Technology
Why Listeria?
Listeria monocytogenes is a common bacterium that is often associated with food poisoning. We have evolved in an environment in which Listeria exists, and we have an immune relationship with it. While not very infectious (people do not spread Listeria from one to another), Listeria can cause disease in people who are immuno suppressed, like 3rd trimester pregnant women or HIV patients, and in normal people if they ingest a large amount of bacteria. Most people encounter Listeria in their food routinely and never know it because Listeria is capable of stimulating a very strong cell mediated immune response which eliminates the microbe before it can do any damage. A cell mediated immune response is the same type of immune response that can be used to kill and clear cancer cells, which is what drew our attention to this microbe in the first place.
Like most bacteria, Listeria is a very strong stimulator of innate immunity, which is a non-specific way to getting the immune system ready to face any threat. Innate immunity sets the stage for an adaptive immune response, which is one directed against a specific target, and usually the stronger the innate response the stronger is the adaptive response.
Listeria has a unique life cycle. It infects Antigen Presenting Cells (APC), which are the cells that activate immune cells and tell them what to attack. Because of this, Listeria becomes perfectly positioned to have the maximum effect on the immune system in terms of directing it against specific targets. Even more unusual is Listeria�s ability to stimulate both helper T cells (CD4+) and killer T cells (CD8+), since both are necessary for an antitumor response and it is unusual for a single pathogen to stimulate both in the way Listeria does.
Antigen Processing Cells normally engulf foreign elements to remove them from the body and present them to the immune system.
Following their ingestion, they are encapsulated and digested in a phagolysosome. Fragments of the digested invader are used to stimulate the immune system through the exogenous pathway (exogenous; since the invader came from outside the cell).
This pathway is associated with the formation of MHC class II complexes and the activation of specific CD4+ helper T cells directed against the invader. This is the most common response to a foreign invader.
A certain percentage of Listeria, however, are able to break out of the phagolysosomes and enter into the cytoplasm of the cell, where they are safe from lysosomal destruction. After escaping from the phagolysosome, the bacteria multiply in the cell. Additionally, Listeria is able to migrate into neighboring cells and spread without entering the extracellular space.
Once in the cytoplasm, Listeria is capable of stimulating the immune system via the endogenous pathway (endogenous; because Listeria is now living within the cell). The endogenous pathway is associated with MHC class I complex formation and resultant CD8+ killer T cells.
Listeria also has other effects; such as the maturation of dendritic cells, which is most powerful APC and is essential for a strong antitumor response.
Thus, Listeria has the ability to stimulate multiple limbs of the immune response simultaneously and in an integrated way that serves to bring a number of immune mechanisms together to attack cancer.
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