Allison A C
Dawa Corporation, Belmont, CA 94002, USA.
Arch Immunol Ther Exp (Warsz). 1997;45(2-3):141-7.
New adjuvant formulations contain a vehicle, which carries antigens to antigen-presenting cells. Examples of vehicles are liposomes, immune-stimulating complexes and microfluidized squalene-in-water emulsions. Adjuvant formulations may contain immunomodulators, which augment cytokine production, such as a synthetic muramyl dipeptide analog or monophosphoryl lipid A. In a primary cascade of cytokine production at the site of antigen + adjuvant injection, TNF-alpha promotes the migration of dendritic cells (DC) to lymphoid tissues while GM-CSF accelerates the differentiation of DC into efficient presenters of antigens to T cells. Adjuvants also up-regulate a secondary cascade of cytokines in lymphoid tissues responding to antigenic stimulation: IL-12 augments the production of IFN-gamma, which favors the production of antibodies of protective isotypes (IgG2a in the mouse). Thus adjuvants can regulate immune responses qualitatively as well as quantitatively. Adjuvant formulations can also activate complement, generating C3d, which binds CD21 on follicular dendritic cells (FDC) and B cells. FDC targeting favors the generation of B lymphocyte memory, which is important for vaccination.
新型佐剂配方含有一种载体,该载体将抗原递送至抗原呈递细胞。载体的例子有脂质体、免疫刺激复合物和微流化水包角鲨烯乳液。佐剂配方可能含有免疫调节剂,可增强细胞因子的产生,如合成的胞壁酰二肽类似物或单磷酰脂质A。在抗原+佐剂注射部位的细胞因子产生的初级级联反应中,肿瘤坏死因子-α促进树突状细胞(DC)向淋巴组织迁移,而粒细胞-巨噬细胞集落刺激因子加速DC分化为向T细胞有效呈递抗原的细胞。佐剂还上调淋巴组织中对抗原刺激作出反应的细胞因子的次级级联反应:白细胞介素-12增强干扰素-γ的产生,这有利于产生保护性同种型抗体(小鼠中的IgG2a)。因此,佐剂可以在质量和数量上调节免疫反应。佐剂配方还可激活补体,产生C3d,其与滤泡树突状细胞(FDC)和B细胞上的CD21结合。靶向FDC有利于B淋巴细胞记忆的产生,这对疫苗接种很重要。