Disruption of the mechanisms of natural immunity in the initial stage of adjuvant disease in rats and guinea pigs

Similar changes in the nonspecific immunity indices were noted in experiments on rats and guinea pigs with adjuvant disease: depression of blood serum bactericidal activity and increase of the lysozyme and complement level, as well as inhibition of the phagocytic activity of leukocytes and production of normal antibodies to O- and Vi-antigens of typhoid bacilli in rats. Changes in disturbances of natural immunity factors in adjuvant disease correlated with the severity of the process in both animal species.     

Host defence against C. albicans infections in IgH transgenic mice with V(H) derived from a natural anti-keratin antibody

Fungal infections have been increasing and life-threatening in recent years, but host immune responses, especially the humoral immunity, to fungi have not been fully understood. In the present study, we report that natural antibodies from unimmunized mice bind to Candida albicans. We established a monoclonal natural antibody, 3B4, which recognized a surface antigen located at germ tubes of C. albicans. The 3B4 antibody protected mice from C. albicans-induced death in passive immunization, by mechanisms involving suppressing germ tube formation and modulating phagocytosis. Interestingly, 3B4 also bound to a self-antigen keratin. To further study the generation and anti-C. albicans activities of natural antibodies in vivo, we constructed a mu chain transgenic mouse (TgV(H)3B4) using the V(H) gene from 3B4. TgV(H)3B4 had elevated serum anti-keratin/C. albicans IgM, and were resistant to C. albicans infections. Analyses of B cell development showed that in TgV(H)3B4, B cells secreting the anti-keratin/C. albicans antibodies were enriched in the B1 B cell compartment. Our findings reveal an important role of keratin-reactive natural antibodies in anti-C. albicans immune responses, and suggest that keratin may function in selecting B cells into the B1 B cell compartment, where natural antibodies are made to fight fungal infections.     

Immune response to immunization via the anterior chamber of the eye. I. F. lymphocyte-induced immune deviation.

The immunizing abilities of alloantigens placed within the anterior chamber of the eye have been studied in inbred rats. Although intracameral inoculation of F1 hybrid lymphocytes into parental strain recipients elicited both cell- and antibody-mediated immunity, a delimited interval was identified postinoculation during which the systemic cell-mediated immune response was suppressed as indicated by prolonged acceptance of orthotopic skin allografts. The prompt appearance of hemagglutinating antibodies in the serum of immunized rats followed a time course which coincided with the suppression of cell-mediated immunity and suggested that the two events are casually related. Since exposure to allogeneic antigens on lymphoid cells via the anterior chamber elicits a transient suppression in cell-mediated immunity, where humoral immunity is preserved, the phenomenon resembles immune deviation.     

Electron microscopy of cellular immunity reactions in B-cell deprived rabbits. Thymus derived antigen reactive cells, their micro-environment and progeny in the lymph node.

Three times sublethal total body X-irradiation with thymus shielding--at 14 days' intervals--established an 'isolated T-cell system'. Cellular immunity reactions in draining lymph nodes of rabbits have been analyzed at the ultrastructural level after challenge with horse spleen ferritin, the chemical sensitizer, 2-phenyl-4-ethoxymethylene-5-oxazolone and after skin allografting. A basic pattern of interdigitating cells (IDC) is described as a specific constituent of the thymus-dependent areas of peripheral lymphoid tissue. Their ultrastructural features and presumable functional relationship to the afferent loop of cellular immunity reactions are presented. The differentiation pathway of two T-cell lines is shown and discussed in relation to cellular and thymus-dependent humoral immunity reactions.     

The natural anti-Pseudomonas aeruginosa and anti-Proteus immunity of the suitable donor population]

The natural anti-pyocyanic and anti-Proteus immunity of donorable population of Kiev before the accident at Chernobyl Atomic Power Plant has been studied. Blood serums of 3024 deliberately non-immunized persons have been studied. It is determined that there are natural anti-pyocyanic and anti-Proteus antibodies in blood serum of people with different group belonging during the all periods of a year (by ABO system). The anti-pyocyanic and anti-Proteus antibodies of high titers in blood serum are found in summer most frequently.     

