question: What stops the mother's immune system rejecting the baby in the womb?
comment: There is no direct connection between the mother and the fetus. The placenta acts as a barrier between the mother and fetus. In rare occurrences it can happen if the RH factor of the blood doesn't match the mother will develop antibodies to attack the fetus' red blood cells.
passages: Section::::Mechanisms.:Other mechanisms.
  
  Still, the placental barrier is not the sole means to evade the immune system, as foreign fetal cells also persist in the maternal circulation, on the other side of the placental barrier.
  
  The placenta does not block maternal IgG antibodies, which thereby may pass through the human placenta, providing immune protection to the fetus against infectious diseases.
   The cornerstone of the immune system is the recognition of "self" versus "non-self". Therefore, the mechanisms that protect the human fetus (which is considered "non-self") from attack by the immune system, are particularly interesting. Although no comprehensive explanation has emerged to explain this mysterious, and often repeated, lack of rejection, two classical reasons may explain how the fetus is tolerated. The first is that the fetus occupies a portion of the body protected by a non-immunological barrier, the uterus, which the immune system does not routinely patrol. The second is that the fetus itself may promote local immunosuppression in the mother, perhaps by a process of active nutrient depletion. A more modern explanation for this induction of tolerance is that specific glycoproteins expressed in the uterus during pregnancy suppress the uterine immune response (see eu-FEDS).
   The fetus has a different genetic makeup than the mother, as it also translates its father's genes, and is thus perceived as foreign by the maternal immune system. Women who have borne multiple children by the same father typically have antibodies against the father's red blood cell and major histocompatibility complex (MHC) proteins. However, the fetus usually is not rejected by the mother, making it essentially a physiologically tolerated allograft. It is thought that the placental tissues which interface with maternal tissues not only try to escape immunological recognition by downregulating identifying MHC proteins but also actively induce a marked peripheral tolerance. Placental trophoblast cells express a unique Human Leukocyte Antigen (HLA-G) that inhibits attack by maternal NK cells. These cells also express IDO, which represses maternal T cell responses by amino acid starvation. Maternal T cells specific for paternal antigens are also suppressed by tolerogenic DCs and activated iTregs or cross-reacting nTregs. Some maternal Treg cells also release soluble fibrinogen-like proteins 2 (sFGL2), which suppresses the function of DCs and macrophages involved in inflammation and antigen presentation to reactive T cells These mechanisms altogether establish an immune-privileged state in the placenta that protects the fetus. A break in this peripheral tolerance results in miscarriage and fetal loss. (for more information, see Immune tolerance in pregnancy).
   Immune tolerance in pregnancy
  
  Immune tolerance in pregnancy or maternal immune tolerance is the immune tolerance shown towards the fetus and placenta during pregnancy. This tolerance counters the immune response that would normally result in the rejection of something foreign in the body, as can happen in cases of spontaneous abortion. It is studied within the field of reproductive immunology.
  
  Section::::Mechanisms.
  
  Section::::Mechanisms.:Placental mechanisms.
  
  The placenta functions as an immunological barrier between the mother and the fetus, creating an immunologically privileged site. For this purpose, it uses several mechanisms:
   Regulatory T cells also likely play a role.
  
  Also, a shift from cell-mediated immunity toward humoral immunity is believed to occur.
  
  Section::::Insufficient tolerance.
  
  Many cases of spontaneous abortion may be described in the same way as maternal transplant rejection, and a chronic insufficient tolerance may cause infertility. Other examples of insufficient immune tolerance in pregnancy are Rh disease and pre-eclampsia:
   Hemolytic disease of the fetus and newborn is similar to a transfusion reaction in that the mother's antibodies cannot tolerate the fetus's antigens, which happens when the immune tolerance of pregnancy is impaired. In many instances the maternal immune system attacks the fetal blood cells, resulting in fetal anemia. HDN ranges from mild to severe. Severe cases require intrauterine transfusions or early delivery to survive, while mild cases may only require phototherapy at birth.
  
  Section::::Types of the rejection.:Transplant rejection.
  
