The spleen is the largest secondary lymphoid organ in the body and contains up to 25 percent of the body's lymphocyte populations. It is not only responsible for initiating immune responses against a multitude of infectious antigens within its white pulp, it also has the exquisite ability to filter the blood and remove, for example, senescent erythrocytes and platelets. This natural process is carried out within the red pulp of the spleen which is composed monocyte-rich connective tissue cords of Billroth intertwined with sinus cavities lined by parallel-oriented endothelial cells that have interendothelial slits which allow for the mechanical sorting of "old" cells. This occurs because of the inability of the senescent cells to properly migrate through the endothelial fenestrae into the venous circulation allowing them to be identified by cells of the reticuloendothelial system (RES) and quickly destroyed by phagocytosis. This process also allows for the efficient recycling of iron from destroyed erythrocyte hemoglobin molecules. There are a wide variety of clinical conditions that can significantly alter the ability of the RES to destroy blood cells including hereditary blood cell defects, inflammation, cancer and abnormal immune responses. This lecture will focus on the central role that the spleen plays in not only generating immune responses against platelets but also in primarily causing the destruction of both senescent and antibody-opsonized platelets leading to thrombocytopenia. It will discuss the soluble and cellular mechanisms of splenic sequestration, destruction and the ability of the spleen to modulate anti-platelet immunity. Mechanisms involving complement activation, Fc Receptor-mediated phagocytosis, antibody dependent cellular cytotoxicity and platelet self-destruction will be addressed. It will compare the spleen's platelet destructive capabilities with other organs, particularly the liver and will detail how immune responses generated in the white pulp can modulate platelet destructive processes in the red pulp.
Semple: Amgen: Consultancy, Honoraria, Speakers Bureau; Rigel: Consultancy, Honoraria; UCB: Consultancy, Honoraria.
Asterisk with author names denotes non-ASH members.