The role of natural antibodies in atherogenesis

Atherosclerosis is now widely recognized as a chronic inflammatory disease that involves innate and adaptive immune responses. Both cellular and humoral components of the immune system have been implicated in atherogenesis. Natural antibodies can be considered humoral factors of innate immunity, and their functional role in health and disease has been reexamined in recent years. Natural antibodies exhibit a remarkably conserved repertoire that includes a broad specificity for self-antigens. For this reason, they are believed to be a product of natural selection and have been suggested to play an important role in "housekeeping" functions. Recent evidence has revealed that oxidation-specific epitopes are important and maybe immunodominant targets of natural antibodies, suggesting an important function for these antibodies in the host response to consequences of oxidative stress, for example, to the oxidative events that occur when cells undergo apoptosis. This review will focus on these recent findings and discuss the emerging evidence for an important role of natural antibodies in atherogenesis.     

Immune response to chemically modified flagellin. IV. Further studies on the relationship between humoral and cell-mediated immunity

Acetoacetylation converts flagellin from an antigen which preferentially induces humoral antibodies to an antigen which exclusively provokes cell-mediated immunity and, under certain circumstances, induces antibody tolerance. Studies reported in this paper revealed that the acetoacetylated flagellins expressed similar immunological properties in flagellin primed rats as in normal rats. Thus, on the one hand, acetoacetylation destroyed the capacity of flagellin to trigger a secondary antibody response, but on the other hand, the acetoacetyl-flagellins very effectively induced delayed-type hypersensitivity reactions in flagellin primed animals. It was concluded from these results that humoral and cell-mediated immunity may be opposing immunological processes in both unprimed and primed animals.Acetoacetylated flagellin induced antibody tolerance in both strain W (low responder) and J (high responder) Wistar rats. Maximum tolerance was induced 12 hr after injection of antigen, but in strain J animals the tolerance had disappeared by 48 hr, whereas in strain W rats tolerance persisted for >28 days. The potential to recover from tolerance in strain J rats appeared to coincide with the level of delayed hypersensitivity at the time of challenge. However, this delayed hypersensitivity disappeared when breaking of tolerance occurred. These results suggest that the T cells which participate in delayed hypersensitivity reactions may also act as “helper” cells in antibody responses. On the other hand, it was found that priming for a secondary antibody response by flagellin appeared to coincide with development of primary antibodies rather than with induction of delayed-type hypersensitivity. The relative importance of specific T and B cells in these phenomena is discussed.     

The incidence of hemocyanin-binding cells in hemocyanin-tolerant rats

The incidence of lymphoid cells which react in vitro with ¹²⁵I-labeled hemocyanin (Jasus lalandii) has been investigated using cells from normal rats and rats made tolerant to HCY by a neonatal course of injections. The absence of humoral or cellular responses to HCY in the tolerant rats was established by their failure to: 1) produce serum anti-HCY antibody, 2) localise ¹²⁵I-HCY in the follicles of the popliteal lymph node, or 3) produce immediate or delayed skin reactions to HCY.     

Dynamics of lymphocyte subpopulations, immunoglobulins and specific antibodies in acute brucellosis

The main lymphocyte subpopulations (T-, B-, T mu-, T gamma, and L-lymphocytes), serum immunoglobulins (A, M, G), and specific antibodies have been analyzed at different periods of the development of acute brucellosis. The heterogeneous pattern of changes in the main characteristics of both humoral and cell-mediated immunity has been revealed. A definite interrelation of cell-mediated and humoral reactions in the immunological process in brucellosis has been established.     

Functional analysis of a T cell line specific for antiidiotypic antibodies to a Schistosoma mansoni protective epitope. II. Induction of protective immunity in experimental rat schistosomiasis.

