Studies on the pathogenesis of periodontal disease from the viewpoint of local immunity

宿主对牙周细菌免疫反应的动态不仅可以从粘膜对这些病原体的特异性保护的角度提供信息，而且可以揭示粘膜免疫反应提供宿主保护的能力。为此，我们在BALB/c小鼠中检测了对该抗原高应答的BALB/c小鼠对经层析纯化的牙龈卟啉菌菌毛的免疫反应，脂质体和佐剂口服或全身给予。口服吉氏假单胞菌菌毛明显增强了菌毛特异性唾液IgA反应。ELISPOT分析显示，在口服免疫水稻的固有层和肠系膜淋巴结中可见到大量的纤维特异性IgA SFC，而在Peyees斑块中则没有。相比之下，抗原特异性IgM和IgG SFC主要见于循环血液单个核细胞。另一方面，经毛皮下注射GM-53后，毛特异性IgG升高，血清IgM和IgA反应随之升高，唾液IgA和IgG反应同时升高。在血清抗体应答方面，口服免疫不如皮下注射有效。皮下注射小鼠唾液抗体水平与口服免疫小鼠相似。在皮下免疫小鼠中，通过ELISPOT法在脾脏、血液和肱淋巴结中检测到纤维特异性SFC。菌毛特异性IgM SFC出现较早，抗原特异性IgG SFC出现较晚。这些结果表明，菌毛与佐剂联合使用可显著提高唾液中的IgA反应和血清中的IgG反应。总之，很明显，宿主在血清和粘膜分泌物中的抗体反应的性质是不同的，并且取决于抗原给药的途径，佐剂和/或脂质体的使用，以及不同免疫方案后体液免疫反应的时间阶段。

The dynamics of tlie host immune response to periodontal bacteria not only may be informative from the standpoint of specific mucosal protection to these pathogens, but also may reveal the capacity of the mucosal immune response to provide protection of the host. To this end, we have examined the immune response to chromatographically purified fimbriae of P. gingivalis administered orally or systemically with liposomes and adjuvant in BALB/c mice, high responders to this antigen.Oral administration of P. giizgivalis fimbriae clearly enhanced the fimbriae-specific salivary IgA response. ELISPOT analysis revealed that significant numbers of fimbriae-specific IgA SFC were seen in lamina propria and mesenteric lymph nodes but not in Peyees patches of rice immunized orally. In contrast, antigen-specific IgM and IgG SFC were seen mainly in the circulating blood mononuclear cells. On the other hand, subcutaneous injection of fimbriae with GM-53 also raised the fimbriae-specific IgG followed by IgM and IgA responses in serum, and both IgA and IgG responses in saliva. Oral immunization was less effective than subcutaneous injection in terms of tlie serum antibody response. However, the salivary antibody level of niece injected subcutwieously was similar to that of mice immunized orally. In the subcutaneously immunized mice, fimbriae-specific SFC were detected in the spleen, blood, and brachial lymph nodes by ELISPOT assay. Fimbriae-specific IgM SFC appeared earlier and antigen-specific IgG SFC were seen later. These results show that the combined use of fimbriae together with the adjuvant results in sharply increased IgA responses in saliva wid IgG responses in serum. In summary, it is clear that the nature of tlie host's antibody response in serum and mucosal secretions are distinct, and depend on tlie route of antigen administration, the use of adjuvant and/or liposomes, and the temporal phase of the humoral inunune response following vwious immunization regimes.