ADAPTIVE IMMUNITY

Adaptive immunity in birds is a specific defense system that develops after exposure to an antigen [102]. This mechanism comprises two main components: a humoral response involving B cells and antibody production, and a cellular response dependent on T lymphocyte activity [103]. These two mechanisms complement each other in specifically recognizing and neutralizing pathogens, while also forming an immunological memory that allows for a faster and more effective response upon subsequent exposure [104].

The humoral response is characterized by the production of various immunoglobulins (Ig), including IgA, IgM, and IgY (equivalent to IgG in mammals) [105]. IgA is the primary antibody on the intestinal mucosal surface and helps protect the epithelium by neutralizing pathogens and toxins, thereby preventing excessive colonization [106]. IgM appears earliest in the first stage of infection and functions to activate the complement system, while IgY provides long-term systemic protection against circulating pathogens [107]. In birds, the bursa of Fabricius is an essential lymphoid organ where B cells mature and differentiate, enabling the formation of a diverse and effective antibody repertoire [108].

The cellular response involves T lymphocytes, which include CD4⁺ (T helper) and CD8⁺ (T cytotoxic) subsets [109]. CD4⁺ cells regulate the activity of various immune cells through cytokine production, while CD8⁺ cells are responsible for recognizing and destroying virus-infected or abnormal cells [110]. The activity of these two types of T cells is influenced by signals from dendritic cells and macrophages, which present antigens [111]. This collaboration ensures the formation of a specific and targeted adaptive immune response. Nevertheless, cytokine modulation does not consistently translate into measurable improvements in protective immunity, indicating that immunological biomarkers and functional protection are not always directly correlated [112].

Probiotic supplementation has been shown to enhance the adaptive immune response in poultry. However, these immunomodulatory effects are highly dependent on the specific probiotic strain, administered dose, duration of supplementation, and the type of vaccine used. These microorganisms can increase B and T cell proliferation, promote mucosal IgA secretion, and increase post-vaccination antibody titers, including against Newcastle disease virus (NDV) and Infectious Bursal Disease Virus (IBDV) [113]. Nevertheless, variations in probiotic dosage and vaccination protocols may lead to differing magnitudes, or even absence, of immune enhancement. Probiotic supplementation has been associated with increased mucosal IgA and, in some cases, enhanced post-vaccination antibody titers [114]. However, enhancement of vaccine responses is not universally observed and appears highly strain-, dose-, and context-dependent.

Nevertheless, several studies have reported inconsistent or limited effects of probiotics on vaccine-induced antibody titers, with some trials showing no significant improvement in NDV or IBDV seroconversion compared with non-supplemented controls (additional references to be included) [115]. In some cases, immune enhancement was transient, marginal, or statistically non-significant, particularly when baseline immune status was already optimal or when suboptimal probiotic doses were used.

Furthermore, probiotics influence cytokine regulation, including increases in IL-10 and IFN-γ, which help balance pro-inflammatory and anti-inflammatory immune responses [116]. However, cytokine modulation does not always translate into measurable improvements in vaccine efficacy, highlighting the complexity of host–microbe–vaccine interactions. These cytokine-modulating effects are context-dependent and may vary according to host genetics, immune status, and vaccine challenge conditions [116]. These effects not only increase resistance to infection but also reduce the risk of tissue damage caused by excessive inflammation.