ORGANS OF THE IMMUNE SYSTEM II
MALT (Mucosal Associated Lymphoid Tissues)

A variety of lymphoid tissues are found at various mucosal sites [within digestive system, respiratory system, and urogenital system].  In humans, these lymphoid tissues function as secondary lymphoid tissues.  Most antigens enter the body via the mucosal route, so the mucosal immune system is incredibly important and was previously under-emphasized by immunologists.

The MALT exists both as loosely organized clusters of lymphoid tissue and as well organized discrete lymphoid structures.
In general, dispersed lymphoid tissue of the digestive mucosa is termed GALT (gut-associated lymphoid tissue).
Dispersed lymphoid tissue of the respiratory tract is termed BALT (bronchus-associated lymphoid tissue).

Organized structures include the 3 tonsil groups:  lingual at the base of the tongue, palatine at the sides of the throat, nasopharyngeal in the roof of the nasopharynx (adenoids).

The appendix and the Peyer's patches are both organized clusters of MALT associated with the digestive tract.

Within the digestive tract, antigens (including microorganisms) are delivered from the lumen of the digestive tract across the epithelial cell boundary of the mucosa by specialized cells known as M cells.  The specialized epithelial cells have broad membrane processes on the lumen side and a deep pocket (termed the basolateral pocket) on the basolateral side of the cell.
Antigens are endocytosed (or enter via transcytosis) into membrane-bound vesicles that move the internalized materials to cells contained within the basolateral pocket of the M cell.  The cells present within the pocket include macrophages, B lymphocytes, and T lymphocytes.  B cells are known to be activated by antigen within the pocket, T cells are presented with antigen by dendritic cells in the underlying lamina propria.  Within the primary follicles of the MALT, B cells begin to enlarge into lymphoblasts and secondary follicles then develop which contain active germinal centers (sites of intense B cell proliferation and differenitation). The resulting plasma cells then secrete large quantities of antigen-specific IgA.

IgA
IgA is the major isotype of Ig present in mucosal secretions.  Two IgA monomers are held together in a dimer conformation by a polypeptide known as the J chain.  The IgA must pass through the mucosal epithelial cells in order to enter the lumen of the digestive, respiratory, or urogenital tract.  The IgA dimers first bind to a protein projecting from the surface of the mucosal epithelial cells known as the poly Ig receptor. The poly Ig receptor - IgA complex is then internalized, and IgA with part of the poly Ig receptor still attached is secreted into the mucus on the lumen side.  The portion of the polyIg receptor which remains attached is termed the secretory component.  The secretory component protects the IgA dimer from proteolysis within the mucus.

Interesting Note--
Several pathogens have exploited the M cell as a portal of entry to mucosal tissues.  Normally, tight junctions between mucosal epithelial cells prevent the entry of microoganisms.  The M cell is used by Vibrio cholerae, Salmonella sp., and the polio virus to establish infection within the digestive tract.

Lymphocyte Traffic
Lymphocytes leave various mucosal sites through efferent lymphatic vessels.  From the lymphatic vessels, the lymphocytes are able to pass through lymph nodes and eventually from the thoracic duct to the left subclavian vein the cells can enter the blood stream.  Once in the blood stream, the lymphocytes will pass through the spleen or can re-enter lymph nodes by extravasating across the High Endothelial Venules of the postcapillary venules.
 

CALT (Cutaneous Associated Lymphoid Tissues)

The skin represents a tough barrier for the vast majority of potential pathogens and clearly represents a very important aspect of our innate immune defense against infection.  In addition to the anatomical/physical barriers to infection, the skin can also serve as an inductive site for the adaptive immune response.

The outer epidermal layer of the skin is comprised of specialized epithelial cells known as keratinocytes. Keratinocytes can be induced to secrete a large number of different cytokines, and during intense inflammation can also be induced to express Class II MHC and function as antigen presenting cells ("non-professional" APCs).

There are also numerous dendritic cells scattered throughout skin tissue.  DCs in the skin are termed Langerhan Cells.
The Langerhan Cells can internalize antigens which enter the skin.  Upon activation, these cells then migrate via the efferent lymphatics and travel to the lymph nodes where they can interact with antigen-specific T lymphocytes.

There are also scattered lymphocytes in the skin (intraepidermal lymphocytes and dermal lymphocytes).  The intraepidermal T cells are primarily T lymphocytes bearing the gamma/delta form of the T cell receptor.  T lymphocytes in the dermis are generally either previously activated T cells or memory T cells.
 

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