I. Miler

The effect of bilirubin on the Fc receptor expression and phagocytic activity of mouse peritoneal macrophages.

The effect of bilirubin on the phagocytic activity of mouse peritoneal macrophages and on the expression of Fc receptors and receptors for SRBC was studied. Intraperitoneally administered bilirubin influenced the expression of Fc receptors for IgM, IgG2B, IgA and IgE, whereas the expression of other receptors as well as the phagocytic activity of peritoneal macrophages remained unchanged. The possible mechanism of the effect of bilirubin on Fc receptors is discussed.

The phagocytic activity of reticuloendothelial system of newborn precolostral pigs to smooth and roughEscherichia coli

The fate of smooth and rough strains ofEscherichia coli in the blood stream of newborn, germ-free, colostrum deprived piglets was studied using blood clearance test with live and radioisotope-labelled (P32) bacteria.Smooth strains are eliminated at an extremly slow rate (hours) whereas rough strains are taken up within 30 minutes. Specific immune serum accelerates rapidly the clearance rate of smooth strains after bothin vitro andin vivo opsonisation of bacteria. Clearance of smooth liveEscherichia coli from the blood stream cannot be stimulated by an endotoxin treatment of newborn piglets. The possible role of complement system as a nonspecific opsonin in phagocytosis of rough strains is discussed. The results demonstrate that RES cells of newborn precolostral piglets are functionally competent as to the capacity to remove gramnegative bacteria from the blood stream provided specific and/or nonspecific opsonins are available.

The immunosuppressive effects of bilirubin

The strong effects of bilirubin on various levels of the immune system are multifactorial. Concerning the mechanisms of these effects, we hypothesize that the primary causes of the described actions of bilirubin are the direct interaction of bilirubin molecules with cell membranes.

Effect of endotoxin on antibody response and resistance to infection in Newborn animals

Summary(1)As distinct from its effect on antibody in adult animals, endotoxin (ofEscherichia coli andSalmonella typhi) was not found to stimulate antibody formation in young animals, either against protein or bacterial antigen.(2)The administration of endotoxin to newborn young significantly increased their resistance to infection, however.(3)Endotoxin produced only slight morphological changes in the tissue of young animals as compared with adult animals.(4)The mechanism of the action of endotoxin in the organism is discussed. The possibility that the stimulant effect of endotoxin on antibody formation is related to elicitation of a hypersensitivity reaction in a sensitized organism is considered.Abstract(1)В отличие от действия эндотоксина на образование антител у взрослых животных, у молодых животных не наблюдалось стимулирующего влияния эндотоксина (эндотоксины Escherichia coli и Salmonella typhi) на образование антител ни против беикового, ни против бактериального антигенов.(2)Тем не менее, будучи введен новорожденным животным, эндотоксин заметно стимулирует их устойчивость кинфекции.(3)В отличие от взрослых животных, в тканях молодых животных эндотоксин вызывает лишь небольшие морфологические изменения.(4)Обсуждается механизм действия эндотоксина в организме. По-видимому, стимулирующее действие эндотоксина на образование антител обусловлено тем, что он вызывает в сенсибилизированных тканях реакцию гиперсенситивности.

Fate of endotoxin in the intestine of newborn bacteria-free piglets monocontaminated withEscherichia coli

