1. Effector function of cytokines Cytokines are involved in the differentiation and maturation of effector cells and enhance the expression of various molecules in effector cell killing. For example, IL-1 can stimulate the proliferation and differentiation of T and B cells, stimulate hematopoietic cells, and participate in inflammation. IL-2 promotes the differentiation and maturation of T and B cells, up-regulates the expression of adhesion molecules on the surface of effector cells such as CTL and NK (such as LFA, CTLA, etc.), and enhances the killing activity of CTL, NK cells and M alpha. IL-4 induces IgE and IgG1 production; IL-5 induces IgA production. IL-12 can promote the killing function of CTL and NK cells, and induce cellular immunity.
As a cytokine, TNF not only has antiviral replication effect, but also has antitumor and cell proliferation control effects. As mentioned above, TNF can kill target cells in a variety of ways. In addition, TNF can still initiate the apoptosis pathway through TNFR1, and its corresponding signal transduction is both similar and different from the Fas-FasL-mediated pathway.
TNF-mediated cell death signal transduction pathway TRADD: TNF receptor-associated death region; RIP: receptor interacting protein; TRAF2: TNF-related factor 2; NIK: NExB-induced kinase; IKK: LxB kinase complex inhibitory factor.
2. Activation and killing of macrophages The mononuclear phagocyte system (MPS) has important biological functions. Not only participate in non-specific immune defenses such as exercising phagocytosis in anti-infection, but also play a key role as APC in specific immune responses. In fact, Mrp is also an important class of effector cells.
(1) Mφ activation: Mrp is activated under the action of certain cytokines. The main ways of activation are: ①CD4Th cells release IFN-) to activate Mφ; ②activated by the interaction of CD40 on the cell surface and CD40L on the surface of T cells; ③In mice, Mφ can also be activated by LPS, TNF and IL-1 . The formation of lysosomes that activate Mφ increases, and the ability to oxidize metabolism and kill target cells increases.
(2) Mechanism of Mφ killing target cells: ①ADCC effect: Like NK cells, M alpha also has Fc receptor (FcTRl) on the surface, which can recognize IgGFc segment. The target cells are killed by IgG. ② Direct killing effect: Mφ can produce damage to target cells by releasing lysosomal enzymes, NO, peroxidase and other substances. ③ Release inflammatory mediators to stimulate acute inflammatory response: Mφ can produce some inflammatory mediators, such as platelet activating factor (PAF), prostaglandin and tissue factor. These factors can activate the coagulation system, cause local coagulation and cause local tissue ischemia, aggravating tissue damage. ④ Secretion of cytokines is involved in the killing of target cells such as tumor cells and chronic inflammatory reactions: when certain bacteria such as Mycobacterium are infected, if Mφ cannot be removed immediately, certain bacterial products such as LSP can stimulate Mφ to synthesize cytokines such as IFN-γ, TNF, IL-1, TGFβ, fibroblast growth factor, enhance the killing ability of Mφ, and locally promote blood coagulation, increase local tissue damage, and stimulate local vascular endothelial cell migration and new blood vessel formation.
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