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In Part I, the history of artificial acclimatization to heat is outlined from its beginnings in the South African gold mines in the early 1930s. Dreosti showed that effective acclimatization could be induced artificially and that the degree of acclimatization could be assessed in that no acclimatized miner had a body temperature above 38·°C in his one hour work-in-heat test. In the early 1960s a method of acclimatization known as controlled hyperthermia was developed by the Medical Research Council. This method has been adapted to mass acclimatization by having the subjects control their own elevated body temperatures by variation of work rate. The test of acclimatization devised by Dreosti has been adapted for use in a portable, heated airdome which also accommodates the acclimatization technique. The whole process including erection and dismantling of the airdome, acclimatization and test of acclimatization can be carried out in one week at any Army Base. Part II is a practical report on the further development of the airdome technique and experience in field trials. [ABSTRACT FROM PUBLISHER]

Immunoglobulin molecules on the surfaced mouse thymus cells have been shown by immunofluorescence. Ninety-ave to 100 per cent of thymus lymphocytes were found to bind polyvalent rabbit and-mouse imrnunoglobulin, although the density of the fluorescence was much less than that on the surface of B lymphocytes derived from the spleen. Two purified antisera, an anti-IgM and an anti-kappa chain strum, also stained the cells. The resynthesis of these immunoglobulin molecules in vitro was demonstrated after they had been removed with pronase. [ABSTRACT FROM AUTHOR]

The effect of a single injection of 300 mg/Kg on the lymphoid cells of normal mice has been studied. The proportions of θ-positive cells in the thymus, lymph nodes and spleen were examined in vitro using a Trypan Blue exclusion cytotoxicity test. Two anti-θ sera of different titre were employed in an attempt to evaluate changes in θ-antigenicity of these cells following azathioprine treatment. In the thymus the drug was found to deplete a particular population of cortical thymocytes without affecting the hydrocortisone-resistant cells. The ability of azathioprine-resistant thymocytes to absorb out the cytotoxic capacity of both antisera was not better than that of hydrocortisone-resistant thymocytes. This result was taken to indicate that, following azathioprine, the residual cells had a decreased frequency of the θ antigen and were in this respect more like hydrocortisone-resistant cells. It is also postulated that the two antisera were of different avid- A decrease in antigenicity was also seen in lymph node cell populations from azathioprine-treated animals. It is therefore suggested that azathioprine given in heavy doses might have at least two effects on lymphoid cells: (i) it depletes certain populations; and (ii) it decreases the θ-antigenicity of others. [ABSTRACT FROM AUTHOR]

Selective depletion of lymphocytes from the lymph follicles and corticomedullary junction in lymph nodes and equivalent non thymus dependent areas of the spleen can be produced by cyclophosphamide (CY) (300 mg/kg) in the mouse and guinea-pig. Despite three such injections on alternate days, thymus dependent areas still contained lymphocytes. Total depletion of lymphocytes from lymph nodes and spleen was produced by combining neonatal thymectomy in the mouse or ALS treatment in the guinea-pig with CY. CY produced depletion of lymphocytes in the cortex of the thymus before the medulla. Maximal depletion occurred at 3 days and in surviving animals repopulation was evident by 7 days at the cortico-medullary junction only. Lymph follicles were found in lymph nodes of neonatally thymectomized CY treated mice following repopulation with bone marrow. These findings suggest that the lymphocytes of the lymph follicles are derived from a population of rapidly dividing cells, part of which at least can be found in the bone marrow. [ABSTRACT FROM AUTHOR]

The article discusses biological activities of soluble lymphocyte products. Due to the lack of a satisfactory physicochemical characterization of soluble lymphocytic products it is necessary to classify them according to their typical biological activity in vitro or in vivo. It must be remembered that one material may possess several activities but that these, apparently different, biological effects may well be due to the mediator affecting a single basic biochemical pathway. Some biological activities attributed to soluble substances released by lymphocytes are, causation of an inflammatory reaction in the skin of normal animals, including the local increase in vascular permeability, stimulation of DNA synthesis in non-sensitized lymphocytes and cytotoxicity towards different cells in tissue culture.

