Immune Functions in the Foetus and Infancy Flashcards
Which cells make up the innate immune system?
Granulocytes, natural killer cells, monocytes/macrophages and dendritic cells
Which cells make up the adaptive immune system?
T and B cells
Why is there so much variation in MHC/HLA receptors?
The genes which encode these receptors are both polygenic and polymorphic
How may the trophoblast play a role in preventing the rejection of a foetus?
The trophoblast doesn’t present any classical HLA molecules so doesn’t instigate T cell recognition. Presents the enzyme IDO which depletes tryptophan (required to activate T cells) so inhibits T cell activation. There is production of anti-inflammatory cytokines, which causes T regulatory cell development. Finally, they display HLA-G which engages inhibitory receptors on NK cells
From which stem cells does the immune system develop in the foetus?
Haematopoietic stem cells
Outline how the sites of haematopoiesis change throughout development of the foetus
1-3 months = yolk sac
1-7 months = foetal liver and spleen
4 months + = bone marrow
What is the immune system like at birth?
There is an abundance of naïve T and B cells in lymph nodes and spleen but few plasma or memory T cells due to little exposure to antigens in utero
When does T cell production begin in foetal development?
8 weeks gestation
Which maternal antibodies passively cross the placenta to the foetus?
IgG antibodies
Why is there a ‘window of susceptibility’ for an infant post-partum?
Antibody levels that were delivered via the placenta are now decaying, and there is a window where they have very minimal immune cells, making them susceptible to infection
How is maternal IgG transferred across the placenta to the foetus?
Via the neonatal FcR transporter
Name two problems that may occur due to the passage of IgG across the placenta
Haemolytic disease of the newborn or antibody mediated autoimmunity
Describe how placental IgG transfer may lead to haemolytic disease of the newborn
If the infant is RhD+ and the mother is RhD-, the IgG antibodies transferred to the infant will recognise them as foreign-antigens on the red blood cells, and therefore act to destroy the foetal blood cells, eliminating their circulatory system - this is generally only an issue in second pregnancy
How may issues with Rhesus factor discrepencies be treated?
Use of prophylaxis with antibodies to RhD (anti- D for example)
Describe how placental IgG transfer may lead to antibody-mediated autoimmunity, such as Graves’ disease
Patient with Graves’ makes anti-TSHR antibodies and these will be transferred across the placenta to the foetus, so the newborn infant with also have Graves’, but ordinarily, the process of catabolism breaks down these maternal antibodies, and the newborn is cured
Why are more antibodies required in order to protect the body than harm, other than IgG, for example?
IgG gives systemic protection but doesn’t protect mucosal surfaces
Where is IgA found in adults?
Lines mucosal surfaces (dimeric IgA) by being secreted onto the epithelia
Outline the function of IgA
Limits access of pathogens without risking inflammatory damage. It excludes and agglutinates pathogens but doesn’t activate complement, recruit inflammatory cells or opsonise for phagocytosis
How is IgA secreted into breast milk?
B cells which recognise intestinal pathogens get activated in mother, then IgA-producing B plasma cells migrate to the breast and secrete IgA antibodies into the milk. On feeding the baby then passively acquires antibodies to the relevant pathogens
How may breastfeeding protect against allergies?
Exposure to antigens early on which leads to the appropriate development of T regulatory cells in the immune system
What are the characteristics of innate immunity in early life?
There are lower responses to PAMPs, reduced dendritic cell numbers and function, hypo-responsive NK cells and lower complement activity
What are the characteristics of adaptive immunity in early life?
There are poor antibody responses with poor responses to T cell help and reduced plasma cell survival
Why may the immaturity of the immune system in early life have consequences for vaccination programmes?
The supplied protective responses of vaccination may be poorly induced or short-lived due to the immaturity of the immune system as well as the potential interfering effects of maternal antibodies (e.g. masking of epitopes or negative signalling)
How may the development of the immune system in early life lead to the development of allergies?
If there is skewing of CD4 T cells responses to favour a Th2 response, this may favour asthma or allergy in some whereas an effective shift towards Th1 responses in early life may protect from allergy
Why is the newborn immune system immature at birth?
In the womb the foetus was required to co-exist with non-inherited maternal antigens, so a full immune system couldn’t exist as rejection would have occurred. There may also be an argument that it is so that commensal microorganisms can help shape immune responses
Why is commensal gut microbiota beneficial?
It’s required for normal development of the immune system, it aids in the digestion of complex carbohydrates and the microorganisms compete with pathogens
