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The suppressive effects of monocytes in the autologous mixed lymphocyte reaction.

The response of isolated T cells to autologous non-T mononuclear cells is called the autologous mixed lymphocyte reaction (AMLR). The responding T cells show immunological memory and specificity. This reaction was present in all thirty normal individuals tested. Since the AMLR in the absence of evidence of in vivo excessive lymphoproliferation must somehow be controlled, we have studied the interactions of enriched T cells, B cells and monocytes in culture as possible means of regulation of this reaction. Increased rate of [3H] thymidine incorporation by T lymphocytes were observed when they were cultured with mitomycin-treated autologous non-T cells. This was increased when the stimulating cells were enriched for B lymphocytes and was significantly decreased when the stimulating cells were enriched for monocytes. Addition of monocyte-enriched cells to B-enriched cells in a 1:1 ratio, significantly suppressed the AMLR (P- less than 0.01). Equivalent numbers of monocytes did not suppress T-cell responses to phytohaemagglutinin (PHA). Monocyte-enriched cells were separated from stimulating B-enriched cells by nucleopore (0.6 mu) or dialysis tubing (0.12 mu) in Marbrook chambers. Soluble products released from monocyte-enriched cells also suppressed the AMLR. The significance of the AMLR in vivo is uncertain but it may be important in immunoregulation, monocytes playing an important role.

Adult↗

The effect of cyclophosphamide on immunological control mechanisms.

Cyclophosphamide (CY) given three days before immunization with a range of antigens increases the intensity of cell-mediated immune responses. CY given around the time of immunization also reverses immunological tolerance, blocks antigenic competition and modifies desensitization. The effect on antibody production is not so predictable. However, it may increase the IgE response without affecting IgG1 or IgG2 response to the same antigen and may abolish immunological memory. The action of CY is on rapidly-turning-over cell populations. Lymphocytes are maximally at risk 48 hours before they transform into large pyroninophilic cells, that is just before the S phase of cell division. CY has a preferential effect on both T- and B- suppressor cells. The application of these findings to experimental cancer models is discussed. These findings are not restricted to CY, as a wide range of cytotoxic drugs with different actions at the cellular level may have similar profound effects on the regulation of the immune response.

Animals↗

[Live vaccines against influenza and measles].

The advantages of live attenuated vaccines over inactivated vaccines in the prophylaxis of some viral infections are shown: attenuated vaccines, apart from their ability to stimulate systemic humoral immunity, are capable of the mobilization of cytotoxic killer reactions with the participation of T lymphocytes and macrophages, the stimulation of local secretory immunity and long-term immunological memory. The organizational drawbacks of the modern vaccinal prophylaxis of influenza and measles with the use of live vaccines manufactured in the USSR are analyzed and effective ways for the elimination of these drawbacks are proposed.

Adolescent↗

Secondary immune response to oral and nasal rough mutant strains of Salmonella typhimurium.

The variations in anti-Salmonella typhimurium antibody levels was measured in BALB/c mice which had been orally and nasally vaccinated with S. typhimurium live mutants of different lipopolysaccharide lengths. Together with the demonstration of immunological memory, the intensity of the secondary response was correlated with the length of the polysaccharide chain at intestinal and serum levels. Nasally administered antigen seemed to be at least as immunogenic as when orally administered.

Administration, Intranasal↗

[Immunologic tolerance to surface polysaccharides of serogroup A and C meningococci].

A single intravenous injection to mice of surface polysaccharides of meningococcal A and C serogroups in doses of 25--50 micrograms induces immunologic tolerance: the animals did not respond to the optimal dose (0.5 micrograms) of homologous antigens but were capable to form normal response to the heterologous polysaccharide Vi-antigen S. typhi. CBA mice were tolerant to polysaccharide A as long as 45 days, while noninbred ones were tolerant to the antigen only for 30 days. This pattern of tolerance did not prevent the formation of the immunologic memory. The animals who had lost tolerance were shown to be capable of forming the secondary response to another injection of antigen A.

Animals↗

[Antineuraminidase serum antibodies in natural influenza A and immunization with influenza vaccines].

