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The article presents a list of words used in several papers published in the December 1974 issue of the periodical "Clinical and Experimental Immunology." Some of the words are agglutinins, allogenic cells, antibodies, cold, cross idiotypic specificity, heterophilic, malarial infection, antigens, smooth muscles, hepatitis B, hyposensitization of mast cells, lymphokines, peripheral blood, T-cells, B-Cells, hookworms, immune response, immunity, cystic fibrosis, immunofluorescence, leprosy, leucocytes migration and leukemia,

This paper describes further confirmation of the successful application of the macrophage electrophoretic mobility (MEM) test to the detection of malignant disease. Results from fifty-one patients and eighteen controls are presented. The apparatus and technique used for the measurement of macrophage elctrophoretic mobility differed from those previously used in other investigations. Further information is presented on the nature and behaviour of macrophage slowing factor(s), and experiments concerning the possible use of cells other than guinea-pig macrophages as indicators of slowing factor production are also described. [ABSTRACT FROM AUTHOR]

Mitogen-transformed human peripheral blood lymphocytes and tonsil blasts were examined by rosette formation to detect the presence of membrane-bound immunoglobulin (Ig) and surface receptors for fixed IgG and fixed C3. In addition, the capacity of these cells to rosette with sheep erythrocytes was evaluated as a reaction characteristic of T lymphocytes. In order for clear morphological recognition of the rosetting transformed lymphocytes and the rosetting tonsil blasts a cytocentrifuge technique was developed and used in conjunction with autoradiography and/or with Romanowsky stains. Using these techniques and the culture methods described in this paper phytohaemagglutinin, pokeweed mitogen, streptococcal filtrates and purified protein derivative stimulated predominantly T cells in the peripheral blood of man. A minority of the transformed cells in these mitogen-stimulated cultures (<24%) did rosette with B lymphocyte markers and presumably represent a B-cell response. No significant differences were found between the T- or B-cell specificity of the mitogens investigated. Lymphoid preparations from tonsils excised from normal donors with recurrent tonsillitis were found to contain 6-15% lymphoblasts and the iarge majority of these cells formed rosettes with the B-cell markers, less than 20% of these lymphoblasts formed spontaneous sheep erythrocyte rosettes. Using a mixed rosetting technique a small proportion (<5%) of PHA-transformed cells and tonsil lymphoblasts were found to have combined sheep Fc or combined sheep C3 receptors. The investigation of B- and T-lymphocyte surface markers on mitogentransformed lymphocytes was extended to neopiastic lymphocyte populations and it was found that the majority of transformed cells (>70%) present in chronic lymphocytic leukaemia cultures stimulated with PHA after 6 days incubation were transformed T lymphocytes. [ABSTRACT FROM AUTHOR]

This paper confirms results showing that TA3 tumour cells coated in vivo with immunoglobulins, lose some of the coat upon transfer to in vitro conditions. By labelling IgG isolated from the ascitic fluid of TA3 tumours it was found that the immunoglobulin coating TA3 cells is dynamically exchanged with immunoglobulin in the corresponding ascitic fluid. Some of the released immunoglobulin is in a degraded state as judged from the fact that most of the released material lost the antigenicity of intact immunoglobulin and has a lower capacity to precipitate with ammonium sulphate at 50% saturation. The degraded immunoglobulin has a higher binding efficiency to tumour cells. In vivo experiments demonstrated that the ascitic fluid of mice bearing TA3 and MCIM tumours contains a material which has some of the physicochemical properties of IgG but which does not precipitate with antisera directed aguinst IgG. [ABSTRACT FROM AUTHOR]

Evidence is provided which supports the concept that a previously characterized monoclonal IgA-λ rheumatoid factor with a medium-binding avidity reacts with a select Fc region antigenic determinant. The interaction between this rheumatoid factor and anti-Rh-coated human erythrocytes is inhibited by IgG1 Fc fragment, IgG1 heavy chains, and a single peptide pool isolated from this tryptic digest by paper chromatography. Cyanogen bromide cleavage of the isolated heavy chains abolishes this reactivity. A methionine residue is assumed to be near, involved in, or necessary for reactivity between the IgA and its antigenic determinant. The data thus provide further evidence for a specific autoantigenic, rheumatoid factor-reactive determinant. [ABSTRACT FROM AUTHOR]

