Pregnancy Foetus Mother

Pregnancy is a state whereby there is a symbiotic union between a mother and her foetus. During this period, all systems of the body change to accommodate the trophoblast, the immune system (a complex biological signalling system responsible for protecting us against infection, disease and foreign objects due to its ability to differentiate between self and non self) being one of these systems also undergoes a number of changes (Markert, 2005). The foetus is like a homograft attached to the uterine wall of the mother via the placenta, it inherits half its genetic makeup from its mother and the other half from its father. The paternal genes that it expresses are seen as antigens by the mothers immune system and are expected to cause the rejection of the foetus as a semi-allogenic tissue graft(2). Instead, the mothers’ immune system teaches itself to tolerate these genes and the development of the foetus is supported and regulated (Marker, 2005). The immunological puzzle that leads to the sustainment of the foetus for the 9 months gestation period is known as the “immunological paradox of pregnancy” (Claman. 1993).

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A question that begets to be asked is how does the maternal body prevent rejection of the histoincompatible foetus and at the same time maintain enough maternal host defence mechanisms to fight disease and infection? To date it is not fully understood how this takes place, but it is known that in order to allow the foetus to escape rejection and immunological attacks by the maternal immune system, this symbiotic relationship must have distinctive immuno-regulatory actions. At the same time the mothers’ immune system must also provide protection against foreign antigens for her as well as her young.

A number of explanations have been proposed during the last century as to why foetal rejection does not take place in healthy pregnancies. It is now agreed upon that the placenta plays an important role in this. The placenta is a very important organ because not only does it aid the transportation of nutrients and waste products and immunity between mother and foetus, it acts as an endocrine organ because it secretes growth factors and female hormones which helps maintain and support the pregnancy (Knobil and Neil, 1994) and finally the placental expression patterns of majorhistocompatibility complexes (MHC) is one of the vital factors that determine if a foetus is accepted or rejected, in humans these complexes are known as human leukocyte antigen (HLA) complexes (Claman. 1993). Although the mechanism for the maternal tolerance of the MHCs expressed by the fetus is still not fully known it is known that in humans, a number of HLA class I expressions have been detected in the placenta, these include HLA-C and HLA-G complexes. HLA-G is essential for the successful implantation of trophoblast and its protection from invasion. It does so by binding inhibitory receptors on T-lymphocytes and maternal uterine natural killer cells and thus protects the trophblast from maternal attacks caused by these cells. They also regulate cytokine secretion of cells, thus offering protection to the foetus (hla class 1 molecules reference). A recent study has also shown that HLA-G might inhibit the migration of NK cells across the placental endothelial cells. Till this day, no evidence has been brought forward to suggest that HLA-A, HLA-B and Class II MHCs are expressed in the placenta thus it is inferred that they are normally absent from the placenta during pregnancy (Bulmer and Johnson, 1985).

Foetuses are protected not only from rejection during the gestation period but also from infections by the transmission of passive immunity from the mother.In 1892, Paul Erlich used mouse models to demonstrate that fetuses and neonates acquire protective immunity from their mothers both in utero and through breast milk. It has been shown that this involves the active transport of IgG from mother to her offspring. Passive immunity is transferred from the mother to her foetus through the placenta in the form of immunoglobulin G (IgG) and also via breast milk postnatally (Arvola et al 2000). IgG is the main defence against bacteria thus it accounts for 70-75% of antibodies found in human serum. Before birth the foetus is immunologically naïve because its synthesis of antibodies is very low. The immature immune system of the foetus is compensated for by the active transport of maternal IgG across the placenta into the foetal circulation. Before IgG reaches the foetal circulation, it has to cross two cellular barriers, the barrier in contact with the maternal blood known as the syncythiotrophoblast and the capillary epithelium of the foetus. IgG antibodies are conveyed across the placenta and the intestinal epithelium via the human Fc receptor (add more).

Although the ability of IgG to cross the placenta acts to convey passive immunity to the foetus there are instances where its ability to cross the placenta can have detrimental effects on the baby. An example of this is a condition called haemolytic disease of the new born (HDN). HDN is an alloimmune disease that develops in rhesus positive foetuses that have a rhesus negative mother. the mother produces IgG antibodies against the rhesus positive red blood cells which cross the placenta and attack red blood cells in the foetal circulation.

It has been established that breast milk are rich in maternal cells including small proportions of epithelial cells, macrophages, leukocytes and T and B lymphocytes which make up a majority of cells found in milk on the other hand, 80% of the total cells found in the colostrum (first milk secreted after delivery) are mononuclear phagocytes. These cells aid the neonate by protecting the lumen of its gut and transferring immunity passively. Breast milk macrophages enter breast milk via the epithelium of the mammary gland, they are found to be highly phagocytic in breast milk and can easily be differentiated from other cells by the lipid rich inclusions found in their cytoplasm (breast milk macrophages reference). Milk and colostrum are also rich in the dimeric immunoglobin A. IgA antibodies are very important to the newborn because they are highly specific for pathogens found in the mucosae of the gut. This form of passive immunity from the mother thus conveys protection to the newborn until its immune response is mature enough to mount a good enough response (PDF2D).

