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.     

Multifactor analysis of the combined action of doxycycline and a peptidoglycan of microbial origin on the immune response

Multifactorial analysis of the combined action of a microbial peptidoglycan and doxycycline on the immune response to antigens of the vaccine EV fraction 1 was made. Nomograms or equal level curves characterizing delayed hypersensitivity (DH) and antibody titers in various doses of the peptidoglycan and the antibiotic were plotted by the experimental data with a computer. The peptidoglycan had a pronounced immunomodulatory action on DH and antibody titers. However, the types of regulation of the both responses markedly differed. With multifactor analysis, the range of the values of the operating parameters, i.e. the drug doses and the time of their administration providing the required levels of DH and antibodies under the conditions of the combined therapy were defined.     

Mechanisms of action of synthetic polyelectrolytes and polyampholytes on the immune response]

We investigated the effect of polyacrilic acid (PAA) on the immune response in mice of various strains on sheep red blood cells and also the influence of poly-2-methyl-5-vinyl-pyridine (PMVY), PAA and their statistical copolymers on antibody-forming cells (AFC) production in cultures of T- and B-lymphocytes in vivo. PAA was seen to increase accumulation of AFC in the spleen of mice depending on their genotypes. PMVP and PAA were found to intensify the cooperating interaction of T- and B-lymphocytes, whereas their copolymers exert quite an opposite effect. The injection of copolymers to the recipients of cooperating T- and B-lymphocytes practically results in the complete elimination of the cooperation effect between T- and B-lymphocytes in the immune response to sheep erythrocytes without cytostatic action of cell proliferation.     

The immunomodulating action of microwaves in the induction of an immune response to Vi antigen

In this work the possibility of using microwaves for immunomodulation in the immunization of animals with thymus-independent antigen was studied. The projection zones of the thymus and adrenal glands of the test animals were subjected to the action of decimeter, or ultrahigh frequency (UHF), waves, while the corresponding zones of the control animals were subjected to imitation UHF irradiation. Vi-antigen was shown to be a thymus-independent antigen for rabbits (according to the results of the evaluation of the functional state of thymocytes, as manifested by the adsorption of acridine orange by the chromatin of thymocyte nuclei and by the content of RNA and DNA in the thymus). The action of UHF waves on the projection zone of the thymus was accompanied by a decrease in the glucocorticoid activity of the adrenal cortex, observed simultaneously with a pronounced immunostimulating effect. The UHF irradiation of the zone of the adrenal glands was accompanied by immunosuppression in combination with enhanced glucocorticoid activity of the adrenal cortex.     

Combined use of mytilan and gentamycin in experimental infections

It was shown that mytilan, a polysaccharide isolated from the mantle of Crenomytilus grayanus stimulated the host nonspecific resistance to infections. This was evident from the survival rate of the animals infected with lethal doses of E. coli and S. aureus. In addition, the combined use of gentamicin and mytilan in treatment of the infections caused by the above organisms enabled to increase the antibiotic therapy efficacy with using lower doses of both the antibiotic and the polysaccharide.     

Role of macrophages in the immune response to soluble protein antigen and in staphylococcal infection]

In experiments on rabbits immunized with soluble protein antigen immune reactions were found to be accompanied by the production of lipofuscin in macrophages. This process was the morphological manifestation of the digestion of antigen by macrophages which thus acquired the ability to migrate in the organ and to form lymphoid follicules in the medullary zone of lymph nodes. The newly formed follicules seem to be the basis of pronounced specific immune response. In staphylococcal bacteriemia the phagocytic activity of macrophages was delayed, thus causing disturbances in lipofuscin production; as a result, the subsequent phases of immune response also lagged somewhat behind in time.     

