Immunology of pregnancy

Question 1

What is the sequence of events that occur during pathogenesis of pre-eclampsia?

Answer 1

1. Failure for spiral artery conversion
2. Decreased blood supply to the placenta
3. Increased placental stress and release of stress-induced factors
4. Stress-induced factors interact with maternal circulation to cause symptoms characteristics of pre-eclampsia.

Question 2

What are the symptoms of pre-eclampsia?

Answer 2

1. Hypertension
2. Proteinuria
3. Oedema
4. Nausea & vomiting
5. Headaches

Question 3

What are the HLA isoforms expressed by extravillous trophoblast (EVT)?

Answer 3

1. HLA-C
2. HLA-E
3. HLA-G

Question 4

What are the types of leukocytes that occur in the decidua and their relative frequencies?

Answer 4

• 70% uterine NK cells
• 10-20% macrophages
• 10-20% T cells
• 1% dendritic cells

Question 5

What are the types of receptors on uNK cells that bind to different HLA isotypes on EVT?

Answer 5

• KIR → HLA-C
• CD94 → HLA-E
• LILRB1 → HLA-G

Question 6

What are the different isotyptes of HLA-C?

Answer 6

1. C1
2. C2

Question 7

What are the KIRs associated with each HLA-C isotype?

Answer 7

1. HLA-C1:
   - KIR2DL3 – Weak inhib.
   - KIR2DL2 – Weak inhib.
2. HLA-C2:
   - KIR2DL1 – Inhib.
   - KIR2DS1 – Stim.

Question 8

What are the common KIR haplotypes found in mothers?

Answer 8

1. KIR A: Contains KIR2DL1, which interacts with HLA-C2 and is strongly inhibitory of placentation.
2. KIR B: Contains KIR2DS1, which interacts with HLA-C2 and promotes placentation.

Question 9

What maternal KIR haplotype and fetal HLA isotype combinations may be dangerous?

Answer 9

1. Maternal KIR-AA + Fetal C1/C2
2. Maternal KIR-AA + Fetal C2/C2

Question 10

What neonatal/maternal conditions are assoicated with low birth weight?

Answer 10

1. Immature organs
2. Neonatal infections
3. Pre-eclampsia

Question 11

What neonatal/maternal conditions are associated with high birth weight?

Answer 11

1. Obstructive labour
2. Birth trauma/asphyxiation
3. Post-partum haemorrhages
4. Vesico-vaginal fistula

Question 12

What maternal KIR haplotype and fetal HLA isotype combinations are associated with decreased birth weight?

Answer 12

Maternal KIR-A + Fetal HLA-C2

Question 13

What maternal KIR haplotype and fetal HLA isotype combinations are associated with increased birth weight?

Answer 13

Maternal KIR-B + Fetal HLA-C2

Question 14

What is the purpose of having maternal KIR and fetal HLA-C isotypes that increase/decreased birth weight?

Answer 14

Provides stabilising selection for combinations of maternal KIR and fetal HLA-C so that the baby isn’t too small for development to be impaired, but isn’t too large to fit through birth canal.

Question 15

What types of maternal immunological during pregnancy?

Answer 15

1. Increased risk of viral infections (inc. influenza, chicken pox).
2. Increased/Decreased risk of autoimmune diseases (Increased: SLE, Decreased: RA, MS)

Question 16

What types of bacteria can be transmitted transplacentally?

Answer 16

1. Brucella spp.
2. Coxiella burnetii
3. Listeria monocytogenes
4. Mycobacterium tuberculosis
5. Salmonella typhi
6. Treponema pallidum

Question 17

What types of parasites can be transmitted transplacentally?

Answer 17

1. Plasmodium falciparum
2. Toxoplasma gondii
3. Trypanosoma cruzii
4. Leishmania spp.

Question 18

What types of viruses can be transmitted translacentally?

Answer 18

1. CMV
2. Rubella
3. Parvovirus B19
4. VZV
5. Lymphocytic choriomeningitis virus

Question 19

How are pathogens able to cross the placental barrier?

Answer 19

1. Blood: Through maternal blood
2. Tissue: Through decidua and placental villi