Asymmetric antibodies (AAb) in the female reproductive tract.

Vaginal mucosa has been shown to play an important role in fertility, since several changes during the estrous cycle determine fertility and pregnancy outcome. The contribution of vaginal fluid IgG antibodies (Abs) to these changes is not fully characterized. Asymmetric Abs (AAb) are a subpopulation of IgG Abs bearing a carbohydrate residue in only one Fab region of the molecule, being therefore functionally univalent and unable to trigger immunological mechanisms tending to destroy the antigens. Here, we investigated the presence of AAb in vaginal secretions of virgin mice. Vaginal fluids were extracted from CBA/J female, where asymmetric IgG molecules were characterized by differential ELISA tests. Additionally, the phenotype of vaginal lymphocytes (VL) was analyzed by flow cytometry. Our data indicate a variation in the percentage of AAb during estrous cycle, since we observed a significant increase in asymmetric IgG molecules levels after ovulation. Regarding the AAbs isotypes, we identified IgG1 as the principal component of the synthesized AAbs. Eighty percent of the AAbs were directed against normal flora, and about 20% of them reacted with vaginal epithelium antigens. Flow cytometry studies revealed TCRalphabeta and gammadelta populations, but a lack of CD8+ T-cells in vaginal mucosa. Since we found a high concentration of AAbs in murine vaginal secretions during metestrus and AAbs were previously found to be protective, it is tempting to speculate that AAbs would provide protection of normal flora in the vaginal lumen. Additionally, we observed that the levels of AAbs decrease when susceptibility to infection in mice occurs at proestrus/estrus, further suggesting a protective role for AAbs.

Modified immunoglobulin G glycosylation pattern during turpentine-induced acute inflammation in rats.

Alterations in the pattern of protein glycosylation have been described during inflammation. In chronic parasitic and tumoral diseases we have reported an increase in the proportion of serum Immunoglobulin G (IgG) molecules possessing an altered Fab glycosylation pattern designated asymmetric antibodies. The alteration results in augmented concanavalin A affinity and functional univalence of the antibody. In addition, Fc agalactosylation has been described as occurring in chronically autoimmune diseases. Therefore, the aim of this paper was to evaluate by analyzing sera whether during an acute inflammatory response in rats produced by subcutaneous inoculation of turpentine oil, there was an alteration in the synthesis and glycosylation of IgG (as revealed by concanavalin A binding). We found that during acute inflammation there was a decrease in the synthesis of IgG which was not affected by prior oral administration of dexamethasone; however, the turpentine-induced increase in IgG binding to concanavalin A was found to be inhibited upon prior administration of the anti-inflammatory agent. As with turpentine, the corticoid used induced an increase in the interleukin-6 levels detected in sera by ELISA. Although we have described an improvement in asymmetric antibody synthesis by low dose of interleukin-6 previously, here we found no correlation between the observed glycosylation pattern of IgG and interleukin-6 concentration assessed in sera of treated rats, probably due to a different dexamethasone mediated pathway.

Comparative immunohistochemical study of M-CSF and G-CSF in feto-maternal interface in a multiparity mouse model.

PROBLEM: Multiparity status has been found to bring beneficial effects both to the maintenance of pregnancy and to the offspring; however, these effects have not been fully explained. We have previously reported that placentae obtained from multiparous females belonging to a syngeneic mouse crossbreeding showed an important increase in the number of placental macrophages, suggesting that they might constitute a protective subpopulation. Taking into account that macrophage-colony stimulating factor (M-CSF) and granulocyte-colony stimulating factor (G-CSF) have proved to modulate macrophage activity and that both factors and/or their receptors have been found at feto-maternal interface, in this paper we analyzed the presence of M-CSF and G-CSF in placental tissue employing the same multiparity mouse model in order to investigate the influence of parity status on local immunoregulation factors of macrophage activity. METHOD OF STUDY: Three groups of mice (CBA/J x CBA/J) were analyzed: Primiparous Young, 3.0 +/- 0.5 months old (PY); Primiparous Old, 8.5 +/- 0.5 months old (PO) and Multiparous Old, 8.5 +/- 0.5 months old, with three to four previous pregnancies (MO). The presence of M-CSF and G-CSF in placental tissue was analyzed by immunohistochemistry. Cytokeratin (CK) and vimentin (VIM) expression and PAS staining were also studied. RESULTS: The three groups showed a similar immunostaining pattern for M-CSF in the whole placental trophoblast, while the expression of G-CSF was significantly higher only in the spongy zone in the MO group. Furthermore, all the MO placentae showed 5-11 layers of cells adjacent to the decidua, where G-CSF and M-CSF were highly detected. Conversely, they constituted a thin layer in PY and PO placentae. These cells were proved to be CK(+) and VIM(-) thus demonstrating their trophoblast origin. In addition, the layers closer to the decidua were also PAS+ suggesting that they could be interstitial cells, a type of invading trophoblast. CONCLUSIONS: In our mouse model, we observed an increase in the expression of G-CSF in placental spongiotrophoblast cells in multiparous females, which have been previously proposed as progenitors of the interstitial cells. Furthermore, this is the first report that indicates that parity status increases trophoblast invasion inducing a proliferative effect of the invading cells on the maternal tissue. We suggest that M-CSF and G-CSF secreted by these invading cells could favor the recruitment of macrophages to the trophoblast and might modulate their activity inducing a switch to a protective, non-inflammatory population.

