The classical proinflammatory adaptive immune response plays a major role in defending nonmucosal tissues such as the spleen, liver, and kidney. This response is coordinated in the local draining lymph nodes through afferent and efferent lymph flow. The systemic immune system mainly consists of T lymphocytes with αβ T cell receptors (TCRαβ T cells) and plasma B cells that produce immunoglobulin M (IgM) and immunoglobulin G (IgG) complement–binding antibodies, which can trigger inflammation.

On the other hand, mucosal tissues (respiratory, gastrointestinal, urinary, and other systems) face the challenge of distinguishing between harmful and harmless agents. Although inflammation is a protective mechanism, it can disrupt normal physiological processes and is generally undesirable unless absolutely necessary. Therefore, mucosal tissues have evolved specialized defense mechanisms that are "noninflammatory" in nature. These mechanisms form the basis of the mucosal immune system and can function independently of the systemic immune system.

The mucosal immune system comprises innate lymphoid cells (macrophages, natural killer cells, dendritic cells [DCs]) and adaptive T lymphocytes with γδ T cell receptors (TCRγδ T cells) and plasma B cells that produce immunoglobulin A (IgA), a nonclassical complement-binding antibody. These innate and unique adaptive responses allow mucosal tissues to prevent or limit responses to nonpathological foreign agents while eliminating pathological agents/substances with minimal or no inflammation.

In cases where the front-line defense system fails or is bypassed, the lungs possess a classical adaptive immune response system. The lymphatic drainage in this system occurs through the mediastinal lymph node, located in the upper region of the thoracic cavity near the main left-right lung bifurcation.

One distinguishing feature of the mucosal immune system is that antigens are processed through lymphoid aggregates instead of true lymph nodes. Unlike true lymph nodes, which have both afferent and efferent lymph flow, lymphoid aggregates only have afferent drainage into the aggregate without efferent flow. This network of lymphoid tissues is known as mucosa-associated lymphoid tissue (MALT). In the gastrointestinal tract, it is referred to as gut-associated lymphoid tissue (GALT), and in the lungs, it is called bronchus-associated lymphoid tissue (BALT).

BALT is present in the conducting airways, where the epithelium primarily consists of ciliated cells with continuous mucus flow. However, the epithelium of BALT is unique in that it lacks cilia and is referred to as lymphoepithelium. This lymphoepithelium creates a break in the mucus flow, allowing substances and particulates to be processed within the lymphoid aggregate or follicle.

There appears to be communication between mucosal tissues, and sensitization of one organ may be transferred to all MALT/BALT tissues through a drainage network similar to lymphatics. The systemic immune system and MALT/BALT may function independently of each other, and sensitization in one may not necessarily occur in the other. This defense mechanism potentially limits sensitization to mucosal tissues only. Lymphocytes also cluster in smaller numbers and density in what is known as tertiary ectopic lymphoid tissue (TELT), where they can process antigens.
In nonmucosal tissues (e.g., spleen, liver, kidney), the body’s primary defense is the classical proinflammatory adaptive, antigen-specific immune response orchestrated in the local draining lymph nodes with afferent and efferent lymph flow. The major adaptive immune cells in the systemic immune system are T lymphocytes with αβ T cell receptors (TCRαβ T cells) for specific antigen recognition and plasma B cells that synthesize immunoglobulin M (IgM) and immunoglobulin G (IgG) complement–binding antibodies, which can induce inflammation. However, mucosal tissues (i.e., those of the respiratory, gastrointestinal, and urinary systems, as well as the eyes, nose, throat, and mouth) must constantly discriminate between what is harmful and what is not, and although inflammation is protective, it usually disrupts the normal physiologic processes and is not desirable unless absolutely necessary. Accordingly, mucosal tissues have developed specialized “noninflammatory” defense mechanisms, which form the basis of the mucosal immune system and can function independently of the systemic immune system. The mucosal immune system contains both specialized innate lymphoid cells (macrophages, natural killer cells, dendritic cells [DCs]) and adaptive T lymphocytes with γδ T cell receptors (TCRγδ T cells) and plasma B cells that synthesize immunoglobulin A (IgA), a nonclassical complement-binding antibody. These innate and unique adaptive responses can prevent or limit responses to foreign nonpathological agents while eliminating pathological agents/substances with little or no inflammation. In addition, if this front-line defense system fails or is bypassed, the lungs do have a classical adaptive immune response system in which lymphatic drainage is via the mediastinal lymph node located in the upper region of the thoracic cavity adjacent to the main left-right lung bifurcation.
A distinctive feature of the mucosal immune system is that antigens are processed through lymphoid aggregates rather than through a true lymph node. Unlike a true lymph node, which has afferent and efferent lymph flow, lymphoid aggregates have only afferent drainage of material into the aggregate without efferent flow. This lymphoid network is commonly referred to as mucosa-associated lymphoid tissue (MALT); in the gastrointestinal tract, it is referred to as gut-associated lymphoid tissue (GALT); and in the lungs, it is known as bronchus-associated lymphoid tissue (BALT;
Fig. 26.2 ). BALT is present in the conducting airways, where the epithelium is composed mainly of ciliated cells with consistent mucus flow. However, an interesting feature of BALT is that its airway epithelium is not ciliated; it is referred to as a lymphoepithelium, which creates a break in the mucus flow (like a drain) and allows the substances/ particulates to be processed in the lymphoid aggregate (or follicle).
It appears that there is communication between mucosal tissues and that sensitization via one organ is transposed to all MALT/BALT tissues via a lymphatic-like drainage network. The systemic immune system and MALT/BALT may work independently of each other, and the fact that one is sensitized may not be true of the other. This may serve as a defense mechanism in limiting sensitization only to mucosal tissue. Lymphocytes also cluster in smaller numbers and density in what is referred to as tertiary ectopic lymphoid tissue (TELT), in which they can also process antigens (see