Parallel HI and virus-elution-from-erythrocytes-inhibition (a simplified method for titration of neuraminidase antibody) tests were used for examinations of 1117 blood serum specimens from 440 adults and children under study, 5250 single serum specimens from healthy subjects from birth to 65 years of age, 38 paired serum specimens from children who experienced influenza A/Texas/1/77 disease in the epidemic of 1979-1980, and 590 paired serum specimens from subjects immunized with influenza vaccines. In 7%-23% of influenza patients and immunized subjects antibody rise was observed to only one of the influenza A virus surface antigens, hemagglutinin or neuraminidase. The protective activity of antibody to influenza A virus neuraminidase was as good as that of antihemagglutinins. Both kinds of antibody interacted in protection against the disease. Antineuraminidase antibody was found to affect the decrease in severity of the infectious process in natural infection with influenza A. The formation of immunological memory in the system of synthesis of antihemagglutinins and antineuraminidase antibodies was shown to have features in common. The pattern of heterologous immune responses in immunized subjects and patients with influenza showed all antigenic varieties of neuraminidase N2 as well as neuraminidases N1 and N2 to share common cross-reacting determinants.

Adult↗

Current status of an oral B subunit whole cell cholera vaccine.

Purified B subunit of cholera toxin retains membrane-binding capacity and protective immunogenicity and yet has no toxic activity as tested in animals. These properties suggest that B subunit might be a promising immunogen, particularly as an oral vaccine, for stimulating protective antitoxic immunity against cholera in man. A method has been elaborated which allows preparation of +/- 10 grams of pure B subunit per fermentor culture cycle. As tested in both Swedish and Bangladeshi volunteers purified B subunit alone or in combination with conventional whole cell vaccine gives no side-effects at all when given orally and only very mild local reactions after parenteral administration. A single peroral or intramuscular immunization with B subunit has given significant intestinal IgA antitoxin antibody formation in 75-85% of Bangladeshi women tested; however, the duration of the response was longer after the oral route. The preliminary results of a recent study (Svennerholm, A.M., Jertborn, M., Gothefors, L., Karim, A., Sack, D. and Holmgren, J., to be published) have further shown that two peroral immunizations of Bangladeshi volunteers with a combined B subunit--whole cell cholera vaccine give rise to mucosal IgA antitoxin as well as anti-lipopolysaccharide antibody formation which closely resemble these antibody responses in cholera convalescents. The combined vaccine also evoked a local immunologic memory comparable to that induced by clinical disease.

Antibody Formation↗

[Anti-tetanus vaccines, serums and immunoglobulins].

Specific immunity to tetanus toxin is only artificially acquired and is provided by the presence in the blood and in the extravascular fluids of an IgG antibody passively administered or actively produced by the organism through vaccine injections. In the first case serum of human origin is now preferred to serum of animal origin due to the lack of major undesirable reactions and longer duration of protection (about 4 weeks versus 7-10 days). Tetanus toxoid is one of the most safe and potent known immunogens. For primary immunization adsorbed toxoid is given on two occasions at 2 months interval with a third reinforcing dose approximately one year after the second. The subsequent antitoxin response persists at protective level for at least 5 years and for a longer time (10 years about) after a booster. The ability to promptly react to a booster injection (immunological memory) is greatly long-lasting in persons who have previously received at least two doses.

Antibodies↗

The extraction of lymphoid cells from the human nasopharynx.

No criteria exist at present for judging the quality, extent, specificity, immunological memory or degree of functional autonomy of the local mucosal immune response in humans owing to difficulty in obtaining suitable specimens for assay. This paper offers a simple, practical, atraumatic technique for the extraction of viable lymphoid cells from the human nasopharyngeal mucosa together with some preliminary figures on the numbers of cells obtained and lymphocyte responses to mitogenic stimuli. The technique is based on the collection of nasal washings with chilled saline and sufficient lymphoid cells have been collected by this method to make multiple in vitro cultures. Cultures have been maintained for over 5 days and significant blastogenic responses have been recorded suggesting that the luminal cells retain some degree of functional competence.

Adult↗

[Results of a study of collective immunity to influenza A virus (H1N1) from 1976 to 1980].

