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Split products of the typhoid bacillus. An experimental study of their antigenic and toxic properties

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MailerR_1923redux.pdf (18.82Mb)
Date
1923
Author
Mailer, Robert
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Abstract
 
 
(1) Typhoid bacilli are naturally resistant to digestion by proteolytic ferments such as Pepsin or Trypsin, but when extracted with acetone for 24 hours, they are almost completely dissolved by 1 2% solutions of Trypsin in 4 - 6 hours. (2) From such digests of B. Typhosus, by appropriate methods, bacterial protein derivatives, corresponding to progressive phases of digestion, can be isolated. (3) These derivatives are, alkali and acid metaprotein, coagulable protein, primary proteose, secondary proteose and peptone. (4) Equal amounts of these bacterial products have been inoculated into rabbits, and the antibody response compared with that obtained by inoculating equivalent amounts of dried undigested Typhoid bacilli. (5) Metaproteins are definitely antigenic, but compared with unaltered Typhoid bacilli, they act only as partial antigens. Agglutinins are not produced in response to inoculation of Typhoid metaprotein, and the other antibodies are present in much less concentration than in the controls. There is no difference to be made out between acid and alkali metaprotein. Though these are the earliest recognisable derivatives of the unchanged bacterial protein, their combination with acid or basic radicals brings about a marked deterioration in their antigenic power. (6) Coagulated. Protein produced all the recognisable antibodies against the Typhoid bacillus, but in lesser concentration than the untreated bacilli. In spite of the alteration in molecular grouping associated with coagulation, this antigen proved more efficient than acid or alkali metaprotein. (7) Proteoses act as very weak antigens. No agglutinins or opsonins were formed, and complement fixation antibodies could not be demonstrated. Their inoculation caused a slight rise in the bacteriolytic pourer of the serum, and a positive precipitin response, demonstrable only in the lowest dilutions of the serum. (8) No demonstrable antibodies against the Typhoid bacillus were formed as a result of inoculations of bacterial peptone. (9) Typhoid bacilli digested for 4 hours with 1% Trypsin were tested as antigens. Inoculation of these filtered digests produced a rise in the bacteriolytic power of the serum greater than that found in the controls receiving undigested bacilli. Agglutinins, precipitins, opsonins and complement fixation antibodies were produced, but to a lesser degree than in the controls. (10) Typhoid bacilli, extracted with acetone, are not thereby appreciably weakened in their antigenic power. (11) The lipoid material, removed from bacilli by extraction with acetone, is completely devoid of antigenic properties. (12) In experimental animals, the titre of antibodies in the serum cannot be accepted as an accurate criterion of the protective power against the living bacillus. (13) Evidence is brought forward to show that antibodies are not all produced together, but in response to different phases of the digestion of bacteria. In this respect Douglas' findings are confirmed. (14) It is suggested that agglutinins are formed in response to a very early phase in the cleavage of the bacterial protein, and that unaltered native protein is necessary for their production. (15) There is also evidence that opsonins are produced in response to an early stage of cleavage of the protein molecule, though not so early as is required for the production of agglutinins. For the production of opsonins, the protein must not have passed the coagulable stage. (16) It is further suggested that bacteriolytic antibodies are produced in association with a later period of digestion of the bacterial protein than either agglutinins or opsonins. (17) The production of precipitins seems to run on a parallel with that of bacteriolysins, but the evidence on this point is inconclusive. (18) It is concluded that agglutinating and precipitating properties of sera are not very closely related, but are really distinct phenomena. (19) Judging from the experiments carried out, it would appear as if bacteriolysins in a serum are only capable of being stimulated up to a certain titre, and this can sometimes be reached after two or three inoculations. Subsequently in spite of the inoculation of larger amounts of antigen, there is a tendency for the bacteriolytic power to decline. This is especially apt to occur where undigested bacilli are employed. (20) The efficacy of so called detoxicated vaccines, which consist of metaproteins and proteoses, is discussed. From experience with Typhoid derivatives, it is concluded that while the constituents of detoxicated vaccines can act as antigens and produce antibodies, the immunisation is only partial. This appears to be due to the fact that chemically treated antigens undergo some alteration., as a result of which they become less effective. (21) Typhoid bacilli digested for 4 hours with i to 2% Trypsin are much more toxic than undigested bacilli. (22) The split products which can be isolated chemically from digests of Typhoid bacilli are less toxic than the original organisms. (23) The primary proteose fraction is the most toxic of the protein split products derived from the Typhoid bacillus. The metaproteins are less toxic than primary proteose, and secondary proteose is the least toxic of all. (24) The symptoms and pathological findings in rabbits, which have received lethal doses of both living and dead Typhoid bacilli, are described. (25) The mode of death, and the post -mortem appear- ances including the congestion of the abdominal organs, the hyperemia and focal haemorrhages in the intestine, and the congested and haemorrhagic condition of the lungs, are very similar to what is found in sensitised rabbits which have received a toxic dose of egg globulin and in which death has occurred comparatively late. (26) The subacute nature of the illness as compared with acute anaphylactic death, points to a solution or partial disintegration of the bacterial protein being necessary before the toxic substances are liberated. (27) The pathological picture in death from inoculation of Typhoid primary proteose is practically the same as in death following inoculation of the whole bacilli or of bacilli which have been digested with Trypsin. (28) Primary proteose, derived from egg albumen, has no power of sensitising animals either towards itself or towards the native protein from which it was derived. (29) The pathological picture following inoculation of animais with Typhoid bacilli is a non -specific one, and can be produced not only by colon bacilli, but by non bacteria]. protein. (30) The symptoms produced in animals Typhoid primary proteose are the same as those descrihod following inoculation with "Peptone ", and peptone shock seems to be dependent on the presence of proteoses -- especially primary proteoses. (31) From a study of the toxic substances derived from Typhoid bacilli, it is probable that the intoxication produced by these bacteria is dependent upon. - (a) Preformed toxins of a simple protein nature, stored up in the bacterial body and liberated by lysis -- endotoxins. (b) Protein split products of the bacterial cell -- e.g. primary proteose. (32) It is suggested that in man, the native bacterial proteins may be associated with the intoxication produced, the system having become sensitised to these proteins during the incubation period.
 
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http://hdl.handle.net/1842/35118
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