- Describe the overall function of iNKT cells and their activation in terms of the following:
- the role of their TCRs
- how they are activated by antigen-presenting cells
- how they promote both innate and adaptive immunity and may also help to regulate the immune responses
Once activated, the iNKT cells rapidly produce large quantities of both TH1 cell and TH2 cell cytokines, including interferon-gamma (IFN-?), interleukin-4 (IL-4), interleukin-2 (IL-2), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-a), interleukin-13 (IL-13), and chemokines. Through the rapid productions of such cytokines, iNKT cells are able to promote and suppress different innate and adaptive immune responses. For example, large amounts of IFN-? are produced by activated iNKT cells. IFN-? activates NK cells and macrophages as a part of innate immunity; it also promotes the maturation of dendritic cells so that they induce a TH1 cell response to induce adaptive immunity.
It has been proposed that if the iNKT cell is repeatedly stimulated by the body's own glycolipids in the ab sense of microbes that this might stimulate the iNKT cell /dendritic cell interaction to produce tolerizing signals that inhibit the TH1 cell response and possibly stimulate the production of regulatory T-lymphocytes (Treg cells). In this way it might suppress autoimmune responses and prevent tissue damage.
There is also growing evidence that early childhood exposure to microbes is associated with protection against allergic diseases, asthma, and inflammatory diseases such as ulcerative colitis. It has been found that germ-free mice have large accumulations of mucosal iNKT cells in the lungs and intestines and increased morbidity from allergic asthma and inflammatory bowel disease. However, colonization of neonatal germ-free mice with normal microbiota resulted in mucosal iNKT cell tolerance to these diseases. It has been proposed that microbes the human body has been traditionally exposed to from early childhood throughout most of human history might play a role in developing normal iNKT cell numbers and iNKT cell responses.