Th1/Th2 Cytokine Network

Abstract

The immune system has evolved different defensive mechanisms against pathogens. The first defensive line is provided by “natural” immunity, including phagocytes, T cell receptor (TCR) γδ+ T cells, natural killer (NK) cells, mast cells, neutrophils and eosinophils, as well as complement components and proinflammatory cytokines, such as interferons (IFNs), interleukin (IL)-1, IL-6, IL-12, IL-18 and tumor necrosis factor (TNF)-α. The more specialized TCR αβ+ T lymphocytes provide the second defense wall. These cells account for the “specific immunity”, which results in specialized types of immune responses which allow vertebrates to recognize and eliminate, or at least control, infectious agents in different body compartments. Viruses growing within infected cells are faced through the killing of their host cells by CD8+ class I MHC-restricted cytotoxic T lymphocytes. Most microbial components are endocytosed by antigen-presenting cells (APC), processed and presented preferentially to CD4+ class II MHC-restricted T helper (Th) cells. CD4+ T cells co-operate with B cells for the production of antibodies which opsonize extracellular microbes and neutralize their exotoxins. This branch of the specific Th cell-mediated immune response is known as “humoral immunity”. Other microbes, however, survive within macrophages despite the unfavorable microenvironment. Antigen-activated CD4+ Th cells are required to activate macrophages, whose reactive metabolites and TNF-α finally lead to the destruction of pathogens.