Wednesday, January 10, 2007
Answering one of the oldest questions in human physiology, researchers at Dana-Farber Cancer Institute have discovered why the body's immune system* - perpetually on guard against foreign microbes like bacteria - doesn't attack tissues in the small intestine that harbor millions of bacteria cells.
In a study in the February issue of Nature Immunology, and which is currently available on the journal's Web site as an advanced online publication, investigators led by Shannon Turley (info), PhD, of Dana-Farber identify an unlikely group of peacemakers: lymph node cells that instruct key immune system cells to leave healthy tissue alone. The finding, which illuminates a previously unknown corner of the human immune system, may lead to new forms of treatment for autoimmune diseases such as Type 1 diabetes and multiple sclerosis.
'We've discovered that cells not generally thought of as part of the immune system actually play an important role in protecting the intestine from immune system attack,' says Turley. 'Because the cells are found in lymph nodes throughout the body, they may offer a way of suppressing a variety of autoimmune diseases,' which result from immune system assault on healthy tissue.
The immune system distinguishes between normal and foreign agents by small proteins, called antigens, on the cell surface. In parts of the body, such as the pancreas, that are sheltered from the outside environment, cells known as dendritic cells display the antigens of their normal neighbors in a way that puts the immune system 'at ease.' By reading those antigens without being on alert, the immune system's T cells learn that such cells are off-limits to attack.
Continued at "Why doesn't the immune system attack the small intestine?"
Based on the paper:
Peripheral antigen display by lymph node stroma promotes T cell tolerance to intestinal self
The intestinal epithelium functions to absorb nutrients and to protect the organism against microbes. To prevent autoimmune attack on this vital tissue, T cell tolerance to intestinal self-antigens must be established. Central tolerance mechanisms involve medullary thymic epithelial cells (mTECs), which use endogenously expressed peripheral-tissue antigens (PTAs) to delete self-reactive thymocytes. The prevailing model for the induction of peripheral tolerance involves cross-presentation of tissue antigens by quiescent dendritic cells. Here we show that lymph node stromal cells present endogenously expressed PTAs to T cells. Moreover, antigen presentation by lymph node stroma is sufficient to induce primary activation and subsequent tolerance among CD8+ T cells. Thus, lymph node stromal cells are functionally akin to mTECs and provide a direct strategy for purging the peripheral repertoire of self-reactive T cells. [Abstract]
*Immune systems are generally characterized by their ability to distinguish between self and non-self cells, tissues, or molecules, and to eliminate the non-self (for review see Janeway 2001). The mammalian immune system is an incredibly complex and intricate system that can recognize non-self and provide protection from a wide variety of pathogens. While there is a high degree of interconnectivity between its components, the immune system can be loosely divided into two subsystems, the innate and the adaptive immune systems. In general, innate immunity is a non-specific, inducible response to pathogens. It is immediate in action, yet short-lived. On the other hand, the adaptive immune system is much more specific, but takes longer to activate. It also features immunological memory, and can augment itself to respond more quickly and with greater specificity to future infections of similar pathogens. Both systems work together to provide protection against a diverse and rapidly-evolving array of pathogens.
While much is known about the evolution of the immune system, the details of its origin remain to be elucidated. The innate immune system is the more ancient of the two systems, with roots deep in the deuterostome branch of the bilaterians, roughly one billion years ago. Conversely, the adaptive immune system appeared more recently and quite suddenly, around 450 million years ago with the emergence of the gnathostomes, more commonly called the jawed vertebrates. Because of its high degree of complexity and interconnectivity, the mammalian immune system has been labeled as "irreducibly complex", and its evolution and origin through "Darwinian" mechanisms challenged. [From Evolving Immunity]
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