The immune system, through efficient processes, fulfills the function of preventing or counteracting the adverse effects of different types of antigens such as viruses, bacteria, parasites, toxins, etc.
Mycotoxins are toxins produced by filamentous fungi, mainly from the genera Fusarium, Penicillium, Aspergillus and Alternaria, which contaminate consumables and feed used in poultry farming.
These toxins have low molecular weight and immunogenicity, affecting not only animal health directly, but also the immune response, with repercussions on:
The effectiveness of vaccination programs.
The duration of response to therapeutic treatments.
Production parameters, generating considerable economic losses.


Understanding the poultry immune system
The immune system aims to protect the host from different types of antigens such as bacteria, viruses, parasites, and toxins.
In birds, the following are among the most important lymphoid organs:
- ⇒Fabricius’ bursa: its function is the development and maturation of B lymphocytes, which are essential to produce immunoglobulins.
- ⇒Thymus: its function is the maturation of T lymphocytes.
- ⇒Spleen: site of lymphocyte differentiation and proliferation, forming part of the so-called innate and adaptive (acquired) immunity (adquirida) (Smith, 2004).

INNATE IMMUNITY
Innate immunity is the first line of defense and is nonspecific, presenting physical, chemical, and biological barriers.
It has specialized cells, such as NK cells and myeloid lineage cells (monocytes, macrophages, and polymorphonuclear granulocytes), which:
- ✓ Identify molecular patterns associated with pathogens (PAMPs) through pattern recognition receptors (PRRs).
- ✓ Perform phagocytosis, antigen presentation to T lymphocytes, and destruction of affected cells.
- ✓ Stimulate the production of cytokines and prostaglandins, regulating the immune response.

ADAPTIVE IMMUNITY
In adaptive or acquired immunity, the response is specific, carried out by:
- ✓ B lymphocytes produced and differentiated in the Bursa of Fabricius.
- ✓ T lymphocytes: they undergo the process of differentiation in the thymus.
Lymphocytes migrate to primary or secondary lymphoid organs, where they are stored until they are mobilized when needed.

The importance of intestinal integrity in bird immunity
The gastrointestinal tract is one of the main entry points for pathogens. Therefore, it has different structures and components that make up the intestinal integrity to prevent this and maintain homeostasis (Figure 1):
- ✓ The presence of microbiota prevents pathogens from adhering to cell receptors through the phenomenon of competitive exclusion.
- ✓ The presence of mucin produced by goblet cells forms a physical-chemical barrier that prevents the persistence of antigens.
- ✓ The tight junctions between intestinal villi cells act as a filter, allowing nutrients and electrolytes to pass through while preventing foreign agents from entering.
- ✓ Components of intestinal integrity include immunoglobulin A (IgA), M cells, B lymphocytes, Peyer’s patches, and gastric-associated lymphoid tissue (GALT), among others.
Figure 1. Different structures and components form the intestinal integrity that is strongly related to immunity. The molecular characteristics of mycotoxins allow them to pass through, altering the immune response and compromising intestinal integrity.
The low molecular weight and lack of immunogenicity of mycotoxins allow them to pass through the intestinal barrier, causing adverse health effects such as dysbiosis and increased endotoxin concentration, affecting poultry productivity.
The impact of mycotoxins will be determined by:
- ⇒The type of mycotoxin
- ⇒The level of contamination
- ⇒Consumption time
- ⇒The age of the birds
- ⇒The production stage
- ⇒Health management

Mycotoxins and immunity
One of the main effects caused by toxins is immunotoxicity, which can be confused with the clinical signs caused by pathogens.
It should be noted that the levels of contamination that cause damage to the immune system are lower than those required to cause more visible effects on health, and that the effects on immunity have a negative impact on production parameters and production costs (Table 1).
They influence the increase in the occurrence, severity, and susceptibility to bacterial infections (Escherichia coli, Salmonella, Clostridium perfringens) and viral infections (inclusion body hepatitis, Marek’s disease, Gumboro disease) and parasitic infections (Eimeria tenella), which leads to low productivity and increased production costs.

Table 1. Summary of the effects of mycotoxins on immunity and their consequences on poultry health and productivity.

