Natural Bactericidal Antibodies: Observations on the Bactericidal Mechanism of Normal Serum

Abstract

1. An analytical study has been made of the mechanism of natural bactericidal action by the serum of various animals (ox, sheep, horse, rabbit, guinea-pig, rat, man) towards certain organisms (B. typhosus, B. dysenteriae Shiga, B. proteus, V. cholerae) exhibiting the maximum reactivity to this effect.2. Serum-complement has no bactericidal action per se, and an antibodylike agent invariably acts as an intermediary agent, “sensitising” the particular organism to the action of the complement and capable of being “absorbed” by it from serum at 0° C.3. This sensitising agent is stable at 55° C. but labile at 60°–65° C. In this respect it resembles natural haemolysins and agglutinins, but contrasts with the more stable immune antibodies and the more labile natural complement-fixing antibodies (for bacterial antigens). It is resident mainly in the carbonic-acid-insoluble fraction of the serum. It is present in the serum of young animals before certain other natural antibodies have developed.4. Absorption tests demonstrate the high degree of specificity of these natural bactericidal antibodies for particular bacteria.5. A non-specific extracellular substance occurs in bacterial cultures which may neutralise or inhibit these antibodies, and interfere with their sensitising action even at 0° C.6. This substance is liberated in large amount in cultures heated at high temperatures (120° C). It can be removed by repeated washing of growths in saline solution. It may inactivate a bactericidal antibody in heated serum, though not in fresh unheated serum, and may inactivate a particular antibody in the serum of one animal species but not in another. Strains of bacteria vary in their production of this substance.7. The observations submitted in this paper, correlated with previous studies of natural antibodies by the authors and others, indicate that immune antibodies have their precursors specifically differentiated in the serum of normal animals and that, in general, immune antibodies are not substances formed de novo.

A Study of the Relationship of the Normal Bactericidal Activity of Human Serum to Bacterial Infection*

“…The findings of Wardlaw and Pillemer (6) confirmed those of Mackie and Finkelstein (7) that the bacterial strains sensitive to the effect of serum are principally from species of gram-negative bacilli and that the degree of sensitivity is a characteristic of the strain rather than of the genus. However, whereas Wardlaw and Pillemer have described the action of the properdin system as being nonspecific and unrelated to antibody, Mackie and Finkelstein presented data showing that the absorption of a serum in the cold by a sensitive strain resulted in the removal of the killing effect only for that strain, leaving the effect against other strains intact.…”

In VitroandIn VivoStudies of Monoclonal Antibodies with Prominent Bactericidal Activity against Burkholderia pseudomallei and Burkholderia mallei

“…This kind of bactericidal effect had been suggested as the result of complement and lowbinding-affinity, broad-spectrum natural antibodies present in these sera (14,17,21,28). Heat inactivation of the sera at 56°C for 30 min effectively abolished the bactericidal effect of these sera, indicating that complement was involved.…”

Resistance of Pseudomonas pseudomallei to Normal Human Serum Bactericidal Action

“…For disease-prcducing bacteria their initial contact with the host defense mechanism upon penetration of tissue barrier is the normal serum which is believed to play a significant role in protection against infection (6,8,12). It is known that a wide variety of bacteria are susceptible to the bactericidal effects of normal mammalian serum (2,8,9,11,22). Invasion of an animal host by P. pseudomallei has been implicated to be via cuts, skin abrasions, or scarification (15).…”