The role of the spleen in humoral antibody formation and in the pathogenesis of immune thyroiditis was studied by splenectomizing four monkeys (Macaca mulatta) prior to thyroid isoimmunization. Splenectomized animals, as well as intact controls, were subjected to sequential immunizations and the course of the immune disease was followed by periodic thyroid biopsies and frequent humoral antibody measurements over a period exceeding 1 yr. Extirpation of the secondary lymphoid organ markedly inhibited agglutinating antibody response, prevented formation of complement-fixing antibodies, but had no effect on thyrocytotoxic antibodies. In animals subjected to immunization in complete adjuvant a trend towards a decrease in serum complement levels was evident at the terminal stages of the experiments. Despite the inhibitory effects on some immunological parameters, splenectomy in monkeys prior to thyroid isoimmunization did not interfere with the initiation and progression of pathological processes in the thyroid. Indeed in all splenectomized animals immunized with thyroid plus complete adjuvant, fibrotic thyroid lesions (4+) with virtual obliteration of thyroid follicles were evident, in some as early as 120 days after primary immunization; in contrast, non-fibrotic and less severe lesions were noted in the intact animal despite being repeatedly subjected to similar immunization procedures over a period of 340 days. Immunization in the absence of complete adjuvant did not induce thyroid lesions in the presence or absence of spleen. In all animals with severe thyroid lesions, thyroid function decreased as revealed by T4 and 131I-T3 resin uptake measurements. Paper electrophoresis of serum specimens from a monkey subjected to thyroid isoimmunization in complete adjuvant (and after equilibration with 125I-T4) showed a pronounced retention of 125I-T4 radioactivity at the gamma globulin region indicating formation of antibodies to thyroxine. On the other hand, in sera with a low thyroid antibody titre as in splenectomized monkeys or in those animals immunized within complete adjuvant, T4-binding antibodies were not evident. It is concluded that removal of the spleen prior to thyroid isoimmunization in monkeys, rather than inhibiting the severity of the disease may even aid and abet immunopathogenic events destructive to the thyroid. [ABSTRACT FROM AUTHOR]

This paper describes the course of infection and certain pathological changes in thymus-deprived and normal CBA mice after oral infection with Trichinella spiralis. Greater morbidity was found among deprived mice and deaths due to trichiniasis occurred solely in this group. The local inflammatory response in the gut and skeletal muscles was defective in deprived animals: compared to normal mice it was slower to develop, contained fewer cells and was inadequately sustained. There was a striking paucity of tissue eosinophils and this was correlated with failure of deprived mice to develop a blood eosinophilia. The parasites appeared to persist longer in the gut of deprived animals and progressively more parasites were recovered from the carcasses of these mice at later stages of the infection. The present findings indicate that thymus-dependent cell populations are implicated in the host response to T. spiralis; and some possible modes of action of T cells are discussed. [ABSTRACT FROM AUTHOR]

In this paper we present in detail the very rapid and sensitive Millipore filter assay technique for measuring tritiated thymidine incorporation during semiconservativé DNA synthesis in human peripheral blood leucocyte cultures. Leucocytes which have been incubated with tritiated thymidine are trapped on a Millipore filter which is then suitably washed and dried. The filter is then immersed in scintillation fluid in a double-vial apparatus designed to ensure a reproducible counting geometry. Alternatively, the filter and its radioactive contents can be combusted to tritiated water, the radioactivity of which is then determined in a homogeneous counting system. The parameters related to the Miilipore filter assay technique are presented, and its present uses and general applicability discussed. [ABSTRACT FROM AUTHOR]

