Fetal and neonatal immunology

Question 1

Immune System Development

what order?

Answer 1

• 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

Question 2

The Immune system and
Intrauterine infections

can the fetus mount an IR?

Answer 2

• The fetus is less capable of mounting IR
• Adaptive immune system is not fully functional

Question 3

Calf’s Immune System Development

Basic order of development by days from conception?

Answer 3

41-thymus
45-blood lymphocytes
56 bone marrow spleen
59 IgM Positive Cells
60Lymph Nodes
90 complement
110Grnaulocytes
130 Serum IgG
135 IGG positive cells
145 Serum IgM
155 Tonsil
175 Peyer’s patches

Question 4

The Immune system and
Intrauterine infections

what Mild or innaparent infections in the mother can be severe or lethal
in the fetus

Answer 4

• Bluetongue virus, Infectious bovine rhinotracheitis, Bovine
  viral diarrhea, Toxoplamosis

Question 5

The Immune system and
Intrauterine infections
The response to infection is determined by the state of…

Answer 5

The response to infection is determined by the state of
immunological development of the fetus

Question 6

The Immune System and Intrauterine
Infection

relationship and timing of: cows, pregnant cows, non-cytopathic BVDV, normal calves and normal calves that are tolerant to BVDV?

Answer 6

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

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

Question 7

The Immune System and Intrauterine
Infection

Infection of pregnant cows with a cytopathic BVDV within the first 100 days
of conception will lead to…

Answer 7

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

Question 8

The Immune System and Intrauterine
Infection

Malformations may occur in calves originating from mothers infected with
cytopathic BVDV between…..

Answer 8

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

Question 9

The Immune System and Intrauterine
Infection

Calves from mothers infected with cytopathic BVDV after 150 days

Answer 9

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

Question 10

Immune Response on Newborn Mammals

The newborn relies on….

Answer 10

The newborn relies on passive
immune transfer from the mother

Question 11

Immune Response on Newborn Mammals

what happens at birth?
are they capable of mounting an innate and adaptive IR?

Answer 11

Birth: animals move from a sterile environment to one with many
pathogens
* Capable of mounting innate and adaptive IR, however, adaptive
mechanisms are not fully functional

Question 12

Immune Response on Newborn Mammals

any adaptive immune will be…

Answer 12

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

Question 13

Innate Immunity on Newborn Mammals

6 identifying features:

Answer 13

Several antimicrobial molecules
* TLR
* Neutrophils
* Deficient bactericidal activity
* Cortisol
* 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

Question 14

Innate Immunity on Newborn Mammals

several antimicrobial molecules?

Answer 14

Several antimicrobial molecules

Question 15

Innate Immunity on Newborn Mammals

TLR?

Answer 15

TLR

Question 16

Innate Immunity on Newborn Mammals

Neutrophils?
characteristics?

Answer 16

• Neutrophils
• Deficient bactericidal activity
• Cortisol

Question 17

Innate Immunity on Newborn Mammals
Serum deficient in C3 and complement components? piglets?

Answer 17

Serum deficient in C3 and complement components
* C3 in newborn piglets reaches adult levels by 14 days of age

Question 18

Innate Immunity on Newborn Mammals
Macrophages?

Answer 18

Macrophages present but immature
* Capable of phagocytizing bacteria, but less efficient at killing, until after 7-10
days

Question 19

Innate Immunity on Newborn Mammals
NK cells?

Answer 19

Fewer NK cells
* Respond more strongly to IL-2 or IL-15 and are more cytotoxic

Question 20

Adaptive Immunity on Newborn Mammals

Responses tend to be predominantly…

Answer 20

Responses tend to be predominantly Th2 based

Question 21

Adaptive Immunity on Newborn Mammals

Delayed development of IL-12-…

Answer 21

Delayed development of IL-12- producing DC1

Question 22

Adaptive Immunity on Newborn Mammals

IL-4 and IL-13

Answer 22

Activities of IL-4 and IL-13 from DC2

Question 23

Adaptive Immunity on Newborn Mammals

IFN-γ foals?

Answer 23

Newborn foals are unable to express IFN-γ
* Associated with placental damage
* 6-12 months to reach adult levels

Question 24

Adaptive Immunity on Newborn Mammals

↑ Lymphocyte counts?

Answer 24

↑ Lymphocyte counts than adults (dogs and cats)
* Low CD8+ count

Question 25

IMMUNITY TRANSFER: From Mother to Offspring dependent of what?

Answer 25

Dependent on the type of placenta

Question 26

IMMUNITY TRANSFER: From Mother to Offspring Dependent on the type of placenta 3 types? to what animal? of what / how?

Answer 26

* Dependent on the type of placenta * Hemochorial - Primates * Allows maternal IgG transfer (not IgM, IgA, or IgE) * Endotheliochorial - Dogs and cats * 5% to 10% of IgG is directly transferred from the mother to the puppy or kitten, * Mostly through colostrum * Syndesmochorial - Ruminants & Epitheliochorial - horses & pigs * No transplacental passage of Ig molecules * Transfer entirely dependent on the colostrum

Question 27

IMMUNITY TRANSFER: From Mother to Offspring explain Hemochorial

Answer 27

* Dependent on the type of placenta * Hemochorial - Primates * Allows maternal IgG transfer (not IgM, IgA, or IgE)

Question 28

IMMUNITY TRANSFER: From Mother to Offspring explain endotheliochorial

Answer 28

* Dependent on the type of placenta Endotheliochorial - Dogs and cats * 5% to 10% of IgG is directly transferred from the mother to the puppy or kitten, * Mostly through colostrum

Question 29

IMMUNITY TRANSFER: From Mother to Offspring explain syndesmochorial

Answer 29

* Dependent on the type of placenta * Syndesmochorial - Ruminants & Epitheliochorial - horses & pigs * No transplacental passage of Ig molecules * Transfer entirely dependent on the colostrum

Question 30

Composition of Colostrum and Milk Horses cattle sheep dogs cats pigs

Answer 30

see graphs

Question 31

Colostrum Absorption what order?

