Lecture 19 - Fetal Immunology Flashcards
Describe the immune system of a newborn domestic mammal.
All immune components are developed. T and B cells are naive, but are ready to function.
Which immune system components develop during an animal’s first trimester in utero?
Primary lymphoid organs (thymus, bone marrow)
Secondary lymphoid organs start to form
Which immune system components develop during an animals second trimester in utero?
Complement, granulocytes
Secondary lympoid organs (tonsils, Peyer’s patches, etc.)
When is an animal’s immune system fully formed in utero?
Third trimester
At this point, the immune system is fully formed and naive. The animal can respond to pathogens and may survive, depending on the type and dose.
Learning Objective 1
Describe the consequences of fetal infection and explain factors that influence the outcome.
Consequences:
Death, malformation and congenital anomalies, tolerance to organism, successful immune response.
Result depends on:
Virulence and type of organism, dose of organism, age of fetus.
Learning Objective 2
Explain when domestic species become immunocompetent.
Third trimester
At this point, the immune system is fully formed. Because it has not yet encountered a pathogen, all cells are naive, there are no memory cells, and all immune responses will be primary responses.
Describe the consequences of fetal infection with bovine viral diarrhea virus (BVDV) at different stages of development.
Early gestation (before 50 days)
- Fetus defenseless. Death, abortion.
Mid-gestation (50-120 days)
- Lymphocyte selection and tolerance is occurring. Fetus will develop tolerance to the virus. Persistent viral infection.
Late gestation (180 days to birth)
- Competent immune system. Fetus will successfully fight virus. Will have circulating IgG, which indicates that it had been infected.
Name some differences between the immune system of an adult and that of a newborn.
Newborn characteristics:
- Decreased complement levels
- Decreased macrophage and neutrophil activity (due to high cortisol levels during parturition)
- Lymphocytes less responsive
- TH2 response predominate
- Even though the immune system is developed, newborn cannot survive without passive immunity from the mother
What are the two major modes of conferring passive transfer of immunity from mother to neonate?
Placental transfer of antibody
Colostral transfer of antibody
Which species rely on placental transfer of antibody?
Primates, rodents
Occurs to some extent in canines and felines
Which antibodies cross the placenta in animals that rely on placental transfer of antibodies?
IgG only
Receptor-mediated transfer
What is colostrum?
The “first milk” produced in the last few weeks of gestation. Contains growth factors, nutrients, and immune components.
IgG is the main immunoglobulin.
Also contains immune cells and cytokines.
Which species rely on colostral transfer of antibodies to the neonate?
Large domestic mammals (cow, horse, pig)
Occurs to some extent in canines and felines
Learning Objective 3
Compare and contrast how neonates of different species receive passive antibody from their mother.
Primates and rodents
- Placental transfer
Cows, pigs, horses
- Colostral transfer
Dogs and cats
- Placental transfer and colostral transfer
Why are colostral antibodies not broken down in the gut of the neonate?
- Neonatal GI tract has low proteolytic activity
- Colostrum contains trypsin inhibitors (prevents activation of proteolytic enzymes)
- Colostrum and GI tract have free secretory component, which protects antibody from breakdown
Suppose a cow has previously been infected with a virus. She passes colostral antibodies to the virus to her neonate. Will the neonate form memory cells to the virus?
NO
Colostrum confers passive immunity. IgG has a half-life of two weeks. Once maternal IgG is gone, the calf will not have immunity to the virus.
To form memory cells against the virus, the calf would have to be exposed to the actual virus.
Learning Objective 4
Explain the absorption of colostral antibody and describe the special features of the neonate’s gut that allows the absorption of whole immunoglobulin molecules.
Special gut epithelial cells take up antibody through:
- nonselective pinocytosis of macromolecules
- receptor-mediated endocytosis that recognize the Fc end of antibodies
Antibodies are then transported to the basolateral membrane and released into the blood stream.
When is colostral antibody absorption the highest in the neonate?
In the first 6 hours after birth
Learning Objective 5
Explain “gut closure” - what it is, when it occurs, and how it occurs.
Neonatal specialized gut epithelium is replaced by normal epithelium, and macromolecules are no longer taken up.
Ability to absorb antibodies diminishes by 24 hours. If the neonate has not received colostrum by this time, they will not have received maternal passive immunity.
What is the usual course of action for a neonate that did not receive colostrum?
Plasma transfusion.
It is critical to get immunoglobulins circulating in the neonate’s bloodstream. Otherwise, it will likely die of an infection.
Learning Objective 6
Compare and contrast colostrum and milk, including type of antibody, source of the antibody, and concentration of antibody.
Colostrum
- antibody type - IgG in large mammals. IgA in primates (not absorbed systemically).