Intercellular adhesion molecule-1/LFA-1 cross talk is a proximate mediator capable of disrupting immune integration and tolerance mechanism at the feto-maternal interface in murine pregnancies.

Our understanding why a woman's immune system does not reject her histoincompatible fetus is still very limited. Distinct insights into the mechanisms involved in pregnancy maintenance may help us to prevent pregnancy complications, e.g., miscarriages or pre-eclampsia. Immune integration and tolerance at the feto-maternal interface appear to be indispensable for successful pregnancy maintenance. Little is known about the cross talk between ICAM-1, expressed on epithelium, endothelium, and APC, and its ligand, LFA-1, at the feto-maternal interface. However, based on the role of ICAM-1/LFA-1 in allograft acceptance or rejection upon transplantation, adhesion molecules are likely to interfere with successful pregnancy outcome. In this study, we tested the hypothesis that ICAM-1/LFA-1 pathways may be involved in pregnancy rejection in murine models. By blocking ICAM-1/LFA-1-mediated intercellular adhesion events, we show that fetal immune acceptance is restored in challenged pregnancies (e.g., upon exposure to sound stress), and adoptive transfer of LFA-1 cells into pregnant mice induces rejection only in abortion-prone mouse models. ICAM-1/LFA-1 cross talk leads to increased recruitment of proinflammatory cells to the implantation site, promotes dendritic cell maturation in the decidua, and subsequently induces additional local Th1 polarization via mature dendritic cells. Furthermore, our observations clearly point out that mechanisms of fetal tolerance, e.g., indoleamine 2,3-dioxygenase expression, presence of CD4+CD25bright regulatory T cells, and synthesis of asymmetric Abs, are ICAM-1/LFA-1 dependent. Hence, our data shed light on a hierarchical network of immune integration at the feto-maternal interface, in which ICAM-1/LFA-1 cross talk is clearly a proximate mediator capable of disrupting successful pregnancy maintenance.

The immunomodulatory action of dexamethasone on monoclonal antibody-producing hybridoma cells.

As found in different studies, glucocorticoid hormones (GCs) as well as interleukin-6 (IL-6) are involved in the modulation of protein glycosylation. In this work we have investigated the immunomodulatory effect of dexamethasone by assessing in vitro IgG glycosylation by monoclonal antibody-producing hybridoma cells. As described in myeloma cell lines, cellular viability and proliferation rates of hybridoma 112D5 cells decrease when cultured with dexamethasone during 24 hours, in a dose-dependent way. Moreover, the corticosteroid triggered apoptosis of the hybridoma, which was observed as soon as 4 h after culturing cells in the presence of the drug. In line with these results, after 24 h, dexamethasone induced a drop in the anti-DNP level of antibodies synthesized by hybridoma 112D5. In previous works we described that asymmetric glycosylation of in vitro synthesized IgG correlated with induction of cell damage. Nevertheless, an increase in asymmetric IgG glycosylation was not observed here, but there was a decrease in the proportion of asymmetrically glycosylated IgG synthesized by the hybridoma after a 4-h culture with the drug. Finally, as results from assessing IL-6 production by ELISA, we conclude that the above described effects of dexamethasone on hybridoma 112D5 cells could not be due to the inhibition of IL-6 synthesis exerted by the corticoid but rather to a direct effect of the drug. Monoclonal antibody (MAb) producing hybridomas provide an excellent in vitro model for the study of the molecular mechanisms involved in immunoglobulin glycosylation.