  Section::::Types of the rejection.:Transplant rejection.:Acute rejection.
   Still, the placenta does allow maternal IgG antibodies to pass to the fetus to protect it against infections. However, these antibodies do not target fetal cells, unless any fetal material has escaped across the placenta where it can come in contact with maternal B cells and make those B cells start to produce antibodies against fetal targets. The mother does produce antibodies against foreign ABO blood types, where the fetal blood cells are possible targets, but these preformed antibodies are usually of the IgM type, and therefore usually do not cross the placenta. Still, rarely, ABO incompatibility can give rise to IgG antibodies that cross the placenta, and are caused by sensitization of mothers (usually of blood type 0) to antigens in foods or bacteria.
   The mother’s immune system is able to provide protection from microbial infections without mounting an immune response against fetal tissues expressing paternally inherited alloantigens. A better understanding of the immunology of pregnancy may lead to the discovery of reasons for miscarriage.
   The placenta and fetus may be regarded as a foreign body inside the mother, and needs to be protected from the normal immune response of the mother that would cause it to be rejected. The placenta and fetus are thus treated as sites of immune privilege, with immune tolerance.
  
  For this purpose, the placenta uses several mechanisms:
  
  BULLET::::- It secretes Neurokinin B-containing phosphocholine molecules. This is the same mechanism used by parasitic nematodes to avoid detection by the immune system of their host.
   BULLET::::- Rh disease is caused by the mother producing antibodies (including IgG antibodies) against the Rhesus D antigen on her baby's red blood cells. It occurs if the mother is Rh negative and the baby is Rh positive, and a small amount of Rh positive blood from any previous pregnancy has entered the mother's circulation to make her produce IgG antibodies against the D antigen (Anti-D). Maternal IgG is able to pass through the placenta into the fetus and if the level of it is sufficient, it will cause destruction of D positive fetal red blood cells leading to development of the anti-Rh type of hemolytic disease of the fetus and newborn (HDFN). Generally HDFN becomes worse with each additional Rh incompatible pregnancy.
   Regulatory T cells (Tregs) appear to be important in the maintenance of tolerance to fetal antigen. Increased numbers of Tregs are found during normal pregnancy. In both mouse models and humans diminished numbers of Tregs were associated with immunological rejection of the fetus and miscarriage. Experiments in mice involving the transfer of CD4+/CD25+ Treg cells from normal pregnant mice into abortion-prone animals resulted in the prevention of abortion. This confirmed the importance of these cells in maintaining immune privilege in the womb.
   BULLET::::- It secretes Neurokinin B containing phosphocholine molecules. This is the same mechanism used by parasitic nematodes to avoid detection by the immune system of their host.
  
  BULLET::::- Also, there is presence of small lymphocytic suppressor cells in the fetus that inhibit maternal cytotoxic T cells by inhibiting the response to interleukin 2.
   Only a few other species besides humans transfer maternal antibodies before birth, including primates and lagomorphs (which includes rabbits and hares). In some of these species IgM can be transferred across the placenta as well as IgG. All other mammalian species predominantly or solely transfer maternal antibodies after birth through milk. In these species, the neonatal gut is able to absorb IgG for hours to days after birth. However, after a period of time the neonate can no longer absorb maternal IgG through their gut, an event that is referred to as "gut closure". If a neonatal animal does not receive adequate amounts of colostrum prior to gut closure, it does not have a sufficient amount of maternal IgG in its blood to fight off common diseases. This condition is referred to as failure of passive transfer. It can be diagnosed by measuring the amount of IgG in a newborn's blood, and is treated with intravenous administration of immunoglobulins. If not treated, it can be fatal.
   Newborn infants have no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. During pregnancy, a particular type of antibody, called IgG, is transported from mother to baby directly through the placenta, so human babies have high levels of antibodies even at birth, with the same range of antigen specificities as their mother. Breast milk or colostrum also contains antibodies that are transferred to the gut of the infant and protect against bacterial infections until the newborn can synthesize its own antibodies. This is passive immunity because the fetus does not actually make any memory cells or antibodies—it only borrows them. This passive immunity is usually short-term, lasting from a few days up to several months. In medicine, protective passive immunity can also be transferred artificially from one individual to another via antibody-rich serum.
   Maternal IgG antibodies cross the placenta, giving the fetus passive immunity against those diseases for which the mother has antibodies. This transfer of antibodies in humans begins as early as the fifth month (gestational age) and certainly by the sixth month.
  
  Section::::Developmental problems.
   Passive immunity is temporary, because the antibodies which are transferred have a lifespan of only about 3–6 months. Every placental mammal (which includes humans) has experienced temporarily induced immunity by transfer of homologous antibodies from its mother across the placenta, giving it passive immunity to whatever its mother became immune to. This allows some protection for the young while its own immune system is developing.
   BULLET::::- There is presence of small lymphocytic suppressor cells in the fetus that inhibit maternal cytotoxic T cells by inhibiting the response to interleukin 2.
  
