Immunity in Piglets

- Primary: this covers the first 4 to 8 weeks of life, or the phase in which immunity is stimulated by contact with the bacterial diversity of the gastrointestinal tract
- Secondary: acquired response in adults

Antibodies (labelled as Ab), also called Ig, are "Y" shaped proteins, secreted by plasmocytes (differentiated B lymphocytes) stimulated by a foreign Ag.

In the porcine species, there are 3 types of immunoglobulins:  the IgG in the blood, the IgA in the mucous membranes and the IgM.

IgM is a large ancestral molecule which has difficulty diffusing and only very rarely exits the blood vessels. The IgG (from the ancestral IgM molecule) are monomers which diffuse very quickly into all the tissue spaces to block the assailant and destroy it. Although they appear at a later stage they generate a memory: their presence therefore lasts for as long as several months. The IgA are the Ac of the mucous membranes where they provide local immunity.  IgA are produced and remain in contact with the mucous membranes, they predominate in nasal secretions, saliva and the intestine (in monogastric animals). Their protective role is essential, since this constitutes the first specific defence against infections which attack through the skin or mucous membranes. The IgA repel the assailant by fixing there, acting like "flypapers". In this way pathogens are eliminated in the faeces without being able to adhere to the mucous membrane. This reduces the transfer of Ag (the bacteria) from one individual to another. In the mouse, the presence of IgA anti-Salmonella limits the risk of diffusion of Salmonellosis from one animal to another or from one litter to another, via faecal matter.

Compartmentation of the organism then exists. Consequently we talk about the skin, systemic and mucous membrane compartment because the concentration and phenotype of the lymphocytes, as well as the distribution and different classes of Ig are different.

- Systemic immunity (extended to the whole organism) rapidly becomes essential in species where the placental barrier prevents the installation of prenatal immunity: if the young fail to take in colostrum, they may die through lack of immune protection.

- The immunity of the mucous membranes is extended to all the mucous membrane areas. In this way the lymphocytes which have been produced in the course of digestive stimulation may circulate in all the mucous membranes, and may even go right to the teat: this phenomenon ensures immune protection for the whole of the mucous territory, and transmission of this immunity to the offspring (via mammary secretions). The main characteristic of immunity of the mucous membranes is the production of IgA.

Transmissible gastroenteritis (TGE) is a very contagious infectious viral diarrhoea, experienced up to the end of the 1980s. It is caused by a Coronavirus, one of whose 2 types of spicules (E1) is responsible for attachment to the mucous membranes and which leads to diarrhoea in the sow, then in the piglet which will only be protected if it suckles the colostrum then the milk of an infected sow.

The neutralising anti-virus IgAs provide protection in the milk. A spontaneous mutant, attenuated and natural, appeared at the end of the 80s with an AA deletion in position 224 of the protein E1: the virus was no longer multiplying in the intestine (with the clinical signs of TGE), but at respiratory level - lungs and bronchi - causing mild influenza. As the virus circulated quickly, the porcine population was rapidly protected and these mild respiratory diseases eliminated the clinical form of TGE.

Even if the viruses differ, there are enough communities to guarantee protection through the cross-reaction of the respiratory virus against the real TGE virus.

In Eutherians, depending on the number of layers of tissue separating the foetus from the mother during gestation, Ig cannot be transferred to the offspring while they are in the in uterus. This passage of IgG and IgM is low in carnivores and rodents. It is significant in rabbits. The human foetus receives IgG which diffuse and guarantee systemic protection. At birth, the only thing they do not have is protection of the mucous membranes. This will be provided by the IgA in the colostrum, followed by the mother's milk. This is known as passive immunity. In ungulates, the presence of 7 tissue barriers between the foetal and maternal blood prevents any transplacental passage of the Ac: offspring are born agammaglobulinemic. It is the colostrum, high in IgG, plus adequate intestinal permeability, which ensures that these large molecules pass into the blood.

The Ig come mainly from the blood by serum transudation and predation before farrowing and are stored in the acini of the mammary gland: accumulation begins 3 to 4 weeks prior to farrowing.

Half of the colostral IgA comes from local synthesis by the plasmocytes. After absorption by the piglet, it will remain in the intestine.

The Ig serum concentration in the piglet depends:

- On the Ig concentration in the colostrum
- On the quantity of colostrum drunk
- On a hypothesis of 100% absorption of these Ig in the intestine
- On hemodilution (blood volume close to 1/12 of live weight)
- On the half-life of the Ig (different according to the Ig studied)

A sow produces approximately 0.5L of colostrum and as much as 1L of milk per day and per teat and therefore almost 60 g/d of IgA at the end of lactation.

From birth up to 24-36 hours old, all the immune elements of the colostrum cross the epithelial cells of the intestine of the newborn: IgG, IgA and IgM and lymphocytes. Subsequently, GUT CLOSURE begins and prevents any passage of these macromolecules: its mechanism is little understood: the effect of lactose in the colostrum is suggested.

Development of Ig in young piglets

Over time the maternal Ig are eliminated. The IgA with lactose inhibit their real production by the piglet. During weaning, their level drops then increases again when local production in the intestines takes over. This late synthesis of IgA is able to ensure tolerance of the commensal flora. Three months are needed for the IgA level to reach that of an adult. Piglets which are weaned too early experience a delay in establishing the IgA, weaning later encourages the "experience" and tolerance to various Ag (commensal bacteria and alimentary Ag).

Recruitment of immune cells prior to weaning

T lymphocytes accumulate during gestation in the mammary epithelium (trophic role or elimination of certain viruses) but without ensuring the synthesis of AC which come from

the maternal blood. B lymphocytes accumulate during lactation in the mammary parenchyma and will ensure the production of IgA.

Certain viruses may be found in the cells of the colostrum (and milk) and contaminate it when transmitted to the offspring.

From a practical point of view, these notions could imply that the lymphocytes from a mother who has been in contact with Ag (e.g.: a respiratory virus) might be retained by the teat prior to farrowing. These lymphocytes, already carriers of immune protection, will probably be excreted in the colostrum, crossing the intestinal barrier of the piglet suckling from his own mother (no rejection, same HLA system), rejoin the thoracic canal then the blood and are fixed again in the tissues whose system they set up (the nose, etc.) thus ensuring the same protection in the piglet as that obtained in the mother.

There are two options for the way in which lymphocytes cross. This is either between 2 cells by diapedesis, or across the endothelial cell. On the surface of the venules there are specific receptors which allow the lymphocytes to be selected and to pass between the cells of the endothelium to reach the epithelium. This specificity between the lymphocyte and the receptor is guaranteed by a 2-figure "code":

- an initial specific receptor which stops the lymphocyte and allows it to adhere to the vessel thanks to the same receptor
- a second specific site activating an extraction chemokine which is able to cross the endothelium


This presentation was given during the S. boulardii 3rd Technical Meeting in Paris-Roissy (France), in November  2010.