Occurrence, properties, and function of asymmetric IgG molecules isolated from non-immune sera.

We have previously demonstrated that 10-20% of the IgG isolated from non-immune sera is asymmetrically glycosylated, in such a way that it fails to trigger immune effector mechanisms. As a result, a major portion of the non-immune asymmetric IgG molecules of the host could be self-specific, acting as auto-protective antibodies. In order to test this hypothesis, we investigated whether asymmetric IgG molecules are capable of recognizing self-antigens. About 40% of F(ab')2 fragment from normal rat IgG was able to react specifically with autologous rat cells. Moreover, upon being purified from normal rat sera, 78% of the asymmetric IgG sub-population showed self-reactivity. We demonstrated that about 14% of rat asymmetric IgG-F(ab')2 fragments was able to react with bacteria isolated from the intestine of uninfected rats. Lastly, in order to test whether there is a correlation between the decline of immune responses during ageing and asymmetric antibody production, we assayed IgG isolated from sera of young and old rats. There was an increase in the asymmetric:symmetric IgG ratio with ageing. We therefore suggest that asymmetric antibodies may exert a beneficial action by protecting self-antigens as well as normal intestinal flora from a deleterious immune response.

Depletion of CD8+ cells abolishes the pregnancy protective effect of progesterone substitution with dydrogesterone in mice by altering the Th1/Th2 cytokine profile.

One of the most remarkable immunological regulations is the maternal immune tolerance toward the fetal semiallograft during pregnancy, which has been referred to as immunity's pregnant pause. Rejection of the semiallogeneic trophoblast cells must be selectively inhibited and pathways presumably include Th2 cytokines unopposed by Th1 cytokines. Steroid hormones, including progesterone, have similar effects. Low levels of progesterone and Th2 cytokines and high levels of Th1 cytokines are attributable for increased abortions in mammalians, which may be triggered by psychoemotional stress. Thus, the aim of the present study was to provide experimental evidence for the mechanism involved in the mediation of immune responses by endocrine signals during pregnancy and stress-triggered pregnancy failure. DBA/2J-mated CBA/J female mice were randomized in three groups: 1) control females, 2) mice exposed to stress on gestation day 5.5, and 3) mice exposed to stress and substituted with dydrogesterone, a progestogen with a binding profile highly selective for the progesterone receptor on gestation day 5.5. On gestation days 7.5, 9.5, and 10.5, mice of each group were sacrificed, and the frequency of CD8(+) cells and cytokine expression (IL-4, IL-12, TNF-alpha, IFN-gamma) in blood and uterus cells was evaluated by flow cytometry. Additionally, some mice were depleted of CD8 cells by injection of mAb. We observed that progesterone substitution abrogated the abortogenic effects of stress exposure by decreasing the frequency of abortogenic cytokines. This pathway was exceedingly CD8-dependent, because depletion of CD8 led to a termination of the pregnancy protective effect of progesterone substitution.

Therapy with dendritic cells influences the spontaneous resorption rate in the CBA/J x DBA/2J mouse model.

PROBLEM: DBA/2J-mated CBA/J female mice are prone to a high incidence of fetal abortions. This fetal wastage can be dramatically reduced by immunizing the female mice with BALB/c, but not with DBA/2J spleen cells during early gestation. Nevertheless, the underlying mechanisms remain to be elucidated. Recently, dendritic cells (DC) have been described at the feto-maternal interface in the human uterus. In this work, we studied the effect of adoptive transfer of DC on the maintenance of pregnancy in the CBA/J x DBA/2J model. METHODS: Bone marrow-derived DC were generated from virgin female CBA/J mice (6-8 weeks old). CBA/J females were inoculated with DC twice before mating. Four different experimental groups were included: (i) no treatment control, (ii) mice injected with culture medium [granulocyte-macrophage colony-stimulating factor (GM-CSF)], (iii) immunized with DC and (iv) immunized with paternal DBA/2J antigens lisate-pulsed DC, n = 5. RESULTS: The control abortion rate was 23.8%, and with GM-CSF alone was 17.6%. Following inoculation of syngeneic DC abortion rates were reduced to 2.2%, but protection was short-lived. Abortion rates with DC pulsed with DBA/2J antigens was 5%. Serum of interleukin (IL)-6 levels were lower in the latter two groups up to the time of abortion. The kinetics of immunoglobulin G asymmetric antibodies synthesis was modified, but there was no correlation between asymmetric antibodies production and the lowering of abortions rates. CONCLUSION: Syngeneic DC prevented abortions and this was linked to a decrease in IL-6 levels, but not with levels of asymmetric antibodies.

