Serum of rabbits infected with Treponema pallidum (Nichols) inhibits in vitro transformation of normal rabbit lymphocytes.
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Biomedical subjects
Publications and source records attributed to J D Folds.
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The serum of a 26-year-old black man with a recent episode of meningococcemia complicated by meningitis and arthritis was found to lack hemolytic complement activity. The sixth component of complement was not detected by functional or immunochemical assays whereas other components were normal by hemolytic assay. His fresh acute-phase serum lacked complement-mediated bactericidal activity against the homologous strain of Neisseria meningitidis, but the addition of fresh normal serum or purified C6 restored bactericidal activity as well as hemolytic activity. The absence of C6 activity could not be accounted for on the basis of an inhibitor. Opsonization and chemotaxis functioned normally. Histocompatibility typing of family members did not demonstrate evidence for genetic linkage of C6 deficiency with the major histocompatibility loci. This report represents the first published case of C6 deficiency associated with bacteremic Neisseria infections in which antimeningococcal bactericidal antibodies have been definitively demonstrated against the homologous strain in the acute phase of the illness.
The Fc fragment derived by proteolysis of human IgG by human polymorphonuclear leucocyte (PMN) elastase was tested for in vitro biological activity. This fragment could attach to the specific IgG receptor of Staphylococcus aureus Cowan I cells (protein A) and could be eluted from the cells with dissociating buffer. Taking advantage of this attachment, it was shown that the Fc fragment is capable of attaching to the antigen-combining site of an IgM rheumatoid factor and can bind to the Fc receptor of human PMN. A similar fragment produced in vivo at sites of inflammation could play a role in regulating the inflammatory response.
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The use of counterimmunoelectrophoresis (CIE) for detection of serum antibodies to staphylococcal teichoic acids was evaluated against teichoic acids prepared by sonic treatment or lysostaphin extraction of Staphylococcus aureus (Lafferty strain). Of 54 patient sera from suspected cases of staphylococcal endocarditis, osteomyelitis, or septicemia, 33 (61.1%) were positive by CIE analysis; however, 128 of 291 sera (44.0%) from normal adult donors were also positive. Selected CIE-positive sera from patient and control groups were titered by Ouchterlony gel diffusion. In the control group of normal sera, 65% were also positive by gel diffusion, but only 15% had titers of >/=1:2. Of the patient sera, 44.4% had gel diffusion titers of >/=1:2. In addition to the specific teichoic acid band, a second precipitation band could be demonstrated with both patient or normal sera by CIE or gel diffusion. This second precipitin band was shown to involve interactions of test sera with staphylococcal protein A present in the teichoic acid extracts. The protein A precipitins were detected at high concentrations of the antigen extracts, whereas the anti-teichoic acid precipitins were optimally detected at lower antigen concentrations. The formation of protein A precipitin bands did not correlate with the presence of anti-teichoic acid antibodies, as most sera tested were positive for protein A regardless of anti-teichoic acid activity. This study suggests that a high incidence of normal people have levels of antibodies to teichoic acids which are detectable by the highly sensitive, but nonspecific, technique of CIE.
Evidence is presented which reinforces the complexity of the host-parasite interaction during the course of syphilis. Infection with Treponema pallidum evokes a complicated antibody response and an assortment of cell-mediated immune reactions in the host. It appears that humoral immunity plays a minor role towards the complete elimination of syphilitic infection while the cellular limb of the immune response may be an important host defence mechanism. Information now available indicates that a state of anergy, or immunosuppression, exists in the early stages of human and experimental rabbit syphilis based upon negative skin reactions to T. pallidum antigen(s), the abnormal histological appearance of lymphoid organs, and impaired in vitro lymphocyte reactivity. It is also evident that in the later stages of the disease cellular immunity becomes activated as delayed type skin reactions can normally be elicited in tertiary syphilitics and lymphocyte behaviour in cell culture appears normal. Several mechanisms have been invoked to explain the delay in an effective immune response against syphilitic infection and the duration of the disease: (1) a capsule-like substance on the outer surface of virulant T. pallidum may act as a barrier against treponemicidal antibody; (2) this material and other biological properties of virulent treponemes could enable spirochaetes to escape being engulfed by macrophages and other phagocytic cells; (3) antigenic competition among different treponemal antigens causing partial tolerance; (4) T. pallidum infection may bring about the elaboration of immunosuppressive substances of host or treponemal origin which inhibit the proper function of lymphocytes, macrophages, and other cell types.
