Fetal and neonatal immunity Flashcards

1
Q

Immune system development

A

The thymus develops first, followed by secondary lymphoid organs
B cells appear soon after the spleen and lymph nodes have developed
Cell-mediated immune responses and antibody production are not usually found until late in fetal life, if at all
TCR diversity is limited in the fetus and neonate, low cytokine production

When born, basic immune components ready to go, but not working totally yet

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2
Q

Calf’s immune system development

A
Conception
41 days- thymus
45 days- blood lymohocytes
56- bone marrow and spleen
59 IgM positive cells
60 lymph nodes
130 serum iGm
135 igg positive cells
145 serum igG
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3
Q

The immune system and intrauterine infection

A

The fetus is less capable of mounting IR- adaptive immune system is not fully functional- cannot generate proper response from beginning
Mild or innaparent infections in the mother can be sever or lethal in fetus (blue tongue virus, infectious bovine rhinotracheitis, toxoplasmosis)
The response to infection is determined by the state o immunological development of the fetus

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4
Q

Bovine viral diarrhea: noncytopathic

A

Noncytopathic BVD: can result in tolerance and persistent infection; normal
If exposed in process of producing first T cells, T cells will think BVD is self

Pregnant cows infected with a non-cytopathic BVDV early in conception up to 120 days will give birth to calves that are tolerant to BVDV and persistently infected

Cows infected with a non-cytopathic BVDV between 120-200 days will give birth to normal calves

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5
Q

Bovine viral diarrhea: cytopathic

A

Cytopathic BVD is more pathogenic- can result in abortion, resorption, mummification; malformations; normal

Infection of pregnant cows with a cytopathic BVDV within the first 100 days of conception will lead to abortion, resorption or mummification of the fetus

Malformations may occur in calves originating from mothers infected with cytopathic BVDV between 100-150 days from conception

Calves from mothers infected with cytopathic BVDV after 150 days from conception may be born normal

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6
Q

Immune response on newborn mammals

A

Birth: animals move from a sterile environment to one with many pathogens
Capable of mounting innate and adaptive IR, however, adaptive mechanisms are not full functional- will respond but will be slow and ineffective
Any adaptive immune will be a primary response
-slow response and low concentrations of antibodies
-innate IR is critical for survival in the first weeks of life
The newborn relies on passive immune transfer from the mother

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7
Q

Innate immunity on Newborn mammals

A

Several antimicrobial molecules
TLR is working
Neutrophils- deficient bactericidal activity associated with high levels of cortisol at birth
Serum deficient in C3 and complement components-C3 in newborn piglets reaches adult levels by 14 days of age
Macrophages present but immature-capable of phagocytizing bacteria, but less efficient at killing, until after 7-10 days
Fewer NK cells- respond more strongly to IL-2 or IL-15 and are more cytotoxic- v effective

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8
Q

Adaptive immunity on newborn mammals

A

Responses tend to be predominantly Th2 based- more shifted toward Ab production instead of cell immunity
Delayed development of IL-12 producing DC1
Activities of IL-4 and IL-13 from CD2
Newborn foals are unable to express IFN-y at significant levels
-associated with placental damage
-6-12 months to reach adult levels
Higher lymphocyte counts than adults (dogs and cats)
-low CD8+ count

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9
Q

Immune response on newborn mammals

A

Born with immune system thats ready but not full effective yet
Transfer of maternal antibodies- dependent on the type of placenta

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10
Q

Hemochorial

A

Primates

Allows maternal IgG transfer (not IgM, IgA, or IgE)

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11
Q

Endotheliochorial

A

Dogs and cats
5% to 10% of IgG is directly transferred from the mother to the puppy or kitten,
Mostly through colostrum

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12
Q

Syndesmochorial

A

Ruminants and Epitheliochorial- horses and pigs

No transplacental passage of Ig molecules
Transfer entirely dependent on the colostrum

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13
Q

Composition of colostrum and milk

A

Ruminant colostrum will have high IgG as will ruminant milk

while nonruminant milk will have majority IgA

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14
Q

Colostrum absorption

A

Once Ig reaches SI they need a way to get internalized and to blood stream
Low protease activity in digestive tract
Ig reach the SI intact and bind with FcRn receptors on intestinal epithelial cells
Ig bound to FcRn are taken up by intestinal epithelial cells and transferred to the lacteals and possibly the intestinal capillaries- lymphatic circulation
Reaches the bloodstream

There are neonatal receptors but appear to stay through adult life- do other functions in adults.

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15
Q

Colostrum absorption: Selectivity of intestinal permeability

A

Horses and pigs
-absorb IgG and IgM; IgA remains in the intestine

Ruminants
-no selectivity

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16
Q

Colostrum absorption: duration of intestinal permeability

A

The highest in the first 6 hours, usually no longer than 24 hours- if suckling not till after 24 hours its a problem

no more expression of FcRn- can vary, can be specific or not

17
Q

Impact of passive transfer

A

Foals have a peak in serum in the first 24 hours
are protected by milk for up to 5 months
so immune system has lots of time to mature

Absorption of IgG from colostrum is required for the generation of systemic immunity
The continuous intake of IgA or IgG1 from milk is required for protection against enteric disease

18
Q

Failure of passive transfer: production failure

A

Failure to produce colostrum or milk
Due to:
premature births (before colostrum is made)
Premature lactation (colostrum before baby)
Individual variation
- up to 28% of mares producing low-quality colostrum
-measures its specific gravity
-1.060 to 1.085 = 3000 to 8500 mg/dL of IgG
-<3000 mg/dL -inadeqate

19
Q

Failure of passive transfer: Ingestion failure

A
Due to:
multiple births
-colostrum production doesnt rise in proportion to the number of newborns
Poor mothering
Weakness in the newborn
Poor suckling drive
Physical problems
20
Q

Failure of passive transfer: absorption failure

A

Major concern
Up to 25% of foals fail to absorb enough Ig
Similar problem with alpacas
Foals require at least 800 mg/dL of IgG 18-24h after receiving colostrum
<400 mg/dL = risk of infections

21
Q

Diagnosing the failure of passive transfer

A

18-24 hours after birth- completed the ig absorption

22
Q

Management of failure of passive transfer

A

75% of foals with 200-400 mg/dL of IgG will stay healthy
-close monitoring
IgG concentrations <200 mg/dL, foals that have not nursed within 6 hours of birth, and foals that have received colostrum with IgG of less than 1000 mg/dL should receive additional colostrum
Colostrum can be stored frozen at -15 to -20 degrees C (1y)
Fresh colostrum from primiparous mares can be used
Foals older than 15h-intravenous plasma infusion

23
Q

Vaccination of neonates

A

Maternal antibodies can interfere with vaccination

  • bind vaccine antigens, preventing the generation of an immune response
  • antigen-antibody complexes formed this way are cleared by cells that posses Fc receptors e.g erythrocytes
  • Maternal antibodies can mask the antigenic epitopes thus preventing B cell responses

Vaccinate after the level of maternal antibodies has declined- no use vaccinating when we know maternal antibodies are still high
this is why there are several booster doses