Showing papers on "Immune system published in 1969"
TL;DR: Results of the present study suggest that natural immunity to meningococcal disease is initiated, reinforced, and broadened by intermittent carriage of different strains ofMeningococci throughout life.
Abstract: Results of the present study suggest that natural immunity to meningococcal disease is initiated, reinforced, and broadened by intermittent carriage of different strains of meningococci throughout life. In young adults, carriage of meningococci in the nasopharynx is an efficient process of immune sensitization. 92% of carriers of serogroup B, C, or Bo meningococci were found to develop increased titers of serum bactericidal activity to their own meningococcal isolate, and 87% developed bactericidal activity to heterologous strains of pathogenic meningococci. The rise in bactericidal titer occurred within 2 wk of onset of the carrier state, and was accompanied by an increase in titer of specific IgG, IgM, and IgA antibodies to meningococci. In early childhood, when few children have antibodies to pathogenic meningococci, active immunization seems to occur as a result of carriage of atypical, nonpathogenic strains. Immunity to systemic meningococcal infection among infants in the neonatal period is associated with the passive transfer of IgG antibodies from mother to fetus. The antigenic determinants which initiate the immune response to meningococci include the group-specific C polysaccharide, cross-reactive antigens, and type-specific antigens.
1,028 citations
TL;DR: It has been shown that the immune response of mice to infection with L. monocytogenes gives rise to a population of immunologically committed lymphoid cells which have the capacity to confer protection and a proportionate level of delayed-type hypersensitivity upon normal recipients.
Abstract: It has been shown that the immune response of mice to infection with L. monocytogenes gives rise to a population of immunologically committed lymphoid cells which have the capacity to confer protection and a proportionate level of delayed-type hypersensitivity upon normal recipients. The cells were most numerous in the spleen on the 6th or 7th day of infection, but persisted for at least 20 days. Further study revealed that the immune cells must be alive in order to confer protection, and free to multiply in the tissues of the recipient if they are to provide maximum resistance to a challenge infection. The antibacterial resistance conferred with immune lymphoid cells is not due to antibacterial antibody; it is mediated indirectly through the macrophages of the recipient. These become activated by a process which appears to depend upon some form of specific interaction between the immune lymphoid cells and the infecting organism. This was deduced from the finding that immune lymphoid cells from BCG-immunized donors, which were highly but nonspecifically resistant to Listeria, failed to protect normal recipients against a Listeria challenge unless the recipients were also injected with an eliciting dose of BCG. The peritoneal macrophages of animals so treated developed the morphology and microbicidal features of activated macrophages. It is inferred that acquired resistance depends upon the activation of host macrophages through a product resulting from specific interaction between sensitized lymphoid cells and the organism or or its antigenic products. Discussion is also made of the possibility that activation of macrophages could be dependent upon antigenic stimulation of macrophages sensitized by a cytophilic antibody.
914 citations
TL;DR: The findings suggest that hereditary MPO deficiency is transmitted as an autosomal recessive characteristic, that the homozygous state conveys enhanced susceptibility to disseminated candidiasis, and that MPO is necessary for candidacidal activity in human neutrophils.
Abstract: The neutrophils and monocytes of a patient with disseminated candidiasis were found to lack detectable levels of the lysosomal enzyme myeloperoxidase (MPO), although they had normal levels of other granule-associated enzymes. Leukocytes from one of the patient's sisters also lacked detectable MPO; leukocytes from his four sons contained approximately one-third of mean normal peroxidase levels. Neither the patient nor his affected relatives had experienced frequent or unusual bacterial infections.
The phagocytic activity of the patient's MPO-deficient neutrophils was intact, and the cells displayed normal morphologic and metabolic responses to phagocytosis. In contrast to normal leukocytes which killed 30.5±7.3% of ingested Candida albicans in 1 hr, however, the patient's neutrophils killed virtually none. His leukocytes also failed to kill the strain of C. albicans recovered from his lesions, as well as other Candida species. These MPO-deficient neutrophils killed Serratia marcescens and Staphylococens aureus 502A at an abnormally slow rate, requiring 3-4 hr to achieve the bactericidal effect attained by normal leukocytes after 45 min. No other abnormalities in his cellular or humoral immune responses were demonstrated.
