Cervical Mucus Properties Stratify Risk for Preterm Birth

Background: Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth. Methods and Findings: To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus. Conclusions: Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.Massachusetts Institute of Technology. Charles E. Reed Faculty Initiative FundBurroughs Wellcome Fund (Preterm Birth Research Grant)National Science Foundation (U.S.). Graduate Research Fellowship Progra

Factors associated to infection by Toxoplasma gondii in pregnant women attended in Basic Health Units in the city of Rolândia, Paraná, Brazil

The aim of the present work was to determine the prevalence of IgG and IgM anti-Toxoplasma gondii antibodies and the factors associated to the infection in pregnant women attended in Basic Health Units in Rolândia, Paraná, Brazil. The sample was divided in two groups: group I (320 pregnant women who were analyzed from July 2007 to February 2008) and group II (287 pregnant women who were analyzed from March to October 2008). In group I, it was found 53.1% of pregnant women with IgG reactive and IgM non-reactive, 1.9% with IgG and IgM reactive, 0.3% with IgG non-reactive and IgM reactive and 44.7% with IgG and IgM non-reactive. In group II, it was found 55.1% with IgG reactive and IgM non-reactive and 44.9% with IgG and IgM non-reactive. The variables associated to the presence of IgG antibodies were: residence in rural areas, pregnant women between 35-40 years old, low educational level, low family income, more than one pregnancy, drinking water which does not originate from the public water supply system and the habit of handling soil or sand. Guidance on primary prevention measures and the quarterly serological monitoring of the pregnant women in the risk group are important measures to prevent congenital toxoplasmosis

Immune response: Tissue specific T-lymphocytes

The lymphatic system forms a 'blind' plexus of vessels that in general are found in tissue which has an inherently high replicative capacity. It is this system that is responsible for the rapid deployment and circulation of tissue-specific T-lymphocytes for the inspection of cell-surface aberrations within the tissue. The presence of tissue-specific T-lymphocytes explains why 90% of lymphocytes are found outside the lymphatic system and why they migrate in a selective manner. The tissue-specific T-lymphocyte is considered to express a common lymphocyte cell surface pattern, the homotype, and a tissue-specific cell-surface pattern, the histotype which may involve MHCA and mHCA. It is the histotypic pattern that is responsible for the tissue specificity of the tissue-specific T-lymphocyte. The presence of tissue-specific T-lymphocytes does pose problems for the immune system. If different tissue-specific T-lymphocytes met within a particular tissue, 'lost' lymphocytes, an immune response will be generated against the intruder (lost lymphocyte), and the intruder will not be able to recruit other immunocompetent cells in that tissue. This immune reaction is an attempt to change the histotypic pattern of the intruder. This situation would explain the autologous immune response. This response however is suppressed in the systemic system by immunosuppressive compounds from the liver. It is only in the tissues that the tissue-specific T-lymphocytes are released from this suppression, in order to initiate immune reactions against aberrant cell-surface patterns

Immunology of pregnancy: towards a unifying hypothesis

The variable findings of hormonal-immunoregulation and the variable cellular and humoral immune responses in pregnancy have been considered in relationship to the physiological response. From such considerations it appears that the peripheral blood lymphocyte/leukocyte response in pregnancy is not important, but rather the local uterine immune response at implantation and throughout pregnancy. It is proposed, and evidence is presented, that a normal allogeneic immune response is initiated at the time of implantation of the blastocyst. This immune response regulates the invasive nature of the trophoblast and initiates the first stage of parturition. The initiation and maintenance of this immune response is based on an interplay between maternal and paternal HLA and trophoblast antigens. In the case of HLA-incompatible donor-recipient blastocyst transplants, a more pivotal role for immunoregulation by trophoblast antigens is proposed. This is because it is considered that the local uterine immune response suppresses the expression of allogeneic HLA. This concept is further developed in terms of haploid HLA suppression on maternal and fetal lymphocytes that cross the placenta. This is considered to allow the interaction of these lymphocytes with each other and explains maternal transfer of cell-mediated immunity

Infertility: Cervical mucus and semen factors

A total of 34 infertile couples whose infertility was considered to be the result of a cervical factor were investigated. The use of pooled human blood plasma was found to significantly stimulate spermatozoal motility relative to that in seminal plasma or tissue culture media. Two additional male factors that may contribute to infertility have been identified, nondirectional spermatozoal motility, and in particular the inability of spermatozoa from some males to survive in normal donor mucus. This is supported by the fact that pregnancies only occurred in those cases (25%) in which the spermatozoa were able to survive in normal donor mucus. These pregnancies were achieved by artificial insemination using the husband's spermatozoa suspended in pooled human blood plasma

