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Veterinary Immunology > Lecture 15 - Neonatal Immunity > Flashcards

Lecture 15 - Neonatal Immunity Flashcards

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1
Q

What are the 2 things that make the fetus a foreign antigen?

A
  1. co-dominant MHC expression
  2. male-specific antigens
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2
Q

When does exposure of fetal “sequestered antigens occur during?

A

development

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3
Q

What is the amount of fetal sequestered antigens depend on

A

placental type

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4
Q

What type of placenta have robust interchange of antigens and why

A

hemochorial bc maternal blood comes into direct contact with fetal chorion

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5
Q

What does the maternal-fetal interaction promote and limit

A

placental and fetal development

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6
Q

What key features of the maternal system help achieve tolerance?

A
  1. progesterone
  2. increased complement regulatory proteins (protease inhibitors)
  3. Th2 response dominates
  4. High levels of Treg
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7
Q

Explain progesterone in how it relates to the maternal system

A

-high levels near trophoblast are immunosupressive @ fetal-mat. interface (PIBF block lymphoid activation)
-low peripheral levels are inadequate to suppress systemic immunity

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8
Q

How does progesterone help acheive tolerance

A

progesterone-induced blocking factor (PIBF) blocks lymphoid activation

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9
Q

How does increased complement regulatory proteins (protease inhibitors) help acheive tolerance?

A

block activation and complement mediated cytolysis of fetal/placental tissues

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10
Q

How does Th2 response dominates acheive tolerance

A

-humoral response
-lowers chance for Th1 mediated cytolysis of fetal tissue

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11
Q

How does the fetal system help acheive tolerance

A
  1. fetal cells downregulate MHCI which lowers expression of self antigens
  2. Th2 cytokines are expressed
  3. Inhibit T cells (progesterone and other cytokines)
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12
Q

Why is the fetus less able to combat infections than an adult

A
  1. reduced or absent adaptive immunity- increases with age
  2. Th2 environment
  3. high T regs
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13
Q

What does it mean that fetus adaptive response is immune

A

relies on innate immunity, passive immunity, and physical barriers

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14
Q

How long is the fetus protected using innate, passive immunity and physical barriers

A

through gestation and beyong (weeks to months)

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15
Q

What does the adaptive immune response development require

A

population of primary and secondary lymphoid organs in 1st trimester

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16
Q

List the development of structures in the adaptive immune response in the fetus

A
  1. thymus
  2. secondary lymphoid tissues
  3. population of organs starts early
  4. adaptive response increases slowly after population of lymphoid organs
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17
Q

When does population of peripheral lymphoid tissue occur in the fetal calf

A

early- 1st trimester

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18
Q

When does lymphoid maturation begin in the fetal calf

A

first 1-5 months

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19
Q

Why is adaptive response in fetal calves reduced in spite of early population of lymphoid tissues

A
  1. limited antibody and T cell diversity due to lack of antigens
  2. no memory cells
  3. reduced cytokine stimulation to promote expansion, affinity maturation
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20
Q

What develops over the first 3 months in fetal calves

A

phagocytic activity of neutrophils and macrophages

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21
Q

What is the result of fetal calves having lower complement levels than the adult and when does it normalize

A
  1. reduces innate response to bacterial infections and prevent damage to placenta
  2. rapidly after birth
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22
Q

Fetal innate response and developing adaptive response can be passively supplemented by

