Little is known of the in vivo role of the immune system in controlling human papillomavirus infection in the genital tract The authors have studied 125 closely monitored patients with genital warts Of these 125 patients, wart regression was seen in 28 patients This study provides evidence that clearance of human papillomavirus from the genital tract is characterized by an active cell-mediated immune response Regressing warts (n = 14) contained significantly more T lymphocytes (P < 05, Wilcoxon rank sum test) and macrophages (P < 01) than did nonregressing controls (n = 14) CD4-positive lymphocytes predominated in regression, both within the wart stroma and the surface epithelium, where there was a significant change in the ratio of CD4+ to CD8+ cells (P < 01) Lymphocytes in regression also showed greater expression of activation markers, and the majority were of the "antigen-experienced" phenotype There was no difference in Langerhans cell numbers, although there was significant induction of the immune accessory molecules HLA-DR and ICAM1 (P < 05) on keratinocytes, and E-selectin and VCAM1 (P < 05) on endothelial cells in regressing warts The changes in regression are consistent with a delayed-type hypersensitivity reaction to foreign antigen, and the ability to induce and mount such a response may be a critical determinant of effective natural immunity to the genital HPVs Specific targeting of delayed-type hypersensitivity responsiveness may increase the efficacy of strategies for immuno-intervention against HPV infection in the genital tract

Immunological events in regressing genital warts.

Cell-mediated immunity (CMI) is key to defense against intracellular pathogens such as Chlamydia trachomatis and viruses that infect the lower female genital tract, but little is known about CMI at this site. Recent studies indicate that there are immunological microenvironments within the female genital tract, and that immune functions are affected by hormones as well as infections and inflammatory processes. To determine the distribution of mediators of CMI within the lower female genital tract, we have enumerated and characterized T-lymphocyte subsets and natural killer and antigen presenting cells (APCs; macrophages and dendritic cells) in the introitus, vagina, ectocervix, endocervix and cervical transformation zone (TZ) from healthy women, and have examined the effects of the menstrual cycle, menopause and inflammation on these parameters. In women without inflammation, T cells and APCs were most prevalent in the cervical TZ and surrounding tissue. Intraepithelial lymphocytes were predominantly CD8+ T cell+; most CD8+ cells in the TZ and endocervix, and a proportion of cells in the ectocervix, expressed T-cell internal antigen-1, a marker of cytotoxic potential. In contrast, the normal vaginal mucosa contained few T cells and APCs. Cervicitis and vaginitis cases had increased numbers of intraepithelial CD8+ and CD4+ lymphocytes and APCs. The menstrual cycle and menopause had no apparent effect on cellular localization or abundance in any of the lower genital tract tissues. These data indicate that the cervix, especially the TZ, is the major inductive and effector site for CMI in the lower female genital tract. Because CD4+ T cells and APCs are primary host cells for human immunodeficiency virus type 1 (HIV-1), these data also provide further evidence that the cervix is a primary infection site of HIV-1, and that inflammation increases the risk of HIV transmission.

https://bioone.org/journals/Biology-of-Reproduction/volume-73/issue-6/biolreprod.105.043133/Immunological-Microenvironments-in-the-Human-Vagina-and-Cervix--Mediators/10.1095/biolreprod.105.043133.pdf

Immunological microenvironments in the human vagina and cervix : Mediators of cellular immunity are concentrated in the cervical transformation zone

Comparison of two methods of predicting outcome in perinatal asphyxia

To assess the predictive value for perinatal brain damage of acidosis at birth, alone or in combination with the Apgar score at 5 minutes, a cohort of 982 liveborn infants delivered over two months was studied prospectively. The umbilical cord was double clamped, and arterial acid-base values were successfully determined in 964 infants and lactate concentration in 931. Reference values defining acidosis (mean +/- 2 SD) were obtained from a subset of 127 term infants who had no complications. The incidence of a low pH was 12% (111 out of 964), high base deficit 7% (70 out of 964), high lactate concentration 9% (83 out of 931), and low Apgar score at 5 minutes (less than or equal to 7) 3% (32 out of 982). Twelve of the 111 infants (11%) with acidosis had a low Apgar score, and 12 out of 29 infants (41%) with low Apgar scores had acidosis. At one year of age 35 infants were lost to follow up and 22 had an adverse outcome unrelated to asphyxia; 883 infants showed normal development but the possible sequelae of asphyxia were four deaths, slight abnormalities in 28 infants, and clear abnormalities in 10. The sensitivity and the positive predictive value of low pH for adverse outcome were, respectively, 21 and 8%, of high lactate concentration 12 and 5%, and of low 5 minute Apgar score 12 and 19%. Metabolic acidosis determined in blood from the umbilical artery at birth is a poor predictor of perinatal brain damage.

https://www.bmj.com/content/bmj/297/6640/24.full.pdf

Perinatal brain damage: predictive value of metabolic acidosis and the Apgar score.

The incidence and severity of post-asphyxial encephalopathy in full-term infants

Do apgar scores indicate asphyxia

Langerhans’cells in human cervical epithelium: effects of wart virus infection and intraepithelial neoplasia

In a prospective audit of the obstetric management of 1210 consecutive deliveries the association was investigated between the need for operative delivery for fetal distress during labour and the condition of the newborn infant. Operative delivery was performed for only 11.5% of the newborn infants with severe acidosis at birth (umbilical artery pH less than 7.12, base deficit greater than 12 mmol (mEq)/1), 24.1% of those with an Apgar score less than 7 at one minute, and 15.8% of those with both severe acidosis and a one minute Apgar score less than 7. Most of the infants delivered operatively were in a vigorous condition at birth and did not have severe acidosis. Fetal blood sampling was done in 4.0% of labours. As none of the fetal blood values were less than 7.20 and only three of the infants sampled in utero suffered severe acidosis at birth, fetal blood sampling would have had to be performed much more often to provide a useful guide to metabolic state at birth. While the large majority of "at risk" fetuses had continuous fetal heart rate monitoring in labour, this had not been provided in 48.7% of the labours of infants with severe acidosis, 38.7% of infants with a one minute Apgar score less than 7, and 47.4% of infants with both severe acidosis and a one minute Apgar score less than 7. Continuous fetal heart rate monitoring was associated with a much higher incidence of operative delivery for fetal distress than was intermittent fetal heart rate auscultation. These results suggest an urgent need to review present methods for assessing the intrapartum condition of the fetus, making the diagnosis of fetal distress, and assessing the condition of the infant at birth.

https://www.bmj.com/content/bmj/287/6397/943.full.pdf

G. S. Sykes

Papers

Do apgar scores indicate asphyxia

Langerhans’cells in human cervical epithelium: effects of wart virus infection and intraepithelial neoplasia

Fetal distress and the condition of newborn infants

Changes in fetal monitoring practice in the UK : 1977-1984

Do Apgar Scores Indicate Asphyxia