Mucosal immunology

Mucosal immunology is the study of immune system responses that occur at mucosal membranes of the intestines, the urogenital tract, and the respiratory system. The mucous membranes are in constant contact with microorganisms, food, and inhaled antigens. In healthy states, the mucus immune system protects the organism against infectious pathogens and maintains a tolerance towards non-harmful commensal microbes and noncancerous substances. Disruption of this balance between tolerance and deprivation of pathogens can lead to pathological conditions such as food allergies, irritable bowel syndrome, susceptibility to infections, and more.

The mucosal immune system consists of a cellular component, humoral immunity, and defense mechanisms that prevent the invasion of microorganisms and harmful foreign substances into the body. These defense mechanisms can be divided into physical barriers (epithelial lining, mucus, cilia function, intestinal peristalsis, etc.) and chemical factors (pH, antimicrobial peptides, etc.).

The mucosal immune system provides three main functions:

Mucosal barrier integrity physically stops pathogens from entering the body. Barrier function is determined by factors such as age, genetics, types of mucins present on the mucosa, interactions between immune cells, nerves and neuropeptides, and co-infection. Barrier integrity depends on the immunosuppressive mechanisms implemented on the mucosa. The mucosal barrier is formed due to the tight junctions between the epithelial cells of the mucosa and the presence of the mucus on the cell surface. The mucins that form mucus offer protection from components on the mucosa by static shielding and limit the immunogenicity of intestinal antigens by inducing an anti-inflammatory state in dendritic cells (DC).

Because the mucosa surfaces are in constant contact with external antigens and microbiota many immune cells are required. For example, approximately 3/4 of all lymphocytes are found in the mucous membranes. These immune cells reside in secondary lymphoid tissue, largely distributed through the mucosal surfaces.

The mucosa-associated lymphoid tissue (MALT), provides the organism with an important first line of defense. The tonsils and MALT are considered to be secondary lymphoid tissue along with the spleen and lymph nodes.

The MALT's cellular component is composed mostly of dendritic cells, macrophages, innate lymphoid cells, mucosal-associated invariant T cells, intraepithelial T cells, regulatory T cells (Treg), and IgA secreting plasma cells.

Intraepithelial T cells, usually CD8+, reside between mucosal epithelial cells. These cells do not need primary activation like classic T cells. Instead, upon recognition of antigen, these cells initiate their effector functions, resulting in faster removal of pathogens. Tregs are abundant on the mucous membranes and play an important role in maintaining tolerance through various functions, especially through the production of anti-inflammatory cytokines. Mucosal resident antigen-presenting cells (APCs) in healthy people show a tolerogenic phenotype. These APCs do not express TLR2 or TLR4 on their surfaces. In addition, only negligible levels of the LPS receptor CD14 are normally present on these cells. Mucosal dendritic cells determine the type of subsequent immune responses by the production of certain types of cytokines and the type of molecules involved in the co-stimulation. For example production of IL-6 and IL-23 induce Th17 response, IL-12, IL-18 and INF-γ induce Th1 response, IL-4 induces Th2 response, and IL-10, TGF-β and retinoic acid induce tolerance. Innate lymphoid cells are abundant in the mucosa where via rapid cytokine production in response to tissue-derived signals, they act as regulators of immunity, inflammation, and barrier homeostasis.