Immunological aspects of infections part 12

Although it is clear that innate immunity is the first line of defense against invading organisms, the TLRs are also playing a role in adaptive immunity, and the dendritic cell (DC) appears to be playing a key role in linking the innate  and adaptive immune responses. As immature cells, they are present in the peripheral tissues. However, with the appearance of invading organisms, DCs recognize these pathogens through their TLRs. Fortunately, they express the full repertoire of TLRs. After activation of the TLRs, the DCs are transformed into more mature cells with high expression of major histocompatibility complex (MHC) and the co-stimulatory molecules CD80 and CD86. The DCs then migrate to the lymph nodes to activate antigen-specific naive T cells. The cytokine milieu being expressed around the cells determines their fate; that is, the production of IL-12 drives these cells to TH1 cells, which produce interferon δ, whereas  IL-4 drives them toward  TH2 cells producing IL-4, IL-5, IL-10 and IL-13. These latter cytokines are of interest as they are also responsible for the development of allergic diseases such as asthma  and account for the regulation of antigen-specific IgE production, accumulation of eosinophils, and activation of mast cells. In this connection, the incidence of allergic disease and atopy has markedly increased in the industrialized countries compared with developing countries over the past decades, and one hypothesis is that this increase is linked to the reduction  of bacterial infections, which occurs in a cleaner  environtment, a hypothesis known as the "hygiene hypothesis ". The discovery that TLR signaling  might be crucially involved in the establishment of TH1/TH2 pathways opens up the field to look for new strategies against diseases such as asthma and atopy