Biomedical subjects
Publications and source records attributed to H Finger.
Properties of the infective agent, pathogenesis, epidemiology and host defenses of hepatitis-virus A and B are described. The usual serological tests for diagnosis of viral hepatitis are outlined and illustrated by six typical cases of different etiology and course.
The immunization of mice with sheep erythrocytes served as model for the materno-fetal transfer of specific antibodies. It could be shown that passively transferred antibodies are able to induce a long-lasting suppression of the primary and secondary immuno-response in the offspring. This holds true both for active immunization before pregnancy and for passive immunization shortly before term. As it can be supposed that similar effects also apply to the human organism, this phenomenon must be considered for the vaccination during pregnancy as well as for the first immunization of children.
Young adult (6--12 weeks old) and aged (20--24 months old) NMRI mice were infected with various intracellular parasites. The following results were obtained: (1) After a sublethal infection with Listeria monocytogenes, aged mice were found to show a resistance similar to that of young adults. A challenge infection with this pathogen was followed by specific immunity of long duration in both age-groups. (2) On the other hand, young animals were significantly more resistant to Salmonella typhimurium than aged mice. It was concluded that this was due to the LD50 which was 14 times greater for 2-month-old than for 20-month-old mice. Furthermore, during 7 weeks after infection there were more S. typhimurium in the spleens of senescent mice than in those of young adult controls. (3) Aged mice showed highly increased susceptibility to the weakly virulent DX strain of Toxoplasma gondii. Almost all aged animals died whereas the control mice survived. When death of the aged mice was prevented by treatment with sulfadiazine after infection with the DX strain, the aged mice were found to be as well protected against subsequent infection with the strongly virulent BK strains as the young adult mice. These results suggest that the susceptibility of the aged animal to infectious agents may considerably vary from one pathogen to another.
Serum levels of immunoglobulins, alpha-2-macroglobulin and complement component C3 were measured from 490 pregnant women shortly before date and compared with the serum concentration of the same proteins in a group of female blood donors. Concentration of immunoglobulin G was found to be significantly (2 p less than 0.001) reduced during late pregnancy, while the serum level of immunoglobulin M in the group of pregnant women was significantly (2 p less than 0.01) increased. No difference between the serum concentration of immunoglobulin A could be observed between both groups. A significant increase (2 p less than 0.01) could also be observed regarding the serum levels of the complement component C3 and of alpha-2-Macroglobulin in the group of pregnant women. The findings are discussed with respect to the alterations during late pregnancy.
Serum concentrations of immunoglobulins A, M and G, of alpha 2-macroglobulin, complement component C 3 and of specific antibodies against streptolysin O, staphylolysin, influenza/parainfluenzavirus and measles virus were measured from 323 German and 167 alien pregnant women. Except from a statistically significant increase of IgG and alpha 2-macroglobulin in the alien group, no measurable differences could be seen. It is concluded that the evaluation of all measured parameters can be equal for both populations.
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Not significant differences in the composition or concentration of specific antibodies against microbial antigens could be measured in five commercially available human immunoglobulin preparations for intravenous use. Prediction of prophylactic or therapeutic efficiency of such preparations according to their antibody content seems to be only partially possible. Human immunoglobulins for intravenous use should be free from irregular antibodies against erythrocyte antigens of the Rh-systems, as found in one of the specimens tested.
Parenteral injection of dextran sulfate 500 (DS 500; 50 mg/kg of body weight) into mice caused a complete loss of resistance to a sublethal (2 X 10(3) to 5 X 10(3)) infection with Listeria monocytogenes. Such loss could be prevented by pretreatment of animals with 3 X 10(9) heat-killed Bordetella pertussis organisms (PO) 5 to 30 days before the administration of DS 500. The increased phagocytic capcity induced by PO was only exhausted when a fourfold dose of DS 500, effecting complete loss of antibacterial resistance (50 mg/kg ob body weight), was administered. Listeriosis in mice treated with DS 500 is characterized by rapid-progressive necro-purulent inflammation of liver and spleen, lack of mononuclear phagocyte response, and 100% lethality within 72 h after infection. In contrast, the time course, extent, and morphological characteristics of listeriosis in animals pretreated with PO before the DS 500 application were not significantly different from those of nonpretreated controls. Evidence is presented that the protective effect of PO is due to activation of the mononuclear phagocyte system, which without such treatment is blocked by the DS 500 administration. The data presented indicate that the protective effect of PO is due only in part to the endotoxic moiety of these bacteria. Differences in the course and morphology of listeriosis in animals with dysfunction of the mononuclear phagocyte system and in animals with deficiency of the cellular immune system are discussed.
The postnatal development of resistance against infection was monitored by the treatment of juvenile mice with a virulent strain of Listeria monocytogenes. It could be shown that until day 10 after birth, young mice succumbed to an infection with even minimal doses of bacteria. Between day 15 and 30, the resistance against infection gradually increases until the rather constant level of grown-up animals is reached (Fig. 1). Juvenile mice that survive the primary infection are able to build up a state of immunity, which is rather similar to that of grown-up mice (Fig 3). Immunity against L. monocytogenes is mainly expressed by a functionally active T-cell system; the maturity of these cells in 15 days old mice could be demonstrated by the transfer of cells to "nude"-mice, which lack a thymus (Fig. 4). A significant increase of the non-specific resistance can be achieved even in 10 days old mice by the injection of adjuvants like pertussis organisms or endotoxin of Salmonella typhi some days before infection (Fig. 5, Fig. 6). Our findings suggest that a deficiency of functionally active macrophages is responsible for the insufficient resistance against infection with L. monocytogenes in young mice.