These findings suggest that hereditary MPO deficiency is transmitted as an autosomal recessive characteristic, that the homozygous state conveys enhanced susceptibility to disseminated candidiasis, and that MPO is necessary for candidacidal activity in human neutrophils. Although lending support to the suggested bactericidal role of MPO in leukocytes, the data indicate that alternative bactericidal mechanisms, effective in the absence of MPO, are functionally dominant in the human neutrophil.
657 citations
TL;DR: A review of the recent important findings concerning "immune response genes" to antigenic determinants of different amino acids can be found in this article, where the authors discuss the genetic control of specific immune responses.
Abstract: Publisher Summary This chapter discusses the genetic control of specific immune responses. The chapter reviews the recent important findings concerning “immune response genes” to antigenic determinants of different amino acids. The immune response to a specific antigen is a complex process that must involve genetic control at various levels. The fact that genetic factors are involved in the response to antigenic stimulus has long been known. The use of synthetic polypeptide antigens played a major role in elucidating the multiple genes that are described in the chapter. The intriguing question of at what level in the immune response these genes act remain to be determined. Genetic and structural analysis of normal immunoglobulins, myeloma proteins, and antibodies has produced a great deal of information about the genetic basis of antibody structure but has not yet given a clear picture of the genetic basis of antibody specificity. Structural analysis of myeloma proteins has led to a similar conclusion for the human and mouse light chain. The chapter summarizes the characteristic features common to the various genetic systems and analyzes the functions controlled by “immune response genes.”
608 citations
TL;DR: The study of the various pathways by which lymphoid cells can become cytotoxic has been helpful for the understanding of effector role of these cells in cell-destructive reactions in general.
Abstract: Publisher Summary This chapter discusses the cytotoxic effects of lymphoid cells in vitro. The chapter discusses the complex problem of different types of cytotoxic effects of lymphoid cells. These outstanding workers in the field have managed to present a cohesive picture of the various effects on the target cells. The role of “nonspecific” factors is particularly well clarified. The interrelationships among contact lysis, release of pharmacologically active substances, and the terminal components of the complement system are given in the chapter for special consideration. In an in vitro model, it is shown that lymphoid cells from sensitized donors destroy tissue culture cells carrying the antigen to which the cell donor is sensitized. This type of cytolytic reactions is encountered in a great variety of immune situations, comprising all those mentioned in the chapter. The cell that initiates in vitro cytotoxic reaction is assumed to be the sensitized lymphocyte, equipped with its own recognition sites for antigen on the cells that are destroyed. Although this may be true in many situations, it now seems clear that “normal” lymphoid cells can become cytotoxic to other cells by a variety of pathways. The study of the various pathways by which lymphoid cells can become cytotoxic has been helpful for the understanding of effector role of these cells in cell-destructive reactions in general.
581 citations
TL;DR: This chapter discusses the essential features of the antibody with respect to the interaction of antigen with preformed, cell-bound, antibody-like receptors and describes certain basic phenomena that are characteristic of the immune response and analyze their mechanism at both the cellular and the molecular levels.
Abstract: Publisher Summary This chapter discusses the essential features of the antibody with respect to the interaction of antigen with preformed, cell-bound, antibody-like receptors. The effect of this interaction on individual cells is determined by the affinity of the antigen cell-bound antibody combination and results in the recruitment or selection of cells and their activation. The chapter also describes certain basic phenomena that are characteristic of the immune response and analyzes their mechanism at both the cellular and the molecular levels. These phenomena are an attempt to formulate a unified concept of the immune response as an antigen-driven proliferation and selection of specific cells that are committed to the synthesis of specific immunoglobulin molecules prior to the contact with antigen. This process, describable in thermodynamic terms, is the central biological event that can explain or predict such features of the antibody response as the progressive increase in average binding affinity of antibody produced, the effect of antigen dose on amount and affinity of antibody, the mechanism of action of adjuvants, the essential role of specific cell proliferation stimulated by antigen, the interference of humoral antibody with antigenic selection of cells, the phenomenon of “original antigenic sin,” and the induction of tolerance.
524 citations
TL;DR: The demonstration of cellular immunity to TSTA implies that autochthonous neoplasms appear in the presence of immune lymph node cells, which can destroy their cells at least in vitro .
