Lecture 15 - Neonatal Immunity Flashcards
What are the 2 things that make the fetus a foreign antigen?
- co-dominant MHC expression
- male-specific antigens
When does exposure of fetal “sequestered antigens occur during?
development
What is the amount of fetal sequestered antigens depend on
placental type
What type of placenta have robust interchange of antigens and why
hemochorial bc maternal blood comes into direct contact with fetal chorion
What does the maternal-fetal interaction promote and limit
placental and fetal development
What key features of the maternal system help achieve tolerance?
- progesterone
- increased complement regulatory proteins (protease inhibitors)
- Th2 response dominates
- High levels of Treg
Explain progesterone in how it relates to the maternal system
-high levels near trophoblast are immunosupressive @ fetal-mat. interface (PIBF block lymphoid activation)
-low peripheral levels are inadequate to suppress systemic immunity
How does progesterone help acheive tolerance
progesterone-induced blocking factor (PIBF) blocks lymphoid activation
How does increased complement regulatory proteins (protease inhibitors) help acheive tolerance?
block activation and complement mediated cytolysis of fetal/placental tissues
How does Th2 response dominates acheive tolerance
-humoral response
-lowers chance for Th1 mediated cytolysis of fetal tissue
How does the fetal system help acheive tolerance
- fetal cells downregulate MHCI which lowers expression of self antigens
- Th2 cytokines are expressed
- Inhibit T cells (progesterone and other cytokines)
Why is the fetus less able to combat infections than an adult
- reduced or absent adaptive immunity- increases with age
- Th2 environment
- high T regs
What does it mean that fetus adaptive response is immune
relies on innate immunity, passive immunity, and physical barriers
How long is the fetus protected using innate, passive immunity and physical barriers
through gestation and beyong (weeks to months)
What does the adaptive immune response development require
population of primary and secondary lymphoid organs in 1st trimester
List the development of structures in the adaptive immune response in the fetus
- thymus
- secondary lymphoid tissues
- population of organs starts early
- adaptive response increases slowly after population of lymphoid organs
When does population of peripheral lymphoid tissue occur in the fetal calf
early- 1st trimester
When does lymphoid maturation begin in the fetal calf
first 1-5 months
Why is adaptive response in fetal calves reduced in spite of early population of lymphoid tissues
- limited antibody and T cell diversity due to lack of antigens
- no memory cells
- reduced cytokine stimulation to promote expansion, affinity maturation
What develops over the first 3 months in fetal calves
phagocytic activity of neutrophils and macrophages
What is the result of fetal calves having lower complement levels than the adult and when does it normalize
- reduces innate response to bacterial infections and prevent damage to placenta
- rapidly after birth
Fetal innate response and developing adaptive response can be passively supplemented by
maternal antibodies
How ddo fetal calves obtain maternal antibodies
absorbed pre-natally through placenta or ingested post-natally through colostrum
What does placental absorption of antibodies depend on
placental type
3 placental types
- epitheliochorial
- endotheliochorial
- hemochorial
What animals have epitheliochorial placenta
swine, horses
Whats the structure of epitheliochorial placental
no loss, diffuse placenta
What is the subdivision of epitheliochorial placenta and what animals have that type
1.syndesmochorial
2. ruminants
3. maternal epithelial modifed/fused but not lost
What is the structure of endothelialchorial placenta
loss of 2 layers
What animals have endotheliochorial placenta
dogs, cats
What animals have hemochorial placenta
primates, rabbits, guinea pigs
What is the structure of hemochorial placenta
loss of 3 layers
What placenta type does NOT receive Ig across the placenta
epitheliochorial
What maternal layers does epitheliochorial placenta retain
endometrial epithelium, connective tissue, uterine endothelium
What maternal layers does endotheliochorial placenta retain
uterine endothelium only
What maternal layers does hemochorial placenta retain
NONE
What can antibodies NOT pass through
multiple epithelial barriers
What species do not transfer antibodies to fetus and why
- horses, ruminant, pig
- maintained maternal endometrial lining and antibodies can’t pass through
What species can transfer antibodies passively through placenta and why
- dog, cat, humans, rabbits, rodents
