Fetal and neonatal immunology Flashcards
Immune System Development
what order?
- 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
The Immune system and
Intrauterine infections
can the fetus mount an IR?
- The fetus is less capable of mounting IR
- Adaptive immune system is not fully functional
Calf’s Immune System Development
Basic order of development by days from conception?
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
The Immune system and
Intrauterine infections
what Mild or innaparent infections in the mother can be severe or lethal
in the fetus
- Bluetongue virus, Infectious bovine rhinotracheitis, Bovine
viral diarrhea, Toxoplamosis
The Immune system and
Intrauterine infections
The response to infection is determined by the state of…
The response to infection is determined by the state of
immunological development of the fetus
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?
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
The Immune System and Intrauterine
Infection
Infection of pregnant cows with a cytopathic BVDV within the first 100 days
of conception will lead to…
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
The Immune System and Intrauterine
Infection
Malformations may occur in calves originating from mothers infected with
cytopathic BVDV between…..
Malformations may occur in calves originating from mothers infected with
cytopathic BVDV between 100-150 days from conception
The Immune System and Intrauterine
Infection
Calves from mothers infected with cytopathic BVDV after 150 days
Calves from mothers infected with cytopathic BVDV after 150 days from
conception may be born normal
Immune Response on Newborn Mammals
The newborn relies on….
The newborn relies on passive
immune transfer from the mother
Immune Response on Newborn Mammals
what happens at birth?
are they capable of mounting an innate and adaptive IR?
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
Immune Response on Newborn Mammals
any adaptive immune will be…
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
Innate Immunity on Newborn Mammals
6 identifying features:
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
Innate Immunity on Newborn Mammals
several antimicrobial molecules?
Several antimicrobial molecules
Innate Immunity on Newborn Mammals
TLR?
TLR
Innate Immunity on Newborn Mammals
Neutrophils?
characteristics?
- Neutrophils
- Deficient bactericidal activity
- Cortisol
Innate Immunity on Newborn Mammals
Serum deficient in C3 and complement components? piglets?
Serum deficient in C3 and complement components
* C3 in newborn piglets reaches adult levels by 14 days of age
Innate Immunity on Newborn Mammals
Macrophages?
Macrophages present but immature
* Capable of phagocytizing bacteria, but less efficient at killing, until after 7-10
days
Innate Immunity on Newborn Mammals
NK cells?
Fewer NK cells
* Respond more strongly to IL-2 or IL-15 and are more cytotoxic
Adaptive Immunity on Newborn Mammals
Responses tend to be predominantly…
Responses tend to be predominantly Th2 based
Adaptive Immunity on Newborn Mammals
Delayed development of IL-12-…
Delayed development of IL-12- producing DC1
Adaptive Immunity on Newborn Mammals
IL-4 and IL-13
Activities of IL-4 and IL-13 from DC2
Adaptive Immunity on Newborn Mammals
IFN-γ foals?
Newborn foals are unable to express IFN-γ
* Associated with placental damage
* 6-12 months to reach adult levels
Adaptive Immunity on Newborn Mammals
↑ Lymphocyte counts?
↑ Lymphocyte counts than adults (dogs and cats)
* Low CD8+ count
IMMUNITY TRANSFER:
From Mother to Offspring
dependent of what?
Dependent on the type of placenta
IMMUNITY TRANSFER:
From Mother to Offspring
Dependent on the type of placenta
3 types?
to what animal?
of what / how?
- 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
IMMUNITY TRANSFER:
From Mother to Offspring
explain Hemochorial
- Dependent on the type of placenta
- Hemochorial - Primates
- Allows maternal IgG transfer (not IgM, IgA, or IgE)
IMMUNITY TRANSFER:
From Mother to Offspring
explain endotheliochorial
- 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
IMMUNITY TRANSFER:
From Mother to Offspring
explain syndesmochorial
- Dependent on the type of placenta
- Syndesmochorial - Ruminants & Epitheliochorial -
horses & pigs - No transplacental passage of Ig molecules
- Transfer entirely dependent on the colostrum
Composition of Colostrum and Milk
Horses
cattle
sheep
dogs
cats
pigs
see graphs
Colostrum Absorption
what order?
- 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
Colostrum Absorption
protease activity in digestive tract–high or low?
- Low protease activity in digestive tract
Colostrum Absorption
Allows Ig reach the….
Allows Ig reach the SI intact
Colostrum Absorption
Binding with FcRn receptors on….
Binding with FcRn receptors on
intestinal epithelial cells
Colostrum Absorption
Taken up by intestinal epithelial cells
and transferred to…
Taken up by intestinal epithelial cells
and transferred to the lacteals and
possibly the intestinal capillaries
Colostrum Absorption
Reaches the…
Reaches the bloodstream
Colostrum Absorption
Selectivity of intestinal permeability
Horses and pigs?
Ruminants
Selectivity of intestinal permeability
* Horses and pigs
* Absorb IgG & IgM; IgA remains in the intestine
* Ruminants
* No selectivity
Colostrum Absorption
Selectivity of intestinal permeability
which animals Absorb IgG & IgM; IgA remains in the intestine
Horses and pigs
Colostrum Absorption
Duration of intestinal permeability
when?
characterized by?
Duration of intestinal permeability
* The highest in the first 6h, usually no longer than 24h
* No more expression of FcRn
Impact of Passive Transfer
Absorption of IgG from
colostrum is required for the…
Absorption of IgG from
colostrum is required for the
generation of systemic
immunity
Impact of Passive Transfer
The continuous
intake of IgA or IgG1 from
milk is required for
The continuous
intake of IgA or IgG1 from
milk is required for protection
against enteric disease
Impact of Passive Transfer
to achieve protection
against enteric disease
The continuous
intake of IgA or IgG1 from
milk is required for protection
against enteric disease
Impact of Passive Transfer
what is required for the
generation of systemic
immunity
Absorption of IgG from
colostrum is required for the
generation of systemic
immunity
Failure of Passive Transfer
Production failure results in:
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
Failure of Passive Transfer
Ingestion failure results in:
- 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
Failure of Passive Transfer
Absorption failure results in
Absorption failure
- Major concern in foals
- Even with good husbandry: 25% of foals fail to absorb enough Ig
- Economic value
- Similar problem with alpacas
Diagnosing the Failure of Passive
Transfer
how to you identify?
when do you test?
- 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
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?
snap
total protein
globulin
snap highest specificity
globulin highest senditivity
see graph
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?
snap highest sensitivity
and specificity
Management of Failure of Passive
Transfer
what are the factors that affect IgG and treatment?
- 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
Management of Failure of Passive
Transfer
can colostrum be stored?
how?
how long?
Colostrum can be stored frozen at −15° to −20° C (1y)
Management of Failure of Passive
Transfer
can fresh colostrum from primiparous mares be used
Fresh colostrum from primiparous mares can be used
Management of Failure of Passive
Transfer
who can get an Intravenous plasma infusion
Foals older than 15h - Intravenous plasma infusion
Vaccination of neonates
what can interfere with vaccination?
Maternal antibodies can interfere with vaccination
Vaccination of neonates
how do Maternal antibodies interfere with vaccination –3 ways?
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
Vaccination of neonates
when should you vaccinate?
Vaccinate after the level of maternal antibodies has declined
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.
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.
