Immunological aspects of recurrent spontaneous abortion

Recent studies emphasise an important role of immunological mechanisms in pregnancy maintenance. Therefore, unravelling mechanisms regulating placentogenesis are critical to understanding the pathogenesis of recurrent spontaneous abortion (RSA). Author gives review concerning about auto- and alloimmunological aspects of RSA.     

Immunological aspects of genital chlamydia infections

Chlamydia trachomatis ascends from the cervix to the Fallopian tubes where it forms a persistent infection. The immune response to this infection results in tubal occlusion and infertility. In its persistent formC. trachomatis produces high levels of a 60-kDa heat shock protein (c-hsp60). There is a human hsp60 (h-hsp60) which shares a 50% amino acid sequence homology with the c-hsp60. Therefore, a chlamydial Fallopian tube infection can induce the development of autoantibodies to h-hsp60. H-hsp60 is one of the first proteins synthesized following fertilization. It is also expressed by epithelial cells in the decidua. Therefore, expression of h-hsp60 in early pregnancy can reactivate the c-hsp60-sensitized lymphocytes, leading to immune rejection of the embryo. The role of C. trachomatis in male infertility requires clarification. Because most C. trachomatis infections occur without defined symptoms, only the screening of sexually active women will reveal whether a woman is infected with this organism. Detection and treatment of a recently acquired infection can prevent development of h-hsp60 autoantibodies and tubal occlusion, preserve fertility, and prevent complications such as ectopic pregnancy.     

Immunological aspects in EPH gestosis]

On the base of the fundamental knowledge on immunological reactions in the normal pregnancy the disease of the EPH-gestosis is described from the immunological viewpoint. The following facts may be significant: 1. The increased occurence of specific and nonspecific crossreacting antibodies against liver, kidney and placental tissue in the blood of pregnant women and puerperas. 2. The increased occurence of placental infarctions and throphoblastic defects as well as fibrinoid deposits in the placenta, the arteriols and in the kidney. 3. Changes in the protein composition of blood. 4. The changed maternal cell-mediated immunity.     

Immunological aspects of the pathogenesis of pregnancy hypertension

Changes involving the immune system may be instigators of, or consequent upon, disorders in other systems in the natural history of gestosis. The extent of the immune 'disorder' may not correlate with the severity of the disease as manifest in either eclampsia or fetal death. A number of variables, e.g. hormonal and genetic, could affect any immunological trigger mechanism or any secondary altered immune response. Thus attempts to find an immunological factor in gestosis that operates in all cases may prove unrewarding. Certain matings, immunogenetic constitutions, or certain feto-maternal immune relationships may predispose to a particular pathology and directly or indirectly potentiate other pathological processes. Others may either have no effect or conceivably have even a homeostatic effect protecting the maternal host from pathological change. The picture of the role of immunological factors in the pathogenesis of pregnancy hypertension is no more, as yet, than a few hesitant, unrelated lines. However, the lines are getting more numerous and stronger.     

Ultrastructural aspects of preeclampsia. II. Mitochondrial changes

Biopsy specimens were obtained under direct vision at the time of cesarean section from 47 patients (35 with preeclampsia and 12 normotensive patients) and from four women with cesarean section hysterectomies (all normotensive) as an extension of previous work. Tissues were obtained from the myometrium near the placental bed and from the opposite side of the uterus. Skin biopsies were also obtained from eight women with preeclampsia and liver biopsies were obtained from two patients with acute microvesicular fatty change of pregnancy (one with and one without concomitant preeclampsia). Specimens were examined histologically and by electron microscopy. Mitochondrial changes in small vessels, principally venules, in myometrial smooth muscle, myometrial interstitial cells, circulating leukocytes, epidermal and dermal cells, and hepatocytes were examined and compared between women with preeclamptic and normotensive pregnancies. These findings were then compared with mitochondria from 500 biopsies over the same 3-year interval to assess the possible role of delay in tissue fixation. There were 12 other biopsies from nonpregnant women of childbearing age. As further control on artifact, other specimens were initially sampled immediately in the operating room and then serially for up to 2 hours later. Artifact as a basis for the mitochondrial changes was ruled out by these procedures. Normal mitochondria undergo a morphologic conformational sequence with physiologic changes in substrate, oxygen consumption, adenosine diphosphate, and respiratory rate. The mitochondria of preeclamptic tissues show a central disruption that is outside this normal sequence or cycle. This disruption occurs more often and is more severe in preeclampsia than in normotensive pregnancies. In addition, the hypertrophic smooth muscle of the pregnant uterus has a complex of cytoplasmic organelles in a paranuclear location, usually apical, that contains a variable mixture of glycogen, the Golgi apparatus, endoplasmic reticulum, mitochondria, and small unidentified microvesicles. This complex has the location and appearance suggestive of a myometrial "power pack" of significance in metabolism and contraction. The presence of similar mitochondrial changes in a limited sample of nonuterine tissues is suggestive of a systemic metabolic disorder as an important feature of preeclampsia.     

Immunological aspects of pathological pregnancy (infertility immunology)

As, theoretically, any of the many mechanisms that appear to operate in normal pregnancy to maintain maternofetal immunologic balance could be altered in pathologic pregnancy, a detailed study of the known immunological aspects of pathological pregnancy is given. After looking into the parental genetic heterozygosity and fertility, a good explanation of the antifetal immunoresponse by the pregnant mother including the antibody formation is shown. The placental transport versus trapping of immunoglobulins is described in detail and it is also shown that the placenta is a source of a number of agents that inhibit cell-mediated immunity (HCG, HPL and steroids). These substances may affect a local inhibition of maternal cell-mediated immunity in the vicinity of the trophoblast. The placenta serves as an effective barrier for transfer of immunocompetent maternal lymphocytes to the fetus. The paramount role of the trophoblast as a barrier, while itself escaping immunologic destruction, calls for further studies.