Sympathetic or reflex footpad swelling due to crystal-induced inflammation in the opposite foot

Sympathetic or reflex footpad swelling occurred in rats when several crystals known to be pathogenic in human joints or soft tissues were injected into the opposite footpad. Monosodium urate (MSU), calcium pyrophosphate dihydrate (CaPPD), hydroxyapatite, calcium oxalate (CaOx), and xanthine (X) suspension induced varying degrees of such reflex or sympathetic swelling. In the second cycle of crystal-induced swelling, the foot that had been the initial or primary site of inflammation reacted with greater reflex swelling, when compared to the first cycle. Similarly, reflex increases in temperature occurred when CaPPD was injected. These reflex increases in swelling and temperature may relate to signs and symptoms of patients with reflex neurovascular dystrophy or shoulder-hand syndrome.     

Cellular immune response to sheep erythrocytes: interrelationship between proliferation of popliteal lymph node cells and footpad swelling

Mice were sensitized with graded doses of sheep erythrocytes by the intravenous or subcutaneous route and challenged for delayed-type hypersensitivity (DTH) at different times thereafter. The DTH response as assessed by footpad swelling (FPS) was compared to the spontaneous proliferative response of the popliteal lymph node cells (PLNC). Proliferation of PLNC was optimal after sensitization regimens resulting in optimal FPS. The same was true for mice sensitized under cyclophosphamide modulation. Proliferation of PLNC induced by SRBC was antigen-specific, although some crossreactivity with horse red blood cells was observed. Proliferation of PLNC could be abrogated by treatment with anti-Thy-1.2 antiserum plus complement demonstrating the T cell nature of proliferating cells. In accordance with published data, FPS of mice presensitized with a high dose of SRBC as well as FPS of recipients of spleen cells from high-dose-sensitized donors was suppressed. In marked contrast, PLNC proliferation was not diminished in these mice. Although proliferation of PLNC did not parallel FPS under all circumstances, it seems to be a correlate of the cellular immune response to SRBC.     

Immune complexes in patients with drug eruptions: the relationship between skin lesions and circulating immune complexes.

The relationship between skin lesions and immune complexes was studied in sixty-two patients with exanthematic drug eruptions. By means of C1q-binding, conglutinin-binding and platelet aggregation tests, immune complexes were detected in a considerable number of sera from these patients. Patients with widespread maculopapular drug eruptions were found to show a relatively high serum level of immune complexes. There was a close association between the disease activity and the amount of the circulating immune complexes. By immunofluorescence, six of seventeen patients with drug eruptions were shown to have deposits of IgG, IgM, IgA or C3 in the skin lesions. These results suggest that certain immune complexes may play a role in some types of drug eruption as a pathogenetic factor.     

Comparison of three tests for measuring footpad swelling in the mouse

Three tests, footpad thickness, footpad weight and footpad dye accumulation have been compared for measuring the local inflammatory reaction developed in the hind footpads of the mouse after injection of increasing doses of heat killed Candida albicans yeasts. The 3 tests showed high correlation indicating that any one of them may be used to evaluate such inflammatory reactions.     

Tissue localization and retention of antigen in relation to the immune response

Antigen persists for months or even years in lymphoid tissues of immune animals and this antigen is believed to participate in the induction and maintenance of B-cell memory as well as in the maintenance of serum antibody levels. In the present report we describe the phenomenon of antigen localization and long-term retention on mouse follicular dendritic cells (FDCs). The antigens used were injected in the hind footpads of immune mice and the popliteal lymph nodes were the lymphoid organs generally studied. In addition to presenting the morphological features of mouse FDCs, we report the results of a study of the mechanism of antigen migration from the site of initial localization in the lymph node subcapsular sinus to the regions of follicular retention in the cortex. The migration was followed by light and electron microscopy. The results support the concepts that immune complexes are trapped in the subcapsular sinus and are transported by a group of nonphagocytic cells to follicular regions. The mechanism of transport may involve either migration of pre-FDCs with a concomitant maturation into FDCs, or cell-to-cell transport utilizing dendritic cell processes and membrane fluidity; or a combination of the two mechanisms may be in operation.     

