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IMMUNOLOGY ()Map CURRENT PAGE (Map)

Introduction

Passive immunity occurs when 'preformed' antibodies are made in one animal and passed onto another. For example a cow passes on her own antibodies to her calve via colostrum (first milk after parturition) and milk.

Antibodies can be transferred to other individuals via colostrum, milk, crossing of the placenta, vaccination, and plasma transfusions.

Neonates require maternal antibodies because:

1. They have poorly developed immune systems and are immunocompromised at birth.

Lymphocytes in neonates: Increased numbers of mostly mature and functional T and B lymphocytes are found in the blood. However the ability to mount an immune response to certain antigens is absent. This may be due to:

1. Immaturity of some cells - T helper cells, B cells and Antigen presenting cells.
2. Lack of expression of genes encoding receptors for each antigen.
3. The presence of maternal antibody which binds antigen and removes it thus preventing the neonate from developing active immunity.

Antibodies in neonates:

2. Neonatal mucosal surfaces are particularly vulnerable

3. Colostral and milk antibodies protect neonates from infections

Passive transfer via placenta

SPECIES	PLACENTA TYPE	IgG TRANSFER?
human	haemochorial	YES
dog/cat	endotheliochorial	SMALL AMOUNT
horse/ruminant/pig	epitheliochorial	NO

Due to the placentas of ruminants and horses having 5 tissue layers between the maternal and fetal circulation there is no transfer of antibodies across the placenta.

Passive transfer via colostrum

In the dam B cells migrate from the MALT to the mammary gland where antibodies are secreted into the colostrum and milk.

==Colostrum== is the pre-milk fluid usually thick and yellow in colour that is secreted from the mammary glands for only a short time after birth by most mammals.

• There is species variation with the composition of colostrum.
• It contains:
  • Immune factors - immunoglobulins, lactoferrins, protein-rich polypeptides, leukocytes, cytokines, trypsin and protease inhibitors.
  • Growth factors: EgF, IGF-I, IGF-II, FyF, PDGF, TgF A and B and growth hormone (GH) - which aid in rebuilding damaged body systems and stimulating the bodies metabolism to burn fat for energy instead of the bodies own muscle tissue.
  • Vitamins and minerals.
• IgG is most abudant in colostrum, followed by [[Immunoglobulin A|IgA]] and IgM
• During the first 30 hours of life, immunoglobulins are absorbed through the intact jejunum and pass to the lacteals, thoracic duct and into the systemic circulation.
• The first diagram (entitled Transfer of IgG across intestine via FcRn) shows IgG being present in the intestine of a neonate, from the ingestion of colostrum. Fc receptors (FcRn) are present on the surface of the intestinal epithelial cell in neonates for the first 30 hours. The IgG binds to the receptors and is transported through the cell by pinocytosis and released into the lacteals unchanged.
• The capacity for immunoglobulin absorption progressively declines from birth due to the FcRn only being present for a limited period of time. After 6 hours a third of the FcRn are non functional.
• It is essential that all animals with epitheliochorial placentas (ruminants, horses, pigs) receive adequate colostrum intake within the first 4 hours (optimal absorption period) of life because no transfer of immunoglobulins via the placenta can occur.
• The second diagram (entitled Passive Transfer) shows the relationship between passive immunity from the mother and the neonatal production of antibodies.
• Colostrum also provides the neonate with a vital energy source to generate heat and enzymes to aid digestion of colostrum products.

==Milk== is the primary source of nutrition for young before they are able to digest other food. In non-ruminants [[Immunoglobulin A|IgA]] is most abundant, followed by IgG and IgM; IgG is most abundant in ruminant milk.

• Milk has approximately 1/100th of the antibody concentration of colostrum.
• Between colostrum and milk there is a period where a substance similar to them both is secreted called transition milk. By approximately 5-7 days milk is being secreted.
• The capacity for immunoglobulin absorption from the gastrointestinal tract is completely absent 30 hours post partum so the main role of milk (apart from a nutritional source) is to protect the intestinal lining.
• IgA remain in the intestine and attach to the intestinal villi protecting the intestinal lining against enteric pathogens.

Colostrum feeding of lambs and kids

Colostrum source	Acceptability
Dam with good quality colostrum	Best source
Another female in the flock/frozen colostrum (must be thawed properly)	Best substitute
A female in another flock (similar disease status)	Next best substitute
Ewe or doe	There is a risk of transferring diseases for example Maedi Visna and Caprine Arthritis and Encephalitis (CAE) viruses.
Cow	Lower in nutrition (milk from coloured breeds is higher in fat), need to feed 1/3 more volume, Johne's risk
Colostrum supplement powder	Nutritious, contains antibodies, expensive
Lamb or kid milk replacer	Only feed after first 24 hours of life as it is not an adequate substitute for colostrum

Maternal Immunity in Birds

• Transfer of maternal IgG into egg yolk (in ovary)
• Transfer of maternal IgM and IgG into albumin (in oviduct)
• Chick embryo absorbs IgG from yolk
• Chick embryo ingests [[Immunoglobulin A|IgA]] and IgM from amniotic fluid

Failure of passive transfer (FPT)

Inadequate absorption of immunoglobulin.

