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Developing Immunity in New-Borns

Introduction

Any new-born animal is born from a sterile environment (e.g. a mother’s womb) into an environment which is filled with microbes and pathogens. Therefore it is important that the newly born animal is able to protect itself in its new, harsh environment. In most species (especially those with longer gestation periods) at birth, the immune system is well on its way to being fully developed but is not yet complete, taking some time (up to several weeks) to become fully functional.

For the immune system to develop, antigenic stimulation must occur, along with the development of antigen sensitive cells. This means that for the first few weeks of a new-borns life they are vulnerable to infection as their immune system is not yet complete. To overcome this, a temporary support system is provided by the mother. The mother is able to pass to her offspring antibodies and T-cells. These are able to temporarily support the animal whilst it builds up its own immune system. This is known as passive immunity.

The Developing Immune System

The development of the immune system in mammals as a foetus follows a consistent pattern. The initial lymphoid organ which develops is the thymus which is then followed by the secondary lymphoid organs (e.g. tonsils, Peyer’s patches, spleen, adenoids, skin etc.). The ability of the foetus to initiate a cell-mediated immune response develops around the same time as antibody production begins.

Below is the length in days that it takes for each of the structures to form in different species:

Species Gestation – Thymus – Lymph Node – Peyer’s Patches – Peripheral Blood – Lymphocytes

Calf                                280                    40                                     60                                       175                                45

Lamb                              145                     35                                     50                                         60                               32

Piglet                              115                     40                                     70

Foal                                340                     60                                    90                                          90                             120

Puppy                              60                       28                                    45                                          45

The Development of Phagocytic Ability

Typically in most species the levels of neutrophils and other phagocytes are almost at mature levels. However during the time of birth, the activity of macrophages is decreased. This may be due to increased amounts glucocorticoids suppressing their proliferation and mobilisation.

Intrauterine Infections

It is possible for the mother to develop a disease which is harmless (to the mother) yet can severely affect the foetus these are what are known as intrauterine infections. Examples are Bovine herpesvirus-1 (BHV-1), Bovine Virus Diarrhoea (BVD) and the bluetongue virus. This is an important concept to consider when planning vaccination schedules for animals, if a vaccine is given to the mother (to whom the vaccine would be non-pathogenic) and the foetus’ immune system is under-developed then it may have severe implications, possibly abortion. For example, a blue-tongue virus vaccine given to a healthy sheep carrying a foetus will cause no pathogenicity to the mother. If the vaccine is given 50 days after conception, this can cause severe legions within the nervous system of the foetal lamb. If given 100 days after conception or when the lamb is born, there will be no such response.

Immune of New-Born Animals

New-born animals are able to initiate immune responses from birth yet they will be primary responses (an initial response to an antigen which is slow and meagre) with a prolonged lag phase and have a reduced amount of antibodies present. Therefore it is possible that an infection which would not greatly affect an adult could kill a new-born animal due to the length of time it takes for the immune system to deal with the pathogen.

Because of this, the mother provides immunological assistance in the form of maternal antibodies. The maternal antibodies are obtained by the new-born either through colostrum (the initial secretion of milk by the mother rich in antibodies) or in some species, also by the placenta. Both antibodies and lymphocytes may be transferred by these means.

Maternal Transfer of Immunity

Maternally derived antibodies which are transferred to the new born pass across in the placenta and colostrum, the method of transfer depends on the anatomy of the placenta.

In Humans:

  • IgG passes through the placenta
  • IgM and IgA transferred in the colostrumIn cats and dogs
  • 5-10% of IgG can be transferred by the placenta
  • The remainder is obtained in the colostrum

In Ruminants, Pigs and Horses:

  • All antibody is obtained from colostrum
  • No placental transmission occurs

Colostrum

Components of Colostrum

Colostrum is a type of milk produced by the mother in the mammary glands in the last few weeks of pregnancy. It differs from normal milk because there is active uptake of proteins from the bloodstream into the colostrum – this is due to hormonal influences (oestrogen and progesterone).

