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Healthy respiratory immune system kicks respiratory diseases

Maximizing the immune response against respiratory pathogens requires a concerted effort to make sure the immune system can respond adequately to respiratory vaccines.

By Chris Chase, South Dakota State University Department of Veterinary and Biomedical Sciences
Porcine respiratory disease complex continues to be a major threat to swine health. This disease results in bacterial pneumonia, chronic disease and major losses in swine productivity. This is a multi-faceted disease involving pathogens, environment, host and management factors (Figure 1).

 Porcine respiratory disease

A number of management factors including processing, vaccination, weaning and handling of pigs have a dramatic effect on the immune system. Psychological factors like social order and fear and flight from inappropriate handling cannot only inhibit the immune system but also cause bacterial pathogens to grow resulting in even more severe disease.

One of the keys to preventing PRDC is a healthy swine respiratory system. The swine respiratory immune system is a dynamic system that uses a variety of defense mechanisms including the epithelial and mucous barriers of the respiratory tract, innate immunity and adaptive immunity (Figure 2). The upper respiratory tract is the first line of defense and consists of epithelial lined airways of the nares, sinuses and turbinates. The airways of the trachea and lower airways of the lung are lined with ciliated epithelium with their tight junctions to prevent pathogens from infecting the URT.

 Respiratory immune responses

A key defense of the respiratory tract is mucous. Mucous traps and moves pathogens out of the respiratory tract and also contains antibacterial factors like lactoferrin and defensins and also immunoglobulin A and G that together form a “kill zone” to stop pathogens (Figure 3). Dehydration greatly reduces the effectiveness of the mucous and is one of the leading causes risk factors for PRDC. These epithelial cells also have important immune functions for both the innate and adaptive immune response including keeping the tight junctions “tight.”

 Defenses of the healthy epithelium (the healthy soldier).

Defenses of the healthy epithelium (the healthy soldier). Epithelial cells act as a barrier against respiratory viruses. The mucociliary apparatus (ciliary movement of mucus) and tight junctions add mechanical, biological and chemical protection. The airway epithelium also regulates both innate and adaptive immune responses, through production of antiviral substances such as IFNs, lactoferrin, β-defensins, and nitric oxide in the mucus layer and production of cytokines and chemokines which recruit and activate immune cells in the submucosa.
 

The cilia of the epithelial cells of the respiratory tract provide the movement necessary to move the mucous up the mucociliary elevator where it is swallowed and cleared through the digestive tract. The mucociliary elevator is important for the clearance of pathogens and particulate material. Irritants like ammonia as well as pathogens like Mycoplasma hyopneumoniae and swine influenza depress cilia movement.

The second line of defense is the innate immune response, which is location specific. In the URT, the innate defenders are predominately respiratory epithelial cells (Figure 3) while in the lower respiratory tract particularly in the lung, alveolar and interstitial macrophages are the defenders. This response starts where pathogens interact directly with epithelium or macrophages and engage the immune system (Figure 3). The epithelium produces the innate molecules including interferon which has anti-viral activity particularly against SIV and the other antimicrobial molecules (defensin, nitric oxide and lactoferrin) that protect the surface of the respiratory tract.

These innate molecules also recruit cells from the circulation with chemokines and cytokines through the inflammatory process and activate more of the innate response (neutrophils, eosinophils, macrophages and natural killer cells) (Figure 3). This activation of the innate immune system then activates T cells of the acquired immune response (Figure 3). Alveolar macrophages in the lower respiratory tract of the lung phagocytize inhaled particles or pathogens, including bacteria that they may encounter. Alveolar macrophages activate T-lymphocytes to initiate an adaptive immune response.

Alveolar macrophages are a major target of porcine respiratory and reproductive syndrome virus, preventing effective antiviral responses and leading to secondary bacterial infections. Pulmonary intravascular macrophages are found in the lungs. They are prominent in pigs and are primarily involved in defense against bacteria in the blood (septicemia) rather than protection from respiratory disease. Pulmonary intravascular macrophages that are actively clearing bacteria (especially gram-negative bacteria) from the bloodstream may release cytokines and inflammatory mediators that contribute significantly to respiratory disease by causing a “cytokine storm.”

The acquired immune response, the third line of defense, with its B cells, T cells, cytokines and antibodies provides the pathogen-specific memory with continued duration of protective immunity (Figure 2). The acquired response is the target for vaccines to generate memory and protection.

In the mucosal lymphoid tissues (Figure 4), mature T cells and B cells that have been stimulated by antigen and produce IgA will leave the submucosal lymphoid tissue and reenter the bloodstream. These lymphocytes will exit the bloodstream into the submucosa of other mucosal associated lymphoid tissue, many that are associated with the respiratory tract (Figure 4). This homing of lymphocytes to other MALT sites throughout the body is referred to as the “common immune system” (Figure 4). Both IgG and IgA are secreted by the respiratory mucosal immune system. Secreted IgA and IgG plays an important role in immunity by making infectious agents clump together, preventing attachment of infectious agents to epithelial cells, and neutralizing toxins. Intraepithelial T lymphocytes are important mediators of immunity at mucosal surfaces. This is especially true for respiratory infections. Pigs have high numbers of intraepithelial lymphocytes that are predominantly T cells (many are cytotoxic T cells that kill virus-infected cells).

 Common mucosal immune system

Final thoughts
PRDC prevention requires good management and animal husbandry practices. Minimizing stress while maintaining the optimal immune response requires daily vigilance in swine operations. Maximizing the immune response against respiratory pathogens requires a concerted effort to make sure the immune system can respond adequately to respiratory vaccines. Vaccines need to be applied strategically at those times that will result in an adequate immune response prior to pathogen exposure.

For the acquired immune response to perform optimally, pigs need to have a proper nutrition plan [energy, protein, immune minerals (copper, zinc, selenium)], low stress (proper density, minimize co-mingling, thermal neutral temperature) and a clean, dry comfortable environment.

Source: Chris Chase of South Dakota State University, who is solely responsible for the information provided, and wholly owns the information. Informa Business Media and all its subsidiaries are not responsible for any of the content contained in this information asset.
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