Abstract: Publisher Summary This chapter summarizes the evidence that tumors possess tumor-specific transplantation antigens (TSTA). Virtually all animal neoplasms contain TSTA. Immune reactions against the specific antigens of syngeneic tumors are similar to allograft reactions by which transplanted normal and tumor cells are rejected if they contain isoantigens that are foreign to the recipients. They are to a large extent mediated by immunologically competent cells—that is, lymphocytes and macrophages. The chapter describes several techniques by which cellular immunity to transplantation antigens can be demonstrated, along with a review of different systems in which such techniques were used to detect lymphocyte-mediated immune reactions to TSTA. TSTA are macromolecules present in tumor cells and absent in the normal cells of the same individual and against which immune reactions can be demonstrated with transplantation techniques. The transplantation methods used to demonstrate TSTA can involve the immunization of recipient animals with tumor cells that have been rendered incapable of multiplication (X-irradiation) or that are inoculated in subthreshold doses. Immunization can be also achieved by the inoculation of living tumor cells and excision of the subsequent tumor nodule. The possible role of cellular immunity to TSTA is also discussed in the chapter. The demonstration of cellular immunity to TSTA implies that autochthonous neoplasms appear in the presence of immune lymph node cells, which can destroy their cells at least in vitro . The chapter reviews the phenomenon of allogeneic inhibition. This phenomenon has been postulated to operate in parallel to the immunological mechanisms as part of the organism's defense against antigenic neoplastic cells.
449 citations
Book•
01 Jan 1969
TL;DR: A chronology of veterinary dermatology (1900-1998) can be found in this paper, where the authors describe the structure and function of the skin diagnostic methods dermatologic therapy bacterial skin diseases fungal skin diseases parasitic skin diseases viral, rickettsial, and protazoal skin diseases skin immune system and allergic skin diseases immune-mediated disorders endocrine and metabolic diseases acquired alopecias congenital and hereditary defects pigmentary abnormalities keratinization defects psychogenic skin diseases environmental skin diseases nutritional skin diseases miscellaneous skin diseases diseases of eyelids, claws, anal sacs
Abstract: Structure and function of the skin diagnostic methods dermatologic therapy bacterial skin diseases fungal skin diseases parasitic skin diseases viral, rickettsial, and protazoal skin diseases skin immune system and allergic skin diseases immune-mediated disorders endocrine and metabolic diseases acquired alopecias congenital and hereditary defects pigmentary abnormalities keratinization defects psychogenic skin diseases environmental skin diseases nutritional skin diseases miscellaneous skin diseases diseases of eyelids, claws, anal sacs, and ears neoplastic and non-neoplastic tumors dermatoses of pet rodents, rabbits and ferrets chronology of veterinary dermatology (1900-1998).
413 citations
TL;DR: The immune responses of inbred mice to a related series of three synthetic polypeptide antigens are genetically controlled traits which are closely correlated with the genotype for the major histocompatibility (H-2) locus.
Abstract: The immune responses of inbred mice to a related series of three synthetic polypeptide antigens are genetically controlled traits which are closely correlated with the genotype for the major histocompatibility (H-2) locus. All strains of the same H-2 type exhibit the same pattern of immune response, independent of the remainder of a given strain's genetic background. There is marked antigen-specific polymorphism between strains of different H-2 types with respect to their patterns of response.
400 citations
TL;DR: The cooperative function of T-lymphoblasts would account for the relationship often observed between delayed hypersensitivity and humoral-antibody formation, and for the occurrence of allergen-induced blastcell transformation of lymphocytes from allergic patients with anaphylactic - type hypersensitivity.
342 citations
TL;DR: Results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody.
Abstract: Glass and plastic bead columns coated with antigenic protein molecules were used as an immunological filter for cell populations containing immune cells of relevant specificity. A selective elimination of these immune cells from the passing cell suspension was regularly noted and it approached, in some experiments, complete abolition of the specific immune reactivity of the filtered cell population. This specific retention of immune cells by antigenic columns could be selectively blocked by the presence of free antigen molecules in the medium during filtration. The results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody. Using the present bead column system, results were obtained indicating that this receptor was an active product of the immune cells and not any passively adsorbed, cytophilic antibody. Antigenic bead columns may very well constitute a tool for the production in vitro of cell populations being specifically deprived of immune reactivity and allow detailed analysis of the characteristics of the cell-associated antibody of immune cells.
