Fetal hydropsia: challenges in etiologies

Introduction: Fetal hydrops is defined as the presence of abnormal fluid collections in two or more extravascular fetal compartments and body cavities. There are about 150 different underlying causes known today potentially leading to this fetal alteration. Objective: To analyze the etiologies involved in the occurrence of cases of fetal hydrops. Methods: A systematic literature review was carried out using the MedLine, Pubmed and Scielo databases, from 2015 to 2021, using the expressions: "fetal, hydrop, etiologies." Discussion: Fetal hydrops is divided into immune and non-immune. Immune results from anemia secondary to erythroblastosis by alloimmunization, so when there is maternal exposure to fetal antigens, it generates an immune response that results in the production of antibodies. History of blood transfusions, previous births, trauma and a history of alloimmunization are characterized as risk factors. Thus, immunoprophylaxis with anti-D immunoglobulin is indicated for all RhD negative pregnant women, with RhD positive male partner, with abundant fetal maternal hemorrhage during childbirth or events with potential sensitizer in the prenatal period. Conclusion: For an effective treatment, it is essential to identify the type of fetal hydrops in the patient and then the etiology of the disease, which is quite variable in Non-Immune Fetal Hydrops.

CD91 Derived Treg Epitope Modulates Regulatory T Lymphocyte Response, Regulates Expression of Costimulatory Molecules on Antigen-Presenting Cells, and Rescues Pregnancy in Mouse Pregnancy Loss Model

The loss of immune tolerance to fetal antigens may result in reproductive failure. The downregulated number and activity of T regulatory lymphocytes, which are critical for the establishment of immune tolerance to fetal antigens, during pregnancy may lead to miscarriage. The adoptive transfer of Tregs prevents fetal loss in abortion-prone mice. Recently, we demonstrated that the administration of tregitopes, which are short peptides found in human and mouse immunoglobulins (IgGs), decreased the incidence of abortions in female CBA/J mice mated with DBA/2J mice. Here, two non-IgG source peptides (SGS and LKD) that can potentially bind to the major histocompatibility complex II (MHC II) with high affinity and induce Treg expansion were designed in silico. The immune dysregulation-induced pregnancy failure mouse model was used to evaluate the effect of SGS and LKD on immune response and pregnancy outcome. The fetal death rate in the SGS-treated group was lower than that in the phosphate-buffered saline-treated group. SGS and LKD upregulated the splenic pool of Tregs and modulated the T-helper cell (Th1)/Th2-related cytokine response at the preimplantation stage. Additionally, SGS and LKD downregulated the expression of CD80 and MHC class II molecules in splenic CD11c+ antigen-presenting cells. Thus, SGS treatment can result in beneficial pregnancy outcomes. Additionally, SGS peptide-mediated immunomodulation can be a potential therapeutic strategy for immune dysregulation-induced pregnancy failure.

Complement in structure and immune homeostasis in placenta

Aberrant complement activation can induce “thrombo-inflammation” attacks to host tissue. Beside kidney and blood vessel, the placenta is also susceptible to these attacks. Complement dysregulation is recently classified as one of the new mechanisms leading to pregnancy disorders. Studies have indicated that dampening complement activation can ameliorate pregnancy outcomes. During pregnancy, the mother’s immune system is finely domesticated to accept the semi-allogeneic fetal antigens. As an important part of the innate immune system, some interesting changes have also taken place in complement system during pregnancy. The complement proteins are highly expressed in placenta, and their split products are increased. They are tuned in maintain placental immunity and structural homeostasis. An abundance of evidence shew that complement protein deficiency lead to autoimmunity disease and pathological pregnancy marked by excessive inflammation. Although complement suppressing strategies have been proven effective in treating some pathological pregnancy in individual case studies. we should take the dual role of the complement into consideration that fully and completely inhibit of complement may not be a wise choice.

Neonatal Immune Incompatibilities between Newborn and Mother

Background: Incompatibilities between the mother and unborn baby can cause complications that must be identified early to initiate the appropriate treatment. For example, neonatal alloimmune thrombocytopenia (NAIT), neonatal alloimmune neutropenia (NAIN), and morbus hemolyticus neonatorum affect children worldwide. Aim: This literature review aims to depict the similarities and differences between these three disorders from a clinical and mechanistic point of view. Material and Methods: The current literature review entailed conducting a systematic search to locate articles on the three conditions. Different electronic databases, including PsycINFO, PubMed, Web of Science, and CINAHL, were searched using the search terms “neonatal alloimmune thrombocytopenia”, “neonatal alloimmune neutropenia”, “morbus hemolyticus neonatorum”, “NAIT”, “FNAIT”, “fetal”, “NAIN”, and “hemolytic disease of the newborn”. Results: This review shows that these three diseases are caused by incompatibilities between the maternal and fetal immune systems. Furthermore, these conditions can lead to severe complications that hinder fetal development and cause death if not well managed. Discussion: The current literature review shows that NAIT, NAIN, and morbus hemolyticus neonatorum are rare conditions that occur when the mother produces antibodies against the fetal immune system. Thus, there is a need for the early detection of these conditions to initiate appropriate treatment before the child experiences adverse effects. Conclusion: The development of NAIT, NAIN, and morbus hemolyticus neonatorum is linked to the production of antibodies against the fetal immune system and fetal antigens. Further studies are required to determine potential interventions to reduce the risk of developing these three conditions.

