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Veterinary Immunology > Lecture 15 - Neonatal Immunity > Flashcards

Lecture 15 - Neonatal Immunity Flashcards

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
Q

3 placental types

A
  1. epitheliochorial
  2. endotheliochorial
  3. hemochorial
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26
Q

What animals have epitheliochorial placenta

A

swine, horses

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27
Q

Whats the structure of epitheliochorial placental

A

no loss, diffuse placenta

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28
Q

What is the subdivision of epitheliochorial placenta and what animals have that type

A

1.syndesmochorial
2. ruminants
3. maternal epithelial modifed/fused but not lost

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29
Q

What is the structure of endothelialchorial placenta

A

loss of 2 layers

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30
Q

What animals have endotheliochorial placenta

A

dogs, cats

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31
Q

What animals have hemochorial placenta

A

primates, rabbits, guinea pigs

32
Q

What is the structure of hemochorial placenta

A

loss of 3 layers

33
Q

What placenta type does NOT receive Ig across the placenta

A

epitheliochorial

34
Q

What maternal layers does epitheliochorial placenta retain

A

endometrial epithelium, connective tissue, uterine endothelium

35
Q

What maternal layers does endotheliochorial placenta retain

A

uterine endothelium only

36
Q

What maternal layers does hemochorial placenta retain

A

NONE

37
Q

What can antibodies NOT pass through

A

multiple epithelial barriers

38
Q

What species do not transfer antibodies to fetus and why

A
  1. horses, ruminant, pig
  2. maintained maternal endometrial lining and antibodies can’t pass through
39
Q

What species can transfer antibodies passively through placenta and why

A
  1. dog, cat, humans, rabbits, rodents
  2. they have lost the maternal endometrial lining within the placenta
40
Q

How much total neonatal serum IgG is transferred via placenta in the dog and cat

A

5-10%

41
Q

How much total neonatal serum IgG is transferred via placenta in the human/rabbit/rodent

A

100%

42
Q

How can all species receive antibodies from the mother

A

post-natally via colostrum

43
Q

When is milk highest in antibody content

A

late in gestation and early post-partum

44
Q

Where are antibodies absorbed from following consumption

A

neonatal intestine

45
Q

When is the maximum amount of antibodies absorbed after consumption

A

Foals/calves: within first 6 hours nd rapidly declines
Other species: within first 12-24 hours

46
Q

How do antibodies get transfered into fetal cells regardless of oral/placenta

A

endocytosis

47
Q

What is the only antibody to pass through placenta

A

IgG

48
Q

What is the main antibody to be absorbed in the intestine from colostrum

A

IgG

49
Q

What do fetal Fc receptors do during transfer of antibodies

A

assist in transport and protects from degradation

50
Q

What are the 2 antibodies in colostrum

A
  1. IgG
  2. IgA
51
Q

What do IgG and IgA do after reaching the intestine in neonates

A

binds Fc receptor on GI epithelium, taken up by epithelial cell, eventually enters circulation

52
Q

While absorption is highest immediately after birth and declines over several hours, what declines rapidly and what increases rapidly

A
  1. fetal Fc receptor expression declines
  2. Intestinal protease activity increases
53
Q

What antibody predominates in ruminant milk vs other species

A

IgG; IgA

54
Q

Cell-mediated immunity can also be ____ transferred

A

passively

55
Q

What has high lymphocyte counts and what percentage are T cells in cows vs humans

A
  1. colostrum
  2. cows-70-80% humans-50%
56
Q

How long do lymphocytes survive in the intestine, and what happens to some of them

A

36 hours; penetrate intestinal wall

57
Q

What are lymphocytes though to enhance

A

initial neonatal response

58
Q

Why may passive immunity have negative aspecits

A
  1. maternal antibody may impair neonatal adaptive immune response
  2. Maternal antibodies may recognize neonatal tissue
59
Q

How do maternal antibodies impair neonatal adaptive immune response

A
  1. FcyRII receptor engagement reduces BCR activation
  2. may bind epitopes and prevent appropriate response to neonatal vaccines
  3. typically just humoral effects
60
Q

What happens when maternal antibodies may also recognize neonatal tissue

A
  1. neonatal isoerythrolysis
  2. Rh disease
61
Q

What is important consideration for neonates and vaccinination

A

timing

62
Q

What are the passive immunity concerns with neonates and vaccines.

A
  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
Q

When do puppies and kittens start vaccines

A

6 weeks, then q 3 weeks x 3

64
Q

When do foals and calves start vaccines

A

no earlier than 3-4 months then q 4 weeks x 3

65
Q

What can neonatal immunodeficiency occur from

A

developmental failure, failure of passive immunity failure

66
Q

What innate response defects can cause neonatal immunodeficiency

A
  1. hereditary cyclic-neutropenia in dogs (elastase processing defect)
  2. trapped neutrophil syndrome in BC
  3. Complement deficiencies
67
Q

What adaptive response defects can cause neonatal immunodeficiency

A
  1. RAG-1/2 mutations
  2. Interleukin receptor mutations
68
Q

What is the most common source of immunodeficiency

A

failure of passive immunity transfer (FPT)

69
Q

What is the major source of passive immunity

A

maternal antibody transfer

70
Q

Causes of FPT

A
  1. production failure- maternal
  2. ingestion failure- placental or neonatal
  3. Absorption failure- neonatal
71
Q

What is the major cause of absorption failure in neonates and what animals does it usually occur in

A

lack of colostral transfer; horses, ruminants

72
Q

On a fetal IgG test kit what would you expect to see with an IgG concentration of <400 mg/dl

A

color intensity of sample spot is lighter than 400mg/dl calibrator spot

73
Q

On a fetal IgG test kit what would you expect to see with an IgG concentration of 400-800 mg/dl

A

color intensity of sample spot is darker than the 400mg/dl but lighter than the 800 mg/dl spot

74
Q

On a fetal IgG test kit what would you expect to see with an IgG concentration of >800 mg/dl

A

color intensity of sample spot is darker than the 800 mg/dl spot

75
Q

What can neonatal immunodeficiency be corrected with if recognized quickly

A

plasma and oral supplementation

76
Q

What do passive mechanisms of immunity transfer differ due to with avian neonate immunity

A

lack of placenta and colostrum

77
Q

How do avian neonates get passive immunity transfer from hen

A
  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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