Lineage, maturity, and phenotype of uterine murine dendritic cells throughout gestation indicate a protective role in maintaining pregnancy.

Dendritic cells (DCs) are known to play a major role in the induction, maintenance, and regulation of immune responses. Recently, DCs have been described to be present at the feto-maternal interface in human decidua. However, only limited information is available about DC presence, phenotype, and--more importantly--function throughout gestation. Thus, we analyzed local (uterine) and systemic (blood) DCs in a murine model. DBA/2J mated CBA/J females with vaginal plugs were separated and killed on Gestation Days (GDs) 1.5, 3.5, 5.5, 6.5, 7.5, 8.5, 10.5, 13.5, 15.5, or 17.5. Frequency of uterine and blood CD11c+ DC, phenotype (coexpression of CD8alpha and major histocompatibility complex class II [MHC II] antigens), and presence of intracellular cytokines (interleukins 12 and 10) were determined by flow cytometry. The morphology of DC in the pregnant uterus was evaluated by immunohistochemistry. In uterus, the relative number of CD11c+ cells increased from GD 5.5, reaching a plateau on GD 9.5 until GD 17.5, while a transient peak of systemic CD11c+ cells was found on GD 8.5 and 10.5. The vast majority of uterine DCs were CD8alpha- and thus, belonged to the myeloid lineage. Interestingly, a significant peak of lymphoid DC was present on GD 1.5 and 5.5. Further, significantly more intracellular interleukin 10 than interleukin 12 was present in CD11c+ cells. Interestingly, mature DCs (MHC II+) were diminished from GD 5.5 to 8.5. Characterization of CD11c+ cell kinetics in uterus and blood reveals variation of phenotype during pregnancy, pointing toward an eminent immunoregulatory role of DCs throughout gestation at the feto-maternal interface.

Murine abortion is associated with enhanced interleukin-6 levels at the feto-maternal interface.

CBA/JXDBA/2J murine abortion is known to be associated with increased local and peripheral Th1-cytokines levels. The role of the pro-inflammatory interleukin-6 (IL-6) in murine abortion remains unclear. In humans, IL-6 was reported to be elevated at the onset of spontaneous abortion. The aim of our study was to evaluate the levels of IL-6 during murine pregnancy in (1) the normal murine pregnancy combination CBA/JXBALB/c and in (2) the CBA/JXDBA/2J abortion prone mating combination. We measured IL-6 serum levels by ELISA and local (placental and decidual) IL-6 levels by flow cytometry and immunohistochemistry. The expression of the IL-6 receptor gp80 was further analyzed. We additionally evaluated the number of mast cells and macrophages at the feto-maternal interface as a putative IL-6 source in reproductive tissues. IL-6 and gp80 were expressed in decidual cells as well as in different trophoblast types. Flow cytometry analysis showed increased numbers of IL-6+ cells in abortion placentas and deciduas compared to control pregnant mice. We observed an elevated number of mast cells and macrophages at the feto-maternal interface from abortion mice in comparison to control mice. Interestingly, we found very high numbers of mast cells, macrophages and IL-6+ cells in resorption tissue compared to control tissues. Flow cytometry studies confirmed that macrophages are being an important source of IL-6 at the feto-maternal interface. The mRNA IL-6 levels were also enhanced in placenta and decidua from mice with high abortion rate compared to normal pregnant mice, as analyzed by RT-PCR. Our results suggest that IL-6 produced not only by immunocompetent cells such as macrophages and mast cells, but also by trophoblasts and decidua cells, is directly involved in the pathology of abortion.

Participación de factores de transcripción en la regulación de la diferenciación linfocitaria / Participation of transcriptional factors in the regulation of lymphocyte differentiation

Los cambios citomorfológicos y la expresión de determinados marcadores en los distintos estadios de la diferenciación linfocitaria son bien conocidos. Los estudios sobre patrones de expresión de genes específicos de las células linfoides y los mecanismos de su regulación, han llevado últimamente a clarificar los mecanismos fundamentales del desarrollo y activación de estas células. Se han aprofundizado los conocimientos sobre los "enhancers" y promotores, elementos regulatorios de esos genes, y de los factores de transcripción que se unen a esos elementos. En el trabajo que se presenta se hace un análisis de estos componentes y de la participación de algunos de ellos, como los PU.1, Ikaros, Aiolos, GATA-3, Egf-1, E2A, EBF-1, PAX-5 (BSAP), TFE-3, Oct-1, Oct-2 y NF-kB en la regulación de los estadios de diferenciación de las series linfoides B y T.