- they have lost the maternal endometrial lining within the placenta
How much total neonatal serum IgG is transferred via placenta in the dog and cat
5-10%
How much total neonatal serum IgG is transferred via placenta in the human/rabbit/rodent
100%
How can all species receive antibodies from the mother
post-natally via colostrum
When is milk highest in antibody content
late in gestation and early post-partum
Where are antibodies absorbed from following consumption
neonatal intestine
When is the maximum amount of antibodies absorbed after consumption
Foals/calves: within first 6 hours nd rapidly declines
Other species: within first 12-24 hours
How do antibodies get transfered into fetal cells regardless of oral/placenta
endocytosis
What is the only antibody to pass through placenta
IgG
What is the main antibody to be absorbed in the intestine from colostrum
IgG
What do fetal Fc receptors do during transfer of antibodies
assist in transport and protects from degradation
What are the 2 antibodies in colostrum
- IgG
- IgA
What do IgG and IgA do after reaching the intestine in neonates
binds Fc receptor on GI epithelium, taken up by epithelial cell, eventually enters circulation
While absorption is highest immediately after birth and declines over several hours, what declines rapidly and what increases rapidly
- fetal Fc receptor expression declines
- Intestinal protease activity increases
What antibody predominates in ruminant milk vs other species
IgG; IgA
Cell-mediated immunity can also be ____ transferred
passively
What has high lymphocyte counts and what percentage are T cells in cows vs humans
- colostrum
- cows-70-80% humans-50%
How long do lymphocytes survive in the intestine, and what happens to some of them
36 hours; penetrate intestinal wall
What are lymphocytes though to enhance
initial neonatal response
Why may passive immunity have negative aspecits
- maternal antibody may impair neonatal adaptive immune response
- Maternal antibodies may recognize neonatal tissue
How do maternal antibodies impair neonatal adaptive immune response
- FcyRII receptor engagement reduces BCR activation
- may bind epitopes and prevent appropriate response to neonatal vaccines
- typically just humoral effects
What happens when maternal antibodies may also recognize neonatal tissue
- neonatal isoerythrolysis
- Rh disease
What is important consideration for neonates and vaccinination
timing
What are the passive immunity concerns with neonates and vaccines.
- maternal antibody can inhibit neonate Ig production (FcyRIIB)
- maternal antibody can bind antibody and block immune response (epitope masking and neutralization of live-attenuated viruses)
When do puppies and kittens start vaccines
6 weeks, then q 3 weeks x 3
When do foals and calves start vaccines
no earlier than 3-4 months then q 4 weeks x 3
What can neonatal immunodeficiency occur from
developmental failure, failure of passive immunity failure
What innate response defects can cause neonatal immunodeficiency
- hereditary cyclic-neutropenia in dogs (elastase processing defect)
- trapped neutrophil syndrome in BC
- Complement deficiencies
What adaptive response defects can cause neonatal immunodeficiency
- RAG-1/2 mutations
- Interleukin receptor mutations
What is the most common source of immunodeficiency
failure of passive immunity transfer (FPT)
What is the major source of passive immunity
maternal antibody transfer
Causes of FPT
- production failure- maternal
- ingestion failure- placental or neonatal
- Absorption failure- neonatal
What is the major cause of absorption failure in neonates and what animals does it usually occur in
lack of colostral transfer; horses, ruminants
On a fetal IgG test kit what would you expect to see with an IgG concentration of <400 mg/dl
color intensity of sample spot is lighter than 400mg/dl calibrator spot
On a fetal IgG test kit what would you expect to see with an IgG concentration of 400-800 mg/dl
color intensity of sample spot is darker than the 400mg/dl but lighter than the 800 mg/dl spot
On a fetal IgG test kit what would you expect to see with an IgG concentration of >800 mg/dl
color intensity of sample spot is darker than the 800 mg/dl spot
What can neonatal immunodeficiency be corrected with if recognized quickly
plasma and oral supplementation
What do passive mechanisms of immunity transfer differ due to with avian neonate immunity
lack of placenta and colostrum
How do avian neonates get passive immunity transfer from hen
- hen actively transfers IgY from serum to yolk- absorbed into bloodstream of developing chick
- IgM and IgA secreted into albumin in oviduct- diffuse into amniotic fluid and swallowed by chick, IgM and IgA in intestine
