Wednesday, March 12, 2014

Secondary Lymphoid Organs

Secondary lymphoid organs include lymph nodes, spleen and mucosa-associated lymphoid tissue (MALT). These structures are passages for blood and lymphatics, and possess distinct areas where T cells and B cells proliferate.

Lymph node
Structure and Histology of a Lymph Node by OpenStax College

B cells, T cells and dendritic cells enter and exit the lymph node through the afferent and efferent lymphatic vessels, or through the blood vessels. In contrast to DCs, follicular dendritic cells (FDCs) reside within secondary lymphoid organs, and present antigen to B cells.

B cells and FDCs are found in the cortex. T cells and DCs are found in the paracortex (not labeled) towards the center of the lymph node. The cortex contains lymphoid follicles (shown in red), also known as primary lymphoid follicles. Active lymphoid follicles are called secondary lymphoid follicles or germinal centers where B cells proliferate and grow.

B cell proliferation
  1. In the lymphoid follicle, FDCs take in opsonized antigen. Both complement proteins and antibodies are recognized by the FDC.
  2. FDCs cross-link B cells and the few B cells that recognize a presented antigen stay and proliferate. 
  3. Proliferated B cells are apoptotic unless activated Th cells migrate to the lymphoid organ and provide costimulation (CD40L).
  4. B cell activation. The B cell also costimulates the T cell (B7) and present antigen. 
  5. Some B cells become plasma B cells and leave to the blood. Others undergo somatic hypermutation and cycle the lymphoid follicle again.

The germination center has a "light zone" where step 5 occurs, and a "dark zone" where steps 3 and 4 occur. It is so named because proliferated B cells move toward the edge to be nearer to Th cells, forming a darker region.

High endothelial venule
Found in the venules, where lymphocytes exit the blood into the lymph (except in the spleen). T cells return to the lymph node via the HEV to be restimulated, proliferate, and stimulate any rare B cells.

Chemokines
FDCs produce CXCL13 to attract naive B cells. B cells that have found their antigen upregulate receptor CCR7 to migrate towards the edge of the germinating center, where they will receive help from Th cells. Likewise, activated Th cells upregulate receptors to migrate towards this same region.

Peyer's patch (MALT)
This is a MALT found in the intestine, with M cells that uptake antigen into the lymphoid organ. There is no incoming lymphatic vessel.

Spleen (blood filter)
There are no lymphatics. Everything from the blood can enter and pass.

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