It occurs because of 4 main reasons:

1. The neonate did not receive any colostrum.
2. The neonate did not receive enough colostrum.
3. The neonate did not absorb enough colostrum.
4. The quality of the colostrum was inadequate.

Colostrum quality (amount of IgG) depends on:

• Breed - antibody and milk fat are correlated, thus Jersey cows have the highest amount of immunoglobulin. Conversely Holsteins have the lowest amount of immunoglobulin.
• Nutrition - it is especially important for cows during the dry period (last 2 months of pregnancy) to have the correct nutrition in order to produce immunoglobulin.
• Season - the lowest quality of colostrum is produced in the late winter months as this is correlated to the quality of forage available.
• Stress - dams under increased stress produce colostrum of reduced quality.
• Immunostatus of the dam - dams exposed to specific diseases mount an immune response and produce antibodies for that particular disease, these antibodies are then transferred to the neonate via colostrum. Dams may also be vaccinated which, if done during the colostrum production period (last 2 months of gestation), will also provide the neonate with some protection via passive transfer.
• Milk yield - increased yield dilutes the amount of immunoglobulins in the colostrum.
• Pre milking - omitting a dry period or mistakenly milking a cow during the dry period removes any colostrum produced.
• Dripping from teats - poor teat confirmation may result in a poor teat seal and thus dripping before the calf has been born or sucked.
• Parity - older cows have better quality colostrum as they have been exposed to more pathogens and may have had multiple vaccinations causing their colostrum to have a higher amount of immunoglobulin.

Colostrum quantity depends on:

• Amount the neonate suckles - a strong neonate and good mothering from the dam increases the amount the neonate suckles. Udder conformation also influences the accessibilty of the teats to the neonate. Dystocia may reduce mothering and produce a weak calf potentially causes an increased time to the first suck and/or reducing the amount the neonate consumes.
• Premature births - if born early the dam has a shorter period of time for concentration of antibodies from the blood to the colostrum. It is more likely that the neonate will also be weaker and smaller, causing the amount of colostrum sucked to be reduced.

Failure of absorption from the intestines:

• If the neonate is provided with colostrum 30 hours post partum the FcRn receptors will be completely absent and thus no IgG will be absorbed.

As a rough guide 8-10% of the neonate's body weight of good quality ('green') colostrum should be given over the first 12 hour period of a neonate's life to prevent FPT. This can be done effectively by hand feeding using bottles or with oesophageal feeders.

Testing colostrum quality

Colostrum quality can not be determined by appearance. Colour and consistency only indicate the fat components of the colostrum, and a measure of the IgG either in the colostrum or in the blood of the neonate is required to determine the immunological quality.

Storage: Colostrum can be stored, however this must be done correctly to prevent reduction in immunological status and to prevent outbreaks of disease. Disease outbreaks may occur from feeding colostrum as it is a very good medium for bacterial growth. The best way to store colostrum is to freeze it immediately after milking in a small, clean, secure container. It can be frozen for a year with minimal reduction in quality. It should be thawed thoroughly before giving it the the neonate by leaving it at room temperature, or by gently warming it in water (no hotter than 38 C). Thawing colostrum at high temperatures or by using a microwave can irreversibly denature the immunoglobulin (proteins) and thus reduce the colostrum's immunological status. Colostrum can be refrigerated for approximately 5-7 days. However, this must be done immediately after milking, and it must be discarded after this period to prevent colostrum with bacterial overgrowth being fed to the neonates.

Pasteurisation: If diseases such as Mycoplasma, Johnes and Bovine Leukaemia Virus are present on the farm it is important not to feed affected colostrum to the new born calves. To prevent the spread of these diseases, long time pasteurisation of the colostrum at low temperatures can be performed. However this causes a 40% reduction of antibody content.

1. Colostrometer

• Used to determine the immunological status (quantity of immunoglobulin especially IgG ) of the colostrum.
• It should be used before giving any foal or calf colostrum.
• Measures the specific gravity of the colostrum which correlates to the IgG concentration.
• The colostrum must be at room temperature (20°C). Below this the colostrometer will overestimate the amount of IgG present, and if it is above, the amount of IgG will be underestimated.