Rish IV. Immunoglobulin diversity

RISH considers that cell surface components involved in like cell identification are not involved in the structure of the plasma membrane per se and are attached to a part of their mRNA. the mRNA then acts as a template for the synthesis of DNA. Thus the component at the cell surface is attached to an RNA DNA receptor. If there is a conformational change in the component (antigen) this will cause a distortion in its RNA DNA receptor. This distortion is then detected by a tissue specific T lymphocyte which removes all or part of the RNA DNA receptor from the aberrant cell and the lymphocyte then undergoes replication. During this process receptor RNA DNA is incorporated into the daughter lymphocyte which becomes a B lymphocyte/plasma cell producing immunoglobulin. The initial tissue specific T lymphocyte becomes a dual functional helper/suppressor cell. The B lymphocytes use the RNA from the RNA DNA receptor to synthesize the variable region of the first antibody, IgMl. This antibody (IgMl) does not react with the antigen, ie. the distorted component, or the receptor RNA, but with receptor DNA. The DNA of the receptor base pairs with its complementary strand in the B lymphocyte, and the complementary DNA acts as a template for mRNA synthesis. This results in the production of IgM2 and IgG that can bind the antigen and receptor RNA. These antibodies (IgMl, IgM2 and IgG) when endocytosed by the stimulating cell will also complex cytoplasmic mRNA and nuclear DNA and prevent the synthesis of the antigen that initiated the immune response. If other classes of antibodies are to be produced they will follow a similar pattern (IgMl, IgA and IgG or IgMl, IgE and IgG). From the codons of the known amino acids, the codons for amino acids from translation of the complementary DNA strand have been calculated. The amino acids derived from the complementary codons are considered to represent sequences of amino acids in the antigen as represented by the DNA of an RNA DNA receptor. For these sequences of amino acids, each has a complementary amino acid as defined by the normal codon. These complementary amino acids are then used in the synthesis of the variable region of the antibody

Immune response: Self-foreignness

The classical basic concept of the immune system as a defence system per se and immunological surveillance against neoplasia have never been satisfactorily verified experimentally. The reason for this lies in the historic development of immunology interms of observations of infectious disease and the interpretation of those observations. Thus, based on a complete lack of understanding of immune events, immunization procedures were developed by Pasteur and his contemporaries. The success of some of these immunization methods, influenced by culture and philosophical thoughts, and based on prima facie evidence allowed the next conceptual step to be taken, culminating in the immune surveillance hypothesis. Central to this hypothesis is selection and tolerance to self-antigens. However, immune reactions to self-antigens are evident and clonal selection is not viable because the number of clones required increases as the frequency of chance of a cell belonging to a particular clone decreases. Also, circadian rhythms in the immune response have not been taken into account. In addition, the problems of haemocytopoiesis have not been addressed, in that it is possible for B-lymphocytes to become terminal macrophages and T-lymphocytes to become mast cells, eosinophils and/or basophils constituting 'dead end' cells in an immune response. The initiation of the immune response begins with a tissue-specific T-lymphocyte being stimulated and undergoes replication. This gives rise to a dual functional helper/suppressor cell and a B-lymphocyte. These basic concepts explain the necessity for auto-reactive lymphocytes, that is the autologous mixed lymphocyte reaction (AMR). The AMR is a natural consequence of having tissue-specific lymphocytes to monitor plasma membrane aberrations

RISH V. Application to monoclonal antibody production

RISH considers that cell surface components involved in like cell identification are not involved in the structure of the plasma membrane per se and are attached to a part of their mRNA. The mRNA then acts as a template for the synthesis of DNA. Thus the component at the cell surface is attached to an RNA DNA receptor. If there is a conformational change in the component (antigen) this will cause a distortion in its RNA DNA receptor. This distortion is then detected by a tissue specific T lymphocyte which removes all or part of the RNA DNA receptor from the aberrant cell and the lymphocyte then undergoes replication. During this process receptor RNA DNA is incorporated into the daughter lymphocyte which becomes a B lymphocyte/plasma cell producing immunoglobulin. The initial tissue specific T lymphocyte becomes a dual functional helper/suppressor cell. The plasma cell after the initial immune response becomes a circulating memory B cell displaying IgM or IgD. If this cell complexes an antigen with its surface IgM or IgD a humoral immune response will be developed as previously described, but in this case the antibodies produced will be anti-idiotypic antibodies. The anti-idiotypic antibodies will regulate the production of the antibody directed against the antigen per se. The anti-idiotypic antibodies will in turn be regulated by a second anti-idiotypic antibody. In RISH five such anti-idiotypic systems may be involved in regulating the immune response to the initial non-immunoglobulin antigen. Based on the RISH anti-idiotypic mechanism a system is briefly described whereby human memory B cells, to a particular antigen, may be isolated. These B cells may then be activated to secrete immunoglobulin with autologous isolated anti-idiotypic antibodies. These activated cells may then be infected with E.B. virus to establish an immortal cell line of B cells secreting the immunoglobulin of interest