The history of allergy makes interesting reading.
In 1872, Wyman pointed towards pollen as the likely cause of symptoms
of allergic rhinitis in the United States, with Blackley publishing
a similar paper based on self experimentation the following year.
In 1900, Curtis reported that immunization with water based extracts
of some pollens appeared to benefit patients with seasonal rhinitis
and asthma. Attempts to protect humans and animals from the effect
of bacterial derived toxins led eventually to the description
of anaphylaxis by Portier & Richet in 1902. Their concept
of hypersensitivity was thereafter applied to hay fever and later
asthma.
Studies of active immunization with allergen
extracts as a treatment for hay fever began so after at St Mary's
Hospital in London. Two papers by Moon & Freeman, from St
Mary's were published in 1911 in the Lancet, and described conjunctival
provocation of patients with allergic rhino conjunctivitis and
successful treatment using subcutaneous inoculation of extract.
From a number of double blinded, placebo-controlled and dose-response
studies of immunotherapy, it is now clear that desensitization
(immunotherapy) is effective in ameliorating the symptoms of approximately
95% of patients with bee venom induced anaphylaxis, approximately
80% of patients with pollen induced allergy, and to other aero
allergens as well. With the exception of bee venom immunotherapy,
systemic reactions to immunotherapy are relatively rare, but do
account for the standard advice of a waiting period of at least
30 minutes after each injection is given.
For many years, the traditional teaching has
been that immunotherapy worked by inducing the production of allergen
reactive IgG antibodies which "block" the interaction
between allergen and IgE on the surface of mast cells. This would
prevent mast cell degranulation and the release of mediators such
as histamine. Allergen specific IgE is also observed to eventually
decrease in concentration, which may be a second mechanism. Unfortunately,
there is a poor correlation between these changes and clinical
efficacy, and it is really only in the last 5 years that more
realistic mechanisms have been proposed.
Most of us, (atopic or not) make immune responses
to substances in our environment that we eat, drink or inhale,
which are detectable using sensitive (research based) testing.
Our immune system can recognize foreign protein in a number of
ways. A white cell known as the B lymphocyte recognizes the conformation
or shape of an intact foreign protein if that B cell has surface
bound antibody capable of binding the foreign protein. If binding
does occur, then the B cell can be stimulated to make the same
antibody (such as IgE) and release it into the surrounding environment
such as the blood stream. IgE released into the blood stream will
bind and thus "arm" tissue mast cells, which will then
react to that protein if it is encountered again. (mast cells
exist between us and the outside world, under the skin, gut and
respiratory tree, and contain granules consisting of histamine
and other inflammatory mediators). B cells do not produce antibody
on their own; rather, the type and amount of antibody released
by B cells is determined by their interaction with other white
cells known as T lymphocytes.
T lymphocytes are "conductors of the immunological orchestra", and can also recognize foreign protein but in a different way to B cells. These T cells communicate with other cells by releasing "cytokines" small chemical messengers which act over very small distances. Depending on the type of cytokines produced, T cells will influence B cells to produce IgG (a Type I response) or IgE (a Type 2 or allergic response). The cytokines released in response to a foreign protein are in part determined by the nature of the antigen, the route by which it is encountered, and the genetic background of the individual concerned. For example, antigens expressed on the protein of parasites provoke a Type 2 or IgE response regardless of genetic background, whereas genetic background appears to be essential for the generation of similar responses to allergens such as dust mite or grass pollen. Since Type I and Type 2 (allergic) responses are mutually inhibitory, individuals tend to have one response predominant over the other.
One hypothesis to explain the efficacy of immunotherapy
(for which there is now strong experimental evidence in both animals
and humans) is that the stimulation of Type I responses by injecting
extracts of allergen (rather than inhaling it) eventually makes
that the dominant response, resulting in inhibition of the allergen
(Type 2) immune reaction. Not only would this result in the eventual
reduction in allergen specific IgE, but the alteration of cytokines
produced such as IL4 and IL5 would also alter the types of cells
which are recruited into the nose or respiratory tree which are
responsible for the late allergic response. The late allergic
response is responsible for the chronic inflammation observed
in patients with chronic allergic rhinitis and asthma, and therefore
the nasal and bronchial hyperreactivity, respectively, observed
in both conditions.