Participación de factores de transcripción en la regulación de la diferenciación linfocitaria / Participation of transcriptional factors in the regulation of lymphocyte differentiation

Los cambios citomorfológicos y la expresión de determinados marcadores en los distintos estadios de la diferenciación linfocitaria son bien conocidos. Los estudios sobre patrones de expresión de genes específicos de las células linfoides y los mecanismos de su regulación, han llevado últimamente a clarificar los mecanismos fundamentales del desarrollo y activación de estas células. Se han aprofundizado los conocimientos sobre los "enhancers" y promotores, elementos regulatorios de esos genes, y de los factores de transcripción que se unen a esos elementos. En el trabajo que se presenta se hace un análisis de estos componentes y de la participación de algunos de ellos, como los PU.1, Ikaros, Aiolos, GATA-3, Egf-1, E2A, EBF-1, PAX-5 (BSAP), TFE-3, Oct-1, Oct-2 y NF-kB en la regulación de los estadios de diferenciación de las series linfoides B y T. (AU)

Modified immunoglobulin G glycosylation pattern during turpentine-induced acute inflammation in rats

Alterations in the pattern of protein glycosylation have been described during inflammation. In chronic parasitic and tumoral diseases we have reported an increase in the proportion of serum Immunoglobulin G (IgG) molecules possessing an altered Fab glycosylation pattern designated asymmetric antibodies. The alteration results in augmented concanavalin A affinity and functional univalence of the antibody. In addition, Fc agalactosylation has been described as occurring in chronically autoimmune diseases. Therefore, the aim of this paper was to evaluate by analyzing sera whether during an acute inflammatory response in rats produced by subcutaneous inoculation of turpentine oil, there was an alteration in the synthesis and glycosylation of IgG (as revealed by concanavalin A binding). We found that during acute inflammation there was a decrease in the synthesis of IgG which was not affected by prior oral administration of dexamethasone; however, the turpentine-induced increase in IgG binding to concanavalin A was found to be inhibited upon prior administration of the anti-inflammatory agent. As with turpentine, the corticoid used induced an increase in the interleukin-6 levels detected in sera by ELISA. Although we have described an improvement in asymmetric antibody synthesis by low dose of interleukin-6 previously, here we found no correlation between the observed glycosylation pattern of IgG and interleukin-6 concentration assessed in sera of treated rats, probably due to a different dexamethasone mediated pathway (AU)#S#a

Modified immunoglobulin G glycosylation pattern during turpentine-induced acute inflammation in rats.

Alterations in the pattern of protein glycosylation have been described during inflammation. In chronic parasitic and tumoral diseases we have reported an increase in the proportion of serum Immunoglobulin G (IgG) molecules possessing an altered Fab glycosylation pattern designated asymmetric antibodies. The alteration results in augmented concanavalin A affinity and functional univalence of the antibody. In addition, Fc agalactosylation has been described as occurring in chronically autoimmune diseases. Therefore, the aim of this paper was to evaluate by analyzing sera whether during an acute inflammatory response in rats produced by subcutaneous inoculation of turpentine oil, there was an alteration in the synthesis and glycosylation of IgG (as revealed by concanavalin A binding). We found that during acute inflammation there was a decrease in the synthesis of IgG which was not affected by prior oral administration of dexamethasone; however, the turpentine-induced increase in IgG binding to concanavalin A was found to be inhibited upon prior administration of the anti-inflammatory agent. As with turpentine, the corticoid used induced an increase in the interleukin-6 levels detected in sera by ELISA. Although we have described an improvement in asymmetric antibody synthesis by low dose of interleukin-6 previously, here we found no correlation between the observed glycosylation pattern of IgG and interleukin-6 concentration assessed in sera of treated rats, probably due to a different dexamethasone mediated pathway.

