Lecture 27 - Immunity in the fetus and the newborn

What major developments occur during the first weeks after birth that affect the health of the neonate?

-Dependence on passive protection provided by colostrum

-Colonization of gut by enteric microbes

-Post-weaning stress

-Gradual development of oral tolerance

-Transition to dependence of it’s own adaptive immunity

What is the critical window of development? Why is it important?

-Period where the neonate can passively absorb antibodies from colostrum

-Vital for major initial protection against pathogens

What is the role of commensal bacteria in providing immunity/homeostasis in perinatal period?

-Colonize neonate intestine and affect functional maturation of mucosa and GALT

-MAMPs (microbe-associated molecular patterns) stimulate adaptive immunity and maturation of lymphoid follicles

-Promotes formation of anatomical structures (ex. Peyer’s patches)

-Promotes development of iTreg (inducible regulator T-cells) and IgA

-Activate intestinal epithelial cells or mesenchymal stromal cells

What do intestinal epithelial cells (IEC) and mesenchymal stromal cells secrete?

PGE2 (maintain mucosal integrity) and TGF-b (activate IgA)

What do MAMPs stimulate to recruit and activate adaptive immune cells?

-ILC-3 (type 3 innate lymphocytes)

-IL-22

-IL-33

-TGF-b (IgA)

-TSLP (thymic stromal lymphopoietin)

What do ILC-3 respond to? What IL do they produce?

-Commensal and pathogenic intestinal bacteria, parasites, and food components

-Produce IL-22

What does IL-22 cause?

-Paneth cells secrete antimicrobial peptides (AMP) and lectins

-Limits microbial colonization and protect intestinal epithelial cells

What does TSLP (thymic stromal lymphopoietin) and IL-25 cause?

Promotes proliferation of ILC-2 and IL-13

What does IL-13 do?

Stimulates mucus production by goblet cells

What are CD103+ DCs function?

Differentiate CD4 cells into iTreg cells (inducible T-regulatory)

What is the function of iTreg cells?

-Maintain gut homeostasis by promoting differentiation of macrophages into M2

-Prevent production of pro-inflammatory cytokines

What cytokines to iTreg cells produce to promote macrophage differentiation?

-IL-10

-TGF-b

What cells do iTreg cells prevent the development of?

-T_H1

-T_H2

-B-cells producing IgE

What two things precludes the development of type I or type IV hypersensitivity in the gut?

-IgA specific for microbial or food antigens

-Treg cells

When is the approximate length of gestation where immune competence is achieved?

Varies by species but at the latest by 75% of gestation

What is immune competency?

The ability to recognize antigens as foreign

What is the outcome of a viral infection by non-cytopathic BVD in fetus’s younger than 120 days?

-Causes persistent infection without inducing immune response

-Subsequent infection results in mucosal disease (fatal)

What is the outcome of a viral infection by non-cytopathic BVD in fetus’s older than 120 days?

Can mount an immune response which might result in malformation or abortion

What is the outcome of an infection by a cytopathic virus?

Able to replicate and destroy fetal tissues causing mortality or congenital defects

Why should you not use a modified live virus in pregnant animals?

May induce infection in the tissues, causing abortion or congenital defects

What is the impact of cortisol levels during the birthing process on the immune system of newborn animals?

High cortisol levels from parturition causes a suppressed immune response

What are the three types of placentation? What species are they common in?

1. Epitheliochorial - pigs, horses, ruminants

2. Endotheliochorial - dogs and cats

3. Hemochorial - primates and rodents

What is epitheliochorial placentation? How much passive transfer is there?

-All 6 layers remain between fetus and mother

-0% passive transfer

What is endothelial placentation? How much passive transfer is there?

-Trophoblast comes into direct contact with maternal endometrium

-5-10% passive transfer

What is hemochorial placentation? How much passive transfer is there?

-Direct connection between chorion and maternal blood

-100% passive transfer

What is the main Ig transferred through colostrum? What other two Ig’s are also transferred?

-IgG (MAIN)

-IgA and IgM less significantly

How does neonatal Fc receptor (FcRn) in the mammary gland help with colostrum production?

Transports IgG from blood into extracellular space of mammary glands (then secreted into milk)

How does neonatal Fc receptor (FcRn) allow for absorption in the newborn’s gut?

Intestinal cells capture IgG and transcytoses across enterocytes into neonate

How long after birth does appropriate Ig absorption decline? How long does it take a calf to fall below 70% absorption? How long does it take a puppy to fall below 50% absorption?

-Declines within 4-8 hours of life

-3 hours in calves

-4 hours in dogs

What are the three main factor that determine the efficiency of passive transfer?

1. Colostrum quality

2. Time feeding after birth

3. Amount of colostrum ingested