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Immune response were examined in 10-year-old boys just before and one month after tonsillectomy, and in young male adults tonsillectomized 10 years earlier. All the parameters studied were found to be quite normal.
Immune responses, specific to the stored donor tissue, were measured in 26 recipients over 4,000 days. CML positive crossmatches were associated with accelerated rejections (three cases). LDA positive crossmatches resulted in primary non-functioning kidneys (three cases). Post-transplantation. CML (16 hour inculation) was associated with rejection (p equals 0.001), highly predictive of rejection (p equals 0.001), and when positive after rejection treatment, was associated with a failure to respond (p equals 0.005 - 0.01). 51Cr-CDA was also associated with rejection (p equals 0.002). Recovery of these immunologic participants from the explanted kidney substantiated that they were important effector mechanisms in vivo.
In this paper, cell-mediated immunity (CMI) as evaluated by in vitro migration inhibition assays an in vivo delayed type skin reactions in experimental immune complex glomerulonephritis (ECGN) was studied as well as the effect of treatment with immunosuppressive drugs on these immune responses. In glomerulonephritic rats MIF production as well as delayed type skin reactions could be demonstrated directed against tubular brushborder antigen (Fx1A) containing immune complexes or to their constituents (FX1A or rabbit IgG). Treatment of the animals with immunosuppressive drugs during settled disease state (autologous phase) abolished these cellular immune reactions. However, neither the glomerular depositions of rat IgG associated with the autologous phase, nor the urinary excretion was influenced. When treatment of the animals was started simultaneously with the induction of the ECGN both cellular and humoral immune responses as well as proteinuria were affected. It was concluded that although in this glomerulonephritis model specific MIF response after specific stimulation in vitro as well as DTH reactions could be detected against immune complexes or their constituents, these immune reactions seem not to play important role in this ECGN in particular with respect to the proteinuria.
A single intraperitioneal injection of L 1210 cells preincubated in interferon or in "false interferon" was given to mice. These mice were sacrificed on the 10th day, and cytotoxicity of the sera against the L 1210 leukemic cells vas determined in the microcytotoxic test (modification of Terasaki's method). Leukemic cells treated with interferon before the immunization caused a more pronounced immune response in comparison with the cells treated under the same conditions with "false interferon". By the results of cytotoxic reaction immune response was enhanced 2-4-fold.
Immunization of mice with either soluble or particulate antigens induced a marked increase in peroxidase activity of spleen cell homogenates. Animals immunized with sheep erythrocytes showed maximum splenic peroxidase activity at 2 days. By the 4th day after immunization, when the hemolytic antibody plaque-forming cell response was maximal, peroxidase activity returned to normal levels. Increased splenic peroxidase activity also occurred in mice immunized with rabbit erythrocytes, as well as with rabbit serum or bovine serum albumin. No change in splenic peroxidase activity occurred in mice injected with syngeneic mouse erythrocytes or serum. Both glass-adherent spleen cell populations, morphologically consisting of 90 to 95% macrophages, as well as nonadherent cells, consisting of more than 90% lymphocytes by the same criteria, showed peroxidase activity. Immunization of mice with sheep erythrocytes resulted in an intracellular redistribution of the peroxidase activity among several distinct subcellular fractions prepared by differential centrifugation. Maximum redistribution occurred with granule-associated enzyme activity. A possible relationship between peroxidase activity with functional activity of lymphocytes and macrophages during humor immune responses seemed likely.
Antibody and cell-mediated immune responses were measured in rabbits immunized with live, UV inactivated herpes simplex virus or with a subunit vaccine containing envelope proteins. All the types of immunization procedures induced the production of antibody as well as a specific cellular immunity. Furthermore, the subunit vaccine was as effective as the immunization with live or UV inactivated virus to prevent death upon challenge with live HSV. Live HSV induced a transient unresponsiveness of both B and T cells to in vitro stimulation with various mitogens.
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.
We tested the ability of pepsin-extracted, highly purified M protein to induce type-specific immunity in experimental animals and humans. M protein was prepared from limited peptic digests of whole group A type 24 streptococci and was purified to chemical homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, quantitative amino acid analysis, and Edman degradation. For vaccination, the lyophilized M24 protein preparation (pep M24) was precipitated in aluminum hydroxide. When injected into laboratory animals, alum-precipitated pep M24 produced type-specific protective antibodies and was free of non-type-specific immunoreactivity. In man, skin tests with 1-microgram doses of pep M24 were negative in all 37 adults tested. 12 adult human volunteers received two-four subcutaneous injections of 100-200 micrograms of alum-precipitated pep M24 at intervals of at least 2 wk. The immune response to pep M24 was measured by a variety of assays designed to detect (a) type-specific humoral antibodies (opsonophagocytic, long chain, and mouse protection tests); (b) total humoral antibodies (complement fixation and enzyme-linked immunosorbent assay); (c) cellular immunity (skin tests); and (d) heart cross-reactive antibodies (immunofluorescence). Type-specific opsonic antibodies developed in 10 of the 12 vaccinees, and positive delayed-type skin tests developed in 11. Immune sera from two of the vaccinees were effective in mouse-protection tests against challenge with M24 but not M6 streptococci. None of the volunteers developed heart-reactive antibodies or antibodies to non-type-specific M protein antigens. Alum-precipitated pep M24 was well-tolerated in man, and no serious local or systemic reactions were observed. Thus, pep M24 induces type-specific, protective antibodies in doses that are well-tolerated in man.
