The correction of the functional activity of alveolar macrophages in inducing a primary immune response in influenza]

The functional activity of alveolar macrophages obtained from mice, both healthy and infected with influenza virus A/Aichi 2/68 (H3N2), as manifested by their capacity to initiate the development of primary immune response to sheep red blood cells and Escherichia coli lipopolysaccharide after the transfer of these macrophages to intact syngeneic recipients was studied. The capacity of alveolar macrophages to perform antigen-presenting functions in the induction of humoral immune response was shown, and at the same time the development of experimental influenza infection was found to essentially decrease these properties. The injection of the immunomodulating agent diuciphon into experimental mice somewhat enhanced the immune response after the syngeneic transfer of alveolar macrophages from infected mice to intact recipients.     

Effect of the spleen extracts on primary immune response in mice]

Experiments were conducted on mice. Direct Jerne's test demonstrated a possibility of intensification of the primary immune response in the sexually mature mice under the effect of the splenic extracts. The significance of the extract dose and of the time of administration for the manifestation of the stimulating action was studied.     

Effects of chorionic gonadotropin on dynamics of primary immune response]

The effect of chorionic gonadotropin (CG) on primary immune response was estimated according to the level of direct and indirect plaque-forming cells (PFC) on day 5, 8 and 12 after immunization of non-castrated and ovariectomized female mice of CBA strain. It was established, that on the 5th day CG (40-200 IU) did not influence the direct PFC level in ovariectomized animals, but stimulated them in non-ovariectomized mice (40 IU). In ovariectomized animals the selective immunodepressive effect of hormone on the IgG-PFC formation processes has been revealed. The CG effect depended on the time of PFC number examination as well as on the hormone dose. In non-castrated animals, where immunomodulating CG effects are partially mediated by ovarian hormones, the injection of hormone only in the dose of 200 IU significantly lowered the number of IgM and IgG-PFC. It is suggested, that sex steroids on the late stages of PFC formation, when the processes of isotype antibody synthesis switch take place, appear to be synergists of CG immunodepressive effect.     

Stimulation of primary immune response by the activation of autoimmune processes]

Experiments were conducted on 220 female mice weighing 20--24 g, with the use of 3 types of antigens (sheep erythrocytes, vaccines from the intestinal and paratyphoid bacilli). There proved to be an increase on the 7th and the 14th day of the formation of specific antibodies under the effect of subcutaneous injection of a homologous blood (0.1--0.3 ml per mouse) 2 hours after the antigen immunization. Hemostimulation not only intensified the antibody-genesis, but also increased the resistance to the infection with the living microbial culture. The stimulating action of the blood injection persisted in irradiation of the mice with gamma-rays in a dose of 300 r. Hemostimulation produced an activation of the normal autoantibody system capable of influencing the function of cells necessary for the antigen assimilation.     

Selective inhibition of the primary humoral immune response in mice with a combination of deoxycytidine with Cytosar]

Cytosine arabinoside administration in lethal doses to C57BL/6j female mice immunized with red blood cells leads, under deoxycytidine protection, to reduction of serum hemagglutinin level on day 5 without toxicosis. Simultaneous injection of the metabolite and the antimetabolite proves to be optimum.     

IgM and IgG rosette formation in the primary and secondary immune response in the system of syngeneic transfer of spleen cells]

In the system of syngenous transfer of cells a study was made of the dynamics of IgM- and IgG- of the rosette-froming cells of the spleen in the primary and secondary immune response in mice of the CBA inbred strain immunized with sheep erythrocytes. It was shown that in prolongation of the interval between donor immunization and the transfer of cells to the recipient with his simultaneous immunization for up to 40 days there occurred an increase of the IgG-memory; as to IgM memory-it is expressed with shorter intervals. It is supposed that rosette-forming cells were not bearers of immunological memory.     

Effect of doxycycline on immune response in a multifactorial experiment]

Multifactorial analysis was applied to studies on the effect of doxycycline on the primary immune response to sheep erythrocytes. The experimental factors were the following: the antibiotic dose, the antigen dose and the time of the onset of the antibiotic therapy with respect to the antigen action. Polynomial statistic models describing the delayed hypersensitivity and antibody titers within wide ranges of factor values were designed by the experimental data. It was shown that the prophylactic use of doxycycline prior to the antigenic stimulus markedly lowered the high-dose tolerance induced by high doses of the antigen.     

Dynamical analysis of a degenerate primary and secondary humoral immune response

Lymphocyte receptor response to antigen is degenerate. Each receptor can have a high affinity to more than one antigen. The optimal level of degeneracy was previously modeled using different methods; all showing that the degeneracy level should be inversely proportional to the probability that an antigen belongs to the self repertoire. Here we develop a new formalism, reproducing the results of previous models, which enables us to study the relation between receptor degeneracy and the pathogen-immune cell interaction dynamics, in primary and secondary response. We begin by developing a general formalismand reproducing the results obtained by Nemazee: (1) that an optimal immune system will have a capacity which is inversely proportional to the fraction of self-antigens and (2) that the number of self-reactive cells that the body destroys is tuned by this capacity optimization to be 63%. We then use our extended framework to relate the minimal number of B cell precursor required to mount an immune response to the naive B cell production rate. Finally, we analyze the dynamics of the interaction between the immune system and a pathogen and show that memory cells may be used as the first line of defense, while newly created cells are used later to refine the immune response.     