Polygenic control of the immune response to F antigen

The ability to produce an autoimmune response to F antigen in mice is underH-2-linked and non-H- 2-linkedIr-gene control. There is an absolute requirement for ak allele atH-2K orI-A in order to produce anti-F antibodies. Low and high responsiveness is controlled by a non-H-2-linkedIr gene which behaves in a similar fashion toIr-3, in that as the dose of F-antigen is lowered, low responders behave as high responders and vice versa. This conversion from low to high responsiveness also occurs within a month after ATX.— Most F₁ hybrids derived from (responder x nonresponder) parents bearing identical F-types behave as dominant nonresponders. As a result of ATX, such F₁ mice convert to high responders. This conversion occurs if the animals are not immunized before day 90. If they receive F antigen prior to that time, they remain nonresponders for 7–9 months. One F₁ combination — AKD2 — behaves as a dominant high responder. Genetic analysis showed that in the presence of ak allele atH-2K orI-A, a non-H-2-linkedIr gene inherited from the AKR mice determined dominant responsivenss. No manipulation of the immune response or combination of genes converted nonresponders lacking ak allele into responders. Such complex genetic control suggests regulation by a number of independently segregating loci whose function it is to limit the autoimmune response to F antigen.     

Effects of multipotent hematopoietic stem cell inhibitory factor on formation of immune response to viral antigen]

An immunostimulating effect of PIF was studied. The augmentation of antibody production to Coxsackie A13 virus as well as protective effect during influenza infection have been found out in mice after PIF injections. An immunostimulating effect of PIF after SRBC immunization of mice has been also revealed. Possible mechanisms of immunostimulating effect of PIF are discussed.     

Tissue localization and retention of antigen in relation to the immune response

Antigen persists for months or even years in lymphoid tissues of immune animals and this antigen is believed to participate in the induction and maintenance of B-cell memory as well as in the maintenance of serum antibody levels. In the present report we describe the phenomenon of antigen localization and long-term retention on mouse follicular dendritic cells (FDCs). The antigens used were injected in the hind footpads of immune mice and the popliteal lymph nodes were the lymphoid organs generally studied. In addition to presenting the morphological features of mouse FDCs, we report the results of a study of the mechanism of antigen migration from the site of initial localization in the lymph node subcapsular sinus to the regions of follicular retention in the cortex. The migration was followed by light and electron microscopy. The results support the concepts that immune complexes are trapped in the subcapsular sinus and are transported by a group of nonphagocytic cells to follicular regions. The mechanism of transport may involve either migration of pre-FDCs with a concomitant maturation into FDCs, or cell-to-cell transport utilizing dendritic cell processes and membrane fluidity; or a combination of the two mechanisms may be in operation.     

Cyclic kinetics and mathematical expression of the primary immune response to soluble antigen

The injected dose of antigen determines not only the duration of its persistence in the injection site but also the intensity of plasma cell response in the regional lymph node. It was found that the logarithmic sum of antigen quantity in the injection site was related to the sum of cell response values, the correlation coefficient approaching 1. The antigen-lymphoid system interrelations appear to obey Weber-Fechner’s law for afferent systems of the organism. The sum of plasma cells appeared to be in direct connection with the logarithm of the dose injected, with antigen persistence in the injection site and also with the tangent of the acute angle adjoining the ordinate. The basic components of the primary immune response of the organism to soluble antigen,viz. logarithm of the dose injected, antigen persistence in the injection place, plasma cell quantity, tangent of the acute angle, transition modulus from antigen to plasma cells, are interconnected by rather simple equations, which represent the structural elements of the mathematical model described in the text.     

Cyclic kinetics and mathematical expression of the primary immune response to soluble antigen

The kinetics and the distribution of antigen and antibody were shown to be similar in four species of experimental animals and in two species of wild rodents immunized with the protein-polysaccharide capsular plague antigen. Serologically active antigen and antibody were detected in homologous conjugating serological tests. Soluble antigen persists at the injection site for as long as a week and adsorbed antigen for two weeks or more. Antigen persists in the blood of animals for 2–4 days. In regional popliteal lymph nodes, antigen was detected for the first days, followed by antibody in both lymph node and blood. Plasma cell response was more intensive in animals inoculated with adsorbed antigen. The gradual decrease of antigen at the injection site shows superimposed up-and-down changes, mostly parallel with the antibody in the popliteal lymph node and blood, as well as with plasma cell response in the regional lymph node. Serological cycles were related to the resistance of immunized white mice to plague infection. Cyclic kinetics of specific polysaccharide in the faeces of dysentery patients was found.     

