The normal fetomaternal immune relationship.
The antigenic status of the preimplantation embryo is ill-defined and there are no clearly recognized maternal immune reactions against this early stage of development. Following implantation, the pregnant female shows evidence of immune recognition of her intrauterine allogeneic conceptus. In a proportion of pregnancies, particularly in multiparous women, there are maternal cytotoxic antibodies exhibiting specificity for the paternally inherited HLA antigens of the fetus. When these are undetectable there may be other antibodies that are non-complement fixing and non-cytotoxic or antibodies that are not present as free molecules and incapable of identification in conventional assays. Anti-HLA antibodies pose no threat to the fetus, principally owing to their absorption by the placenta and, very likely, the harmless binding of any that do reach the fetal circulation. No potentially deleterious cytotoxic T lymphocyte generation occurs in most pregnancies. The extent to which this is due to maternal immunoregulatory control processes is not yet established. The fetal trophoblast is able to act as a protective barrier by virtue of unique properties, including a lack of conventional class I and class II HLA molecules, that render it insusceptible to immune attack. The nature and significance of any maternal recognition of non-HLA antigens on trophoblast await elucidation. Maternal immune cell traffic across the placenta occurs only at a very low level, if at all, in normal pregnancy. This may take place to a greater degree in some of the rare instances of fetal graft-versus-host disease, but this is complicated by the associated fetal immunodeficiency. Maternal IgG antibodies are transmitted across the placental trophoblast by receptor-dependent mechanisms to provide immediate protection for the neonate against environmental pathogens. Leakage of fetal erythrocytes, leukocytes and platelets into the maternal circulation can elicit IgG isoantibodies that take advantage of the same mechanisms to gain access to the fetus, with pathological consequences. Autoantibodies in women with various disease states may similarly pass into the fetus but these normally produce only mild and transient effects. The development of the fetal immune system begins at an early stage of gestation. It is competent to respond to intrauterine infections from as early as 12 weeks and has full functional potential at birth. Maternally acquired IgG is available for up to 9 months of life until the infant's own immune system has been adequately primed and activated following first exposure to specific antigens. The normal fetomaternal immune relationship represents a remarkable harmonious association between two genetically disparate individuals.(ABSTRACT TRUNCATED AT 400 WORDS)
Billington
W D
WD
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, UK.
D000906:Antibodies / Q000276:immunology; D005260:Female; D005333:Fetus / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008895:Milk, Human / Q000276:immunology; D010920:Placenta / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology
D000906:Antibodies; D006680:HLA Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G