In our previous work on the idiotypic network in the rat model of schistosomiasis we showed that immunization with an IgE mAb specific for 26/56-kDa parasitic Ag resulted in the production of anti-anti-Id antibodies of both the IgG and IgE classes. Further studies demonstrated that anti-Ab2 T cell lines, obtained by immunization with Ab2 antibodies, functioned as conventional Th cells; they were MHC-restricted and required APC to proliferate in the presence of the native schistosomula Ag and the Ab2 antibodies. We report the involvement of these anti-Ab2 cells in the regulation of protective immunity. The transfer of long term culture anti-Ab2 T cell lines into LOU/M rats, followed by a challenge infection by Schistosoma mansoni 1 day after the cell transfer led to a slight increase in the worm burden. On the contrary, the transfer of anti-Ab2 T cells 90 days before S. mansoni infection induced a significant reduction of the worm burden (up to 57%). T cells recovered from the protected rats were stimulated by the native schistosomula Ag as well as by tryptic fragments of IgG isolated from the Ab2 sera, in the presence of irradiated thymic cells as APC. We also analyzed the humoral response developed by the rats after transfer with the anti-Ab2 T cell lines. The sera induced various inflammatory cells into cytotoxic effectors against the larvae of S. mansoni, arguing for the presence of functional IgE in the sera. Moreover, when these sera were passively transferred into rats infected 1 day later, a significant reduction of the worm burden was observed. However, antibody-dependent cytotoxic mechanisms efficient 10 days after the anti-Ab2 T cell transfer did not correlate with the protective immunity which required a 90-day delay to be established. These data suggest that the protective immunity induced by the anti-Ab2 cells is supported both by the cellular and humoral components and that in a future vaccinating strategy the idiotypic network may play a crucial role.     

The in vitro induction of T cells which mediate delayed-type hypersensitivity toward horse red blood cells.

Humoral and cell-mediated immunity to the antigen horse red blood cells (HRBC) were induced in vitro. The type of immune response induced, however, was dependent on the concentration of antigen present in the culture. Whereas intermediate concentrations of HRBC induced antibody-forming cells, high and low concentrations of HRBC induced T cells which, on transfer, mediated delayed-type hypersensitivity reactions. The inverse relationship between humoral and cell-mediated immunity often observed in vivo is, therefore, also evident when lymphocytes are stimulated with antigen in vitro.     

Immunological tolerance to pig-serum partially inhibits the formation of septal fibrosis of the liver in Capillaria hepatica-infected rats

Systhematized septal fibrosis of the liver can be induced in rats either by repeated intraperitoneal injections of pig-serum or by Capillaria hepatica infection. The relationship between these two etiological factors, as far as hepatic fibrosis is concerned, is not known, and present investigation attempts to investigate it. C. hepatica-induced septal fibrosis of the liver was considerably inhibited in rats previously rendered tolerant to pig-serum. Pig-serum-tolerant rats developed antibodies against pig-serum when infected with C. hepatica, but this did not happen when the infection occurred in normal rats. On the other hand, anti-C. hepatica antibodies failed to recognize any epitope in pig-serum, by Western blot. However, no evidence of an immunological cross reactivity was found, at least at the humoral level. Alternatively, cell-mediated mechanisms may be involved, and further investigations are warranted.     

Living on three time scales: the dynamics of plasma cell and antibody populations illustrated for hepatitis a virus

Understanding the mechanisms involved in long-term persistence of humoral immunity after natural infection or vaccination is challenging and crucial for further research in immunology, vaccine development as well as health policy. Long-lived plasma cells, which have recently been shown to reside in survival niches in the bone marrow, are instrumental in the process of immunity induction and persistence. We developed a mathematical model, assuming two antibody-secreting cell subpopulations (short- and long-lived plasma cells), to analyze the antibody kinetics after HAV-vaccination using data from two long-term follow-up studies. Model parameters were estimated through a hierarchical nonlinear mixed-effects model analysis. Long-term individual predictions were derived from the individual empirical parameters and were used to estimate the mean time to immunity waning. We show that three life spans are essential to explain the observed antibody kinetics: that of the antibodies (around one month), the short-lived plasma cells (several months) and the long-lived plasma cells (decades). Although our model is a simplified representation of the actual mechanisms that govern individual immune responses, the level of agreement between long-term individual predictions and observed kinetics is reassuringly close. The quantitative assessment of the time scales over which plasma cells and antibodies live and interact provides a basis for further quantitative research on immunology, with direct consequences for understanding the epidemiology of infectious diseases, and for timing serum sampling in clinical trials of vaccines.     