Colostrometer readings

Colostrometer colour	Colostrum quality	Quantity of immunoglobulin (mg)	Suitability for use
Green	Good	50-140 or more	Give to neonates for the first 24 hours or for longer if in abundance
Yellow	Fair	20-50	Only use in the first 24 hours if no 'green' colostrum is available
Red	Poor	<20	Only use after 24 hours for 2-3 days

2. Zinc Sulfate Turbidity (ZST) test

• An easy, quick test to determine the immunological status (amount of immunoglobulins)/adequacy of passive transfer in foals and calves.

Calves:

ZST test results for calves

Amount of serum immunoglobulin (ZST UNITS)	Outcome	Cause of death/outcome
<10	Death	E.Coli infection; effects of diarrhoea and pnemonia
10-30	Less likely to die	Recurring diarrhoea that can lead to death and/or pneumonia
>30	Healthy	May have slight diarrhoea and/or pneumonia

Foals:

• If the foal has not nursed effectively from the mare 2-3 hours post partum then at least 1L of good quality colostrum must be given. The quality can be determined using a colostrometer. Specific gravity >1.060 is roughly equal to a colostrum IgG concentration of >3000 mg/dl.
• The immunological status is especially important in foals to prevent infection.
• IgG levels in foals peak at 18 hours post parturition.

Ideally check ZST at 12-18 hours or earlier if:

• Suspicion of FPT (eg. inadequate suckling etc).
• If colostrum is available.

Check ZST at 48 hours if:

• Foal is clinically normal.
• Financial constraints (can only afford to do the test once).
• No colostrum available to use at 12-18 hours anyway, so if there is a problem a plasma transfer would have to be performed to provide adequate antibodies.

Serum immunoglobulin levels in foals

Amount of serum immunoglobulin (mg/dl)	Age of foal	Action needed
<200	<18 hours old	IV plasma infusion
200-400	<18 hours old	Antibiotics treatment at first sign of infection and IV plasma infusion
>400	<24 hours	Oral colostrum

800 mg/dl is considered normal and these foals are at less risk of infection compared to foals with failure of passive transfer.

3. Total serum protein

• It can be used as an on farm assessment of antibody levels in calves.
• A blood sample is taken when the calf is 2-8 days old.
• The total serum protein is measured using a refractometer.

The total serum protein values for calves

Total serum protein (mg/dl)	Amount of colostrum absorption
<4.5	None
4.5-4.9	Inadequate
5.0-5.2	Poor
5.3-5.4	Borderline
5.5-7.0	Acceptable

Alloimmune haemolytic anaemia of the newborn

An alloantigen is an antigen existing in alternative (allelic) forms in a species, thus inducing an immune response when one for is transferred to members of the same species who lack it. So alloimmune haemolytic anaemia occurs when a neonate inherits the sire's blood type and drinks colostrum from the dam, which contains antibodies against the sire and thus the neonate's red blood cells.

It can naturally occur in humans (Rhesus disease) and foals (neonatal isoerytholysis) and can be induced in pigs and cattle by vaccines containing allotypic red blood cell antigens.

Neonatal Isoerytholysis (NI)

Occurs in some foals, and always occurs in mules due to the incompatibility of the sire and dams blood types.

First pregnancy from a stallion with incompatible blood type to the mare:

• Mare is mated with a stallion with an incompatible blood type.
• The neonate may inherit the sire's blood type.
• At parturition, or because of placentitis, RBCs from the foal enter the maternal circulation.
• The surface of the foal's RBCs possess an antigen (usually Aa or Qa) that the mare's RBCs lack.
• The mare begins to mount an immune response towards the foal's RBCs.
• There are no antibodies against the foal's RBCs in the mare's colostrum as there has not been sufficient time to mount an immune attack and secrete them into the colostrum.
• The foal's intestine stops absorbing maternal antibodies after 30 hours (as previously discussed) and thus, when the alloantibody is secreted in the milk, it does not affect the foal.

Subsequent pregnancy from the same stallion or same blood group as previously exposed to

• Foal is born and suckles from the mare.
• Colostrum already contains alloantibodies against the foal's RBCs causing there to be RBC destruction or removal from the circulation (type II hypersensitivity reaction) leading to haemolytic anaemia and jaundice.
• When the foal's intestines are no longer able to absorb maternal antibody (approximately 30 hours post partum) it is safe to return the foal to the mare.

Almost all mule pregnancys result in NI due to the mare lacking a factor called donkey factor.

References

Books

A.H. Andrewa Bovine Medicine - Diseases and Husbandry of Cattle Blackwell Publishing 2004 2nd Edition

Koterba, Drummound and Kosch Equine Clinical Neonatology Williams and Wilkins 1990

P. Lydyard, A. Whelan and M.W. Fanger Immunology Garland Science 2nd Edition 2004

Websites

www.sheepandgoat.com

Materno-fetal Immunity Flashcards