Enhanced elimination of Listeria monocytogenes at the site of delayed footpad reaction.

The protective activity against a challenge infection with Listeria monocytogenes was investigated at the site of a delayed footpad reaction in mice immunized with viable or killed listeria. Delayed footpad reactivity was induced only in mice immunized with viable bacteria. Rapid and marked elimination of challenge bacteria was observed only at the site of reaction in mice immunized with viable bacteria but not in mice immunized with killed bacteria. Macrophage migration inhibitory activity was observed equally in both groups of mice. These results suggest that the delayed footpad reaction contributes directly to the elimination of bacteria irrespective of macrophage migration inhibitory activity.     

Immune responses to P. falciparum-MSP1 antigen: lack of correlation between antibody responses and the capacity of peripheral cellular immune effectors to respond to this antigen in vitro.

Protective immunity to P. falciparum blood stage infection is thought to be dependent on IgG antibodies, although the mechanisms that underlie such immunity are not clearly understood. One of the antigens thought to be involved in this protective response is MSP1. The present study has examined the levels and distribution of IgG (and IgM) antibodies to the C-terminal 19 kDa fragment of MSP1 in plasma from P. falciparum immune adult Senegalese and the capacity of the peripheral blood mononuclear cells from these patients to either proliferate or secrete IFN-gamma, IL-10 or IL-4 in vitro in response to this antigen. Specific antibodies were found in 74% of individuals' plasma; 44% of mononuclear cells proved capable of proliferating in vitro and IFN-gamma, IL-10 and IL-4 were detected in 37, 23 and 0% of culture supernatants, respectively. No significant association was found between the presence of antibodies and immune cell reactivity under the culture conditions used. This study emphasizes the complexity of the mechanisms responsible for the sustained production of potentially protective antibodies in response to proposed T-cell dependent P. falciparum blood stage antigens.     

A new reliable method for evaluation of foot pad swelling as an experimental in vivo immune phenomenon.

Weight determination of replicas of the feet from living mice is described as a new method for evaluating the degree of the experimentally induced foot pad swelling in immunized mice. The new method gives objective, well documentable results and offers advantage to the commonly used assay with the dial calliper gauge when there is need for a good documentation or whenever there is a large number of animals to be tested within a narrow time margin.     

Allergic arthritis induced by cationic antigens: relationship of chronicity with antigen retention and T-cell reactivity.

In order to define the antigenic properties necessary for sustained allergic arthritis, we prepared a range of differently charged bovine serum albumin (BSA) species with increasing isoelectric points (4.5, 4.5-7.4, 7-8, 8.5-9 and greater than 9). The highly cationic BSA greater than 9 appeared to be in a polymeric form. We investigated three properties of these proteins: (i) antigen retention, (ii) T-cell reactivity, and (iii) arthritis induction. Injection of the respective radiolabelled antigens in the knee-joints of immunized mice showed that antigen retention increased with cationicity of the proteins, with the best retention found for BSA with pI greater than 9. However, sustained joint inflammation was only found with BSA8.5-9, and not with a level BSA of lower or even higher pI. T-cell reactivity in vivo as measured by delayed-type hypersensitivity (skin testing) was similar for the tested antigens, with the exception of polymeric BSA (greater than 9). The latter appeared to be a poor antigen. In vitro, T-cell reactivity ([3H]-thymidine incorporation) against the cationized BSA species was slightly higher as compared to native BSA. The combination of excellent antigen retention and adequate T-cell reactivity appears to be optimal for the induction of chronic arthritis.     

Immune elimination and enhanced antibody responses: functions of circulating IgA.

Passively transferred MOPC 315 IgA myeloma protein accelerated the elimination of DNP-ovalbumin, to which the myeloma protein bound with antibody-like affinity, from the circulation and increased the subsequent antibody response to hapten and to carrier, when injected with or without adjuvant.     

The relationship between lymphocyte transformation and immune responses. II. Correlations between transformation and humoral and cellular immune responses

Rabbits were immunized against purified proteins, tissue extracts or sheep erythrocytes, with or without Freund's adjuvant. Skin reactions of the delayed type were found only in animals given antigen with adjuvant, although all rabbits developed serum antibodies and most of them Arthus type reactions. Lymphocytes of all animals, however, showed similar transformation activity when cultured with the immunizing antigen.