Cellular defence reactions and their depression in insects]

In insects the main cellular defence reactions are phagocytosis and encapsulation of foreign bodies. Free cells of haemolymph called haemocytes are the effectors of these reactions. They are achieved under the control of humoral factors of the plasma or of the serum. Humoral factors are able to enhance or to decrease the cellular defence reactions. As in mammals, potential parasites or pathogens need to avoid or to inhibit the defence reactions before developing inside the insect body. As an example of the depression of immunity induced by a parasite we will study the relationships between an insect and a nematobacterial complex.     

Islet transplantation in experimental diabetes of the rat. X. Induction of cytotoxic antibodies and islet-cell-surface-antibodies after homologous islet transplantation in rats

The mechanisms of islet allograft rejection are still unknown. 350 allogeneic rat islets (BDE/Han) were transplanted into the liver of Streptozotocin-diabetic rats (Lewis/Han). Animals were killed either on day 4, 7, 10 or 14. Immunofluorescence analysis for islet-cell-surface-antibodies (ICSA) was performed on BDE-islet-single-cells yielded by Collagenase-Dispase digestion. In order to detect cytoplasmic islet cell antibodies, immunofluorescence technique was used on BDE-pancreas cryosections. Cytotoxicity assay was tried out using 51Cr-release-test. After successful intraportal transplantation, rejection took place between day 7 and 10. ICSA could be observed on day 10 and 14. Cytoplasmic antibodies were not detected at any time. A specific cytotoxic activity in the recipient serum revealed itself on day 10 (23.0%) and day 14 (27.7%). Transplantation of freshly isolated allogeneic islets induced ICSA and cytotoxic antibodies. These results indicate an involvement of humoral mechanisms in islet allograft rejection.     

Inhibition by serum of autoimmune aspermatogenic orchitis.

Inhibition by serum of experimental autoimmune orchitis (EAO) was studied in guinea-pigs. It was found that the capacity of an autoantigen, antigen P, purified from guinea-pigs' spermatozoa, to produce lesions of EAO could be inhibited by mixing antigen P with a small amount of normal human serum before injection into guinea-pigs. In protected animals, cell-mediated immunity and humoral antibodies to antigen P were also significantly suppressed.     

Early adaptive humoral immune responses and virus clearance in humans recently infected with pandemic 2009 H1N1 influenza virus

Few studies on the humoral immune responses in human during natural influenza infection have been reported. Here, we used serum samples from pandemic 2009 H1N1 influenza infected patients to characterize the humoral immune responses to influenza during natural infection in humans. We observed for the first time that the pandemic 2009 H1N1 influenza induced influenza A-specific IgM within days after symptoms onset, whereas the unit of IgG did not changed. The magnitude of influenza A-specific IgM antibodies might have a value in predicting the rate of virus clearance to some degree. However, the newly developed IgM was not associated with hemagglutination inhibition (HI) activities in the same samples but correlated with HI activities of subsequently collected sera which were mediated by IgG antibodies, indicating that IgM was critical for influenza infection and influences subsequent IgG antibody responses. These findings provide new important insights on the human immunity to natural influenza infection.     

Study of immunoregulating properties of an interferon inducer in animals with various reactions to the antigen

Influence of dsRNA isolated from killer yeast of S. cerevisiae on humoral and cellular immune responses in mice CBA/CaY and C57Bl/6Y with opposing reaction to the antigen was studied. It was shown that after administration of the yeast dsRNA preparation to the animals simultaneously with the antigen there was an increase in the number of the antibody forming cells in the spleen and the titer of hemolytic antibodies in blood serum of the animals with high and low reactions to the antigen. After sensitization with different doses of sheep red blood cells (10(7) and 10(8)) the preparation had immunomodulating action on development of DTH in mice CBA/CaY. The effect of the dsRNA preparation on the immunity system depended on the preparation dose, antigen loading and animal genotype and was the most marked in mice CBA/CaY with interferon levels in blood serum 2-3 times higher than those in mice C57Bl/6Y.