TL;DR: The quantity of interferon produced by antigen stimulation was related to concentration of antigen over a relatively narrow range; with higher concentrations induction was decreased, and phytohemagglutinin-induced Interferon was primarily produced during the first 4 days in culture.
Abstract: Human blood lymphocytes stimulated with nonviral antigens in vitro produce an antiviral substance with the biological and biochemical characteristics of interferon. The induced response was specific for cells obtained from immune donors. Cells from nonimmune donors did not produce interferon on exposure to these substances. The quantity of interferon produced by antigen stimulation was related to concentration of antigen over a relatively narrow range; with higher concentrations induction was decreased. Interferon production was maximum during days 4 to 7 in culture. In contrast, phytohemagglutinin-induced interferon was primarily produced during the first 4 days in culture.
TL;DR: It was found that sera from hosts with progressively growing neoplasms could abrogate the inhibitory effect of lymphocytes which were immune to the specific antigens of the corresponding tumor type.
Abstract: The combined effect of immune lymphocytes (lymphnode cells or blood lymphocytes) and serum from tumor-bearing donors was assessed in four tumor systems with the use of the colony inhibition assay: (a) Moloney virus-induced sarcomas in mice, (b) Shope papillomas in rabbits, (c) spontaneous mammary carcinomas in mice, and (d) two adenocarcinomas of the colon and two adenocarcinomas of the lung in humans. The neoplasms studied had previously been shown to possess tumor-specific antigens, against which cellular immunity could be detected in vitro. In all four systems, it was found that sera from hosts with progressively growing neoplasms could abrogate the inhibitory effect of lymphocytes which were immune to the specific antigens of the corresponding tumor type. Studies with Moloney sarcomas, in particular, showed that the serum effect had at least some degree of specificity.
TL;DR: This chapter discusses the immunology of schistosomiasis, where much work has concerned the immunopathology of the disease, particularly granuloma formation, and a number of in vitro systems have been described in which antibodies and cells combine to damage and kill young schistsomules.
Abstract: Publisher Summary This chapter discusses the immunology of schistosomiasis. The only developments relating to innate immunity refer to the death of cercariae in the skin. Concomitant immunity has been shown to operate in a number of experimental systems, and there are encouraging reports that it may operate in human infections. A good deal of circumstantial evidence implicates host antigens as playing a role in concomitant immunity, but more direct evidence is needed to show that they indeed serve to protect the mature parasite from immune attack. The use of small animals, particularly those where syngeneic strains are available and in vitro cultivation, has increased the understanding of the immune mechanisms. In particular, a number of in vitro systems have been described in which antibodies and cells combine to damage and kill young schistosomules. It is essential to determine whether the differences described for these several systems truly reflect a multiplicity of host responses or merely represent differences in technical approach to a single system. Much work has concerned the immunopathology of the disease, particularly granuloma formation. Although the granuloma contributes significantly to the pathology, it does seem to protect the host liver from the toxic secretion of the egg. A number of approaches for the immunological control of schistosomiasis are currently under investigation, including the use of live cercariae and schistosomules and the use of more or less purified antigens.
TL;DR: The ability of antigen-reactive cells to react with antigen was immunologically significant and they were distinguished from cells present because of a prior experience of the animal with a related antigen.
Abstract: A QUESTION of current interest is whether the initial stages of an immune response—either the induction of antibody formation or of specific tolerance—may involve the reaction of an antigen with a specific lymphocyte. Naor and Sulitzeanu1 have demonstrated, both in vivo and in vitro, a reaction of 125I-labelled bovine serum albumin with a small proportion (about 1/5,000) of mouse spleen lymphocytes. We have since shown2 that both flagellin and polymerized flagellin (Salmonella adelaide) and haemocyanin (Jasus lalandii) labelled with 125I or 131I react in vitro with certain cells from spleens of rats and mice. Of the strongly reactive cells, almost all are mononuclear with a high nuclear/cytoplasmic ratio and 7–12 microns in diameter and, for any one antigen, comprise about 1/5,000 of the total cell population. These reactive cells adsorb between 4,000–40,000 molecules of labelled protein when allowed to react at 0° C with labelled protein (about 3 × 1012 molecules/ml.) in 10 per cent foetal calf serum. A similar proportion of such reactive cells was observed in cell suspensions from lymph nodes and thoracic duct lymph, while peritoneal exudate contained a higher proportion and thymus a lower proportion of these cells2. The reaction was not inhibited by concentrations of sodium azide which restricted the uptake of labelled antigen by macrophages but was inhibited, using mouse cells, by rabbit anti-mouse globulin serum. Spleen cells from germ-free and conventional mice reacted equally well with 131I-labelled flagellin2. We wished to know whether the ability of these cells to react with antigen was immunologically significant. Experiments were devised to distinguish between the following possibilities: that the reactive cells were (1) cells present because of a prior experience of the animal with a related antigen, (2) antigen-reactive cells3,4 which had not had prior antigenic experience but which were capable of contributing to a specific immune response such as formation and secretion of antibody, and (3) cells coated non-specifically with cytophilic antibody.
