Immune System in Pregnancy

Immune System in Pregnancy

• Aims/Learning outcomes:
  • Consolidate understanding of the normal immune system function.
  • Identify significant pregnancy-related immune system changes, their causes, and implications for childbearing women and pregnancy outcomes.
  • Explain why Rh-negative women might receive donated Anti-D during pregnancy and after birth.

Questions to Consider

• List physical barriers preventing pathogenic microbe invasion.
• Define innate/non-specific immunity.
• Define specific immunity, including antigens and antibodies.
• Explain why the body rejects transplanted tissue unless immunosuppressant medication is taken.

Blood Cells

• 500 billion blood cells are produced daily in the bone marrow from hematopoietic stem cells.
• Mast cells are rich in histamine, acting as an early warning system for immune response in vulnerable tissues; they also influence sleep-wake cycles.
• Neutrophils are the most common white blood cells, circulating to infection sites, phagocytosing pathogens, and dying to form pus.
• Basophils play a role in inflammatory responses, releasing histamine.
• Eosinophils defend against parasites and worms, and are involved in allergic responses.
• Erythrocytes (red blood cells) carry oxygen.
• Thrombocytes (platelets) are involved in blood clotting.
• Macrophages and dendritic cells phagocytose pathogens and alert other cells.
• Natural killer cells recognize and destroy virus-infected cells and cancer cells by detecting stress markers.
• Lymphocytes are another type of white blood cell, including T cells (cytotoxic, helper, regulatory), and B cells (plasma cells capable of antibody production).

Blood & Immune Responses Questions

• Red blood cells (RBCs) lack a nucleus for efficient oxygen transport.
• Platelets are essential for blood clotting.
• Neutrophils are the first white blood cells to arrive at infection sites.
• Histamine is released by mast cells, basophils, acting in inflammatory responses.
• Natural killer cells (NKCs) are vital for a successful pregnancy, defending against pathogens.
• Antibodies are proteins that bind to specific antigens.
• Antigens are foreign substances that initiate immune responses.
• T-cells and B-cells mature in different areas of the lymphatic system.
• Macrophages are efficient at phagocytosis.
• T-helper cells trigger further immune responses.
• T-regulatory cells suppress immune responses.
• The body rejects transplanted tissue unless the tissue type matches and immunosuppressant medication is used to suppress the body's rejection response.

Why Doesn't the Mother's Body Reject the Fetus?

• The immune system normally targets foreign cells and proteins.
• Fetal tissue has unique MHCs (major histocompatibility complexes).
• The uterus has factors that prevent rejection.

Summary - Key Immune System Changes in Pregnancy

• Hormonal and physical changes may increase the risk of bacterial infections, while innate immunity is enhanced.
• B-cell responses to most infectious agents are enhanced
• Responses to foreign MHCs are suppressed to reduce rejection risk, but can also reduce protection from viral infections.
• Specific immunological responses in the endometrium and placenta are key.
• Changes in some autoimmune disease processes occur.

Innate/Non-Specific Immunity

• Early general defenses against foreign antigens (within 1-4 days) include physical and biochemical barriers, circulating factors, and the complement system.
• Inflammation, including phagocytosis (by neutrophils) and lysis (breakdown by NK cells), is triggered by tissue injury.

Alterations in Non-Specific/Innate Immunity in Pregnancy

• White blood cell counts, especially neutrophils increase early in pregnancy, likely for targeting stray trophoblast cells.
• Phagocytosis is faster due to estrogen effects on macrophages and neutrophils.
• The placenta often has some inhibited immune activity; for example, proteins block phagocytosis.
• Natural killer cell activity is suppressed by progesterone, especially in the second and third trimesters.
• This decreased NK activity increases vulnerability to viral infections later in pregnancy.

Normal Adaptive/Specific Immunity

• Protective responses defend against specific antigens.
• Immunological memory is established, and these responses are not usually reactive to the host's own MHCs.
• Antibody production, assisted by Th2 helper T-cells, forms B-lymphocytes that make and release antibodies (immunoglobulins).
• Some B-cells develop into long-term memory cells, enhancing faster reactions to future exposure to a pathogen.

Adaptive (Specific to Organism) Immunity

• Cell-mediated immunity destroys cells with foreign MHCs, cancer cells and cells harboring intracellular microbes (certain viruses and bacteria like Listeria).
• T-cytotoxic cells (Tc) are involved in this cell destruction.
• T-helper cells (Th1) assist.
• These cells are also involved in rejecting transplanted tissue.
• Regulatory T-cells (T-regs) suppress immune responses once invaders are controlled, preventing our own tissues being targeted.