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Human polymorphonuclear lysosomal granules contain a neutral protease which is capable of digesting human immunoglobulins. The protease is located in the azurophil granules and enzymatically cleaves IgG, producing a Fab-like piece which is recoverable. The Fc-like fragment is not crystallized. The Fab-like fragment competes effectively for ligands formed by native antibody from which the fragments were produced.
The in vitro response of peripheral blood lymphocytes from rabbit infected with Treponema pallidum was examined using various mitogens and avirulent Treponema reiteri. For the first 4 weeks after treponemal infection, the response of lymphocytes from syphilitic rabbits to phytohemagglutinin and pokeweed mitogen was markedly reduced in comparison to uninfected controls. Lymphocytes from both groups of rabbits responded normally to class-specific immunoglobulin anti-sera (anti-immunoglobulin M and anti-immunoglobulin G) and T. reiteri.
Peritoneal exudate cells from rabbits infected with Treponema pallidum Nichols were used as indicators of macrophage migration inhibitory factor activity. Between 3 and 15 weeks after infection, the migration of peritoneal exudate cells was inhibited in the presence of 3 to 25 microgram of T. phagedenis biovar Reiter protein per ml. Before this period, the migration patterns of peritoneal exudate cells from infected animals were uninhibited and similar to those from noninfected control rabbits. These observations were correlated with the development of active cell-mediated immunity during experimental T. pallidum infection.
The blastogenic response of nylon wool-separated peripheral-blood lymphocytes from Treponema pallidum-infected rabbits was tested in vitro with mitogens and T. pallidum antigens. The mitogenic response of the enriched T-cell population to concanavalin A and phytohemagglutinin was depressed during the first 3 to 4 weeks of infection, similar to the pattern observed with unfractionated cells. Shortly thereafter, levels of blastogenesis returned to values of uninfected cultures. Enhanced blast transformation was seen immediately when purified T-cells from infected rabbits were exposed in vitro to T. pallidum antigens. Although these relatively high levels of blastogenesis were maintained for the duration of the experiment, cultures of unfractionated lymphocytes from infected rabbits did not exhibit an increased blastogenic response to the same antigen preparation until 3 to 4 weeks after infection. Autologous serum from infected rabbits decreased the lymphocyte response to T. pallidum antigen. The stimulatory effects of anti-immunoglobulin G and lipopolysaccharide on nylon wool-fractionated or unfractionated lymphocytes from both infected and control rabbits were similar throughout the course of infection. During the first 6 weeks of experimental disease, there was a 25 to 31% increase in the number of lymphocytes circulating in the peripheral blood of T. pallidum-infected rabbits.
MOPC 104E is a mouse plasmacytoma which produces an IgM (lambda) myeloma protein. This IgM protein has a binding specificity for dextran B-135s. This report describes a variant of the MOPC 104E tumor which secretes a myeloma protein which does not react with the dextran. The apparent variant of MOPC 104E arose spontaneously during routine passage of the MOPC 104E tumors in Balb/C mice and appears to be stable.
The cytotoxicity activity of an anti-HL-A2 antiserum cross-reactive with W28 appeared in three distinct peaks after the serum was subjected to isoelectric focusing. The pH at which the peaks formed was reproducible using pH 5-8 or pH 3.5-10 gradients. Anti-HL-A2 activity occurred in each peak, but the cross-reactive anti-W28 cytotoxicity appeared to be largely confined to the second and third peaks. The first peak was exclusively IgG, the second contained IgG and IgM, and the third contained IgG, IgA, and IgM.
Peripheral blood lymphocytes isolated from rabbits in the early stages of Treponema pallidum infection responded poorly when exposed to concanavalin A in vitro. Maximal depression of blastogenesis occurred when lymphocytes were cultured in the presence of autologous serum in comparison with fetal calf or normal homologous rabbit serum.
Hydroxystilbamidine (HSB) is a potent suppressor of the plaque-forming cell response of mice injected with heterologous erythrocytes. HSB, given in varying doses and injection schedules, suppressed both the primary and secondary immune responses to bovine serum albumin. Apparently the effect is not simply a toxic effect on spleen cells, because there was no appreciable difference in cell numbers between control and HSB-treated mice. The effect of HSB was most apparent in the early phase of the immune respone.
An anti-HL-A 3 antiserum with cross-reacting activity for HL-A 1 and HL-A 11 was subjected to isoelectric focusing over a pH 5-8 gradient. The cytotoxic activity of the serum focused into three distinct peaks, one at the basic end of the gradient, one between pH 6 and pH 7 and one at the acidic end. The first and second peaks reacted with HL-A 3 positive cells and HL-A 3 negative cells positive for cross-reacting antigens. The third peak reacted only with HL-A 3 positive cells.