Development of B cell lineages during a primary anti-hapten immune response

Cell lineage relationships were examined in large numbers of hybridomas derived from a single mouse at 7 days and from a single mouse at 12 days after a primary immunization. The properties of these developing lineages provide unique insight into their biologic selection and differentiation. The unique VDJ junctions, the characteristics of the somatic mutations, and the nonproductive H chain gene rearrangements observed at day 12 all indicate that the hybridomas were derived from a limited number of progenitor B cells. Clonally related hybridomas were also observed at day 7. The activation of these lineages occurred very early, because somatic variants were strongly selected for within a few days after the primary immunization.     

Interaction of allogeneic lymphocytes and precursor cells during the primary and secondary immune response]

A mixture of lymph node cells from CBA mice and spleen cells from C57Bl/6J mice stimulated by the cheep erythrocytes fro the first or second time was transplanted in the lethally irradiated mice (CBA X C57Bl/6j)Fl. The interaction of allogenic cells during the secondary immune response was accompanied by the complete inactivation of antibody producents. Under the ratio of interacting cell elements 1 : 1-1 : 2, 93-96% of precursor cells and 98% of antibody forming cells were inactivated. Under the ratio 1 : 5, the index of inactivation of precursor cells fell down to 35%. During the primary response, under the ratio 1 : 1, only 20-48% of precursor cells and 68% of antibody forming cells were inactivated. Under the ratio 1 : 2, no inactivation of precursor cells was observed and, under the ratio 1 : 10, the antibody formation was stimulated. Following the delayed by 1-3 days transplantation of CBA lymphocytes, the cooperative effect was registered with respect to the spleen cells from C57Bl/6J mice stimulated by the erythrocytes for the first time. The interaction of allogenic cells resulted in the 3-4-fold increase in the number of antibody forming cells.     

Mathematical model of the immune response]

A model of immune reaction is suggested, ahich takes into account the delay in the development of an immune response. The model depending on parameters values describes: an asymptotic decrease of antigene quantity, approach of its quantity towards constant value, periodic course of the illness, unlimited growth of the antigene quantity. It is shown that the course of the reaction essentially depends on the duration of delay. Parameters regions corresponding to different regimes are determined.     

Effect of pefloxacin on immune response]

The influence on cellular immune response of different doses of the pefloxacin was studied in vivo as well as in vitro experiments. The pefloxacin in super bactericidal concentrations (2.0 mg/ml and 0.4 mg/ml) possess pronounced supressing effect the T-lymphocyte proliferation in blast transformation reaction. While in concentration 0.08 mg/ml pefloxacin does not show such activity. The pefloxacin in maximal effective concentration (200 mg/kg) suppressed activity in delayed hypersensitivity skin reaction of intact mice towards sheep erythrocytes on 20.3 percent only.     

Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen.

The immune response to a thymus-dependent antigen was depressed in vivo and in vitro in spleen cells from mice injected with LPS i.p. a few days before challenge with the antigen. Spleen cells from LPS-injected mice could, however, respond with increase DNA synthesis after activation with polyclonal B and T cell activators in vitro. The LPS-activated spleen cells could actively suppress normal cells in their response to the antigen sheep red blood cells. The suppressor cells contained in the LPS-activated spleens were most likely B lymphocytes, and the possible mechanism for their inhibitory function is discussed.     

Cellular events during the primary immune response in the spleen

Summary The cellular events during the primary immune response in T and B cell compartments in the splenic white pulp were analysed in germfree mice immunized with sheep erythrocytes. Light, fluorescence and electronmicroscopic studies revealed that the initial formation of lymphoid blast cells occurs in the thymus-dependent area, i.e. the central periarteriolar lymphatic sheath (central PALS), 2 days after immunization. Lymphoblasts were found in close relation with erythrocyte-containing macrophages and with interdigitating cells. With fluorescence microscopy these blast cells were Ig negative. Lymphoblasts in the central PALS showed many polyribosomes in the cytoplasm, but were virtually devoid of endoplasmic reticulum. The ultrastructure of lymphoblasts in the central PALS, and their relation with interdigitating cells, suggests that these cells are the progeny of antigen-activated T cells.Cells with a positive cytoplasmic fluorescence, plasmablasts, appeared 3 days after immunization in the peripheral part of the PALS. During the progress of the immune response these cells accumulated around branches of the central arteriole, and moved along marginal zone bridging channels towards the red pulp. In the electron microscope plasmablasts showed many polyribosomes, short strands of rough endoplasmic reticulum close to mitochondria, and a few electron-dense bodies. The cell organelles of plasmablasts were frequently gathered in a so called uropod, which is a morphological sign of active cell movement.Germinal center formation started within primary follicles, 4 days after immunization. Blast cells in germinal centers did not show cytoplasmic fluorescence. During the course of the immune response, germinal centers extended in diameter, and fluorescent dendritic cells appeared at the periphery of the germinal center.From the present observations we conclude that: (1) cellular cooperation between different lymphoid and non-lymphoid cell types during the immune response against SRBC takes place in the PALS, (2) the cellular cooperation in the PALS results in the differentiation of B cells into immunoglobulin-producing plasmablasts, (3) the cellular cooperation in the PALS preceeds the formation of germinal centers in primary follicles, hence germinal centers are not involved in early T-B cell cooperation.