Two liver-specific antigens are known: a water soluble protein (LP-2) and a water insoluble macromolecular low density lipoprotein (LP-1). In this paper the relative role of the two antigens in the development of experimental immune hepatitis has been investigated. Immunization of rabbits with a human preparation containing both antigens, led in all animals to lesions characteristic of an immune hepatitis. Immunization of the animals with a purified water soluble liver protein proved less efficient: only two out of six animals developed characteristic lesions which were less severe than those in the first group. It was deduced that although not a prerequisite, the liver-specific lipoprotein plays an important supportive role in the development of immune hepatitis, [ABSTRACT FROM AUTHOR]

Intradermal inoculation of the guinea-pig with Leishmania enriettii results in a self-healing cutaneous lesion which provides a laboratory model of human cutaneous leishmaniasis and which is dominated by cell-mediated immunological responses (Bryceson et al, 1970). In this study we sought to design experimental situations resembling non-healing forms of cutaneous leishmaniasis in man and to determine whether these experimental situations were accompanied by abnormalities in the immunological response to infection. This paper describes three procedures which impair the resistance of guinea-pigs to leishmanial infection: (i) induction of partial immunological tolerance to leishmanial antigen; (ii) systemic injection of anti-lymphocyte serum (ALS); and (iii) regional antigenic competition produced by multiple injections of bacterial adjuvants. Injection of soluble leishmanial antigen (PSA) during the third week of foetal life suppressed resistance to neonatal infection with L. enriettii; local infections were severe and were accompanied by metastatic spread and by impaired development of delayed hypersensitivity (DH). Injection of PSA into the 6-week foetus and into the adult guinea-pig led to impaired DH after leishmanial infection, but resistance to infection was only slightly suppressed. Transient impairment of DH was induced by a short injection course of adult animals with ALS during the first 3 weeks of infection, which resulted in large primary lesions with temporary metastatic spread. Multiple regional injections of tubercle- and corynebacterial-adjuvant emulsions markedly suppressed resistance to subsequent leishmanial infection; large ulcerative lesions were accompanied by widespread nodular metastases, the unusual appearance of haemagglutinating antibody, and death of some animals. [ABSTRACT FROM AUTHOR]

Target cell killing by lymphocytes can be induced by appropriate antibody complexed to target cell antigens. In this paper it is shown that this form of lymphocyte mediated cytotoxicity is susceptible to inhibition by third party immune complexes which compete with target cell bound antibody for receptors for immunoglobulin on the cytotoxic lymphocytes. The physical state of the complexes is investigated in relation to their inhibitory efficiency. Evidence is presented to show that soluble complexes which exist in antigen-antibody equilibrium or slight antigen excess are the most effective inhibitors. No evidence could be obtained to support the hypothesis that soluble immune complexes can induce indiscriminate cytotoxic activity in lymphocytes. The biological significance of this effect is discussed in relation to chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]

This paper describes the course of infection and the immunological response in thymus-deprived and normal CBA mice after intradermal inoculation with promastigotes of L. tropica. Infection of normal mice resulted in the development of a cutaneous ulcer healing within 12 weeks. As the infection progressed and the draining lymph nodes increased in weight, changes in the paracortical and follicular regions were accompanied by the development of delayed hypersensitivity and the production of antibodies detectable by immunofluorescence and a parasite agglutination test. Lesions in thymectomized irradiated mice healed more slowly and the draining lymph nodes were smaller than in normal mice. Follicular reactions were feeble and paracortical activity depressed. The most noticeable feature of these lymph nodes was a persistent and intense macrophage infiltration. Delayed hypersensitivity and antibodies detectable by immunofluorescence were correspondingly low; but parasite agglutinating antibody was not depressed. The course of infection and immunological response of a control group of sham thymectomized, irradiated mice resembled that of normal mice. These experiments indicate that thymus-dependent cell populations play an important role in the response of mice to infection with L. tropica. [ABSTRACT FROM AUTHOR]