TL;DR: This paper has attempted to summarize what is known about immunity to schistosomiasis in man and in experimental animals, and paid particular attention to the rhesus monkey, in which the stimulus to acquired immunity is defined more clearly.
Abstract: After some 20 years of international research in immunity to schistosomiasis, our knowledge of the mechanism of resistance to this disease remains largely unknown, and the possibility of a rational progress toward control by immunological methods is still remote. Nevertheless, it is important that work in this field be fully supported. An understanding of the immunology of schistosomiasis means an understanding of one vital aspect of the host/parasite relationship. Findings and interpretations in this field will have a strong influence on many practical aspects of controlling the disease, especially on future approaches to chemotherapy. In this paper we have attempted to summarize what is known about immunity to schistosomiasis in man and in experimental animals. Particular attention has been paid to the rhesus monkey, in which we have defined more clearly the stimulus to acquired immunity. We have speculated about the mechanism that enables the adult worms t o survive for long periods without being affected by the immune response. Finally, we have attempted, as far as we can, to relate our findings in the rhesus to man.
TL;DR: Mouse spleen cells were found to associate in cell clusters during the primary immune response to sheep erythrocytes in vitro, and the integrity of cell clusters was required for the proliferation of antibody-forming cells, and prevention of clusters by mechanical means or by excess antibody blocked the immune response.
Abstract: Mouse spleen cells were found to associate in cell clusters during the primary immune response to sheep erythrocytes in vitro. About 10% of the cell clusters had the following unique properties; (a) they contained most, if not all, antibody-forming cells, (b) they contained only cells forming antibody to one antigen when cell cultures were immunized with two antigens, (c) the cells in clusters reaggregated specifically after dispersion, and (d) the specific reaggregation of clusters appeared to be blocked by antibody to the antigen. The integrity of cell clusters was required for the proliferation of antibody-forming cells, and prevention of clustering by mechanical means or by excess antibody blocked the immune response. Antibody and antigenic determinants on the surfaces of cells probably provide the basis for interaction. The unique microenvironment of cell clusters was essential for the primary immune response in vitro.
TL;DR: The results suggest that double-stranded RNA functions as a potent antigen in New Zealand mice, and a similar pathogenetic mechanism may be operative in some humans with systemic lupus erythematosus.
Abstract: Antibodies to DNA and RNA were induced in young NZB/NZW F(1) (B/W) female mice following multiple injections of the interferon-inducer polyinosinic.polycytidylic acid (poly I.poly C). Despite serum concentrations of interferon adequate to inhibit the C-type murine leukemia viruses, there was an acceleration of the autoimmune disease in these animals. Anti-RNA, but not anti-DNA antibodies, were induced in B/W male mice, as well as in NZB and NZW mice. Anti-RNA antibodies were also found in 50 per cent of female B/W mice who had never received poly I.poly C and in 8 of 24 sera from patients with systemic lupus erythematosus. These results suggest that double-stranded RNA functions as a potent antigen in New Zealand mice. Naturally occurring nucleic acids (e.g., viruses) probably act as stimuli to a genetically hyperreactive immune system. According to this hypothesis, the unusual feature in this disease is not a unique virus, but rather the unique genetic susceptibility of the B/W (particularly female) host to immunization with nucleic acids. A similar pathogenetic mechanism may be operative in some humans with systemic lupus erythematosus.
