Allergen recognition in the origin of asthma.
Allergic respiratory diseases such as bronchial asthma are believed to result directly from the repeated local expression in airway tissues of T helper (Th) 2-polarized T cell immunity to inhaled allergens. Recent evidence suggests that these T cell responses are typically primed in utero and subsequently reshaped during postnatal allergen exposure via immune deviation, leading to the eventual emergence of stable allergen-specific T cell memory which is polarized towards the Th1 (normal) or Th2 (atopic) phenotype. The underlying Th1/Th2 switching process is influenced by a number of host and environmental factors that are poorly understood. Prominent amongst these are factors that affect the kinetics of maturation of immune competence during the early postnatal period. In particular, there is mounting evidence that the immunological milieu at the materno-fetal interface is naturally skewed towards the Th2 phenotype (possibly an evolutionary adaptation to protect the placenta against the toxic effects of Th1 cytokines). Furthermore, this bias appears to be preserved for varying periods into infancy, which may account for the presence of a high risk 'window' for allergic sensitization in early postnatal life. It is hypothesized that the principal impetus for postnatal development of a normal Th1/Th2 balance (and hence closure of the high risk sensitization window) is provided via contact with Th1-stimulatory commensal and pathogenic micro-organisms at the body's major mucosal surfaces.
Holt
P G
PG
TVW Teletbon Institute for Child Health Research, West Perth, Western Australia.
Yabuhara
A
A
Prescott
S
S
Venaille
T
T
Macaubas
C
C
Holt
B J
BJ
Björkstén
B
B
Sly
P D
PD
D000485:Allergens / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D002648:Child; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007223:Infant; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D000941:Antigens; D007073:Immunoglobulin E