Extracellular: Abs, complement, phagocytosis, antimicrobial peptides. Intracellular: CD8 T cells, NK cells, T-dependant macrophage activation.
Th2 IL-4 leads to over production of IgE, which binds to mast cells.
MHC genes are polymorphic - many different alleles of the genes in the population. Most of use are heterozygotes for these genes (copies from mum and dad are probably different). This means that individual are likely to express different MHC molecules and be heterozygous, so allografts are rejected due to immune recognition of MHC antigens present in donor but not recipient.
Why is the foetus (technically an allograft) accepted (repeatedly)? It contains MHC inherited from dad not present in mum.
There is immune recognition - IgM Abs to dad’s MHC molecules found. The placenta sequesters the foetus from maternal T cells. The trophoblast also has protective features:
- No classical MHC molecules = no T cell recognition
- IDO on trophoblast depletes tryptophan which inhibits T cell activation
- Production of anti inflammatory cytokines
- HLA-G on trophoblast engages inhibitory receptors on NK cells
- Rejection can occur and may contribute to repeated pregnancy loss*
What does the immune system develop from?
Describe how the site of haematopoiesis changes through development.
Where are the major cellular components of the immune system found at birth?
When does T-cell production begin?
Haematopoietic stem cells.
Initially: yolk sac. From 1-7m = foetal liver and spleen. From 5m-birth and onwards = bone marrow (mainly skull, ribs, sternum, spine, pelvis and femurs).
Lots of T and B cells in lymph nodes and spleen. Few plasma cells or memory T cells.
Early gestation (8w)
How are immune responses in early life different from those in adults?
How do serum Abs change with age? Explain why.
What is the Ig ‘window’?
Innate: lower responses to PAMPs, reduced dendritic cell numbers and function, hypo-responsive NK cells, lower complement activity.
Adaptive: skewed to Th2 responses (and Treg), poor Ab responses (to T cell help).
IgG v high in newborn, then decreases and rises again slowly (maternal IgG can cross placentra to protect foetus/newborn). IgM and IgA rise from newborn, IgA steeper.
As maternal Abs (IgG) decay away, there is a window before the child’s own IgG production starts - risk of infection.
How is maternal IgG transported across the placenta?
What 2 problems can passage of IgG across the placenta cause?
How is IgA transferred from mum to baby? What does it do?
Actively by neonatal FcR (FcRn) binds to Fc of Ab and transports it across. Also active in adults - sequesters IgG from degradation in endothelial cells and prolongs Ab T1/2.
1) Haemolytic disease of the newborn
2) Antibody mediated autoimmunity e.g. Graves’ disease
Breastfeeding. Gives systemic protection but doesn’t protect mucosal surfaces. Limits access of pathogens without risking inflammatory damage. Excludes and agglutinates. DOESN’T activate complement, recruit inflammatory cells or opsonise for phagocytosis. In adults, mucosal surfaces protected by dimeric IgA Abs secreted across the epithelium.
What is haemolytic disease of the newborn and how is it treated?
What is antibody mediated autoimmunity (e.g. Graves’ disease) and how is it treated?
Multiple Rh antigens, RhD is most immunogenic (people either RhD+ (have antigen) or RhD- (no antigen)). Issue when RhD+ foetus in RhD- mother (baby’s RhD comes from dad). Second pregnancy = IgG Abs can cross placenta and destroy baby’s RBC. Treat: passively transfuse mum with anti-D Abs during 1st and subsequent pregnancies = prevents activation of her B cells specific for RhD.
Patient with Graves’ makes anti-TSHR Abs -> transfered to foetus -> newborn also suffers from GD. Treat with plasmapheresis to remove maternal anti-TSHR Abs before damage has occured.
How is IgA secreted into breast milk?
How might breastfeeding protect against allergies?
What are 3 consequences of the neonatal immune response?
B-cells that recognise intestinal pathogens get activated in mum, IgA-producing plasma B-cells migrate to breast and secrete IgA Abs into milk. Baby passivley acquires while feeding and they coat/protect gut from infection. Window of susceptibility as breastfeeding declines.
Dietry/environmental antigen -> antigen processing by maternal digestive system -> maternal milk contains antigens, IgA etc. -> transferred to baby’s gut -> tolerence.
1) Susceptibility to infection: increased in window where maternal Abs decay and child’s immune system not fully developed.
2) Responses to vaccination: may be poorly induced/short-lived due to immaturity or interfering/masking effects of maternal Ab.
3) Development of allergies: skewing of CD4 T-cell responses to Th2 may favour development of asthma/allergy.
What 2 things is vaccination in early life often a balance between?
Why is the immune system in the newborn like this?
What early life experiences can lead to an altered gut microbiota (dysbiosis) and diseases of immune regulation?
Optimal response (maturity of immune system/decay of maternal Abs) and minimising period of susceptibility.
To foster colonisation with commensal microorganisms? They are required for normal development of immune system, digest complex carbs, and compete with pathogens. The host immune system can shape the composition of microbiota.
Diet (breast vs formula), birth (C-section vs vaginal), infection, antibiotic exposure, household size/siblings, pets
