Causes: Immaturity & Pregnancy – Secondary Immunodeficiency Diseases

00:01 When we are very young, our immune system is not fully developed.

00:05 So immaturity can also be a cause of secondary immunodeficiency.

00:10 Neonates have a relatively immature immune system, particularly if delivered pre-term.

00:15 There is susceptibility to infection and this correlates with the degree of prematurity.

00:22 Both T-cells and B-cells in the neonate are naïve, they haven’t encountered antigen yet.

00:29 And therefore they respond relatively slowly to infection.

00:35 In some infants there is a transient hypogammaglobulinemia of infancy in which IgG levels remain low following catabolism of placentally-transferred maternal IgG.

00:49 This is usually asymptomatic.

00:52 Maternal IgG is transported across the placenta by the neonatal IgG-Fc receptor (FcRn).

01:03 So antibodies from the mother are picked up by FcRn and transferred across the placenta, and released into the fetal circulation.

01:15 The newborn therefore contains the same antibody specificities as the mother because the antibody is coming from the mother rather than being produced by the fetus.

01:24 In immaturity, maternal IgA and IgG in breast milk is particularly important for the newborn.

01:33 Ingested secretory IgA protects the newborn against microbial colonization in the gut.

01:40 Whilst ingested IgG antibodies are transported into the infant’s circulation by the FcRn on gut epithelium.

01:50 Here we can see the serum immunoglobulin levels in the newborn as a percent of adult values.

01:59 Our own B-cells are beginning to make IgM antibodies before we’re born, but only very small levels are produced by the time of birth.

02:10 But within the months following birth, IgM levels within a year or so reach the level that you would find in the adult.

02:20 IgG follows a little bit later on, remember IgM is characteristic of the primary immune response and IgG of the secondary immune response.

02:29 And at the time of birth, there is very little IgG in the infant’s circulation that is being produced by the infant’s own B-lymphocytes.

02:38 They’re just reaching the stage of maturity when they can begin to make antibody.

02:44 IgA levels are also vanishingly small at the time of birth but will increase over time.

02:54 However, with respect to IgG, there is in fact quite a lot of IgG in the fetal circulation and in the newborn circulation.

03:05 And that’s because IgG is transferred across the placenta as we’ve just seen using the FcRn.

03:15 This maternally derived antibody will begin to be catabolised once the newborn has been born.

03:23 And IgG has a half life of around about three weeks.

03:29 So three weeks after birth, half of the maternal antibody will have been catabolised.

03:35 Six weeks after birth, there’ll only be 25% of the maternal antibody.

03:39 But the infant is now beginning to make their own IgG, so there will be a dip in the level as the maternal IgG is catabolised, but then the infant’s own IgG will come up and eventually there will be a rise in the overall IgG level.

04:00 Pregnancy is a condition in which there is a natural immunosuppression.

04:06 This occurs in order to avoid rejection of the semi-allogeneic fetus.

04:11 Remember, half of the genes in the fetus, will have come from the male partner.

04:19 Immunosuppression is largely focused at the maternal-fetal interface in the placenta, to stop an immunological rejection of this semi-allogeneic fetus where half of the genes are from the dad.

04:33 However, there is some degree of systemic suppression of the immune response.

04:38 And pregnant women have a degree of increased incidence and severity of infection.

04:46 There is no evidence of risk of vaccinating pregnant women with inactivated virus or bacterial vaccines or with toxoids, which are inactivated bacterial toxins.

04:57 However, live virus vaccines are contraindicated because of the theoretical risk of transmission of live virus to the fetus.