Adaptive Immunity to L pneumophila Infection

The adaptive immune response to bacterial infection follows initial exposure to microbes, not necessarily active infection, and is transferable to naive recipients by lymphocytes. The humoral antibody response to bacterial infection is a typical adaptive immune response when an individual is exposed to bacterial antigens and a heightened specific antibody response then occurs after secondary stimulation by antigens from the same microbe or active infection. The role of antibodies in resistance to infection varies according to the bacterium. In the case of Legionella infection, various specific virulence factors and specific components or antigens have been elucidated20. However, the importance of these antigens for the humoral immune response in humans has not yet been clearly defined. In contrast, the role of many immune factors involved in Legionella immunopathogene-sis in experimental animals has been characterized. Antibodies to Legionella antigens and other components promote uptake and replication of the bacteria in macrophages rather than promoting microbe elimination55,49. Therefore, antibodies and humoral immunity to Legionella are thought to have a minimal role in resistance or as a second line of defense to infection

The role of cellular adaptive immunity to Legionella infection, however, is critical. Delayed type hypersensitivity (DTH) reactions and CMI activity of

IL-18

IL-18

Cannabinoid And Adaptive Immunity

Cell-mediated Immunity

Antibody Immunity

IL-2 IFNy IgG2a

IL-4 IL-5 IL10 IgG1

Figure 9.5. Th1 and Th2 helper cell activity stimulated by DCs and APC. Solid lines indicate promotion of cell function and dotted lines indicate inhibition.

Cell-mediated Immunity

Antibody Immunity

IL-2 IFNy IgG2a

IL-4 IL-5 IL10 IgG1

Figure 9.5. Th1 and Th2 helper cell activity stimulated by DCs and APC. Solid lines indicate promotion of cell function and dotted lines indicate inhibition.

lymphoid cells from either immunized animals or patients recovered from legionellosis are readily detected. For example, peripheral blood lymphocytes from recovered patients, as compared to non-infected controls, show a marked proliferative response when cultured with L. pneumophila48. After stimulation with Legionella, peripheral blood cells from recovered patients secrete immunoregulatory cytokines which restrict growth, indicative of CMI. In particular, Th1-defining cytokines like IFN7 and IL-12, which restrict Legionella growth, are elevated in blood cell culture supernatants from recovered patients. Furthermore, animal studies show that both Th1 and Th2 helper cell defining cytokines develop after Legionella infection in vivo (Fig. 9.5). It seems evident that Th1 and Th2 helper cell development is under the control of antigen-recognizing cells like DCs and antigen presenting cells (APCs). As evident in Fig. 9.5, Th1 CD4+ cells are stimulated to produce proinflammatory cytokines such as IL-2 and IFN7 important in CMI. Th2 CD4+ cells produce IL-4, IL-5 and IL10 and these are involved in humoral (antibody) immunity.

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