  However, the Placental barrier is not the sole means to evade the immune system, as foreign fetal cells also persist in the maternal circulation, on the other side of the placental barrier.
  
  Section::::Functions.:Other.
  
  The placenta also provides a reservoir of blood for the fetus, delivering blood to it in case of hypotension and vice versa, comparable to a capacitor.
  
  Section::::Clinical significance.
  
  Numerous pathologies can affect the placenta.
   This process of negative selection ensures that T and B cells that could initiate a potent immune response to the host's own tissues are eliminated while preserving the ability to recognize foreign antigens. It is the step in lymphocyte education that is key for preventing autoimmunity (entire process detailed here). Lymphocyte development and education is most active in fetal development, but continues throughout life as immature lymphocytes are generated, slowing as the thymus degenerates and the bone marrow shrinks in adult life.
  
  Section::::Peripheral tolerance.
   The body’s capability to react to antigens depends on a person's age, antigen type, maternal factors and the area where the antigen is presented. Neonates are said to be in a state of physiological immunodeficiency, because both their innate and adaptive immunological responses are greatly suppressed. Once born, a child’s immune system responds favorably to protein antigens while not as well to glycoproteins and polysaccharides. In fact, many of the infections acquired by neonates are caused by low virulence organisms like "Staphylococcus" and "Pseudomonas". In neonates, opsonic activity and the ability to activate the complement cascade is very limited. For example, the mean level of C3 in a newborn is approximately 65% of that found in the adult. Phagocytic activity is also greatly impaired in newborns. This is due to lower opsonic activity, as well as diminished up-regulation of integrin and selectin receptors, which limit the ability of neutrophils to interact with adhesion molecules in the endothelium. Their monocytes are slow and have a reduced ATP production, which also limits the newborn's phagocytic activity. Although, the number of total lymphocytes is significantly higher than in adults, the cellular and humoral immunity is also impaired. Antigen-presenting cells in newborns have a reduced capability to activate T cells. Also, T cells of a newborn proliferate poorly and produce very small amounts of cytokines like IL-2, IL-4, IL-5, IL-12, and IFN-g which limits their capacity to activate the humoral response as well as the phagocitic activity of macrophage. B cells develop early during gestation but are not fully active.
   Neonatal myasthenia gravis is a very rare condition in which a mother with myasthenia gravis passes down her antibodies to her infant through the placenta, causing the it to be born with antibodies that will attach self-antigens.(reference 12)
   Organs engineered from amniotic epithelial cells obtained from the placenta associated with a particular person's birth would not be rejected by that person; such organs would have the same genotype as that person and thus be fully compatible with that person's immune system.
  
  Section::::Expansion.
   The "ductus arteriosus" normally closes within one or two days of birth, leaving the "ligamentum arteriosum", while the umbilical vein and "ductus venosus" usually closes within two to five days after birth, leaving, respectively, the liver's "ligamentum teres" and "ligamentum venosus".
  
  Section::::Immune system.
  
  The placenta functions as a maternal-fetal barrier against the transmission of microbes. When this is insufficient, mother-to-child transmission of infectious diseases can occur.
   Maternal passive immunity is a type of naturally acquired passive immunity, and refers to antibody-mediated immunity conveyed to a fetus by its mother during pregnancy. Maternal antibodies (MatAb) are passed through the placenta to the fetus by an FcRn receptor on placental cells. This occurs around the third month of gestation. IgG is the only antibody isotype that can pass through the placenta. Passive immunity is also provided through the transfer of IgA antibodies found in breast milk that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its antibodies. Colostrum present in mothers milk is an example of passive immunity. 
   Section::::Immunological memory.:Passive memory.
  
  Passive memory is usually short-term, lasting between a few days and several months. Newborn infants have had no prior exposure to microbes and are particularly vulnerable to infection. Several layers of passive protection are provided by the mother. "In utero", maternal IgG is transported directly across the placenta, so that, at birth, human babies have high levels of antibodies, with the same range of antigen specificities as their mother. Breast milk contains antibodies (mainly IgA) that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its own antibodies.
   Susceptibles have been exposed to neither the wild strain of the disease nor a vaccination against it, and thus have not developed immunity. Those individuals who have antibodies against an antigen associated with a particular infectious disease will not be susceptible, even if they did not produce the antibody themselves (for example, infants younger than six months who still have maternal antibodies passed through the placenta and from the colostrum, and adults who have had a recent injection of antibodies). However, these individuals soon return to the susceptible state as the antibodies are broken down.
  
raw_presuppositions: The mother's immune system interacts with the baby.
raw_corrections: The placenta separates the mother and fetus.