IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 23. Hypersensitivity - Type I

FACTORS DETERMINING THE DEVELOPMENT OF ALLERGY

It is now well established that not only genetic factors, but also other factors discussed below, play a crucial role in The Development of allergy.

Atopy is associated with T-Cell deficiency

There is abundant Evidence for the role of T Cells in both the development and suppression of the IgE response (see Figs. 23.5 and 23.6). This led to the hypothesis that atopy might be caused by some form of T-cell defect, specifically involving "suppressor T cells." Indeed, patients with eczema show a decreased number of CD8⁺ suppressor T cells (Fig. 23.24), and patients with severe atopy (eczema) also exhibit an impaired T-cell response to mitogens. This impairment of T-cell responses measured in vitro correlates with depressed cell-mediated Immunity, which in vivo may manifest as a suppression of delayed-type hypersensitivity Skin reactions.

Class="center">

Fig. 23.24. Patients with severe atopic eczema (but not those with rhinitis or asthma) show a decreased count of CD3⁺ T cells, and this reduction is almost entirely due to a drop in CD8⁺ T cells, a population believed to include "suppressor" cells. The depletion of this cell population in the Blood often correlates with the markedly elevated IgE levels observed in patients with atopic eczema.

It remains unclear whether such T-cell deficiency is a cause or a consequence of atopic disease. Nevertheless, some evidence for a causal relationship between T-cell deficiency and atopy does exist, though only in relation to artificially fed infants. According to Soothill and colleagues, eczema is less common in breastfed infants; other authors have found that bottle-feeding infants with cow's milk correlates with a reduced number of certain regulatory T-cell subpopulations and elevated IgE levels (Fig. 23.25). However, it is uncertain whether artificial feeding directly affects T-cell counts. There is no doubt that other environmental factors also play an important role in the Pathogenesis of allergic diseases.

Fig. 23.25. Effect of artificial feeding on T cells and IgE levels. When examining children with low blood T-cell counts, it was found that serum IgE levels were higher in infants fed cow's milk than in those who were breastfed. The IgE levels in the latter group were similar to those in children with normal T-cell counts, regardless of their feeding method. These findings, indicating that feeding practices and T-cell numbers influence IgE levels, suggest that the development of an atopic state may be driven by a T-cell defect combined with environmental factors (mode of feeding).

It also remains to be determined how the differences in suppressor T-cell numbers identified in earlier studies relate to the recently established importance of the Th1/Th2 balance for the Immune Response.

Environmental pollutants increase antigen-specific IgE levels

Environmental pollutants such as sulfur dioxide, nitrogen oxides, and airborne diesel exhaust and soot particles can increase mucosal permeability, facilitating allergen penetration into the body and the triggering of IgE-mediated reactions. Diesel exhaust particles (DEPs) can act as a potent adjuvant that enhances IgE production (Fig. 23.26). These particles are less than 1 μm in diameter; they persist in the atmosphere of polluted cities for a long time and affect the respiratory tract. The concentration of DEPs in urban air averages about 1 μg/m³, can reach 30 μg/m³ on major roadways, and may spike up to 500 μg/m³ during heavy traffic periods. When DEPs are administered intranasally along with an antigen, the level of antigen-specific IgE rises sharply. This adjuvant effect is also evident at low antigen concentrations comparable to those found in the environment.

Fig. 23.26. Effect of pollutants, specifically diesel exhaust particles (DEPs), on the IgE response to egg albumin in mice. Following intranasal immunization of mice with egg albumin (EA), small increases in IgE antibody levels are observed only at weeks 5 and 8, but not later. When DEPs are added to EA, There is a dose-dependent enhancement of the IgE response. Thus, DEPs act as a potent adjuvant boosting IgE production, which may partly explain the rising incidence of allergies in recent years. (Figure kindly provided by Dr. S. Takafuji from J. Allergy Clin Immunol., 1987; 79: 639-456, with permission.)

The incidence of allergic rhinitis and asthma has been increasing over the past 30 years in parallel with rising levels of air pollution. Therefore, environmental pollutants that promote the IgE response may contribute to the growing prevalence of allergic diseases. It should be noted that the prevalence of atopy also depends to some extent on family size, as the risk of developing such conditions is particularly high in first-born children.

The Effect of smoking appears to be dose-dependent: IgE levels rise with a low number of cigarettes smoked and decline with a high number. In active smokers, the Immune Response to inhaled Antigens is significantly impaired, whereas passive "smoking" may increase the risk of developing asthma in children.