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Biomedical subjects

C D Severson

Publications and source records attributed to C D Severson.

At least 19 recordsLinked to original sources
PubMed1987

An alternative method of panning for rat B lymphocytes.

A new method of panning for B lymphocytes is described in which the ability of the sIg+ cells to adhere depends on the nature and concentration of nonspecific protein used rather than on the use of anti-immunoglobulin. Rat lymph node cells were suspended in 3% bovine serum albumin in Tris-buffered Hanks' and incubated in tissue culture flasks to allow adherence to the plastic. The recovered bed of adherent cells was shown by flow cytometry to be greater than 90% surface immunoglobulin positive and MHC class II positive while containing very few T cells. This adherent fraction was subsequently treated with anti-T cell antibody plus baby rabbit complement to produce a highly purified sIg+ cell population containing no detectable T cells. The sIg+ cells obtained by this panning procedure were functionally active in BCGF and BCDF assays. This method provides an easy and inexpensive alternative to conventional panning with anti-immunoglobulin and also eliminates the possibility of B cell activation by exposure to anti-immunoglobulin-coated surfaces.

Animals↗
PubMed1984

Role of complement in the immune response.

Evidence has accumulated that shows that fragments of C3 are potent inhibitors of immune responses. A low-molecular-weight fragment of C3 and fragments possessing leukocyte-mobilizing activity have been shown to block both antigen- and mitogen-induced human T cell proliferation, and to block mixed lymphocyte culture responses and the generation of cytotoxic lymphocytes. The same fragments inhibit the development of secondary in vitro antibody responses of rat lymphocytes. C3b can be shown to inhibit the polyclonal activation of human lymphocytes by pokeweed mitogen, but it has no effect on T cell proliferation or on the generation of cytotoxic T cells. We now propose that different C3 fragments selectively act on various lymphocyte subsets and thus play a profound role in regulating both immune effector functions and the intensity of the immune response.

Animals↗
PubMed1980

New granulocyte antigens demonstrated by microgranulocytotoxicity assay.

Although granulocyte transfusions and bone marrow transplantation are becoming common clinical modalities, our knowledge of surface nonerythroid, nonlymphoid, non-HLA hematopoetic antigens remains very incomplete. Accordingly, we have systematically screened sera from recipients of multiple granulocyte and whole blood transfusions, and immunoneutropenic patients for antibodies directed primarily at granulocytes. The initial screens demonstrated that >50% of the sera from the above sources contained non-HLA cytotoxic and/or agglutinating antibodies. Preliminary clustering indicated seven possible new specificities detected by microgranulocytotoxicity. Calculations for Hardy-Weinberg goodness of fit based on a study of 98 unrelated donors plus informative families established that 5 of these were alleles of a single new locus termed Human Granulocyte Antigen (HGA)-3a, b, c, d, and e. Absorptions indicated that these antigens were present on mature granulocytes but absent from platelets, lymphocytes, monocytes, and myeloid precursors. A single antigen of another separate locus, HGA-1, was also identified. Absorptions revealed a quite different distribution for HGA-1 than HGA-3, this antigen being detected on monocytes and myeloblasts as well as on mature granulocytes. Independent segregation of the three loci from HLA, from the NA-NB and the 5a-5b antigens, and from themselves was confirmed in informative families.Finally, it seems likely that other antigens will be identified because several other sera that react with both monocytes and granulocytes have been detected.

Alleles↗
PubMed1980

Studies on levamisole--induced agranulocytosis.

Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet-induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia.

Agranulocytosis↗
PubMed1977

Microgranulocytotoxicity.

The microcytotoxicity assay technique has been extensively refined to permit the use of granulocytes as target cells in an effort to identify neutrophil-specific antigens. Virtually every aspect of the test required revision to obtain clear, reproducible results. The most radical modification was the adoption of double-fluorescent vital staining to detect cytotoxicity. The reactions detected with this new assay did not correlate with defined human histocompatibility systems (e.g., HLA, ABH, NA, NB, NC), nor were the target antigens detected on lymphocytes or platelets. Cytotoxicity was highly specific and was produced by the immunoglobulin fraction of alloantisera only in the presence of complement, thus implicating an antigen-antibody phenomenon rather than variable viability of the ephemeral PMN's in vitro. These specificities may have an impact on some aspects of human transplantation (especially of bone marrow) as well as playing a role in some febrile transfusion reactions. Of perhaps greater import is the suggested role of the antigens in immunoneutropenias and therefore in the response of myelosuppressed patients to adjunctive leukocyte transfusion therapy.