Alterations in Adaptive/Specific Immunity in Pregnancy

• Progesterone affects the balance of Th1 and Th2 cells, decreasing Th1 (cell-mediated) responses and enhancing Th2 (antibody-mediated) responses, potentially leading to worse effects with viral infections.
• T-regulatory cells (T-regs) increase.

Interactions of Fetal Tissue & Maternal Immune Response at the Placenta

• Mothers need a strong immune response for a healthy pregnancy (eg contributing to proper spiral artery remodeling).
• Trophoblast cells have a unique MHC-1 antigen (HLA-G) that blocks cytotoxic action from NK cells.
• An enzyme (tryptophan) breaks down, limiting T-cell proliferation.
• Natural killer cells at the placenta are highly active.

Natural Killer Cells at the Placental Site

• NK cells in the blood normally recognize and attack infected or foreign cells.
• At the placenta, local prostaglandins change how NK cells act.
• A placental protein (HLA-G) makes NK cells less likely to destroy trophoblast cells.
• NK cells produce cytokines (IL-8 and IL-10) to stimulate trophoblastic invasion and vascular remodeling.

Effects of Semen on the Woman's Immune System

• Semen causes cytokine release to increase T-reg cells, calming the body's rejection response.
• Semen's impact on embryo implantation and surrogate mothers, and its role in transmission of sexually transmitted infections.

Pre-eclampsia

• Pre-eclampsia is associated with poor placental development, likely due to insufficient immune response (NK cell-dependent) remodeling of spiral arteries, possibly related to limited exposure to partner semen (especially first pregnancies, and longer intervals between pregnancies).

Maternal Susceptibility to Infection

• Increased risk of serious viral illness, especially in the last trimester, includes elevated infection rates for viral hepatitis, flu, and Covid-19.
• Latent infections may worsen during pregnancy, such as tuberculosis, malaria, or HIV. Increased immune responses often lead to increased risk of bacterial and other UTIs.

Protecting the Fetus from Infection

• Most viruses and bacteria can't cross the placenta; membranes, amniotic fluid, and placental cell factors form a barrier.
• Trophoblast cells secrete antimicrobial factors.

Trans-placental Passage of Antibodies

• Neonates are born with an immature immune system but gain temporary passive immunity from IgG antibodies that cross the placenta, especially after 34 weeks.
• Breast milk provides additional IgA passive immunity.
• Maternal anti-D antibodies can also cross the placenta, leading to Rhesus incompatibility issues.

Rhesus Incompatibility in Pregnancy

• If a Rh-negative mother carries a Rh-positive fetus, her immune system might respond by creating anti-D antibodies.
• These newly formed antibodies can cross the placenta and attack the fetus's red blood cells, causing problems like anemia and jaundice.
• Prior Rh incompatibility pregnancies or exposures will make subsequent responses stronger.

Rh (Anti-D) Antibodies

• Maternal anti-D antibodies can cause fetal red blood cell destruction and severe neonatal problems, such as anemia and jaundice.
• The severity increases with each subsequent pregnancy, making prevention crucial.

Prophylactic Anti-D Administration

• Anti-D administration to Rh-negative mothers can prevent the formation of anti-D antibodies in response to a Rh-positive fetus, protecting subsequent pregnancies.
• This involves testing for fetal cells and administering Anti-D injections within 72 hours of birth or other exposures to fetal blood.

Immune System & Labour

• Cervical ripening, SRM (stress response mediators), and initiation of contractions involve white blood cell (WBC) activity and inflammatory processes.
• WBC counts increase during and after labor, helping reduce genital tract infections.
• Labor and vaginal birth stimulate WBC formation in the fetus

The Neonate

• The neonate's immune system is immature, making them vulnerable to infection.
• Breastfeeding, which colonizes the gut with maternal bacteria, helps protect from pathogens, taking several weeks for effective colonization.
• Gut microbiome formation and functions are related to immune responses.

Open Book Example Questions

1. Five key immune system changes during pregnancy and why each is important for mothers and/or babies.
2. The physiological process of Rh incompatibility and the reasons why Rh-negative women may need donated anti-D after birth.

MCQ Examples

• Neutrophils are the first phagocytes to arrive at infection sites.
• Maternal immunoglobulins cross into the fetus around 34 weeks.

Explore how the immune system functions during pregnancy, including significant changes and their implications for maternal and fetal health. This quiz covers innate and specific immunity, as well as the role of blood cells and physical barriers against pathogens. Understand key concepts crucial for childbearing women.