The question of the mechanism by which the Gram-negative intestinal microflora acts as an antigenic stimulus for the development of immune reactions in the newborn was studied. Using newborn bacteria-free piglets artificially monocontaminated withE coli P-1 as the model, it was determined whether somatic antigens are released and absorbed in the intestine and infiltrate into the organism. The presence of specific antigen was determined by haemagglutination inhibition, 2–13 days after contamination, in organ homogenates (liver, spleen, mesenteric nodes, kidney) extracted with water and phenol. The results show that specific antigen was not demonstrated by haemagglutination inhibition in any of the test organs of newborn piglets contaminated per os with a living strain ofE. coli. In the control group, to which a large dose of purified endotoxin (1–10 mg./kg.) was administered into the lumen of the intestine or into the blood stream, the findings in the organs were positive. This shows that if a sufficient amount of endotoxin is present in the intestine, it is resorbed and can be demonstrated by the given technique, particularly in the liver and mesenteric nodes.AbstractИсследовался вопрос механизма действия грамотрица тельной кишечной микрофлоры как антигенного импульса развития реакции иммунитета у новорожденных.На модели новорожденных безмикробных поросят, зараженных исключительно монокультурой штамма E. coli P-1, изучали вопрос, имеют ли место выделение и всасывание сома тических антигенов в кишечнике и их проникновение в организм. Присутствие специфического антигена определяли в гомогенатах органов (печень, селезенка, брыжеечные узлы, цочки), экстрагированных водой и фенолом, в период со 2-го по 13-й день после заражения по реакции торможения гемагглютинации. Из полученных до сих пор результатов вытекает, что у безмикробных поросят, зараженных per os живой монокультурой. E. coli, по реакции торможения гемагглютинации невозможно обнаружить специфический антиген ни в одном из тестировавшихся органов.В группе контрольных поросят, которым вводили высокие дозы (1–10 мг/кг) очищенного эндотоксина в полость кишечника или в кровяное русло, исследования органов давали положительные результаты. Это доказывает, что, если эндотоксин присутствует в кишечнике в достаточном количестве, он всасывается и может быть обнаружен с помощью применявшейся нами техники, в особенности в печени и брыжеечных узлах.

Studies on the phagocytic activity of the reticuloendothelial system (RES) to rough and smoothEscherichia coli in young conventional and germfree guinea pigs

The functional (phagocytic) capacity of the reticuloendothelial system (RES) of young conventional and germfree guinea pigs was studied using thein vivo blood clearance test of living bacteria (rough and smoothEscherichia coli). It was found that as previously shown in newborn germfree piglets, the smooth strain was taken up from the blood stream of germfree guinea pigs very slowly whereas roughEscherichia coli was phagocytosed effectively. The inability of the RES of germfree guinea pigs to phagocytose the smooth strain is not due to a functional incapability of phagocytic cells, but it reflects rather the lack of serum opsonins to this strain. This was demonstrated in experiments in which smooth bacteria, sensitized prior to injection into the blood circulation with specific antiserum, were phagocytosed as effectively as the rough strain. It is assumed that effective phagocytosis of rough strain is due to the presence of non-specific opsonins (e.g. components of the complement system). In young conventional guinea pigs both strains,i.e. smooth and rough, were taken up from the blood stream very effectively thus indicating that sufficient levels of serum opsonins for both strains were present. This fact could be correlated with the finding that in sera of conventional guinea pigs haemagglutinating antibodies to both strains ofEscherichia coli could be detected, whereas in sera of young germfree guinea pigs, no antibodies to usedEscherichia coli strain were found. The importance of serum opsonins for effective phagocytosis of bacteria by RE cellsin vivo is discussed.

The protective effect of endotoxin in X-irradiated mice

In mice X-irradiated with lethal dose (750 r) and mid-lethal dose (550 r) the protective effect of bacterial endotoxin isolated from strains ofSalmonella typhi has been found to be limited to a short period before irradiation and administration of endotoxin in repeated doses did not enhance protection. Application of endotoxin 4 days after X-rays resulted in increase of lethality of irradiation and earlier deaths of experimental animals were observed. Active intravenous and intraperitoneal immunization with endogenous strains ofEscherichia coli isolated from the intestinal flora of mice had a demonstrable protective effect when compared with passive immunization.

Changes in susceptibility to bacterial endotoxin and infection during the early postnatal period in rats.

