|Turned up to eleven: Fair and Balanced|
Friday, September 20, 2002
What follows is a comment I tried to leave at Gene Expression with respect to this very short post by Razib.
That is what the hygiene hypothesis suggests. The suggestion is that environmental exposure induces a state of tolerance in the immune system. Basically, immune cells, in particular B-cells, produce specific responses to antigens, i.e. foreign substances in or on body surfaces. During the maturation of the B-cell, a process called isotype switching is responsible for directing what sort of immune response is attached to each foreign object. In particular, in B-cells, there are four main types of "isotype", called IgM (for immunoglobulin M), IgG, IgA, and IgE. IgM is the "immature" type, present on the surface of the B-cell after it has been produced in the bone marrow and is either circulating in the blood, or resident in the spleen or lymph nodes. IgM is also the first type that circulates in the blood when the B-cell matures into a plasma cell after specific stimulation by an antigen. When the isotype switch occurs (this is one of the few types of non-germline genetic rearrangements known), the B-cell produces one of the other three types.
The switch seems to depend on a number of factors, but is transduced through signals received at the cell surface, and is thus dependent, to large extent, on where in the body the cell resides. IgA is part of the immune response in mucosal layers (the GI tract, for example), IgE is responsible for the histamine response (allergies and asthma are "misfires" of this response), and IgG is responsible for humoral immunity in the bloodstream and tissue. So the propensity to switch to IgE antibodies in response to harmless antigens such as pollens and dust is the root of allergy, and by extension, asthma. This seems to be connected to when in the course of development people are first exposed to these antigens. The hygiene hypothesis implies that early exposure induces tolerance, rather than activation. This is quite complex, but it might be good for me as a refresher in some of the broader concepts of immunology, so I may delve deeper in a future post.
Of course, there is still much to understand about why this occurs, and whether or not being kept too clean is really the reason is open to debate.