The time course of the levels of circulating antihemagglutinins to influenza A (H1N1) virus in the populations of the towns in different geographical zones of the USSR was shown to be similar. The intensity of herd immunity in some areas differed considerably, however. The population of older age groups most of whom had no clinically manifest diseases during the influenza A (H1N1) epidemic was shown to experience immunological changes upon exposure to this agent. The intensity and the rate of changes in the immunological structure of this portion of the human population exceeded similar parameters among the subjects under 20 years of age who had experienced manifest forms of infection. Some people with immunological memory to influenza A (H1N1) virus developed antibody in response to infection or immunization with influenza A (H3N2) strains.

Adult↗

[Immunological principles of polysaccharide-protein conjugate vaccination].

Haemophilus influenzae and Streptococcus pneumoniae are bacteria with a polysaccharide capsule. The production of specific antibodies against capsular polysaccharide plays a pivotal role in the defence against these organisms. However, children under the age of two years do not at all or only poorly respond to an infection with encapsulated bacteria or after vaccination with purified capsular polysaccharide antigen. In contrast, protein antigens, e.g. tetanus- and diphtheriae-toxoid, are good immunogens in this age group. The difference between polysaccharide antigen and protein antigen is that the former are T-dependent antigens whereas the latter are T-independent. The reason for this age dependent "immunodeficiency" is not clear. A functional immaturity of a B-cell population seems to be the reason for the unresponsiveness of young children against Ti-2 antigens. The Haemophilus conjugate vaccine contains the capsular polysaccharide chemically conjugated to a carrier protein. This results in an immune response against the polysaccharide with characteristics of a T dependent antigen, giving high immunogenicity even in children under the age of two years, resulting in high antibody-production and the induction of immunological memory.

Antibodies, Bacterial↗

Intestinal absorption of colostral lymphocytes in newborn lambs and their role in the development of immune status.

Two model experiments were conducted to study the intestinal absorption of colostral lymphoid cells and the role of these cells in the development of immune status in newborn lambs. In experiment I, 17 lambs of 14 Merino ewes were used. Suspensions of lymphoid cells separated from the colostrum (cell density: 5 x 10(6)/ml) and blood (3 x 10(6)/ml) were labelled with technetium (Na99mTcO4) of 37 MBq/ml radioactive concentration. In three groups of lambs, 10-ml volumes of the cell suspensions were injected directly into the duodenum after laparotomy, while in a fourth group (group Ia) the same volume was administered to the animals through an oesophageal tube. The labelled cells revealed that colostral cells of the lamb's own dam are absorbed from the gastrointestinal tract and get into the newborn lamb's lymph circulation irrespective of the route of application. In experiment II, involving 40 lambs of 40 ewes, we studied the effect of absorbed colostral lymphocytes on the development of the newborn lamb's immune status. Twenty ewes (group A) each were treated with 3 ml tetanus anatoxin twice, while the remaining animals (group B) were left uninoculated. Lambs of group A (designated A2) were separated from their dams immediately after birth, then were administered, through an oesophageal tube, 10 ml of a suspension of lymphoid cells (cell density: 5 x 10(6)/ml) separated from the maternal colostrum. Subsequently, the lambs were interchanged with lambs of nonimmunized ewes of group B (designated lambs B1), i.e. were mutually put out to nursing. At three days of age, lambs of groups A1, A2, B1 and B2 were inoculated with 3 ml tetanus anatoxin, then blood samples were taken from them 5 times in a period of 27 days for comparative examination of the humoral and cellular immune reactions. The results demonstrate that lymphoid cells from the colostrum of the lambs' own dam become absorbed into the newborn lambs' lymph circulation, remain immunologically active and may transfer, besides immunological memory, also cellular activity.

Animals↗

[Stress and viral infection: dynamics of expression of influenza A viral antigens during immobilization stress].

The level of expression of influenza virus antigens in the target organ is an important characteristic of the severity of a viral process, as was shown on a model of experimental influenza A. Stress exposure augmenting the severity of the infection stimulates the expression of viral polypeptides in the acute period of the disease. Injection of an antioxidant ionol which is effective in influenza may prevent stress-enhanced synthesis of viral proteins. Stress-induced disorder of the mechanisms of formation of immunological memory is paralleled by accumulation of high levels of virus-specific proteins in the lungs after repeated exposure of an animal to a homologous virus. Hence, the level of viral antigens synthesized in the course of reinfection also helps assess the degree of body protection from this agent.

