See also Macrophages and T cell priming by DCs
Introduction:
Cells of the monocytic lineage play an essential role in initiating and maintaining immune responses by acting as antigen-presenting cells. They process and present antigenic peptides via and express costimulatory molecules such as b7.1 and B7.2. Antigen presenting cells can internalize antigen by phagocytosis, endocytosis, or both.
Monocytes circulate in the blood stream for about 8 hours during which time they enlarge, migrate into the tissues and differentiate into specific tissue macrophages which with the neutrophils are the main phagocytes in the body. Monocytes also give rise to which are also migratory cells that can ingest foreign substances but which have a main role as presenters of foreign antigens to lymphoctyes.
Identification of Monocytes:
Monocytes can be stained for CD14 and CD11b.
Factors secreted by Monocytes:
secretion of TNF-alpha: Monocytes are most notably known for the production of TNF-alpha, one of the most potent inflammatory cyotokines.
Activation of Monocytes:
Monocytes are activated via binding of C3a and C5a to their responsive receptors. (see components of the complement system)
Role in Tolerance:
The body routinely reinforces tolerance to “self” antigens thorugh the processing of apoptotic bodies form dying cells, which is performed thorugh a clearing process by antigen-presenting cells (APCs).
COUR is using a nanoparticle platform harnesses the immune system’s own learning power to induce tolerance to specific problematic antigens, while preserving all immune functionality. Upon infusion, COUR nanoparticles bind to immune cells called monocytes. The particles surface is functionalized to enhance uptake, ensuring optimal targeted delivery. These cells then travel to the spleen and liver, where they undergo apoptosis. There, the autoimmune disease-specific antigens encapsulated within the particles are released. The resulting debris is consumed by antigen presenting cells, which present the disease-specific antigens along with negative co-stimulating factors to the adaptive immune system. Adaptive immune T-cells interact with the antigen-presenting cells, and in the absence of inflammatory signals they “perceive” the antigen as self. These T-cells respond by undergoing deletion or anergy… or by inducing a T regulatory response.