# Immunomodulatory Properties of Probiotics and Their Derived Bioactive Compounds
## 2 Hallmarks of Innate and Adaptive Immunity  
The first step in host immunoprotection from invading pathogens is their identification, conducted by the pattern recognition receptors (PRRs) [22], which, based on their localization, are classified into transmembrane receptors (toll-like receptors, TLRs), and intracellular receptors (NOD-like receptors, NLRs) [23]. Their action is related to the recognition of miscellaneous signaling molecules, including microbe-associated molecular patterns (MAMPs) on pathogens and endogenous damage-associated molecular patterns (DAMPs) on host cells [24; 25]. PRRs bridge innate (nonspecific) and adaptive (specific) immunity [26], with both immunity types functioning as reciprocal defense mechanisms to provide protection against inflammatory or autoimmune diseases [27]. The innate immunity mainly involves anatomical and physical barriers such as skin and mucous membranes, the microbiota, chemical barriers such as antimicrobial molecules and enzymes, and specialized effector cells promoting phagocytosis of foreign pathogens, rendering it the first line of defense [27; 28]. Innate immune response distinguishes normal host cells from intruding pathogens via the identification of pathogen-associated molecular patterns (PAMPs) and of endogenous molecules released from damaged cells (DAMPs), a process mediated by PRRs [27]. The interaction of PAMPs with PRRs elicits an intracellular signal transduction in immune cells [29]. A great variety of components, including antimicrobial enzymes (e.g., lysozyme), acute phase proteins in blood serum (e.g., complement factors, C-reactive protein), antimicrobial peptides (AMPs) (e.g., defensins), cells with phagocytic capacity (i.e., neutrophils, monocytes, macrophages, and dendritic cells (DCs)), and pro-inflammatory cytokine producing cells (e.g., macrophages, mast cells, natural-killer (NK) cells) act in synergy in addition to physical barriers [14; 27]. If pathogens manage to penetrate the first line of defense, the adaptive immunity is activated [28]. Adaptive immunity, as a second line of defense against pathogens, is related to antigen-specific responses and provides long-lasting immunological memory to the host [28]. Unlike the immediate action of innate immunity from minutes to hours, the maximum response of adaptive immunity is observed days after exposure to an antigen [14]. The connection between innate and adaptive immunity depends on the activation of professional antigen-presenting cells (APCs), which include DCs, macrophages, and B cells [28; 30]. The two main classes of adaptive immunity, humoral and cell-mediated immune response, are mediated by B cells and T cells, respectively [31]. B cells, following maturation, migrate through blood to lymph nodes, where they are bound to foreign antigens, proliferate, and further differentiate into antibody-secreting plasma cells and memory B cells [28; 32]. Plasma cells secrete five distinct types of immunoglobulins (Ig) to directly neutralize antigens or indirectly mark the pathogens for destruction. Memory B cells present extended survival and immediately respond upon re-exposure to the same antigen [32; 33]. T cells, the mediators of cell-mediated immunity, mature in thymus to naive T cells [33], which interact with the major histocompatibility complex (MHC) expressed on the surface of APCs [32]. Following this interaction, they proliferate and differentiate into CD4+ T helper cells (Th cells) and CD8+ cytotoxic T cells. Although CD8+ T cells are critical for the host defense against virally infected cells and tumor cells, those that carry out the action of stimulating other immune cell types are CD4+ T cells [28; 32]. The latter can differentiate into seven major subtypes [34], namely Th1 [35], Th2 [35; 36], Th9 [37], Th17 [38], Th22 [39], T regulatory (Treg) cells [36; 40], and T follicular helper (Tfh) cells [41], and are distinguished by the expression of specific cytokines and transcription factors [33].