## 2 Mucosal Immune System of the Avian Gastrointestinal Tract  
Regardless of host species, the functionality of the gastrointestinal tract is maintained through physical and chemical barriers preserved by various cells in the intestinal epithelium, leukocytes, and the local commensal microbiota [4]. A major barrier with physical and chemical properties in the gastrointestinal tract is mucus: a viscous, aqueous layer of glycosylated proteins that prevent microbes in the lumen from contacting intestinal epithelial cells [15]. Mucus is synthesized by goblet cells in the microvilli of the intestinal epithelium where it has direct contact with the intestinal lumen and creates a physical--(a thick layer with adhesins and secretory IgA) and chemical--( antimicrobial peptides, RegIII proteins, defensins, and cathelicidins) barrier that prevents the movement of pathogens past the epithelium [4; 16]. Microbes in the lumen reside on this mucus layer where they metabolize short-chain fatty acids, synthesize lactic acid, and secrete ATP to communicate with the host immune system [17]. Further protection from microbial invasion is maintained by the glycocalyx, which consists of a complex system of glycolipids, carbohydrates, and mucin proteins that are associated with the intestinal epithelial surface [15]. A diverse array of cells coexists within the mucosal epithelium and is essential for signaling to the local immune system. Between intestinal epithelial cells are tight junctions which further prevent microbes from traveling through the epithelial layer. Additionally, Paneth cells reside at the bottom of crypts and secrete defensins (antimicrobial peptides) into the mucus layer [4]. Within the epithelial layer, there are intraepithelial leukocytes primarily consisting of \(\gamma\delta\) T cells with cytotoxic potential (CD3\({}^{+}\)CD8\({}^{+}\)TCRy\(\delta^{+}\)) and natural killer T cell-like leukocytes (CD3\({}^{-}\)CD8\({}^{+}\)) along with a marginal population of CD8\({}^{-}\)\(\gamma\delta\) T cells (CD3\({}^{+}\)CD8\({}^{-}\)TCRy\(\delta^{+}\)) that traverse within the epithelium [4; 18; 19]. Intestinal epithelial cells, dendritic cells, macrophages, natural killer cells, and innate lymphoid cells all exist within the epithelium to initiate inflammatory responses through pattern recognition receptors (TLRs, NLRs, RIG-like receptors, and C-type lectin receptors) and respond to anti-inflammatory molecules (short-chain fatty acids, bile acids, commensal microbe ATP, cytokines) to maintain gut homeostasis [16; 17; 18]. Below the intestinal epithelium is the lamina propria, where additional leukocytes reside in lymphatic tissues. Avian species (which lack lymph nodes) have diffuse lymphatic aggregates throughout the gastrointestinal tract as well as organized, non-encapsulated lymphatic tissues such as Peyer's patches, Meckel's diverticulum, and cecal tonsils [20]. Mammalian species also have encapsulated lymph nodes that receive lymph from the lymphatic ducts draining from the epithelium [21]. Even so, both organisms exhibit well-organized lymphatic structures along the gastrointestinal tract, where the lymphatic tissue's germinal centers contain B lymphocyte populations and parafollicular zones contain T lymphocyte, macrophage, and dendritic cell populations. These leukocytes in the lamina propria migrate through the tissue to phagocytize microbes and/or secrete cytokines to activate or de-escalate the inflammatory responses at the surface of the epithelium [4]. The epithelial lining above these gastrointestinal lymphatic tissues is referred to as the follicle-associated epithelium and physiologically differs from other regions of the epithelium in the gastrointestinal tract: goblet cells are absent from the epithelium (reducing mucus presence), microvilli are shorter, and microfold (M) cells actively bind to microbes and antigens present in the lumen [22].