The influence of killed Bordetella pertussis cells (B.p.) on the cell-mediated resistance of mice against infection with virulent germs of Listeria monocytogenes has been studied. Resistance of mice was decreased, when 3 X 10(9) B.p. were injected 1 day before, simultaneously with or 1 day after infection, resulting in augmented amounts of viable Listeriae recovered from the spleens 3 days after infection (figure 1). The LD50 was strongly reduced (Table 1). Transfer of immune spleen cells to recipient mice, which had been treated 1 day previously with 3 X 10(9)B.p., did not support resistance definitely (Table 2). Therefore, it can be concluded that probably the macrophage system was impaired just after B.p. injection. When, however, B.p. were given several days before infection, resistance was increased. A maximum of resistance enhancement was seen 7-14 days after B.p. treatment. Thereafter, this beneficial effect gradually decreased but persisted for at least 67 days (figure 1). This resistance enhancing effect of B.p. was surely not due to adjuvant effect of B.p. on the T-lymphocyte-mediated immune reaction to Listeriae, since in B.p.-pretreated mice the development of immunity during the primary infection to a secondary listeric infection has even been lacking (Table 3). It is more likely that the macrophage system was stimulated at this time by B.p. In mice treated 7 days prior to infection the elimination of Listeriae from the spleens was supported from the very beginning of the infection (figure 2).
The adjuvant activity of the synthetic muramyl-dipeptide (MDP) N-acetyl-muramyl-L-alanyl-D-isoglutamine upon immunization of mice with BSA or SRBC was studied. MDP was found to significantly increase BSA-antibody formation and to favour the induction of anaphylactic reactions to BSA. In contrast, under the conditions employed, MDP only weakly stimulated the immune response to SRBC.
NMRI mice were infected intravenously with a sublethal dose of Listeria monocytogenes and divided into four groups. One group served as the control and the other three were treated with ampicillin beginning 4, 8 or 24 hours after infection. The animals were injected in the morning and in the evening each time with 4 mg ampicillin subcutaneously until a total dose of 48 mg was reached. As demonstrated by counting of the bacteria in the spleen, Listeria could multiply in the ampicillin treated mice in comparison to the control group at best delayed but the infection continued to persist for some days at a level of 10(3)-10(4) Listeriae per spleen independent from the starting point of the treatment. Eight days after the first infection all animals received a challenge dose of 10(4) Listeriae. Compared with the control animals the ampicillin treated mice had a clearly reduced immunity, even in the group in which ampicillin application had been started 24 hours after the primary infection. If the challenge infection was given at first after an intervall of six weeks between primary and secondary infection, only a reduced immunity was found. Furthermore, whereas spleen cells of mice 7 days after infection were able to transfer immunity to untreated recipients, spleen cells of ampicillin treated mice were unable to do so. Finally, an attempt was made to cure chronic listeric infection in thymusless nude mice by the application of high doses of ampicillin. The observation of a continuous infection in these animals showed that the T-cells played a primary importance in the elimination of the bacteria.
It is generally believed that antibody-mediated immunosuppression can be only produced in non-primed individuals, and that this applies both to experimental animals and Rh-negative women at risk. However, in this paper it is reported that the additional injection of 0.2 ml of an antiserum to sheep erythrocytes (SE) together with a secondary antigenic stimulus of 10(8) SE into mice, primarily immunized by a tiny dose of 5 x 10(5) SE 28 days before, was capable of producing effective suppression of the secondary immune response.
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Congenitally dysthymic nude (nu/nu) NMRI mice showed increased resistance to viable Listeria monocytogenes cells during the initial phase of infection as compared with euthymic control mice. The intravenous mean lethal dose (LD50), as determined for euthymic mice after an observation time of 7 and 14 days, amounted consistently to 6 X 10(4) Listeria. The corresponding values determined in nude mice were found to be increased by either 20-fold (1.2 X 10(6) Listeria after an observation time of 7 days) or 4-fold (2.4 X 10(5) Listeria after an observation time of 14 days). The transfer of spleen cells from immune euthymic donor mice into chronically infected nude mice caused almost complete elimination of Listeria within 1 week. The injection of dextran sulfate 24 h before a secondary infection with L. monocytogenes caused loss of antibacterial resistance in both chronically infected nude mice and Listeria-immune euthymic mice, this being expressed by a rapid increase in the numbers of bacteria in the spleens as well as the occurrence of serious signs of illness.
Regarding the adjuvant activity of gram-negative bacteria we have to distinguish at least 4 different potencies, i.e., 1) increase in the production of circulating antibodies during the primary and secondary immune responses; 2) induction of susceptibility to systemic anaphylaxis; 3) prompt production of experimental "allergic" diseases, and 4) increase in resistance to infections. Although all gram-negative bacteria contain several structural components with adjuvant potencies, the immunopotentiating effectiveness of the corresponding whole bacteria becomes--with the exception of killed cells of Bordetella pertussis--only detectable to a weak degree.
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Mice fed with a vitamin A free diet for several months did not develop signs of vitamin A deficiency. However, chemical analysis revealed a reduced content of vitamin A in the liver of such mice. The ability of these animals were latent vitamin A deficiency to produce antibodies against parenterally applicated sheep erythrocytes was not hampered. Similar numbers of antibody producing cells could be detected in the spleen of these mice compared with control animals. Resistance against intravenous infection with L. monocytogenes of these mice with latent vitamin A deficiency was not altered. The numbers of viable germs recovered from spleen and liver 2 days after infection were similar in both vitamin A deprived and normal mice.