Seventy-seven lymph nodes were examined histologically from sixty-two leprosy patients representing the whole range of the disease spectrum from the high resistance form (tuberculoid) to the specific immunity deficiency form (lepromatous). At the lepromatous end of the spectrum paracortical areas were infiltrated with undifferentiated cells of the histiocyte-macrophage series which failed to eliminate mycobacteria. As resistance to infection increased across the leprosy spectrum, histiocytes became more differentiated eventually appearing epithelioid. This was paralleled by increasing numbers of small lymphocytes in the paracortical areas. In the borderline tuberculoid form of the disease an appearance was seen similar to that found in sarcoidosis. In polar tuberculoid leprosy where there is a high degree of cellular immunity, paracortical areas were well developed and populated with lymphocytes and immunoblasts. The immunological significance of these findings are discussed, especially the relation of the changes in morphological appearance of cells of the histiocyte series to the ability of the patient to develop cell-mediated immune reactions. [ABSTRACT FROM AUTHOR]

The effect of anti-thymocyte serum, anti-lymph node cell serum and anti-lymph node permeability factor serum have been compared on the peripheral manifestation of contact hypersensitivity in the guinea-pig and certain models of acute inflammation in the guinea-pig and the rat. Anti-lymph node permeability factor serum has a similar effect to the anti-lymphocyte sera on contact hypersensitivity. However, its effect on non-specific inflammation is very much less. The mechanism of action of anti-lymphocyte sera on the models of non-specific inflammation has been studied more thoroughly to attempt to work out the level at which inhibition occurs. The central effect of these different antisera on lymph nodes reacting during the development of sensitivity to a chemical sensitizer has also been studied. Anti- serum prepared against cells derived from lymph nodes has the same specific effect on the thymus-dependent area of the lymph node as antiserum prepared against cells derived from the thymus. These changes are compared with those produced by anti-lymph node permeability factor serum and anti-epidermal cell serum. [ABSTRACT FROM AUTHOR]

A state of immunological unresponsiveness to bovine serum albumin (BSA) or human gamma globulin (HGG) can be produced in guinea pigs by contact with these proteins either before and soon after birth, or even soon after birth alone. As judged by failure of treated animals to show immune elimination of the antigen, or anaphylaxis on reinjection, the animals were completely unresponsive when tested up to 5 months after birth. Administration of 6-mercaptopurine to guinea pigs, even in lethal doses, did not prevent the development of antibodies to HGG. After administration of BSA or HGG, labelled with 131I, to pregnant guinea pigs, their offspring at term contained significant amounts of the labelled proteins. HGG was catabolized in new-born guinea pigs with the same half-life as in adults. [ABSTRACT FROM AUTHOR]

A comparison is made of the titres of complement from different animals when reacting with antisera from different species, in the immune-adherence phenomenon. A failure of reaction between rabbit antibody and horse and pig complement is noted. This may be overcome by the addition of heated guinea pig serum. Whereas a similar failure of reaction between rabbit antibody and horse complement in immune haemolysis is also overcome by the addition of ammonia-treated guinea pig serum, this does not occur in immune-adherence. This is interpreted as meaning that there is a further heat-stable ammonia-sensitive co-factor necessary for immune-adherence in addition to the four components of complement. This co-factor is also inactivated by zymosan. The behaviour of mouse complement in immune-adherence indicates a relative deficiency in C'2 as in immune haemolysis. Conglutinin is shown to inhibit immune-adherence irrespective of the species of complement used. [ABSTRACT FROM AUTHOR]

Immune-adherence has been demonstrated by haemagglutination with four soluble antigens, two polysaccharide and two protein. A zone phenomenon occurs with the immune-adherence of soluble antigens similar to that found with other antigen-antibody reactions. It is suggested that the failure of immune-adherence with two soluble antigens, despite marked fixation of complement, is due to the failure of the antigen-antibody complexes to fix all four components of complement. [ABSTRACT FROM AUTHOR]

Sephadex purified PPD and Con A induced mediator rich fractions (MRF) were applied to guinea-pig macrophages cultured in vitro. At varying times after the addition of the MRF, cells were removed from culture for morphological study and for cytochemical tests. Respiratory enzyme activity and lysosomal acid phosphatase activity were estimated and the former was quantitated using an integrating microdensitometer. Early changes, 1 hr after MRF contact, were, observed and subsequent alterations in activity up to 48 hr after the addition of MRF were also seen. These changes have been related to `the inhibition of migration and subsequent `activation' of the macrophages which has been observed morphologically at times up to 3 weeks after MRF addition. It is suggested that alterations in the cytochemistry of the macrophages after MRF contact could help explain changes in the behaviour of the cells under these experimental conditions. [ABSTRACT FROM AUTHOR]

The spleens and livers of mice were investigated histologically on various days subsequent to infection with Plasmodium berghei yoelii using immunofluorescence and autoradiography. At the height of the parasitaemia, at a time when non- specific immunosuppression is known to occur, the `thymus-dependent area' round the central arteriole of the spleen was replaced by proliferating lymphoid cells many of which were IgG containing plasmablasts. There was also at this time a considerable decrease in small lymphocytes in this area. The significance of these findings is discussed in relation to the non-specific immunosuppression. In addition evidence for immune complex deposition was obtained in a number of tissues. [ABSTRACT FROM AUTHOR]