Cyclic kinetics and mathematical expression of the primary immune response to soluble antigen

The conveyer hypothesis is based on the fact that because of clone predetermination, antibody production takes place in an organism without the presence of antigen as a result of natural cell differentiation. Soluble antigen is an analogue of a specific mitogen which gives rise to reproduction mainly of cells carrying on their surface the immunoglobulin receptors to the given antigen. The mathematical model of the conveyer hypothesis takes into account the initial conditions, among them the background level of antibody-producing cells before injection of a soluble antigen, migration of precursor cells in the draining lymphoid organ, and the rate of precursor differentiation, including the rate of the change of the immunoglobulin receptor number on the cell surface. Changes of antigen concentration in blood determine the intensity of precursor proliferation. Comparison of real experiments (intraperitoneal injection of capsular antigen ofPasteurella pestis into inbred mice) with calculations done on the basis of the developed mathematical model shows a definite qualitative resemblance with the kinetics of antibody-producing cells and free antibodies as well as with the decrease of free antigen concentration in blood. In spite of some differences between model experiments and real experiments the conveyer hypothesis and its mathematical model appear suitable for describing the primary immune response of mice immunized with low doses of capsular antigen ofPasteurella pestis.     

Cyclic kinetics and mathematical expression of the primary immune response to soluble antigen

A mathematical expression of the accumulation of the plasma cells in the spleen of CBA mice immunized intraperitoneally is presented. The dependence of the plasma cell reaction in the spleen on the kinetics of antigen concentration in the blood was confirmed. For the transition from antigen to plasma cells, index A was proposed. The mean values of index A were used for comparison of the calculated and experimental values of the plasma cell reaction and the recorded differences were not great. In a similar way, index A was used for prediction of plasma cell accumulation in the spleen of animals, immunized with a mixture of two soluble antigens — capsular antigen ofPasteurella pestis and complete antigen ofFrancisella tularensis. The calculated values of plasma cell reaction corresponded to experimental values.     

Role of the B-G-region antigen in the humoral immune response to the B-F-region antigen of chicken MHC

In the chicken MHC there exist two regions, designated F and G, which were separated by crossing-over. The F region contains genes controlling all functions characteristic of the MHC. So far only one gene has been assigned to the G region and it is responsible for the presence of an RBC antigen. When cross immunizing animals of the congenic lines CB and CC with erythrocytes, we have found that both F- and G-specific antibodies were produced. By using the recombinant haplotypes B ^R1 and B ^R2 we were able to dissociate the F from the G antigen and immunize with them separately. It was found that production of F antibodies required the copresence of the G antigen, whereas G antibodies were formed regardless of the presence or absence of the F-region antigen. It could be demonstrated that a prerequisite of the role of the G antigen with respect to the F antigen was the localization of both antigens on the same erythrocyte. Possible mechanisms underlying this phenomenon are discussed.Abbreviations used in this paper MHC major histocompatibility complex - RBC red blood cells - PBL peripheral blood lymphocytes - GVH graft-versus-host - MLR mixed lymphocyte reaction - i.v. intravenous - PBS phosphate-buffered saline - ME mercaptoethanol     

Effect of antimicrobial surface-active agents on the immune response to thymus-dependent antigen in mice

The study showed that miramystin, a cationi surfactant, was an immunostimulant inducing an increase in humoral and cellular immunity in response to sheep red blood cells. The observed dose-dependent stimulating effect of miramystin on antibody production and development of DTH recommends its use as an immunologic adjuvant in the laboratory practice. It also indicated to the prospects in investigation of immunologic adjuvant properties of other preparations belonging to surface-active substances.     

Combined action of antibiotics and deoxyribonuclease on bacteria]

The impact of DNase on formation of biofilms by grampositive and gramnegative bacteria was studied. The enzyme was shown to inhibit the biofilm formation and have no toxicity to bacteria. When applied to the formed associations, DNase potentiated the effect of antibiotics on the bacteria located in them. An increase in the antimicrobial effect of various nonrelated antibiotics was not connected with a change in the bacteria susceptibility but likely resulted from a break of the genetic cooperation of the cells' community, connected with functions of extracellular DNA of the biofilm's matrix.