A

maternal antibodies

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23
Q

How ddo fetal calves obtain maternal antibodies

A

absorbed pre-natally through placenta or ingested post-natally through colostrum

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24
Q

What does placental absorption of antibodies depend on

A

placental type

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25
3 placental types
1. epitheliochorial 2. endotheliochorial 3. hemochorial
26
What animals have epitheliochorial placenta
swine, horses
27
Whats the structure of epitheliochorial placental
no loss, diffuse placenta
28
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
29
What is the structure of endothelialchorial placenta
loss of 2 layers
30
What animals have endotheliochorial placenta
dogs, cats
31
What animals have hemochorial placenta
primates, rabbits, guinea pigs
32
What is the structure of hemochorial placenta
loss of 3 layers
33
What placenta type does NOT receive Ig across the placenta
epitheliochorial
34
What maternal layers does epitheliochorial placenta retain
endometrial epithelium, connective tissue, uterine endothelium
35
What maternal layers does endotheliochorial placenta retain
uterine endothelium only
36
What maternal layers does hemochorial placenta retain
NONE
37
What can antibodies NOT pass through
multiple epithelial barriers
38
What species do not transfer antibodies to fetus and why
1. horses, ruminant, pig 2. maintained maternal endometrial lining and antibodies can't pass through
39
What species can transfer antibodies passively through placenta and why
1. dog, cat, humans, rabbits, rodents 2. they have lost the maternal endometrial lining within the placenta
40
How much total neonatal serum IgG is transferred via placenta in the dog and cat
5-10%
41
How much total neonatal serum IgG is transferred via placenta in the human/rabbit/rodent
100%
42
How can all species receive antibodies from the mother
post-natally via colostrum
43
When is milk highest in antibody content
late in gestation and early post-partum
44
Where are antibodies absorbed from following consumption
neonatal intestine
45
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
46
How do antibodies get transfered into fetal cells regardless of oral/placenta
endocytosis
47
What is the only antibody to pass through placenta
IgG
48
What is the main antibody to be absorbed in the intestine from colostrum
IgG
49
What do fetal Fc receptors do during transfer of antibodies
assist in transport and protects from degradation
50
What are the 2 antibodies in colostrum
1. IgG 2. IgA
51
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
52
While absorption is highest immediately after birth and declines over several hours, what declines rapidly and what increases rapidly
1. fetal Fc receptor expression declines 2. Intestinal protease activity increases
53
What antibody predominates in ruminant milk vs other species
IgG; IgA
54
Cell-mediated immunity can also be ____ transferred
passively
55
What has high lymphocyte counts and what percentage are T cells in cows vs humans
1. colostrum 2. cows-70-80% humans-50%
56
How long do lymphocytes survive in the intestine, and what happens to some of them
36 hours; penetrate intestinal wall
57
What are lymphocytes though to enhance
initial neonatal response
58
Why may passive immunity have negative aspecits
1. maternal antibody may impair neonatal adaptive immune response 2. Maternal antibodies may recognize neonatal tissue
59
How do maternal antibodies impair neonatal adaptive immune response
1. FcyRII receptor engagement reduces BCR activation 2. may bind epitopes and prevent appropriate response to neonatal vaccines 3. typically just humoral effects
60
What happens when maternal antibodies may also recognize neonatal tissue
1. neonatal isoerythrolysis 2. Rh disease
61
What is important consideration for neonates and vaccinination
timing
62
What are the passive immunity concerns with neonates and vaccines.
1. maternal antibody can inhibit neonate Ig production (FcyRIIB) 2. maternal antibody can bind antibody and block immune response (epitope masking and neutralization of live-attenuated viruses)
63
When do puppies and kittens start vaccines
6 weeks, then q 3 weeks x 3
64
When do foals and calves start vaccines
no earlier than 3-4 months then q 4 weeks x 3
65
What can neonatal immunodeficiency occur from
developmental failure, failure of passive immunity failure
66
What innate response defects can cause neonatal immunodeficiency
1. hereditary cyclic-neutropenia in dogs (elastase processing defect) 2. trapped neutrophil syndrome in BC 3. Complement deficiencies
67
What adaptive response defects can cause neonatal immunodeficiency
1. RAG-1/2 mutations 2. Interleukin receptor mutations
68
What is the most common source of immunodeficiency
failure of passive immunity transfer (FPT)
69
What is the major source of passive immunity
maternal antibody transfer
70
Causes of FPT
1. production failure- maternal 2. ingestion failure- placental or neonatal 3. Absorption failure- neonatal
71
What is the major cause of absorption failure in neonates and what animals does it usually occur in
lack of colostral transfer; horses, ruminants
72
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
73
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
74
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
75
What can neonatal immunodeficiency be corrected with if recognized quickly
plasma and oral supplementation
76
What do passive mechanisms of immunity transfer differ due to with avian neonate immunity
lack of placenta and colostrum
77
How do avian neonates get passive immunity transfer from hen
1. hen actively transfers IgY from serum to yolk- absorbed into bloodstream of developing chick 2. IgM and IgA secreted into albumin in oviduct- diffuse into amniotic fluid and swallowed by chick, IgM and IgA in intestine

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