Partial purification of soluble products of guinea-pig lymphocyte activation (LAP) was undertaken by fractional precipitation with ammonium sulphate, ion-exchange and Sephadex chromatography, and by immune precipitation of inducing antigen and of contaminating serum protein. During these purification steps the activity of macrophage migration-inhibition factor (MIF) was concentrated up to 1300-fold and separated from inducing antigen and serum protein. An endpoint assay was devised for expressing antigen-induced MIF activity of LAP fractions as weights of material giving 30% inhibition of migration (MI30 doses). MIF activity precipitated between 50% and 80% saturated ammonium sulphate and eluted from DEAE-cellulose at pH 7-9 at intermediate salt concentrations (0-03-0-2 M phosphate). On Sephadex gel filtration MIF activity was concentrated in fractions of molecular weight range 56,000-82,000 with a smaller amount of activity eluting from 20,000-56,000. After immune precipitation of extraneous protein and elution from DEAE-cellulose, LAP material was found to have an MI30 dose of 0-4 /μg. Materials representative of antigen and serum protein-depleted MIF were selected for intralymphatic injection in order to determine whether MIF-rich LAP fractions were able to induce paracortical distension in guinea-pig lymph nodes (see following paper). [ABSTRACT FROM AUTHOR]

In a previous paper it had been shown that up to 40% of human peripheral lymphocytes will make rosettes with sheep red cells. In this study the inhibitory effect of antilymphocyte serum (ALS) and of certain other preparations on this rosette phenomenon is described. ALS was prepared in horses by injection of human peripheral lymphocytes and rosette-inhibiting, cytotoxic and agglutinating titres were determined during immunization. The ALS had been tested in vivo by regional administration to vervet monkeys bearing skin allografts. It was found t h a t the peak of rosette-inhibiting titre appeared to provide a good index of immunosuppressive activity. These peaks, and the accompanying periods of immunosuppressive activity, were of short duration, in contrast to the levels of cytotoxic and agglutinathig titres. Antihuman lymphocyte sera had considerable rosette-inhibiting titres against the lymphocytes of the baboon (Papio papio) but little against those of the vervet monkey (Cercopithecus aethiops). Inhibition by ALS of the phenomenon described by us is unaffected by complement. Antihuman globulin serum and phytohaemagglutinin had no inhibitory effect. Digestion of ALS with pepsin to obtain the F (ab')2 fragment had only a slight effect on rosette-inhibiting titres, while it reduced the cytotoxic activity very considerably. The phenomenon described by us is probably different from that reported by other workers, in which only a small proportion of lymphocytes form rosettes. [ABSTRACT FROM AUTHOR]

This paper describes the course of infection and development of immunity in guinea-pigs after intradermal inoculation of Leishmania enriettii, and the use of in vivo and in vitro techniques to characterize the immunological response to infection and artificial immunization. Inoculation of 106 amastigotes into the ear produced a nodule which ulcerated in 2-3 weeks and healed in 8-16 weeks. 8% of animals developed cutaneous metastases which healed with the original lesions. Histology of the primary lesions showed epidermal necrosis overlying a mass of parasitized macrophages which, after 4-6 weeks, became surrounded and infiltrated by lymphocytes. Histological changes in the draining lymph node began after 3 days and proceeded for 6 weeks; both germinal centres and paracortical areas were hyperplastic and the medulla contained many plasma cells. Superinfection produced an 'isophasic" lesion, but reinfection after healing elicited only a delayed hypersensitivity response. Artificial immunization with soluble and insoluble antigenic extracts of L. enriettii in Freund's complete adjuvant partially protected against infection; extracts of other leishmanial species Jailed to protect. Immunological paralysis, attempted with intravenous injections of soluble antigen, increased the severity of subsequent infection. Both infection and immunization were accompanied by delayed hypersensitivity which could be transferred passively by lymphoid cells. Cell-mediated immunity was studied in vitro by the ability of soluble leishmanial antigens to transform lymphokine, to inhibit macrophage migration, and to induce the production of lymphokine factors from lymphocytes of sensitized animals. A target cell system was devised in which sensitized lymphocytes destroyed monolayers of parasitized macrophages. Cross reactivity of leishmanial with mycobacterial antigens was shown in skin tests and in target cell destruction, but not in cell transfer or in the other cell culture systems, The phagocytic activity of peritoneal macrophages from recovered animals was increased for homologous but not for heterologous species of Leislumania; the growth of ingested organisms was not however reduced. Circulating antibodies were not demonstrated by passive cutaneous anaphylaxis, or by agglutination of antigen coated sheep erythrocytes, in the sera of infected or convalescent animals, although some convalescent animals showed active cutaneous anaphylaxis. However, antibodies were demonstrated by both these techniques in immunized animals, which also showed anaphylactic and Arthus hypersensitivity when skin tested with. the soluble antigens. The results are taken to indicate that cellular mechanisms are prominent in the development of immunity of the guinea-pig against L. enriettii, and ways in which the host may eliminate the parasite are discussed. It is concluded that this model provides an experimental counterpart of human cutaneous leishmaniasis and that it is suitable for the analysis of the role of cell-mediated specific immunity in resistance to intracellular infection. [ABSTRACT FROM AUTHOR]

