4.2 局部应用细胞因子
细胞因子在IgA合成中的关键作用,使人联想到使用适当的细胞因子来选择性地提高IgA水平。而基因工程技术的进展,使得细胞因子在粘膜免疫组织局部的应用更为合理、高效。 选择适当的载体,将IL-4、IL-6等细胞因子基因插入载体中,通过载体将细胞因子的基因 选送至粘膜局部。载体往往是一种侵袭性病原体的减毒变异体,如灭毒的沙门氏菌[17 ]以及减毒病毒[18],通过载体对粘膜组织的感染从而将细胞因子基因植入局部 免疫组织中表达。 此外,微包装技术的发展使得直接局部应用细胞因子成为可能,例如用 脂质体包装细胞因子并在粘膜局部应用,可提高粘膜免疫组织的合成IgA的能力。
4.3 IgA抗体直接在粘膜表面的应用
在预防肠腔条件致病菌的机会感染方面,国外有人将分泌型IgA应用到粘膜局部,结果表明,IgA能有效地抑制细菌移位的发生[19]。此外,通过制备抗致病菌的IgA型单 抗,然后将IgA型抗体用于粘膜局部,可较好地预防肠道致病菌[14]感染。目前这 方面工作尚有待深入,但是对于粘膜免疫机制存在障碍的患者,被动粘膜免疫是一种迅速、 有效的粘膜保护措施。
总之,粘膜免疫屏障是保证机体免受粘膜表面来源的病原体感染的机制之一。粘膜免疫 组织对抗原的识别及产生免疫应答方式均有其特点,对于这些特点的认识不断深化,有助于 人们将这一内源防御机制运用于对一些传染病如艾兹病、肝炎及其它粘膜来源的病原体感染 的防治。
作者简介:白晓东,男,30岁,主治医师,讲师,博士
作者单位:(第三军医大学附属西南医 院烧伤研究所) 重庆,400038
参考文献
1 Neutra M R, Pringault E, Kraehenbuhl J P. Antigen sampling acro ss epithelial barriers and induction of mucosal immune responses. Ann Rev immu nol,1996,14:275
2 Brandtzeg P, Sollid L M, Thrane P S, et al. Lymphoepithelial intera ctions in the mucosal immune system. Gut,1988,29(8):1116
3 Reynaud C A, Mackoy C R, Miller RG, et al. Somatic generation of di versity in a mammalian primary lymphoid organ, the sheep ileal peyer's patches, Cell,1991,64(5):995
4 Gebert A, The role of M Cells in the protection of mucosal membrane, Hi sto Chem cell Biol,1997,108(6):455
5 Kagnoff M F, Mucosal immunology, new frontiers. Immunity Today,1996,17( 2):157
6 Kramer D R, Sutherland R M, Bao S S, et al. Cytokine mediated effec ts in mucosal immunity.Immunology and Cell Biology,1995;73(5):389
7 Kawanishi H, Saltzman L E, Strober W. Mechanisms regulating IgA class- specific immunoglobulin production in murine gut-associated lymphoid tissues , J Exp Med,1983,157(2):433
8 Ehrhardt RO, Strober W, Harriman GR. Effect of transforming growth fact or-β1 on IgA isotype esxpression.J Imunol,1992,148(12):3830
9 Vajdy M, Kosvo-Vibois M H, kopf M, et al. Impaired mucosal immune responses in interlukin-4 targeted mice. J Exp Med,1995,181(1):41
10 Kraehenbuhl J P, Neutra M N. Molecular and cellular basis of i mmune protection of mucosal sufaces .Physiol, Rev,1992,72(4):853
11 Shroff K E, Meslin K, Cebra J. J. Commensal enteric bacteria engender a self limiting humoral mucosal immune response while permenanty colonizing the Gut ,Infec Immun,1995,63(10):3904
12 Berlin C, Berg E L, Briskin M J, et al. α4β7 integrin media tes lymphocyte binding to the mucosal vasculer addressin MADd CAM-1 Cell,1993, 74(1):185
13 Parr MB, Parr EL, Protective immunity against HSV-2 in the mouse vag ina. J Reprod Immunol,1997,36(1~2):71
14 Michetti P, Mahan M J. Monoclonal secretory immunoglobulin A Protect mice against oral challenge with the invasive pathogen salmonella typ hunurium Infect Immun,1992,60(5):1786
15 Ball J M, Herdy M E, Atmar RL, et al .Oral immunization with rec ombinant Norwalk virus like particles induces a systemic and mucosal immune response in mice. J virol,1998,72(2):1345
16 Sultan F, Jin L L, Jobling M G, et al. Mucosal immunogenicity of a holotoxin -like molecule containing the serine -rich Entarnoeba histolytica p rotein (SREHP)fused to the A2 domain of cholera toxin, Infect Immun,1998,66(2 ):462
17 Denich K, Borlinp, O'Hanley PD, et al. Expression of the murine in terleukin -4 gene in an attenuated aroA strain of salmonella typhimurium :persi stence and immune-response in BALB/C mice and susceptibility to macrophage kill ing. Infect Immun,1993,61(11):4818
18 Remsay AJ, Husband AJ, Ramshaw 1 A et al. The role of imterleukin -6 in mucosal IgA antibody responses in vivo Science,1994,264(22.Apr):561
19 Maxson,et al. The protective role of enteral IgA supplement in neonata l gut origin sepsis. J Pediatr surg,1995,30(2):231