Mice F1(CBA X C57BL/6) were immunized intraperitoneally with a single injection of L-1210 cells preincubated in interferon or control "false" preparation. CBA mice were injected with MX-11 cells: similarly treated according to the same scheme. Injection of interferon-treated cells was accompanied by the enhancement of the cellular immune response. The greatest cytotoxic activity was possessed by the lymphocytes of mice to which M-11 cells were administered together with interferon in which the cells were formerly incubated.
C57BL and CBA mice, with low or high reaction to immunization with sheep erythrocytes, respectively, were given transplantation of the syngenous lymphoid or bone marrow cells. Transplantation of the syngenous cells to C57BL mice intensified the production of antibody-forming cells to sheep erythrocytes and depressed it in transplantation to CBA mice. A different effect of transplantation of the lymphoid and bone marrow cells on the immune response, depending on the recipient's genotype, is discussed.
The primary antibody response of iron-deficient children to diphtheria and typhoid immunization was measured. In 5 children immunized with diphtheria toxoid, there was no increase in antitoxin titre. Of 8 children who were given typhoid vaccine, 6 showed an increase in Salmonella typhi O agglutinin titre. All the iron-deficient children had normal isohaemagglutinin titres.
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Exposure to alloantigen via the anterior chamber of the eye elicits a transient suppression of cellular immunity, whereas humoral immunity is preserved--i.e. F1 LI-ID. The majority of lymphoid cells inoculated into the anterior chamber are retained within the posterior segment of the eye. The latter serves as a depot of alloantigen, allowing the chronic egress of small numbers of cells into the vascular tree. The persistence of this antigen depot is essential to the development of F1 LI-ID. Since there is a preferential distribution of cells that migrate from the eye to the spleen, the functional integrity of the latter is also necessary to elicit F1 LI-ID. It is concluded that an anatomically intact spleen, i.v. presentation of antigen, and persistence of antigen within the eye are all important to the elicitation of this phenomenon.
The effects of Q acid-11, Q-7 and vitamin A palmitate on humoral immune response to two different types of antigens were examined. Particulate T-dependent antigen (SRBC) and T-independent antigen (DNP-Lys-Ficoll) were used to study the mode of action on immune system. Sodium-salt of Q acid-II (Q acid-11 Na) in the form of saline solution or water-in-oil emulsion showed suppressive effect on the direct and indirect PFC responses when administered simultaneously with SRBC. The suppressive effect of Q acid-II Na, however, was not observed when Q acid-II Na was administered two days before immunization. When Q acid-II Na was administered one day after immunization, the suppressive effect of Q acid-II Na was diminished and the level of PFC response was nearly equal to that of the control group. On the other hand, Q acid-II Na, Q-7 and vitamin A palmitate markedly enhanced the immune response to DNP-Lys-Ficoll (T-independent antigen). From the comparison of these humoral immune response, their modes of action are discussed.
The dynamics of the immune response to streptococcal extracellular antigens as measured by the streptozyme agglutination test have been defined in experimental animals andcompared with the dynamics of the immune response as determined by three established neutralization tests for streptococcal antibodies (ASO, anti-DNase B,and anti-NADase). In rabbits immunized with streptococcal extracellular Streptozyme-measured antibodies rose more quickly and peaked earlier than did antibodies to streptolysin O, streptococcal DNase-B, and streptococcal NADase. Additional studiesrevealed that the early peak was primarily due to 2-mercaptoethanol-sensitive (19S) antibody and that the later rise in Streptozyme-measured antibodies was due to 2-mercaptoethanol-resistant (7S) antibody. Preliminary observations using sucrose gradient ultracentrifugation tended to confirm this interpretation. These data provide a possible explanation for the early detection of a streptococcal antibody response by the Streptozyme test which has also been described in humans. The data suggest a theoretical advantage for the Streptozyme agglutination test in patients with streptococcal infections and their sequealae. However, the complexity of the Streptozyme reagent suggests that more extensive studies are needed to assure the consistent reproductivity of results with different lots of the test reagent.
The primary and secondary immune response to the antigen bovine pancreatic alpha-chymotrypsin was investigated in inbred mice. It was found that strain differences in the immune response only became apparent after secondary immunization. The genetic control of the immune response was investigated in twelve different strains of mice, F1, F2 and F1 backcross hybrids, following secondary immunization. A continuous distribution for the mean antibody responsiveness was obtained. High responsiveness was associated with both the H-2 haplotype and three non-H-2 loci. Furthermore the F1 hybrids produced a greater quantitative antibody response to chymotrypsin than either of the corresponding parental strains.
The present study describes the respiratory immune response of mice to locally administered antigen, and the modulation of this response by systemic immunization. Intranasal immunization of mice with the A/PR/8/34 strain of influenza virus evoked local antibody response of the IgA type. The titer of the IgA antibodies declined to a nondetectable level in 40--50 days. If at that time a second intranasal dose was administered, a secondary IgA response was evoked. On the other hand, administration by the intramuscular route resulted in a mixed population of IgA and IgG antibodies. The relevance of this finding to problems of immunization against respiratory viral infections is discussed.