TL;DR: The aim was to determine whether a strict strain and species specificity occurs in animals vaccinated with sporozoites, or if a much broader spectrum of protective immunity develops.
Abstract: VACCINATION against malarial infections remains a goal to be achieved. Even if it were feasible, it might be difficult to obtain necessary amounts of the parasitic antigen, and only homologous species or strains of the parasite may be immunologically effective. Protective immunity is often a highly strain specific phenomenon as has been shown in experiments using the blood stages of the parasite as the immunizing agent1,2. Strain specificity of the immune response also occurs in natural human malaria3. Our aim was to determine whether a strict strain and species specificity occurs in animals vaccinated with sporozoites, or if a much broader spectrum of protective immunity develops.
Journal Article•
TL;DR: The conclusion may be drawn that the retention of small quantities of antigen by macrophages plays an essential role in some, but probably not all types of immune response.
Abstract: The immunogenic capacity of protein antigens has been compared for the free and peritoneal exudate cell (PEC)-bound forms. The response of CBA mice to BSA provides the reference system, but lysozyme, ovalbumin, HSA and modified BSA were also studied. Uptake is approximately equally efficient in vivo and in vitro. PEC-bound antigen, estimated by radioactivity is far more potent than the free form in inducing primary immunization. The following properties were also found: (i) viable PEC are required; (ii) irradiation of the cell donor 2–7 days before giving antigen inhibits immunization, but irradiation after uptake does not do so; (iii) mice are susceptible to immunization during their phase of recovery from paralysis; (iv) PEC do not retain large amounts of antigen for long; (v) the activity does not depend solely on a minor, phagocytosisprone fraction of the antigen; (vi) allogeneic transfer of PEC reduces their immunogenic capacity; (vii) paralysed hosts are not susceptible to immunization, but PEC from paralysed donors are effective; and (viii) the enhancement of immunogenic capacity does not apply to the secondary response. The conclusion may be drawn that the retention of small quantities of antigen by macrophages plays an essential role in some, but probably not all types of immune response.
TL;DR: Investigation of the immunological reactions of Gambians constantly exposed to infection with Plasmodium falciparum malaria found that antigens are probably derived from the malaria parasite, but red-blood-cell antIGens may also be involved.
Journal Article•
TL;DR: The kinetics of the antibody response to purified pneumococcal polysaccharides was studied at the cellular level using the technique of localized hemolysis-in-gel in conjunction with erythrocytes sensitized with immunizing antigen, suggesting that direct plaque-forming cells may represent only 30% to 50% of the total number of antibody-formed cells produced following immunization.
Abstract: The kinetics of the antibody response to purified pneumococcal polysaccharides was studied at the cellular level using the technique of localized hemolysis-in-gel in conjunction with erythrocytes sensitized with immunizing antigen. The overall pattern of the antibody response was similar, with respect to the number of direct plaqueforming cells produced, to that reported for other antigens. However, using antisera specific for various classes of mouse immunoglobulins to characterize the types of specific plaque-forming cells produced, it appears that the antibody response to pneumococcal polysaccharides is exclusively macroglobulin in nature; two types of macroglobulin antibodies, differentiated on the basis of their efficiency in participating in immune hemolysis, are produced. The data suggest that direct plaque-forming cells may represent only 30% to 50% of the total number of antibody-forming cells produced following immunization.
TL;DR: Defective cellular immunity, both in vivo and in vitro, were identified in an 11-year-old patient with chronic mucocutaneous candidiasis and the defect appears to be genetic, as there are other affected members in the family.
TL;DR: It is reported that in the case of tuberculin hypersensitivity in mice, guinea-pigs and man, non-specific toxic materials are released when the cells are cultured in the presence of specific antigen.
Abstract: ALLOGRAFT immunity and delayed hypersensitivity reactions are caused chiefly by the action of host immune lymphoid cells1. Although these reactions have been much studied in vivo and in vitro, the mechanism of cell destruction is essentially unknown. There have been reports from this laboratory that a cell-free toxic factor released by immune and phytohaemagglutinin (PHA)-stimulated non-immune mouse lymphocytes is essential in the in vitro destruction of target L cells2. This factor, termed lymphotoxin (LT), caused in vitro cytolysis of both continuous and primary cells obtained from many animal species3. Later work showed that lymphocytes from various animal species, including man, could be stimulated in vitro to release LT, in the absence of target cells, by treatments which induce lymphocyte transformation, that is the mixed lymphocyte reaction, PHA and xenogeneic antibody4. It was therefore of interest to investigate whether lymphoid cells obtained from animals with delayed hypersensitivity to soluble antigens could be induced in vitro to release LT-like materials. We wish to report here that in the case of tuberculin hypersensitivity in mice, guinea-pigs and man, non-specific toxic materials are released when the cells are cultured in the presence of specific antigen.