Answer 31

* Low protease activity in digestive tract * Allows Ig reach the SI intact * Binding with FcRn receptors on intestinal epithelial cells * Taken up by intestinal epithelial cells and transferred to the lacteals and possibly the intestinal capillaries * Reaches the bloodstream

Question 32

Colostrum Absorption protease activity in digestive tract--high or low?

Answer 32

* Low protease activity in digestive tract

Question 33

Colostrum Absorption Allows Ig reach the....

Answer 33

Allows Ig reach the SI intact

Question 34

Colostrum Absorption Binding with FcRn receptors on....

Answer 34

Binding with FcRn receptors on intestinal epithelial cells

Question 35

Colostrum Absorption Taken up by intestinal epithelial cells and transferred to...

Answer 35

Taken up by intestinal epithelial cells and transferred to the lacteals and possibly the intestinal capillaries

Question 36

Colostrum Absorption Reaches the...

Answer 36

Reaches the bloodstream

Question 37

Colostrum Absorption Selectivity of intestinal permeability Horses and pigs? Ruminants

Answer 37

Selectivity of intestinal permeability * Horses and pigs * Absorb IgG & IgM; IgA remains in the intestine * Ruminants * No selectivity

Question 38

Colostrum Absorption Selectivity of intestinal permeability which animals Absorb IgG & IgM; IgA remains in the intestine

Answer 38

Horses and pigs

Question 39

Colostrum Absorption Duration of intestinal permeability when? characterized by?

Answer 39

Duration of intestinal permeability * The highest in the first 6h, usually no longer than 24h * No more expression of FcRn

Question 40

Impact of Passive Transfer Absorption of IgG from colostrum is required for the...

Answer 40

Absorption of IgG from colostrum is required for the generation of systemic immunity

Question 41

Impact of Passive Transfer The continuous intake of IgA or IgG1 from milk is required for

Answer 41

The continuous intake of IgA or IgG1 from milk is required for protection against enteric disease

Question 42

Impact of Passive Transfer to achieve protection against enteric disease

Answer 42

The continuous intake of IgA or IgG1 from milk is required for protection against enteric disease

Question 43

Impact of Passive Transfer what is required for the generation of systemic immunity

Answer 43

Absorption of IgG from colostrum is required for the generation of systemic immunity

Question 44

Failure of Passive Transfer Production failure results in:

Answer 44

Production failure * Premature births * Premature lactation * Individual variation * Up to 28% of mares producing low-quality colostrum * Measure its specific gravity * 1.060 to 1.085 = 3000 to 8500 mg/dL of IgG * <3000 mg/dL - Inadequate

Question 45

Failure of Passive Transfer Ingestion failure results in:

Answer 45

* Ingestion failure * Multiple births * Colostrum production doesn’t rise in proportion to the number of newborns * Poor mothering * Weakness in the newborn * Poor suckling drive * Physical problems

Question 46

Failure of Passive Transfer Absorption failure results in

Answer 46

Absorption failure * Major concern in foals * Even with good husbandry: 25% of foals fail to absorb enough Ig * Economic value * Similar problem with alpacas

Question 47

Diagnosing the Failure of Passive Transfer how to you identify? when do you test?

Answer 47

* Ideal: IgG >800 mg/dL * Failure of Passive Transfer - IgG <400 mg/dL * Partial Failure: IgG >400 - <800mg mg/dL * Test after at least 18 to 24h after birth * Multiple tests available

Question 48

Diagnosing the Failure of Passive Transfer Comparison of sensitivity & specificity of different methods in detecting serum IgG what 3 tests? at <800mg/dl in foals which has highest sensitivity? which has highest specificity?

Answer 48

snap total protein globulin snap highest specificity globulin highest senditivity see graph

Question 49

Diagnosing the Failure of Passive Transfer Comparison of sensitivity & specificity of different methods in detecting serum IgG what 3 tests? at <400mg/dl in foals which has highest sensitivity? which has highest specificity?

Answer 49

snap highest sensitivity and specificity

Question 50

Management of Failure of Passive Transfer what are the factors that affect IgG and treatment?

Answer 50

* 75% of foals with 200-400 mg/dL of IgG will stay healthy * Close monitoring for infections * 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

Question 51

Management of Failure of Passive Transfer can colostrum be stored? how? how long?

Answer 51

Colostrum can be stored frozen at −15° to −20° C (1y)

Question 52

Management of Failure of Passive Transfer can fresh colostrum from primiparous mares be used

Answer 52

Fresh colostrum from primiparous mares can be used

Question 53

Management of Failure of Passive Transfer who can get an Intravenous plasma infusion

Answer 53

Foals older than 15h - Intravenous plasma infusion

Question 54

Vaccination of neonates what can interfere with vaccination?

Answer 54

Maternal antibodies can interfere with vaccination

Question 55

Vaccination of neonates how do Maternal antibodies interfere with vaccination --3 ways?

Answer 55

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

Question 56

Vaccination of neonates when should you vaccinate?

Answer 56

Vaccinate after the level of maternal antibodies has declined

Question 57

Vaccination of neonates what effect of the presence of maternal antibodies to canine parvovirus in 653 puppies on their response to a modified live parvovirus vaccine.

Answer 57

Effect of the presence of maternal antibodies to canine parvovirus in 653 puppies on their response to a modified live parvovirus vaccine. The pre- vaccination antibody titer profoundly inhibits the response of the puppies to the vaccine.