Immune Functions in the Foetus and Infancy

Question 1

Which cells make up the innate immune system?

Answer 1

Granulocytes, natural killer cells, monocytes/macrophages and dendritic cells

Question 2

Which cells make up the adaptive immune system?

Answer 2

T and B cells

Question 3

Why is there so much variation in MHC/HLA receptors?

Answer 3

The genes which encode these receptors are both polygenic and polymorphic

Question 4

How may the trophoblast play a role in preventing the rejection of a foetus?

Answer 4

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

Question 5

From which stem cells does the immune system develop in the foetus?

Answer 5

Haematopoietic stem cells

Question 6

Outline how the sites of haematopoiesis change throughout development of the foetus

Answer 6

1-3 months = yolk sac
1-7 months = foetal liver and spleen
4 months + = bone marrow

Question 7

What is the immune system like at birth?

Answer 7

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

Question 8

When does T cell production begin in foetal development?

Answer 8

8 weeks gestation

Question 9

Which maternal antibodies passively cross the placenta to the foetus?

Answer 9

IgG antibodies

Question 10

Why is there a ‘window of susceptibility’ for an infant post-partum?

Answer 10

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

Question 11

How is maternal IgG transferred across the placenta to the foetus?

Answer 11

Via the neonatal FcR transporter

Question 12

Name two problems that may occur due to the passage of IgG across the placenta

Answer 12

Haemolytic disease of the newborn or antibody mediated autoimmunity

Question 13

Describe how placental IgG transfer may lead to haemolytic disease of the newborn

Answer 13

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

Question 14

How may issues with Rhesus factor discrepencies be treated?

Answer 14

Use of prophylaxis with antibodies to RhD (anti- D for example)

Question 15

Describe how placental IgG transfer may lead to antibody-mediated autoimmunity, such as Graves’ disease

Answer 15

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

Question 16

Why are more antibodies required in order to protect the body than harm, other than IgG, for example?

Answer 16

IgG gives systemic protection but doesn’t protect mucosal surfaces

Question 17

Where is IgA found in adults?

Answer 17

Lines mucosal surfaces (dimeric IgA) by being secreted onto the epithelia

Question 18

Outline the function of IgA

Answer 18

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

Question 19

How is IgA secreted into breast milk?

Answer 19

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

Question 20

How may breastfeeding protect against allergies?

Answer 20

Exposure to antigens early on which leads to the appropriate development of T regulatory cells in the immune system

Question 21

What are the characteristics of innate immunity in early life?

Answer 21

There are lower responses to PAMPs, reduced dendritic cell numbers and function, hypo-responsive NK cells and lower complement activity

Question 22

What are the characteristics of adaptive immunity in early life?

Answer 22

There are poor antibody responses with poor responses to T cell help and reduced plasma cell survival

Question 23

Why may the immaturity of the immune system in early life have consequences for vaccination programmes?

Answer 23

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)

Question 24

How may the development of the immune system in early life lead to the development of allergies?

Answer 24

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

Question 25

Why is the newborn immune system immature at birth?

Answer 25

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

Question 26

Why is commensal gut microbiota beneficial?

Answer 26

It’s required for normal development of the immune system, it aids in the digestion of complex carbohydrates and the microorganisms compete with pathogens