Biology Reference
In-Depth Information
investigation and has been detected in experimental allergic asthma.
15,16
Basophils are cells traditionally related to the effector phase of the allergic
response and immunity to helminths. Recently their role during the early
Th2 response to allergens, supplying IL-4 or acting as antigen-presenting
cells, has also raised considerable interest
17
and controversy.
18
The char-
acteristic infiltrate of eosinophils, mononuclear cells, and mast cells, as
well as the hyper-production of mucus by goblet cells, are consequences
of the activation of diverse genes and cytokines; these cells, in turn, will
help to increase the severity of the reaction if the allergenic stimulus
persists.
The allergen-specific IgE bound to receptors on mast cells and
basophils is central to initiate and maintain the chronic allergic
inflammation and in some acute allergic manifestations, such as
anaphylaxis, is the main trigger of the cascade leading to the release of
vasoactive and inflammatory molecules that cause symptoms.
19
The
allergic response, as detected by specific IgE to allergens, occurs in
around 30% of the general population (considered atopic) and in almost
100% of subjects with allergic diseases. The fact that only a small
percentage of atopic individuals develop allergic diseases suggests that
clinical allergies such as asthma, rhinitis, and atopic eczema have
additional genetic predispositions. The immunology of
Ascaris
and the
immunomodulation it induces is described in Chapter 1 of this topic.
Most of the mechanisms of the allergic reaction are shared by the
immune response to helminths and particularly to
Ascaris
; however,
there are important differences.
First, the degree of immunomodulation is higher in helminthiases and
increases with parasite load and disease severity. It is parasite-induced
(several products are already known and others predicted by genome
sequencing data
20
) and mediated in several ways, including the action of
immunoregulatory cells (such as Treg, Breg, and alternatively activated
macrophages) as well as cytokines such as IL-10 and transforming growth
factor beta (TGF-
).
21,22
In addition, total IgE production during
helminthiases is associated with immunomodulation, although the
mechanisms are not defined. As has been long suspected and supported
recently,
23
e
26
the polyclonal production of total IgE during severe
helminth infections may inhibit the biologic pro-inflammatory effects of
specific IgE, diminishing the expected allergic symptoms potentially
induced by the infection itself in a normal population or symptoms in the
allergic population. In contrast, the immunomodulation is weak during
the allergic responses, which is characterized by an uncontrolled Th2
hyper-responsiveness,
27
also present during the chronic inflammatory
process of asthma.
28
This deficiency makes the identification of the
parasite-driven immunosuppressor effects of heavy ascariasis on allergic
inflammation easier. Whether the high total IgE level characteristics of
b
