Jaarboek no. 87. 2008/2009 - Koninklijke Maatschappij voor ...

130 Diligentia
frequent in children with older siblings and those from large families. He suggested that
frequent exchange of childhood infections among siblings in large and less affluent families
was responsible for the lower incidence of allergic disorders. Following interest in the
hygiene hypothesis numerous studies have examined the relationship between infections
and allergic disorders using approximations to measure infections.
Several associations between viral, bacterial and parasitic infections and allergies have
been shown with indirect measurements of infections. Antibodies to hepatitis A, to Toxoplasma
gondii or H. Pylori, as well as cellular responses to mycobacterial antigens were
shown to be inversely associated with prevalence of asthma or skin prick test positivity.
The only studies that have related the actual presence of infections to allergic disorders are
those measuring viral or parasitic infections in the cohorts studied. Whereas respiratory
viral infections have been shown to be associated with exacerbation of asthma, parasitic
helminth infections have often been shown to be negatively associated with allergic disorders.
However, the latter relationship is complex as a number of studies have indicated
that helminth infections do increase the risk of allergic sensitization, atopy and symptoms.
In most studies where an exacerbation is seen, the helminth infection loads were light or
humans were not the definitive host. The current thinking is that the protective effects of
helminth infections on allergic disorders would only be seen if helminth infections are
chronic in nature and intense.
Interestingly, short-term application of anti-helminth drugs (12 months) in Ecuador did
not change the prevalence or atopy nor of clinical signs of allergy (wheeze) in comparison
to the untreated group. However, long-term anti-helminth treatment in Venezuelan (> 22
months) or Gabonese (> 30 months) children resulted in increased skin prick test reactivity
to house dust mite, supporting a direct effect of helminth infections on allergic atopy.
The cellular immunological explanations of the Hygiene Hypothesis
In Western countries where the increase in allergic disorders had been observed, the
hypothesis was put forward that allergic responses might result from a faulty maturation
and polarizaiton of the immune system. It was presumed that the decrease in exposure
to bacterial and viral infections might lead to a slower development of Th1 adaptive responses,
allowing pro allergic Th2 responses to develop unhindered. Birth cohort studies
in affluent countries seem to support the notion that a slow developing Th1 response
could indeed be responsible for increased susceptibility to allergic disorders.
The distorted balance between Th1 and Th2 becomes interesting when considering developing
countries and in particular the rural areas in these countries, where infections leading
to Th2 type responses are highly prevalent. The parasitic helminths are the strongest
natural stimuli for the development of Th2 responses, characterized by IL-4,IL-5 and IL-13
secretion from T cells and resultant increased IgE antibodies and eosinophils in peripheral
blood. Importantly, these infections being present during pregnancy of an infected
mother, can affect the immune response of the foetus. Increased Th2 responses have been
measured in neonates born to mothers with parasitic helminths.
The question how a Th2-inducing infection might be associated with decreased risk of
atopy has been addressed in some studies, but as yet there is no definitive proof. The possible
mechanisms that may explain why helminth infections that lead to a strong Th2 do
not lead to the development of allergies and even seem to play a protective role, may be
as follows:
1. the functional capacity of the IgE generated to an allergen during helminth infections
might be different, in such a way that no mast cell degranulation occurs when these
antibodies, present on mast cells, bind an allergen.
2. one of the important properties of helminth infections, namely their capacity to induce
regulatory responses may be responsible for the suppression of the effector phase of the
allergic response.
Immunologie van de hygiëne-hypothese