- source of antibody - mother’s blood. colostral antibody concentration mirrors maternal plasma.
- concentration of antibody - high
Milk
- antibody type - IgA in non-ruminant. IgG in ruminant.
- source of antibody - local plasma cells in submucosa of mammary gland.
- concentration of antibody - low compared to colostrum.
Do chickens rely more on placental transfer or colostrum for passive transfer?
Um, neither? Chickens lay eggs and don’t produce milk, Greg. Go drink some coffee.
Which antibody isotype can be found in the yolk of a chicken egg?
IgY (most similar to IgG)
Absorbed into the bloodstream of the chick
Which antibody isotype can be found in the albumin of the chicken egg?
IgA
Will be eaten by the chick
Learning Objective 7
Describe passive immunity in the chick
IgY (similar to IgG) found in the yolk will be absorbed into the chick’s bloodstream.
IgA found in the albumin will be eaten by the chick and absorbed by the gut epithelium.
What is the half-life of maternal IgG in the neonate?
1.5-2 weeks
When is a neonate that has received normal passive transfer most vulnerable to infection?
There is a point when maternal IgG has substantially declined and the neonate’s antibody titer has not sufficiently risen to provide protection.
This is termed the “window of vulnerability.”
Occurs at 1-3 months of age.
Learning Objective 8
Part 1
Draw and label a graph of the “window of susceptibility.”
Learning Objective 8 Part 2
Compare and contrast a neonate’s susceptibility to disease to its responsiveness to a vaccine and the factors that influence each.
Maternal antibody has a blocking effect on both pathogens and vaccines. When maternal IgG is high, a neonate has protection against a pathogen. At the same time, its immune system will not recognize the pathogen because of the blocking effect of maternal IgG.
The same is true for vaccines. If the vaccine is in too low of concentration, it will be blocked by maternal antibody and not recognized by the neonate’s immune system, rendering it ineffective.
Decreasing maternal antibody titers both increases disease susceptibility and responsiveness to vaccines.
Learning Objective 9
Explain the term “breakthrough” of maternal antibody.
If enough vaccine or virus is present, it will bind all of the maternal IgG in the neonate and affect the neonate’s immune system.
For a vaccine to be effective in early life, it must be in high enough concentration to break through maternal antibody.
A virulent virus can often break through maternal antibody and cause infection.
What is the most common cause of immunodeficiency in the foal?
Failure of passive transfer (FPT)
Learning Objective 10
List the reasons for failure of passive transfer in a foal.
- Mare fails to produce colostrum
- IgG fails to concentrate in colostrum
- Premature lactation or dripping
- Ingestion failure by the foal
- Absorption failure by the foal
What are the clinical signs of failure of passive transfer (FPT)?
Infections at mucosal surfaces
Respiratory and GI tract infections are the most common
How does the timing of symptoms of a foal with failure of passive transfer (FPT) compare to a foal with combined immunodeficiency (CID)?
A FPT foal received no maternal antibody, so will start showing signs of infection very early on.
Recall that CID foals are unable to produce antibody of their own. Assuming that the foal received colostrum and is nursing, it will have protection until about 2 months of age. As maternal antibody declines and the foal is weaned, it will begin showing signs of infection.
What does SRID stand for?
Single Radial Diffusion Assay
Used to test IgG levels in the colostrum or serum. Effective but expensive. Takes 18-24 hours.
What is the zone of optimal proportions in terms of antigen/antibody binding?
The point at which antigen/antibody binding will create a visible precipitate.
Learning Objective 11 Part 1
Explain the basics of the SRID test used in diagnosis of FPT.
- Gels containing anti-IgG with holes poked in the agar for standards and test sample
- Add reference standards to the standard wells
- Add the patient’s serum to the test well
- Incubate 18-24 hours
- Antibodies will precipitate at the zone of optimal proportions, depending on how much antibody is present
- Create a standard curve
- Determine IgG concentrations in the patient’s serum
Learning Objective 11 Part 2
Explain the basics of the SNAP test and how it is used to diagnose FPT.
- Anti-equine IgG immobilized in the sample spot. Will bind any serum IgG floating through the matrix
- Serum mixed with conjugate. Conjugate contains enzyme-labeled anti-equine IgG. Will bind to equine IgG in the serum
- Snap releases enzyme substrate. If enzyme-linked anti-IgG is present and has bound serum IgG, the circle will change colors.
Learning Objective 12
Describe the consequences of FPT and the options for treatment. Include how and why time influences treatment options.
Consequences: infection at mucosal surfaces and death.
Treatment options
- If before 24-hour gut closure: administer colostrum, oral serum, or commercial colostrum substitute.
- If after 24-hour gut closure: IV plasma or whole blood, intraperitoneal or subcutaneous immunoglobulins.
