Phosphorylated STATs form dimers that translocate into the nucleus to initiate gene transcription Transcription factors (STATs) bind to the phosphorylated receptors, and are in turn phosphorylated by the activated JAKs JAK kinase active STAT dimer 3-17 Chemokines released by macrophages and dendritic cells recruit effector cells to sites of infection.
All the cytokines produced by macrophages in innate immune responses have important local and systemic effects that contribute to both innate and adaptive immunity, and these are summarized in Fig. 3.27. The recognition of different classes of pathogens by phagocytes and dendritic cells may involve signaling through different receptors, such as the various TLRs, and can result in some variation in the cytokines expressed by stimulated macrophages and dendritic cells. This is one way in which appropriate immune responses can be selectively activated, as the released cytokines orchestrate the next phase of host defense. In response to activation by PRRs, macrophages and dendritic
Fig. 3.27 Important cytokines and chemokines secreted by dendritic cells and macrophages in response to bacterial products include IL-1β, IL-6, CXCL8, IL-12, and TNF-α. TNF-α is an inducer of a local inflammatory response that helps to contain infections. It also has systemic effects, many of which are harmful (discussed in Section 3-20). The
Local effects Systemic effects IL-12IL-1˜Fever Production of IL-6 Fever Mobilization of metabolites Shock Fever Induces acute-phase protein production Activated macrophages secrete a range of cytokines CXCL8TNF-°IL-6 Activates vascular endothelium Activates lymphocytes Local tissue destruction Increases access of effector cells Lymphocyte activation Increased antibody production Chemotactic factor recruits neutrophils, basophils, and T cells to site of infection Activates NK cells Induces the differentiation of CD4 T cells into TH1 cells Activates vascular endothelium and increases vascular permeability, which leads to increased entry of IgG, complement, and cells to tissues and increased ˜uid drainage to lymph nodes chemokine CXCL8 is also involved in the local inflammatory response, helping to attract neutrophils to the site of infection. IL-1β, IL-6, and TNF-α have a crucial role in inducing the acute-phase response in the liver and inducing fever, which favors effective host defense in various ways. IL-12 activates natural killer (NK) cells and favors the differentiation of CD4 T cells into the TH1 subset in adaptive immunity.
MOVIE 3.8