Modified immunoglobulin G glycosylation pattern during turpentine-induced acute inflammation in rats

Alterations in the pattern of protein glycosylation have been described during inflammation. In chronic parasitic and tumoral diseases we have reported an increase in the proportion of serum Immunoglobulin G (IgG) molecules possessing an altered Fab glycosylation pattern designated asymmetric antibodies. The alteration results in augmented concanavalin A affinity and functional univalence of the antibody. In addition, Fc agalactosylation has been described as occurring in chronically autoimmune diseases. Therefore, the aim of this paper was to evaluate by analyzing sera whether during an acute inflammatory response in rats produced by subcutaneous inoculation of turpentine oil, there was an alteration in the synthesis and glycosylation of IgG (as revealed by concanavalin A binding). We found that during acute inflammation there was a decrease in the synthesis of IgG which was not affected by prior oral administration of dexamethasone; however, the turpentine-induced increase in IgG binding to concanavalin A was found to be inhibited upon prior administration of the anti-inflammatory agent. As with turpentine, the corticoid used induced an increase in the interleukin-6 levels detected in sera by ELISA. Although we have described an improvement in asymmetric antibody synthesis by low dose of interleukin-6 previously, here we found no correlation between the observed glycosylation pattern of IgG and interleukin-6 concentration assessed in sera of treated rats, probably due to a different dexamethasone mediated pathway (AU)#S#a

Los anticuerpos bloqueantes: ¿beneficiosos o perjudiciales para el huésped?: importancia de su identificación y dosaje / Blocking antibodies: beneficial or harmful to the host?: significance of their identification and quantification

Durante una respuesta inmune ocurren cambios en la cantidad y calidad de los anticuerpos que se sintetizan. En el presente trabajo se describen las propiedades fisicoquímicas y el comportamiento biológico de los anticuerpos asimétricos, así como su funcionamiento beneficioso o perjudicial para el huésped, de acuerdo con la naturaleza del antígeno y la situación particular en la que actúan. Estos anticuerpos son de la clase IgG, actúan como bloqueantes, univalentes, incapaces de formar complejos adecuados para la activación de los mecanismos biológicos que llevan al daño del agente agresor. Tienen dos paratopes, uno de los cuales es de muy baja afinidad para el antígeno, lo que es consecuencia de un impedimento estérico originado por un hidrato de carbono del tipo high mannose, que determina la asimetría funcional, haciendo que se comporten como univalentes. Cuando los anticuerpos asimétricos tienen especificidad para antígenos propios son beneficiosos para el huésped, participando en los mecanismos de la tolerancia, siendo perjudiciales cuando los antígenos son extraños, como ocurre en las infecciones microbianas crónicas. Los anticuerpos asimétricos cumplen una función beneficiosa durante la preñez, no obstante de que los antígenos fetales de origen paterno, responsables del proceso son extraños para el huésped. La placenta secreta factores (moléculas) que regulan la síntesis de éstos anticuerpos, favoreciendo por éste mecanismo la sobrevida del feto en el útero materno. Finalmente, en el trabajo se describen métodos para detección y dosaje de anticuerpos bloqueantes así como ejemplos para la interpretación de los resultados obtenidos

Los anticuerpos bloqueantes: ¿beneficiosos o perjudiciales para el huésped?: importancia de su identificación y dosaje / Blocking antibodies: beneficial or harmful to the host?: significance of their identification and quantification

Durante una respuesta inmune ocurren cambios en la cantidad y calidad de los anticuerpos que se sintetizan. En el presente trabajo se describen las propiedades fisicoquímicas y el comportamiento biológico de los anticuerpos asimétricos, así como su funcionamiento beneficioso o perjudicial para el huésped, de acuerdo con la naturaleza del antígeno y la situación particular en la que actúan. Estos anticuerpos son de la clase IgG, actúan como bloqueantes, univalentes, incapaces de formar complejos adecuados para la activación de los mecanismos biológicos que llevan al daño del agente agresor. Tienen dos paratopes, uno de los cuales es de muy baja afinidad para el antígeno, lo que es consecuencia de un impedimento estérico originado por un hidrato de carbono del tipo high mannose, que determina la asimetría funcional, haciendo que se comporten como univalentes. Cuando los anticuerpos asimétricos tienen especificidad para antígenos propios son beneficiosos para el huésped, participando en los mecanismos de la tolerancia, siendo perjudiciales cuando los antígenos son extraños, como ocurre en las infecciones microbianas crónicas. Los anticuerpos asimétricos cumplen una función beneficiosa durante la preñez, no obstante de que los antígenos fetales de origen paterno, responsables del proceso son extraños para el huésped. La placenta secreta factores (moléculas) que regulan la síntesis de éstos anticuerpos, favoreciendo por éste mecanismo la sobrevida del feto en el útero materno. Finalmente, en el trabajo se describen métodos para detección y dosaje de anticuerpos bloqueantes así como ejemplos para la interpretación de los resultados obtenidos (AU)