The concept of pertussis as a toxin‐mediated disease
The concept of pertussis as a toxin‐mediated disease
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DOI：
10.1097/00006454-198409000-00019
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发表时间：
1984-09
期刊：
影响因子：
--
通讯作者：
M. Pittman
中科院分区：
文献类型：
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作者：
M. Pittman
百日咳是由B引起的一种两阶段疾病（呼吸道定植和毒素介导的疾病）。百日咳。细菌是独一无二的。它是一种致病性寄生虫，仅在人类中栖息。在体外和体内以致病形式生长需要允许百日咳毒素（PT）（也称为组胺致敏因子、淋巴细胞-白细胞促进因子、胰岛活化因子和百日咳毒素原）表达的条件。生长和PT的表达似乎是遗传相关的。对于体外增殖，培养基必须不含抑制制备PT所需的酶促作用的物质，如脂肪酸。在体内，细菌独特地定位于呼吸道上皮的纤毛，在那里它们繁殖。在原位，细菌抑制呼吸道的天然防御（纤毛，吞噬细胞和其他活动）;它们往往不会扩散，也不会侵入下面的组织。定植区域的程度与感染接种物中的细菌数量直接相关，影响产生的毒素量，从而影响临床症状的强度。影响临床疾病的其他因素是婴儿的过度易感性和遗传控制的易感性。PT在感染最初建立中的具体作用尚不清楚，但PT特异性免疫在约4至5周内影响定植清除似乎是肯定的。当细菌减少时，临床症状变得明显。这种清除受伊加抗体和百日咳毒素抗体合成的影响，这些抗体可能通过抑制生长所需的“酶”或通过另一种机制起作用。该病的病理是毒素致敏细胞功能改变的结果，而不是组织学损伤。PT由两种功能成分组成，与其他导致感染性疾病（例如白喉，霍乱）的外毒素一样。一种成分上的某些位点使PT能够与组织细胞上的特定受体结合并进入细胞。毒素ADP核糖基化细胞质膜的调节蛋白，从而改变细胞的功能。受影响的（致敏的）细胞是胰腺的胰岛素分泌胰岛、淋巴细胞和白细胞、心脏细胞和其他尚未明确鉴定的细胞，例如影响发作和神经紊乱的细胞。在体外，细胞功能的改变是不可逆的，而在体内，特定组织功能的恢复似乎取决于细胞的更新。（400字处截断摘要）
Pertussis (whooping cough), a two-stage process of disease (respiratory colonization and toxin-mediated disease) is caused by B. pertussis. The bacterium is unique. It is a pathogenic parasite with habitat only in human beings. Growth in the pathogenic form, both in in vitro and in vivo, requires conditions that permit the expression of pertussis toxin (PT) (also known as histamine-sensitizing factor, lymphocyte-leukocyte-promoting factor, islet-activating factor and pertussigen). The expression of growth and PT appear to be genetically interrelated. For multiplication in vitro the medium must be free of substances, such as fatty acids, that inhibit the enzymatic action required for elaboration of PT. In vivo the bacteria are uniquely localized to the cilia of the respiratory epithelium where they multiply. In situ the bacteria inhibit natural defenses of the respiratory tract (cilial, phagocytic and other activities); they tend not to spread and do not invade the underlying tissue. The extent of the areas of colonization, directly related to the number of bacteria in the infecting inoculum, influences the amount of toxin elaborated and consequently the intensity of the clinical symptoms. Other factors that influence the clinical disease are the inordinate susceptibility of the infant and genetically controlled susceptibility. A specific role for PT in the initial establishment of the infection is not clear, but it seems definite that PT-specific immunity influences the clearance of colonization in about 4 to 5 weeks. The clinical symptoms become manifest when the bacteria are waning. This clearance is influenced by the synthesis of IgA antibodies and pertussis toxin antibodies that may act by inhibiting the "enzyme" required for growth or by another mechanism. The pathology of the disease is the result of altered cellular functions of toxin-sensitized cells, not by histologic damage. PT is composed of two functional components like other exotoxins that cause infectious disease (e.g. diphtheria, cholera). Certain sites on one component enable PT to bind to specific receptors on tissue cells and enter the cell. The toxin ADP ribosylates a regulatory protein of the cytoplasmic membrane and thereby alters the function of the cell. Affected (sensitized) cells are insulin-secretory islets of the pancreas, lymphocytes and leukocytes, heart cells and others that have not been clearly identified, e.g. those that effect paroxysms and neurologic disturbances. The altered function of the cell in vitro is irreversible, and the restoration of the function of a particular tissue in vivo appears to be dependent on the renewal of the cells.(ABSTRACT TRUNCATED AT 400 WORDS)