As well as transference of immunity, a mother can also convey infections to her foetus. The maternal transmission of an infection such as HIV, Hepatitis B and syphilis to foetus in utero, as a result of body fluid transmission during child birth and through breast milk is known as vertical transmission. During pregnancy, the maternal transmission of infection can result in a number of sequela. Infections found in mother have the potential of infecting the foetus or newborn. Side effects of infections include abortion or stillbirth, acute illnesses, congenital abnormalities, neonatal death and many more. The newborn can acquire infections in utero also known as intrauterine (congenital), during child birth (intrapartum) or after birth (postpartum). Different forms of infections can be vertically transmitted, these include viral and bacterial infections which are both covered in this essay.

The most common examples of viral infections transferred from mother to her unborn child are cytomegalovirus, rubella both of which may cause severe neonatal disease or congenital defects, HIV and Hepatitis B.

The human immunodeficiency virus (HIV) is a sexually transmitted virus that attacks the immune system by infecting CD4 cells thus leaving the host vulnerable to other infections. This virus can lead to the acquired immunodeficiency syndrome which is characterised by a very low CD4 cell count (less than 200/ml). The transmission of this virus from mother to child can occur in utero, during child birth and via breast milk. The most common mode of transmission of HIV occurs during labour or at child birth, about 50-80% of vertical transmission occurs via this route. The reason being that the fetus is in direct contact with infected blood and secretions, as a result of ruptured membranes and transmission of maternal blood to the foetus during labour (birth by caesarean section before the beginning of labour and membrane rupture is proven to reduce this risk of transmission of HIV) (www.aafp.org).

HIV transmission can also occur in utero. The foetus can become infected if it comes in contact with infected maternal blood and secretions. This contact can be the result of placental haemorrhage or by the foetus swallowing some amniotic fluid (www. the-aids-pandemic.blogspot.com).

The final mechanism by which vertical transmission if HIV can take place is through breast milk which occurs in 16-29% of cases (www. the-aids-pandemic.blogspot.com).

Hepatitis B is a viral infection of the liver caused by the hepatitis B virus (a double stranded DNA virus which caused liver damage). In 2004, Zhang et al provided evidence that the main route of transmission of hepatitis from mother to foetus was via the placenta. Mothers that have the acute form of the virus and that are also infected in the first trimester of pregnancy have a 10% chance of passing the virus to their neonates. This percentage increases to a staggering 80-90% if the mothers were infected in the 3^rd trimester. 90% of neonates on the other hand acquire the infection if the virus chronically infected the women (Hieber et al 1977).

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Transmission is also caused by the exposure of the foetus to infected blood and body fluids. A hepatitis positive mother has a 20% chance of passing the infection to her offspring during child birth, this risk increases to 90% if the mother is also positive for the hepatitis B e antigen (www.perinatology.com). According to Hill et al (2002), breast milk of infected individuals contains HBV DNA, but using appropriate immunoprophylaxis nullifies the transmission of HBV.

Rubella (the German measles) is a condition caused by the rubella virus. This virus is moderately contagious. It can cross the placenta causing a condition known as congenital rubella syndrome (CRS) which leads to a number of side effects to the baby including low birth weight, deafness, mental retardation, congenital heart failure and death. The severity of the effect depends on the period that the fetus is infected; during the first two months of gestation the chances of foetal damage caused by infection is 65-0%, this chance decreases to 30-35% during the third month and finally to a mere 1-2% in the 20^th week.

There are two routes through which a newborn can acquire a bacterial infection, these routes include intraturerine (transplacental and assending infection) and intrapartum when the new born comes in contact with infected secretions and blood during delivery.

Congenital syphilis is a severe and life threatning multisystem infection caused by the vertical transmission of the spirochete Treponema palladium to the foetus. The transplacental transmission rate is 60-80% Vertical transmission of congenital syphilis can occur at anytime during pregnancy although the infection is more likely to be transmitted by women in the primary and secondary stages of the disease as opposed to the latent stage.Just like in adult syphilis, this infection is categorised into early disease which is seen in children two years or younger and late disease which is seen in children over the age of two(http://www.merck.com).

During child birth organisms such as N. gonorrhoea, B. streptococci and C. trachomonas bacteria that are naturally found in the female reproductive system can also colonise the newborn. A list of these bacteria are shown in fig 1 of the appendix attached.

Vertical transmission of Immunity during pregnancy is complex and one that intrigues many a soul. Till this date its mechanisms are not fully known. What is known is that a number of complex systems are involved in the process and without the foetus will either be rejected or infected by pathogens.