Animals↗

[Immune response to sheep erythrocytes fixed in formaldehyde].

Treatment of sheep erythrocytes with 1.5% of formaldehyde alter their immunogenic properties. On the background of immune response to nonfixed erythrocytes, the performed studies showed the following peculiarities in the reaction of mice to fixed erythrocytes: 1) the primary response of animals, in ected with fixed erythrocytes, was rather weak after its determination by the number of rosette forming cells (RFC), antibody forming cells (AFC) in the spleen and by the of hemagglutinins (HA) in serum; 2) in contrast to the primary response the fixed erythrocytes induced a good secondary response, which was considerably higher/according to the number of RFC and titre of HA/in mice sensibilized by nonfixed erytrocytes in advance than in those presensibilized by fixed cells. Therefore the fixed erythrocytes were weaker inducers of immunologic memory than the nonfixed under equal other conditions. 3) In contrast to the nonfixed the fixed erythrocytes did not induce the formation of large amounts of direct AFC during the secondary response as well even then when the animals were presensibilized by nonfixed form of the antigen.

Agglutinins↗

Gene therapy approaches in urologic oncology.

The tools and concepts of cytokine gene-based immunotherapy are being applied to the development of potentially effective new adjuvant treatment modalities for urologic malignancies. In preclinical models for the most prevalent urologic cancers, such as renal cell, bladder, and prostate carcinoma, it was shown that cytokine secreting, growth inactivated, tumor cell preparations (1) are capable of inducing a T-cell response against even nonimmunogenic tumors, (2) have considerable therapeutic benefit in tumor bearing animals, and (3) establish effective immunologic memory in cured animals. These studies have advanced further our understanding of the efficacy and therapeutic use of cytokine secreting tumor cells and form the rationale for translating these preclinical results into a clinical setting. It is realistic to speculate that in the foreseeable future alternative or complementary approaches to cytokine gene-based immunotherapy will be developed that would augment immune responses in cancer patients. Genetically modified dendritic cells transduced with genes encoding isolated tumor rejection antigens or costimulatory signals, such as B7, may be even more potent immune stimulators to induce systemic immune responses. Although animal studies have shown considerable promise and investigational clinical trials are underway, additional research and further development still is required to realize the full benefit of this approach, and some forms of cancer eventually may respond to this form of cancer immunotherapy.

Animals↗

[NK cells and their characteristics and immunogenetic aspects].

This review summarizes knowledge of history and development of the "new" biological phenomenon. NK cells play a pivotal role in immune surveillance against tumors and virus-infected cells. They are also involved in natural resistance to bone marrow transplantations and in the regulation of the growth and activity of immunocompetent and hematopoietic cells. Unlike cytotoxic T lymphocytes NK cell activity is not dependent on thymus maturation and an expression of class I MHC antigens. They lack immunological memory and develop directly from precursor cells of the bone marrow. The lytic activity of NK cells is associated with the population of large granular lymphocytes (LGL). In human peripheral blood there is about 5% of LGL. A great deal of the study is given to still actual about the possible role of class I MHC antigen expression in regulation of NK-cell cytotoxicity. (Fig. 1, Tab. 2, Ref. 118).

Animals↗

Purified and cell-bound CD26: enzymatic inhibition, antibody binding profile, and expression on T cells in relation to other surface markers.

The CD26 activation antigen (Ag), which is expressed on a subpopulation of human T cells, has been characterized as dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5). We investigated some molecular and inhibition characteristics as well as the monoclonal antibody (mAb)-binding profile of this molecule purified from human lymphocytes. Among the antibodies we explored, two, anti-BT5/9 and anti-TA5.9, exhibited a high affinity for both purified and cell-bound CD26 Ag. Their significance in the study of immunologic memory and lymphocyte activation is discussed in relation to other markers of lymphocyte activation. Among 4 types of inhibitors studied, Pro-boroPro proved to be the most promising substance for further research on the physiological role of dipeptidyl peptidase IV (CD26).

Antibodies, Monoclonal↗