Journal Article•
TL;DR: In the system employed, adjuvants were shown to exert their enhancing effects on antibody-producing cells only after uptake by macrophages, and adjuvant action did not require the presence of antigen and adjuvant in the same macrophage.
Abstract: Bordetella pertussis vaccine or beryllium sulfate proved to be potent adjuvants in increasing the antibody response to Maia squinado hemocyanin in mice Antigen-containing macrophages treated with B pertussis in vitro elicited much higher antibody titers when injected into mice than they did in the absence of the adjuvant Lymph node cells treated in vitro with adjuvants and injected into irradiated mice gave the same antibody titers as they did in the absence of adjuvants Hence in the system employed, adjuvants were shown to exert their enhancing effects on antibody-producing cells only after uptake by macrophages Adjuvant-treated macrophages injected simultaneously with antigen-containing macrophages also led to increases in the immune response; thus adjuvant action did not require the presence of antigen and adjuvant in the same macrophage The overall catabolism and retention of 131 I-labeled hemocyanin in macrophages was not significantly altered in the presence of adjuvants
TL;DR: Four lines of evidence indicated that the suppression of anti-Listeria resistance with ALG depends upon destruction of immune lymphoid cells and not to any action it has on host macrophages, inferring that immunity to L. monocytogenes depends upon a two cell system in which the donor lymphoids cells provide the immunological reactivity to the organism and recipient macrophage provide the mechanism through which resistance is expressed.
Abstract: The specificity of anti-lymphocyte globulin (ALG) has been used to analyze an immune mechanism which is mediated by immunologically committed lymphoid cells to the apparent exclusion of humoral antibody. Rabbit antimouse lymphocyte globulin completely suppressed the immunity which can be passively transferred with Listeria-immune lymphoid cells from actively infected donors. When prospective donors were given a single dose of 1.0 mg of ALG, it remained active against immune lymphoid cells transferred 24 hr later; yet immune cells in the spleens of donors could not be inactivated in situ by even larger doses of ALG given 24 hr prior to cell harvest. In keeping with this finding, the immunity to reinfection with Listeria was not suppressed by a single dose of ALG, indicating that the immunologically active cells in the spleen are not accessible to intravenously administered ALG. On the other hand, protracted treatment with ALG did abolish most of the memory of a previous infection in intact animals. From this and other evidence, it was concluded that immunologically committed cells are vulnerable to attack by ALG only if they circulate. While in circulation, they make contact both with ALG and the phagocytic elements of the reticuloendothelial system which appear to be responsible for their destruction. Four lines of evidence indicated that the suppression of anti-Listeria resistance with ALG depends upon destruction of immune lymphoid cells and not to any action it has on host macrophages. It is possible to infer from this that immunity to L. monocytogenes depends upon a two cell system in which the donor lymphoid cells provide the immunological reactivity to the organism and recipient macrophages provide the mechanism through which resistance is expressed. Accompanying papers provide additional support for this view, and reasons for believing that delayed-type hypersensitivity and acquired cellular resistance are mediated by the same population of immunologically committed lymphoid cells.
TL;DR: In contrast to an undetectable immune response to bovine serum albumin (BSA) in infants not fed the antigen, 63 per cent of the infants fed BSA were immunized against this antigen.
TL;DR: It was found, that immunological tolerance may be induced to a significant degree in vitro within a period of 15 min, suggestive evidence that the initial step in tolerance induction is related to the direct interaction between the surface of immune competent cells and antigen molecules.