The main antibody component of colostrum is the immunoglobulin IgG, constituting around 65-90%. As the colostrum begins to change to milk, the IgG content reduces and there is a proportionally larger amount of IgA. In the colostrum, most of the antibody content is derived from serum, (all IgG, most IgM and half IgA), whereas in normal milk, antibodies are produced locally by the udder.

Colostrum has greater antibody content than milk. For example, in a cow the amount of IgA produced in colostrum is 100-700 mg/dl, the content of normal milk is just 10-50 mg/dl.

Absorption of Colostrum

Due to the high antibody content of colostrum it is essential that the young animals take in the colostrum. The colostrum enters the gastrointestinal tract; the proteins in the colostrum are not degraded however due to low proteolytic activity in the digestive tract during this period of time.

This brief window or reduced proteolytic action allows the proteins to pass to the small intestine where they can bind with temporary specialised Fc receptors (FcRn) on the intestinal epithelial. These receptors begin to decline in number/activity after 6 hours after birth, becoming very low by 24 hours. The immunoglobulin units are bound, actively pinocytosed and quickly reach the lymphatics and circulation systems.

Due to the small period of receptivity to colostrum (which is due to the brief period of activity of the FcRn receptors) it is important that the new born receives a large amount of colostrum (up to 1L) within the first 6 hours of birth. New born animals which do not receive this will have very low amounts of circulating antibodies which could be hazardous for their health. The protection by the maternal antibodies declines over a number of weeks (after which, it reaches unprotected levels), with peak levels being reached 12-24 hours after birth.

In both horse and pigs IgG and IgM are selectively absorbed, meaning IgA remains in the intestine. However in ruminants all the Ig types are absorbed.

Failure of Passive Transfer

If failure of passive transfer occurs (i.e. the transfer of maternal antibodies) then due to the serious lack of Ig circulating in the new-born, serious infections can occur. The uptake of IgG protects against septicaemia and the uptake of IgA protects against enteric (intestinal) diseases. Failure of uptake of either may lead to the development of such disease.

Reasons for the failure of passive transfer may be due to a failure in production, ingestion or absorption.

It is possible to diagnose the failure of passive transfer by testing the new born sera for immunoglobulins.

Treatment of Failure of Passive Transfer

If diagnosed early, additional colostrum may be given to the new-borns with low sera immunoglobulins. This usually comes from other mothering animals and should be given to the new-born within 15 hours. After 15 hours there will be no oral absorption so plasma must be given to the new-born intravenously.

Colostrum and Cell-Mediated Immunity

Colostrum has high concentrations of lymphocytes, whereas milk has almost none. The lymphocytes in the colostrum are able to survive in calves (for up to 36 hours) and they penetrate the intestinal walls to reach gastrointestinal lymph nodes and Peyer’s patches. This enables cell mediated immunity and humoral immunity.

Neonatal Animal Immune Response

Animals which have consumed maternally derived antibodies will produce their own antibodies more slowly than those animals which didn’t. This is due to the maternally derived antibodies inhibiting the local production of antibodies in the new-born.

Vaccinating Young Animals

Due to maternally derived antibodies inhibiting the synthesis of antibodies by the neonate, prevention of successful vaccinations may occur in young animals.

The rate at which maternally derived antibodies are removed from the young animals system varies greatly even within the same species. This makes it difficult to arrange vaccination schedules. In dogs for example, maternally derived antibodies may persist up to 10-12 weeks later. As a result dogs are vaccinated at 6-9 weeks and 9-12 weeks, whereas colostrum deprived puppies may be vaccinated as early as 2 weeks.

  • If the vaccination is given to early (the maternally derived antibodies are still present) then the vaccine will not work.
  • If the vaccine is given to late, then the puppy may have already contracted the disease being vaccinated against.