Lecture 21

Question 1

How does the skin of preterm infants put them at risk of increased infection

Answer 1

The outer layer of the skin (stratum corneum) is usually the first barrier to infection this layer only builds up in the third trimester so preterm infants are at increased risk due to their skin being underdeveloped
2-3 weeks the post partum skin will provide adult protection regardless of gestational age

Question 2

Where are Neutrophils produced in the embryo?

Answer 2

These are produced in the fetal yolk sac at 6-8 weeks and in the liver and bone marrow at 8-12 weeks

Question 3

How do the neutrophils of foetuses and preterm infants compare to those of adults?

Answer 3

There are low number of neutrophils found in mid gestation foetuses and preterm infants
The preterm neutrophils are functionally deficient with things such as migration and adherence

Question 4

How do the monocytes and macrophages of foetuses and preterm infants compare to those of adults?

Answer 4

The fetus can produce adult numbers of these cells byt there function is reduced with reduced synthesis of cytokines, reduced response to GM-CSF and reduced migratory activity

Question 5

Where are monocytes and macrophages produced in the fetus?

Answer 5

In the first trimester they are produced in the yolk sac and in from the 2nd trimester they are produced in the bone marrow

Question 6

In the first trimester they are produced in the yolk sac and in from the 2nd trimester they are produced in the bone marrow

Answer 6

Yes they are one of the dominant fetal cell types in the placenta, there function is unknown but it may be to do with stimulating placental angio and vasculogenesis

Question 7

When are complement proteins produced by the fetus?

Answer 7

At term the fetus has 50% of adult levels of complement proteins and adult levels are reached within 6-18 months

Question 8

Where are B cells produced in the fetus?

Answer 8

At 3 weeks they are produced in the yolk sac

At 8 weeks they are produced in the liver and after 12 weeks they are produced in the bone marrow

Question 9

What is the developmental process of B cells which occurs in foetuses?

Answer 9

From 10 weeks pre B cells are present, at week 15 they start producing IgM, week 20 they produce IgG and at week 30 they produce IgA
In 22 weeks there are adult levels of B cells

Question 10

What is the difference with regards to class switching between foetal and adult B cells?

Answer 10

Fetal and neonatal B cells differentiate to IgM secretory cells readily but will not readily udergo class switching to IgG and IgA until 2 and 5 years respectively

Question 11

How do T cells develop in the fetus?

Answer 11

The thymus is formed by 8 weeks, pre T cells will migrate to the thymus from the yolk sac, liver and bone marrow
At 16 weeks the thymus is similar in structure to term, from 16-20 weeks T cells and T cell subpopulations CD4 and CD8 are at adult levels

Question 12

When does the fetus gain the ability to produce an acquired immune response?

Answer 12

At 20 weeks the fetus has the ability to mount an acquired immune response this allows preterm infants of greater than 23 weeks to mount an immune response similar to that of a full term neonate

Question 13

Is the uterus sterile?

Answer 13

This is still not certain though it is believed that at most the microbial presence is very low

Question 14

What is the fetus’ mains source of antibodies?

Answer 14

The fetus gains antibodies by active transport of IgG from maternal blood across the placenta
It is not certain exactly how this occurs but it is most likely to be the FcgammaRn, most of this transport will occur after 22 weeks and maternal levels are reached after 34 weeks
Following delivery and exposure to antigen the neonate begins production of Igs

Question 15

How does breast feeding provide immune protection for the fetus?

Answer 15

IgA is a major immunological factor in milk with 5-7.5mg/L of sIgA causing a breastfed infant to receive upto 0.5mg IgA/day
This plays a key role in insuring that the correct microbial species to colonize the infants gut

Question 16

What is the link between the GALT and the mammary immune tissue?

Answer 16

Breast milk is rich in IgA reactive orgnaisms present in the maternal gut
Oral immunisation can lead to hyperimmune breast milk containing IgA specific for the immunogen

Question 17

What is haemolytic disease of the newborn?

Answer 17

This is a maternal immune reaction to Rhesus antigens, particularly RhD this can occur if the mother is Rh negative but the father is Rh positive
The first pregnancy like this will be unaffected but during birth the mother will become exposed to the Rh antigen by fetal blood moving into the maternal circulation
This leads to sensitization of the maternal immune system and the production of anti-Rh antibodies which will cross the placenta in subsequent pregnancies and destroy fetal red blood cells

Question 18

What are the treatments for haemolytic disease of the newborn?

Answer 18

If the mother has not been exposed to the Rh antigen then an antiD prophylaxis treatment can be used this is where antibodies to the Rh antigen are transferred to the mother just before birth this allows the passive immunisation to destroy the transferred fetal red blood cells before the mother has the ability to generate a memory response
If the mother has been previously exposed then an intrauterine transfusion can be performed, here the fetus is transfused in utero with maternal-compatible blood injected into the umbilical vessel or abdominal cavity alternatively there can be intravenous immunoglobulin transfusion

Question 19

How does the fetus protect the mother from autoantibodies?

Answer 19

IgM and IgA autoantibodies do not enter the circulation this can lead to protection against antibodies such as rheumatoid factor etc
Organ non-specific antibodies may encounter their antigen and be trapped in the placenta through the placental sink

Question 20

What can occur if autoantibodies do cross the placenta?

Answer 20

They may cause symptoms in the placenta these may be transient diesases like myasthenia gravis (caused by an acetyl choline receptor antibody) and thyrotoxicosis (by an antibody which stimulates the thyroid) which will resolve upon catabolism of the maternal antibody or they may may cause permanent damage such as SSA/Ro and/or SSB/La which can cross the placenta and cause congenital heart block and/or neonatal lupus

Question 21

What are the most common autoantibodies in reproduction?

Answer 21

Antiphospholipid antibodies these are capable of causing fetal death
The exact mechanisms for this are unknown but they appear to attach to the placental trophoblast
They rapidly enter the syncytiotrophoblast through a receptor alternative to FcgammaRn and disrupt mitochondrial function

Question 22

How can autoantibodies have an in direct effect on the fetus?

Answer 22

They can affect the mothers ability to carry the baby to term