Abstract: When normal mouse spleen, cells in suspension are cultured in vitro in the presence of polymer from S. adelaide flagellin, an immune response can be obtained as measured at the level of single antibody-forming cells. Cultures were stimulated with different doses of antigen, ranging from 0.2 ng to 3 µg/ml of tissue culture fluid and it was found that the peak number of approximately 500 antibody-forming cells per 106 harvested cells by day 4 was antigen dose dependent, 2–20 ng/ml being the optimal concentration. When more than 1 µg/ml of polymer from S. adelaide together with either 20 ng/ml of polymer from S. waycross or with 4 x 106 sheep erythrocytes were placed in the system, unresponsiveness to S. adelaide, but immunity to the other antigens occurred simultaneously. Cells made immunologically tolerant in vitro to S. adelaide H antigens were transferred into syngeneic lethally irradiated recipients and challenged with the same antigen. The adoptive immune capacity in these mice, as measured at the level of the immunologically competent cell was reduced by 80–90% as compared with relevant controls. Attempts to induce low zone tolerance in vitro were without success. To study the kinetics of tolerance induction in vitro, cells were cultured with tolerogenic doses of antigen for various periods of time, washed, and subsequently cultured with immunogenic doses of antigen for 4 days. It was found, that immunological tolerance may be induced to a significant degree in vitro within a period of 15 min. Similar results were obtained when spleen cells were exposed for various lengths of time to tolerogenic doses of antigen but at a temperature of 4°C instead of 37°C. The results are taken as suggestive evidence that the initial step in tolerance induction is related to the direct interaction between the surface of immune competent cells and antigen molecules.
TL;DR: Serial tests for long-acting thyroid stimulator (LATS) and antithyroglobulin antibodies were performed in 32 patients with toxic diffuse goiter submitted to 131I therapy and in 29 patients receiving antithYroid drugs.
Abstract: Serial tests for long-acting thyroid stimulator (LATS) and antithyroglobulin antibodies were performed in 32 patients with toxic diffuse goiter submitted to 131I therapy and in 29 patients receiving antithyroid drugs. The level of detectable LATS and the incidence of positive assays tended to increase transiently following 131I therapy and to decrease during the administration of antithyroid drugs. Statistical analysis of the LATS changes detected at the time interval of 46–180 days after treatment showed that the differences between the 2 therapeutic groups were significant. A transient rise of circulating antithyroglobulin antibodies occurred in several patients treated with radioiodine, but individual changes showed no parallelism with the course of LATS. No definite pattern was noted in the behavior of antithyroglobulin antibodies during the administration of antithyroid drugs. Twentysix patients with toxic adenoma previously treated with radioiodine and 26 untreated controls were tested for ...
TL;DR: Four drugs, representing four different categories of cytotoxic agents, were studied for their effect on the immune response to Listeria infection in mice, offering a useful means of assessing the immunosuppressive activity of drugs and of determining the time-course of their action.
Abstract: Four drugs, representing four different categories of cytotoxic agents, were studied for their effect on the immune response to Listeria infection in mice. The development of the host's immune response is revealed by a progressive change in the slope of the bacterial growth curve in spleen and liver. It has its onset at 24 hr in untreated mice, but in the presence of effective immunosuppression the organism multiples uninterruptedly until the animal dies from overwhelming infection. When administered as single injections at the time of infection, cyclophosphamide, vinblastine, and azathioprine all produced an effective immunosuppression, characterized by continuous bacterial multiplication. Methotrexate was also immunosuppressive, but unlike the others its effects were reversible. They could be sustained, however, by further treatment. Studies of the time-response relationship indicated that cyclophosphamide was highly active over a broad time-span ranging from 2 days before infection to 4 days after infection. Vinblastine on the other hand was maximally active when given on the day of infection, while methotrexate had its greatest effect when given 48 hr after infection. These differences indicate that these three drugs act on different cell populations involved in the host's immune response. The effects observed have been discussed in relation to what is known of the modes of action of the drugs tested. An observation of interest was the phenomenon of enhanced immunity in animals treated with cyclophosphamide or vinblastine 7–11 days before, and with methotrexate 4 days before infection; reactive hyperplasia of lymphoid tissue following withdrawal of drug was again advanced as an explanation for the occurrence of this paradoxical effect. The experimental model employed is simple, requiring only routine bacteriological facilities and minimal equipment. It seems to offer a useful means of assessing the immunosuppressive activity of drugs and of determining the time-course of their action; it could also be of value in the screening of anticancer agents.