Immune function during pregnancy varies between ecologically distinct populations

Background and objectives Among placental mammals, females undergo immunological shifts during pregnancy to accommodate the fetus (i.e. fetal tolerance). Fetal tolerance has primarily been characterized within post-industrial populations experiencing evolutionarily novel conditions (e.g. reduced pathogen exposure), which may shape maternal response to fetal antigens. This study investigates how ecological conditions affect maternal immune status during pregnancy by comparing the direction and magnitude of immunological changes associated with each trimester among the Tsimane (a subsistence population subjected to high pathogen load) and women in the USA. Methodology Data from the Tsimane Health and Life History Project (N = 935) and the National Health and Nutrition Examination Survey (N = 1395) were used to estimate population-specific effects of trimester on differential leukocyte count and C-reactive protein (CRP), a marker of systemic inflammation. Results In both populations, pregnancy was associated with increased neutrophil prevalence, reduced lymphocyte and eosinophil count and elevated CRP. Compared to their US counterparts, pregnant Tsimane women exhibited elevated lymphocyte and eosinophil counts, fewer neutrophils and monocytes and lower CRP. Total leukocyte count remained high and unchanged among pregnant Tsimane women while pregnant US women exhibited substantially elevated counts, resulting in overlapping leukocyte prevalence among all third-trimester individuals. Conclusions and implications Our findings indicate that ecological conditions shape non-pregnant immune baselines and the magnitude of immunological shifts during pregnancy via developmental constraints and current trade-offs. Future research should investigate how such flexibility impacts maternal health and disease susceptibility, particularly the degree to which chronic pathogen exposure might dampen inflammatory response to fetal antigens. Lay Summary This study compares immunological changes associated with pregnancy between the Tsimane (an Amazonian subsistence population) and individuals in the USA. Results suggest that while pregnancy enhances non-specific defenses and dampens both antigen-specific immunity and parasite/allergy response, ecological conditions strongly influence immune baselines and the magnitude of shifts during gestation.

Specific immunological areactivity formation during gestation period in pregnant sows

Changes in immunological reactivity to viral and bacterial antigens may cause increased susceptibility to infectious diseases. Different levels of this condition in newborn and adult animal organisms should be based on the fact that the fetus and newborn after birth first comes into contact with the antigen, while the adult body already has partial sensitization. Chronic carrier of pathogens in animals and their influence on the spread of the infectious process is an urgent problem of modern veterinary medicine. The possibility of vaccination in newborns is limited by the presence of maternal antibodies that have an immunosuppressive effect. A high level of functional reserves of the pregnant body is important in the prevention of intrauterine infection. On the one hand, infection in the prenatal period of development affects the processes of growth and development of the fetus, on the other hand, during this period, the mother's body is isoimmunized by fetal antigens, accompanied by increased sensitivity of the body with the predominant manifestation of cellular phenomena in the absence of enhanced antibody synthesis.

Mixed signature of activation and dysfunction allows human decidual CD8+ T cells to provide both tolerance and immunity

Understanding how decidual CD8+ T cell (CD8+ dT) cytotoxicity is regulated and how these cells integrate the competing needs for maternal–fetal tolerance and immunity to infection is an important research and clinical goal. Gene-expression analysis of effector-memory CD8+ dT demonstrated a mixed transcriptional signature of T cell dysfunction, activation, and effector function. High protein expression of coinhibitory molecules PD1, CTLA4, and LAG3, accompanied by low expression of cytolytic molecules suggests that the decidual microenvironment reduces CD8+ dT effector responses to maintain tolerance to fetal antigens. However, CD8+ dT degranulated, proliferated, and produced IFN-γ, TNF-α, perforin, and granzymes upon in vitro stimulation, demonstrating that CD8+ dT are not permanently suppressed and retain the capacity to respond to proinflammatory events, such as infections. The balance between transient dysfunction of CD8+ dT that are permissive of placental and fetal development, and reversal of this dysfunctional state, is crucial in understanding the etiology of pregnancy complications and prevention of congenital infections.

Modification of immune response to xenogeneic embryonic proteins by adjuvants of microbial origin

<p>Blood serum of BALB/c mice immunized with chicken embryonic proteins (CEP) in combination with adjuvants<br />of microbial origin has been investigated by methods of enzyme immunoassay and immunoblotting. The analysis<br />of accumulation of antibodies to CE P and the study of antibody-dependent cytotoxicity of lymphocytes against the<br />tumor cells of the model suggest that the use of adjuvants of microbial origin, such as protein-containing metabolites<br />of culture fluid (18.5 and 70 kDa) and lipid fraction of В. subtilis B-7025 cells; S. aureus cell-wall peptidoglycan,<br />contributes to credible strengthening of immune response to fetal antigens. The results of the study are the basis<br />for creating xenogenic cancer vaccine.</p>

Immunity

Immunological health relies on a balance between immune responsiveness to foreign pathogens and tolerance to self-components, commensals, food-derived components, and semi-allogeneic fetal antigens. Disruptions of this balance are hallmarks of immunodeficiency diseases, autoimmune diseases, and pregnancy failure. Patients with chronic kidney disease are immunologically unique in demonstrating features of both chronic inflammation and acquired immunodeficiency—predisposing these individuals to the two commonest causes of death, namely cardiovascular disease and sepsis. Defects and abnormalities in almost all components of the immune system can be observed, although it is difficult to say whether the observations denote mechanism or effect. This chapter reviews, briefly, measurable immune system abnormalities in chronic kidney disease and some of the potential underlying mechanisms.