This paper describes technical details of a micro-reaction for the in vitro detection of agglutinating potency of antilymphocytic serum produced in rabbits with chicken, rat and dog thymus cells, The titration of antilymphocytic serum includes the use of microtitre plastic plates and lymphocytes treated with formalin and stained with trypan blue stain. Formalinized and stained lymphocytes represent a stable antigen of long durability, and the application of those cells in leucoagglutination increases the accuracy and sensitivity of the reaction. [ABSTRACT FROM AUTHOR]

In this paper the specificity of the skin-reactive guinea-pig immunoglobulin in the homologous PCA test has been reconsidered. Extensive purification of this immunoglobulin by chromatographic methods results in the isolation of a small fraction or medium speed immunoglobulins that contains all skin reactivity. No correlation could be found with the 7S immunoglobulins IgGγ1 and Igγ1A suggesting a separate class of biologically active immunoglobulins. The PCA active antibody belongs to either an IgG subclass or is a heat stable homocytotropic antibody. Rabbit and chicken antisera against isolated fractions of guinea-pig immunoglobulins show the existence of 7S subclasses. Some suggestions for a revised nomenclature are given. [ABSTRACT FROM AUTHOR]

The mononuclear cells from. the joint fluid of certain patients with inflammatory arthritis are shown to be more cytotoxic to a polyploid strain of homologous liver cells than were equivalent numbers of peripheral blood lymphocytes From the same donors. The diagnostic categories of these patients are essentially similar to those of a group of patients studied by Hedberg (1967) in whom joint fluid mononuclear cells were cytotoxic to monolayers of human foetal fibroblasts. Evidence is presented to show that this cytotoxic activity is attributable to lymphocytes, as opposed to polymorphonuclear leucocytes or phagocytic mononuclear cells which adhere to glass. It is not excluded that the latter population may also have some cytotoxic potential. It is argued that the target cell damage described in this paper is probably not induced by any antigen on the target cell. The implications of this suggestion are discussed in relation to the pathogenesis of inflammatory joint disease. [ABSTRACT FROM AUTHOR]

To examine the validity of the old idea of the possible significance of mites for housed use atopy it was necessary to study the mite fauna of house dust. The most important findings in this investigation are that mites occur regularly, rather than occasionally, in house dust, and that the mite genus Dermatophagoides is represented by much higher numbers than any of the other genera found in dust. Furthermore, it appears that there is a seasonal periodicity in the numbers of mites in dust with a maximum from August to October, and also that the numbers of mites in the dust from various houses differ considerably. House dust from high- mountain areas contains very few mites. These observations fit very well the knowledge of the seasonal and topographical Variation in the allergen content of various dust samples. Based on laboratory observations on the temperature and humidity requirements of Dermatophagoides, a mode! is constructed which makes the relation between the degree of dampness of houses and the numbers of mites in the dust understandable. In this paper only very short mention is made of the many experiments showing the identity between the house dust allergen and the allergen produced by Dermtophagoides. From the comparison of skin reaction to equivalent extracts of different species of mites it appears that the allergenic products of mites of one family lend to be identical. [ABSTRACT FROM AUTHOR]