The mechanism of the 'flare up' reaction of previous epicutaneous skin test sites in guinea-pigs sensitized to potassium dichromate seems to be similar to that of the Arthus phenomenon and different from that of contact skin sensitivity. No circulating antibodies were found in the serum of these animals but it was possible to transfer the capacity of developing 'flare up' reactions by an intradermal injection of peritoneal exudate cells from sensitized donors to normal recipients in which a `flare up' could be elicited by intravenously injecting the hapten 4 days later. 'Flare up' reactions could also be transferred by cells from animals permanently desensitized to contact hypersensitivity to chromium. This is in agreement with the ability to produce 'flare up' reactions in desensitized animals. The assumption that the 'flare up' reaction is produced by humoral antibodies released by sensitized lymphocytes in the skin test site is further supported by the finding of an activity in the supernatant of cultures of sensitized lymphocytes with a chromium conjugated guinea-pig serum which when injected intradermally into normal recipients can produce an Arthus-like reaction. [ABSTRACT FROM AUTHOR]

The article presents studies on the effect of systemic administration of sensitizers in guinea pigs with contact sensitivity to inorganic metal compounds. Permanent specific immunological unresponsiveness can be produced in guinea pigs already sensitive to potassium dichromate by the combination of an intravenous injection of 20 mg/kg potassium dichromate and an epicutaneous contact with potassium dichromate within 24 hr. A combination of cyclophosphamide and anti-thymocyte serum for 1 week at the time of the intravenous injection prolonged the unresponsiveness for 2 months, but the animals regained sensitivity by 3 months. The addition of prednisolone to this combination, reduced the duration of unresponsiveness.

The article focuses on the studies related to the effect of systematic administration of sensitizers in guineapigs with contact sensitivity to inorganic metal compounds II. Histological examination of the flare-up site shows an infiltration with polymorphonuclear leucocytes. Flare-up reactions can be blocked by an antiserum directed against polymorphonuclear leucocytes but not by anti-LNPF serum which blocks contact sensitivity reactions specifically. The demonstration that both a flare-up of previous contact reaction sites and a generalized erythematous rash could be observed in guinea-pigs sensitive to potassium dichromate or beryllium fluoride given respectively potassium dichromate or beryllium lactate intravenously, acted as a stimulus to look further into the mechanism of these two phenomena.

The article focuses on the studies related to the effect of systematic administration of sensitizers in guineapigs. The induction of immunological unresponsiveness to simple chemical contact sensitizing agents by the systemic administration of a large dose of the chemical as late as 24 hour after attempted sensitization. In initial studies on the effect of the intravenous injection of large doses of potassium dichromate intravenously to guinea-pigs which were already sensitive, it was found that it was possible to produce a prolonged state of specific unresponsiveness. It was, therefore, decided to study further the effect of the intravenous injection of different doses of the compound and also to find out to what extent the unresponsiveness could be modified by prolonging the time between the intravenous injection of the compound and the subsequent application of potassium dichromate to the skin to determine whether the animal was still sensitive or had become unresponsive.

The article informs that Lupus erythematosus (LE) is associated with multiple autoimmune phenomena, and in the skin lesions deposits of antigen-antibody complexes have been demonstrated by immunofluorescence. The factors which contribute to imitate these lesions appear to be multiple. It has been suggested that leakage of enzymes from connective tissue cells might be involved, and the effect of chloroquine or hydrocortisone on LE could then be explained by a stabilization effect on lyosomes, while ultraviolet light which exacerbates LE is known to disrupt lysosomes.

Delayed pressure urticaria in 15 patients has been investigated. It is characterized by the development of deep painful swelling 4-6 hours after pressure has been applied to the skin. It is sometimes accompanied by systemic manifestations such as a leucocytosis and rigors. Delayed pressure urticaria is unaffected by antihistamines but it is controlled by steroids. The injection into the skin of saline and various pharmacological agents also causes delayed wealing. Prior treatment of the skin with 48/80 prevents the reaction. Immunofluorescent studies showed that the affected tissues contained no excess fibrinogen, immunoglobulins or complement. It is suggested that delayed pressure urticaria is related to delayed dermographism and may be due to a disorder of kinin activity. The timing and depth of the changes in vascular permeability characteristic of urticaria can be correlated. They are influenced by many mediators and by the pattern of the vasculature of the skin. A change in the timing or depth of the urticaria is the most that should be expected from the use of a single pharmacological agent in the treatment of urticaria. [ABSTRACT FROM AUTHOR]