For example, fusaric acid is a mycotoxin produced by fungi of the genus Fusarium that causes oxidative stress, decreased protein production, and damage to the immune system.
It is considered to have low to moderate toxicity, but when present alongside other fusariotoxins, it potentiates their immunosuppressive effect (Dilkin, 2021).
The following is a detailed description of data on specific mycotoxins:
FUMONISINS
Fumonisins are toxins produced by fungi of the genus Fusarium that affect the integrity of the intestinal mucosa and the proper development of lymphoid organs, resulting in lower weight compared to the lymphoid organs of non-intoxicated animals.
⇒They cause morphological alterations in the thymus cortex and follicular bursa, while lymphoid depletion and lymphocyte damage with nuclear pyknosis and karyorrhexis (characteristic of cell death) are observed in the spleen.
When the immune system is compromised, alterations may occur in the concentration of post-vaccination antibodies, IgG, and in the phagocytic activation capacity of macrophages. In addition, they inhibit immune mediators such as interleukins (1β and 2) and interferons (γ and β).
Low concentrations of fumonisins induce an increase in corticosteroid concentrations, which leads to immunosuppression and metabolic alterations, increasing susceptibility to infections such as salmonellosis and subclinical necrotic enteritis caused by Clostridium perfringens.

TRICHOTHECENES
Trichothecenes produced by fungi of the genus Fusarium are highly immunosuppressive toxic metabolites.
⇒With the ability to bind to ribosomes, inhibiting protein synthesis and nucleic acid production, they are efficiently transported between plasma membranes until they reach the cytoplasm of target cells.
Absorption and biotransformation vary depending on the type of trichothecene.
For example, the absorption of deoxynivalenol (DON) in the gastrointestinal tract is lower than that of T-2 toxin. However, DON generates greater oxidative stress by increasing the production of free radicals, which causes damage to genetic material, atrophy, apoptosis, and necrosis in intestinal cells in birds and has a negative effect on the production of interleukins, interferon, and transforming necrosis factor, triggering immunosuppression.
Trichothecenes can cause paralysis of the cilia in the upper respiratory tract in birds, which affects the primary protection that these structures provide against the entry of antigens.
They also cause damage to the structure of the intestinal mucosa and the tight junctions present in the cells of the intestinal villi, affecting nutrient absorption and weight gain.
They also influence innate immunity, affecting the cell division of lymphocytes and fibroblasts, and causing lymphoid depletion in the spleen, bursa of Fabricius, thymus, lymph nodes, and bone marrow.
AFLATOXINS
Aflatoxins are toxins produced by fungi of the genus Aspergillus, which are mainly hepatotoxic and highly immunosuppressive.
⇒They affect the phagocytic capacity of macrophages and monocytes, reducing the migration of lymphocytes and leukocytes to sites of infection and inflammation.
During antigen processing, reactive oxygen species (ROS) are produced in phagocytic cells, which aid in the degradation and processing of antigens. However, in the case of aflatoxicosis, the intermediate components for ROS production are reduced, leading to an inefficient immune response and persistent infections.
The synergy of aflatoxins with T-2 toxin increases the immunosuppressive effect, strongly affecting the response to vaccines and increasing the susceptibility of birds to infectious processes.
OTHER MYCOTOXINS
Other mycotoxins have also been shown to have effects on bird immunity.
Ocratoxin A is associated with reduced weight of the bursa of Fabricius, thymus, and spleen.
Zearalenone inhibits the proliferation of B and T lymphocytes.
Moniliformin affects the differentiation of monocytes into dendritic cells and macrophages.
Cyclopiazic acid causes focal necrosis in the spleen, liver, heart, bursa of Fabricius, kidneys, and pancreas (Dilkin, 2021).

Recommendations for minimizing exposure to mycotoxins
Perform periodic checks (representative sampling) to determine the presence and levels of mycotoxins.
Evaluate the use of fungistats and anti-mycotoxin additives with proven efficacy for polar and non-polar mycotoxins.
Store supplies and food in clean, well-ventilated places, ensuring humidity levels below 13% and using whole (undamaged) grains.
Implement biosecurity programs that reduce bacterial, viral, and parasitic loads and enable pest control.

REFERENCES
1. Antonissen, G., Martel, A., Pasmans, F., Ducatelle, R., Verbrugghe, E., Vandenbroucke, V., Li, S., Haesebrouck, F., Van Immerseel,F. (2014). The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases. Toxins, 6(2), 430–452.https://doi.org/10.3390/toxins60204302.
2. Smith, K. G., & Hunt, J. L. (2004). On the use of spleen mass as a measure of avian immune system strength. Oecologia, 138(1),28-31.
3. Dilkin, P. (2021). Micotoxinas en aves. Ed. Palloti, 304 p. Santa Maria-RS. Brasil.