Respiratory infections (RI) are one of the major complaints in children and adolescents, and represent a demanding challenge for the pediatrician. It has been estimated that at least 6% of Italian children younger than 6 yr of age present recurrent respiratory infections (RRI). Children with RRI are not affected by severe alterations of the immune system. RRI represent essentially the consequence of an increased exposure to infectious agents during the first years of life, when immune functions are still largely immature. Several social and environmental factors, such as day-care attendance, family size, air pollution, parental smoking, and home dampness, represent important risk factors for airway diseases and may contribute in various degrees to determine the incidence of RRI. The main problem for the pediatrician is to discriminate normal children with high RI frequency related to an augmented exposure to environmental risk factors from children affected by other underlying pathological conditions (immunological or not), predisposing to infectious diseases. When RRI diagnosis has been formulated, removal of environmental risk factors (i.e. precocious day-care attendance, smoking in the household) must first be suggested.

Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by altered immune tolerance to specific proteins leading to a selective destruction of insulin-producing beta cells in genetically predisposed individuals. T1D is likely to be triggered by environmental factors, including virus infections in genetically predisposed individuals. Rotaviruses are the main cause of severe diarrhea among children worldwide, but they seem to have a role also in T1D induction. Epidemiological data may be consistent with a similar hypothesis. Mechanisms hypothesized include molecular mimicry, bystander activation (with or without epitope spreading), and viral persistence. In this review the authors analyze the factors accounting for rotavirus ability to prime islet autoimmunity and cause T1D. A thorough comprehension of their potential pathogenetic mechanisms may allow preventive strategies to be designed.

Autoimmunity implies disturbances at several levels of the immune control. Self-tolerance and discrimination between self and non-self synergize to avoid the development of autoimmunity. Negative selection in the thymus, the transcription factor AIRE, CD4+CD25+ regulatory T cells, and dendritic cells cooperate to produce and maintain tolerance. Cytokines modulate deriving immune processes and influence the local micro-environment. Multiple mechanisms are involved in tolerance breakdown: genetic factors (major histocompatibility complex haplotypes, polymorphisms in the cytotoxic T lymphocyte antigen gene and epigenetic alterations), environmental factors (mainly infections), impaired apoptosis, and the emergence of autoreactive naive lymphocytes. These events may be involved in the pathogenesis of endocrine diseases at several levels.