This memorandum proposes a standardized system of reporting the histology of human lymph nodes based on commonly used simple staining techniques. The purpose is to provide a uniform, internationally acceptable system by which the histological structure of lymph nodes can be correlated with other parameters of immunological status. The proposed protocols are intended to provide information that is not available in conventional written reports that use such terms as `hyperplasia' or `nonspecific lymphadenitis'. [ABSTRACT FROM PUBLISHER]

Contact sensitivity and production of anti-DNP-antibodies induced by epicutaneously applied dinitrochlorobenzene (DNCB) can be permanently suppressed by a previous intravenous injection of a high dose of dinitrobenzene- sulphonate (DNBSO3). The animals fail to develop a paracortical area rich in pyroninophilic cells, in lymph nodes regional to the local application of hapten, characteristic of sensitized controls. Following the injection of lymphoid cells from normal syngeneic donors into these unresponsive animals, large pyroninophilic cells develop in the paracortical area 4 days after sensitization and in some cases antibody production is restored. However, contact sensitivity remains suppressed. If a high dose of DNBSO3 (600 mg/kg) is injected intravenously on the same day as DNCB is applied locally, or when a low dose of DNBSO3 (60 mg/kg) is administered 12 weeks before DNCB, contact sensitivity and production of anti- DNP-antibodies are also suppressed but in such animals the development of a paracortical area containing large pyroninophilic cells is not inhibited. In both cases an immune reaction can be suppressed in the presence of a paracortical area containing large pyroninophilic cells. Therefore it appears that this state of unresponsiveness is not exclusively conditioned by the absence of large pyroninophilic cells in paracortical areas and may be associated with other factors. [ABSTRACT FROM AUTHOR]

The distribution of five epidermis specific antigens in three fractions of guinea-pig epidermis (epidermal cells, intercellular substances and the superficial epidermis, or granular and horny layers) was investigated and compared with the antigens found in guinea-pig embryo and adult epidermis and in guinea-pig hairs. Four of the antigens were considered to be non-bacterial as they were demonstrated in embryo epidermis as well as in the adult tissue, These antigens appeared to be synthesized in the epidermal cells, after which they migrated to the superficial epidermal layers, where they were shown to accumulate and, in some cases, undergo fragmentation. Only one antigen was found in any quantity in the intercellular spaces, however although three of these antigens were found to be stable in 8 M urea, none of these could be demonstrated in guinea-pig hairs. The fifth antigen (Sp4), not found in the embryo tissue, could be of bacterial nature, as its presence, in small amounts, in the epidermal cells is probably due to contamination of this fraction by material from the superficial layers of the epidermis. [ABSTRACT FROM AUTHOR]

Peritoneal exudate lymphocytes (PEL), purified on glass beads and lymph node (LN) cells from guinea-pigs immunized with tubercle bacilli were cultured for 24 hours, in serum-free medium, without and with various concentrations of Tuberculin PPD. Supernatants obtained from cultures with 10 μg PPD/107 lymphocytes provoked an intense inflammatory reaction, when injected into the skin of normal guinea- pigs. PEL were more active than LN cells from the same animals. The reaction was characterized by erythema and induration, with a peak between 3 and 6 hours and histologically a mixed polymorphonuclear-mononuclear infiltrate in the dermis was seen. When fractionated on Sephadex G-200, skin activity of both PEL and LN supernatants was concentrated in a peak corresponding to the molecular weight of serum albumin, while in LN material some activity was also present in a small molecular weight peak. The active material could be separated from albumin by chromatography on DEAE-cellulose. Immunoelectrophoretic analysis of skin reactive peaks detected a slow α-globulin in both PEL and LN supernatants. PPD in the form of a complex with a protein precipitated by anti-γG antiserum, was detected in the skin-active Sephadex peak III of LN supernatants, by radio- immunoelectrophoresis. Skin activity was precipitated with ammonium sulphate at 66 per cent saturation and was destroyed by pepsin treatment. Formation of the skin-active material was depressed by Puromycin and Actinomycin-D and the development of skin inflammation was suppressed by pretreatment of the recipient with anti-lymph node extract serum. Evidence for antigen induced specific synthesis and release of an α-globulin in PEL and LN cultures was found but its relation to the skin active material is unknown. [ABSTRACT FROM AUTHOR]

Only a proportion of outbred guinea-pigs can be sensitizcd to K2Cr2O7, BeF2 and HgCl2. Inbred Strain II can he sensitized to K2Cr2O7 and BeF2, but not to HgCl2. Inbred strain XIII can be sensitized to HgCl2 but not to K2Cr2O7 or BeF2. The ability to become sensitized appears to be transmitted as a dominant characteristic which is not sex linked. [ABSTRACT FROM AUTHOR]