Summary(1)The toxicity of inactivatedSalmonella nella paratapyhi B was tested in young rats of different ages (1, 5, 10 and 15 days). During the first two weeks of life an approximately sevenfold increase occurs in the susceptibility of young rats to the endotoxic effects of this microorganism, which persists into adult life.(2)The resistance of young rats (1, 5, 15 and 30 days) to infection with livingSalmonella paratyphi B was studied. During the first month of life a manifold increase occurs in the resistance of young rats (LD60 for one-day-old rats was 1.5 X 104 and for 30-day-old rats 2.4 x 107 bacterial cells).(3)In an attempt to transfer the hypersensitivity of adult rats to the endotoxic effect ofSalmonella paratyphi B to non-susceptible young rats by the implantation of mesenteric lymph node cells, the reverse effect was obtained. Transfer of the cells 24 hours before injecting inactivatedSalmonella paratyphi B made the young animals resistant to the endotoxic effect of this microorganism.(4)The cutaneous reaction of young rabbits to endotoxin was studied. Complete reactivity to endotoxin comparableAbstract(1)На крысятах различного возраста (1, 5, 10 и 15-днeвных) тeстировали токсичность инактивированного штамма Salmonella paratyphi B. B тeчeниe пeрвых 2 вeдeль жизни чувствитeльность крыс044F;т к эндотоксичeскому дeйствию этого микроба повышаeтся приблизитeльно в 7 раз. Это повышeнная чувствитeльность сохраняeтся и во взрослом состоянии.(2)Исслeдовалась устойчивость новорождснных (1, 5, 15 и 30-днeвных) крысят к заражeнию живым штммом Salmonella paratyphi B. B тeчeниe пeрвого мeсяца жизни устойчивость крысят рeзко по0432;ышаeтся (LD50 у l-днeвных крысят равна 1,5 . 104, тогда как у 30-днeвных — 2,4 . 107 бактeриальных клeток).(3)В оытe пeрeноса гипeрсeнситивности к эндотоксичeскому дeйствию Salmonella paratyphi B co взрослых крыс Ha нeчувствитeльных крысят путeм пeрeсадки клeток брыжeeчных узлов были получeны нeожиданно противоположныe рeзультаты: в рeзультатe ввeдeнин клeток брыжeeчных узлов за 24 часа до инъeкции инактивированной культуры Salmonella paratyphi B крысяса оказалиись устойчивыми по отношeнию к эндотокси;чeсккму дeйствию этого микроба.(4)Исслeдовалась кожная рeакция молодых крольчат Ha эндотоксин. Холь ко около 6-го мeсяца жизни крольчата достигают пплой стeпни рeактивности по отншeнию к эндотоксину, которую можно сравнивать с рeeактивностью взросиых животных.(5)Обсуждаeтся отношeниeмeжду наличиeм Грам‐отрицатeльной кищeчной флоры и чувствитeльностью организма к эндотоксину.

Changes in the level and character of colostral immunoglobulins during the lactation period in sows.

A profound decrease in the concentration of colostral proteins (among immunoglobulins primarily IgG) during the first three days of lactation is accompanied by changes in the molecular heterogeneity of IgA. In the course of lactation, the amount of 7S IgA increases in relation to 10S IgA. The total amount of IgA, after the initial decrease during the first three days, maintains a gradual increase. In addition, a transient increase of natural haemagglutinating antibodies toEscherichia coli (serotype O55) was found in fractions corresponding to IgA and IgG during lactation.

Course of the post-irradiation syndrome after irradiation with lethal doses in newborn conventional, germ-free andEscherichia coli-monoassociated piglets

The influence of whole-body irradiation with lethal doses of ionizing radiation (60Co) was studied in conventional, germ-free andEscherichia coli-monoassociated newborn piglets. The dose 1,200 R produced an acute intestinal death (i.e. within 3–4 days) in conventional animals, whereas survival was three times as long in their germ-free counterparts. Artificial colonization of the intestinal tract of germ-free piglets with non-pathogenic strain ofEscherichia coli, prior to irradiation with the same dose, produced the conventionalization of these animals and reduction in the survival time almost to the level of conventional animals. In conventional animals, profound focal regressive changes of the epithelium accompanying the denudation of intestinal villi were found already on the 2nd–3rd day after irradiation with 1,200 R. On the other hand, the intestinal epithelium of germ-free piglets, irradiated with 1,200 R, was found to be intact on the 7th–9th day of post-irradiation, and the first signs of damage started to occur around the 9–10th days. The morphological characteristics of the intestinal mucous membrane ofEscherichia coli-monoassociated piglets were comparable to those of conventional, irradiated piglets. The role of the presence of the microbial factor for the turnover and radiosensitivity-resistance of enterocytes, and for the survival-death rate of animals irradiated with doses producing the post-irradiation gastro-intestinal syndrome, is discussed.