Antigen-Antibody Reactions↗
PubMed1976

Antileukocyte antibody in postpartum and renal transplant subjects. A comparison of capillary agglutination and lymphocytotoxicity reactions.

Sera were obtained from 48 gravida II prenatal and 211 multiparous nonpregnant females and examined for leukocyte antibodies comparing a standard lymphocytotoxicity (CY) test with capillary agglutination (CA). Antibody was detected in 41% of the samples in both groups but only CA tests were positive with approximately one-half of the prenatal and three-fourths of the multiparous specimens. Although, CA reactions, when accompanied by positive CY responses, usually correlated with HLA, no correlation with HLA, 5b, or the neutrophil antigens was determined for 35 of the 48 sera reacting only by CA. As a model to test the specificity of CA positive-CY negative antisera, four extensively studied sera were further analyzed in 16 families. Independent segregation from the HLA complex and ABO and Rh antigens was confirmed and two of the sera appeared to detect separate clusters of reactions in conjunction with some of the other reagents. Pre- and postgraft samples obtained from 23 living related and 75 cadaveric renal transplanted patients were investigated and compared for graft function and prospective tissue typing. Although direct crossmatches were negative prior to surgery, 17.9% of the pretransplant samples from living related and 28.0% from cadaveric recipients contained detectable antibody when tested against a cell panel. Similar to the prenatal and multiparous groups, the majority of these responses were detected by CA. Following engraftment, antibody first became evident in 11 of 19 (58%) living related and in 23 of 53 (48.2%) cadaveric hosts. There was a striking association between the development of CA and CY antibody and failure, as contrasted to 100% 9-month or greater survival in 10 of 10 living related and 15 of 15 cadaveric transplants in whom only CA antibodies arose postoperatively. In total, these studies indicate that CA reacts with HLA antigens in common with CY tests. In addition, CA may detect HLA when CY is negative but many other reactions appear to be directed at non-HLA specificities. The relevance of CA-only responses to clinical transplantation remains uncertain, but we may speculate that they have an enhancing effect on the course of renal transplantation and are associated with important histocompatibility determinants.

Agglutination Tests↗
PubMed1972

Relationship of mixed lymphocyte culture response to HL-A histocompatibility antigens. Effect of allele plus one antigen match.

The influence of varying degrees of incompatibility for HL-A antigens on one-way mixed lymphocyte cultures (MLC) has been investigated. Reactions have been compared to a simple expression of HL-A antigens, allele compatibility, and a proposal considering the potential influence of antigen matching in relationship to allele compatibility. As expected, HL-A compatibility was associated with nonstimulated cultures, but significant correlation was not observed when incompatibility was expressed in terms of HL-A antigen or allele mismatching. When the relationship of both was considered, however, a second distinctive group was demonstrated that shared one allele plus one antigen of the second allele. Within this group no stimulation, even with augmented culture conditions, was observed in some families. Employing these same criteria, there was no significant difference in the MLC response in those groups that were incompatible for both alleles regardless of the number of matched antigens or the group that shared an allele but differed by both antigens of the second allele. These results support the concept of an intimate relationship between the loci coding for HL-A antigens and mixed culture reactions. They suggest that HL-A haplotype incompatibility acting as a unit is the primary stimulus of the MLC response, and that the immunogenicity of the haplotype also relates to whether or not one antigen is common to the stimulating and responding cell.

Alleles↗
PubMed1972

Immunological distinction of mycobacterial beta-lactamases.

Beta-lactamase-containing fractions have been isolated from Myobacterium tuberculosis strain R(1)R(v) and M. smegmatis strains NCTC 8158 and T-64. Antisera raised in rabbits to these fractions demonstrated no cross-reactivity with a commercial Bacillus cereus beta-lactamase. Antiserum to either strain of M. smegmatis revealed no cross-reactivity with M. tuberculosis R(1)R(v), one specificity in common with the other M. smegmatis strain, and two specificities unique to the immunizing fractions. Further characterization of the common specificity was not possible, but beta-lactamase activity was related to the strain-specific precipitin lines in each case. These studies demonstrate the feasibility of isolating beta-lactamase enzyme fractions that may prove useful in the classification and diagnosis of mycobacteria.

Adjuvants, Immunologic↗