Thus the blast transformation phenomenon correlates well with both cellular and humoral immune responses and not with the delayed type hypersensitivity only.

     

Mouse footpad Langerhans cells as an indicator for safety of foot and mouth disease virus vaccines.

The effect of various vaccines against foot and mouth disease virus (FMDV) was tested on Langerhans cell density in the footpad epidermis of mice. Injection of monovalent, bivalent and trivalent FMDV vaccines caused a reduction in Langerhans cell density in the murine skin, which was more marked at the center of the footpad, the site of injection, than at the periphery. Testing of the various components of the vaccine showed that saponin caused a marked reduction in Langerhans cells while injection of aluminium hydroxide had a lesser effect and the virus alone had no effect on these cells. Thus Langerhans cell density could serve as an efficient marker to test the safety of vaccines to FMDV since the integrity of Langerhans cells, which are the antigen-presenting cells in the skin epidermis, is needed for an effective immune response to the vaccine.     

IL-33与免疫细胞的关系

IL-33是IL-1家族的新成员,在炎性刺激后由多种细胞表达IL-33,并且在细胞溶解过程中释放.IL-33的膜表面受体包括ST2和IL-1受体辅佐蛋白,机体广泛表达ST2,尤其是在Th2型细胞和肥大细胞等免疫细胞中.IL-33通过结合免疫细胞膜表面的ST2将活化信号传递到胞内,经过一系列的信号传递,引起IL-5等免疫因子的释放,起到调节免疫应答等功能.     

HLA-B27 and antigen presentation: At the crossroads between immune defense and autoimmunity

The HLA-B27 is historically studied as a susceptibility factor in spondyloarthropathies and, primarily, in ankylosing spondylitis (AS). Over the recent years however, it has been rediscovered as protective factor against some severe viral infections. This is due to the high capacity of virus-specific, HLA-B27-restricted CD8+ T cells for both intrinsic (i.e. polyfunctionality, high avidity, low sensitivity to Treg cell-mediated suppression) and extrinsic (i.e. rapid and efficient antigen processing and presentation) factors. It is tempting to speculate that these two aspects are not independent and that the association of B27 molecules to autoimmunity is the downside of this superior functional efficacy which, in given genetic backgrounds and environmental conditions, can support a chronic inflammation leading to spondyloarthropathies. Still, the pathogenic role of HLA-B27 molecules in AS is elusive. Here, we focus on the biology of HLA-B27 from the genetics to the biochemistry and to the structural/dynamical properties of B27:peptide complexes as obtained from atomistic molecular dynamics simulation. Overall, the results point at the antigen presentation as the key event in the disease pathogenesis. In particular, an extensive comparison of HLA-B*2705 and B*2709 molecules, that differ in a single amino acid (Asp116 to His116) and are differentially associated with AS, indicates that position 116 is crucial for shaping the entire peptide-presenting groove.     

Studies on the quantitative relationship between specific antigen recognition and manifestation in delayed hypersensitivity.

Delayed skin reactions or peritoneal cell migration inhibition were elicited in guinea-pigs or rats with egg albumin, diphtheria toxoid, or tuberculin-purified protein derivative either separately or with various combinations of two antigens. When the skin reactions or migration inhibition with the component antigens alone were relatively strong, the corresponding combination elicited weaker reactions than calculated assuming that the antigens would add upon each other independently, i.e. the non-specific phase was limiting the manifestation. When the reactivity to both components was undetectable or very weak, the combination elicited stronger reactions than calculated, implying synergism of antigen recognition. The combinations of two weakly positive or intermediate reactivities were close to the calculated values in both the diameter of erythema, skin thickness and migration percentage. These results may help in assessing the biological significance of findings in delayed hypersensitivity: even minor differences in strong manifestations may mean great differences in terms of specific lymphocytes, while marginal changes of antigen recognition may lead to apparently great changes of manifestation, when very weak reactivities are measured.     

The relationship between body sway and foot pressure in normal man

The relationship between the movement of the centre of foot pressure in the anterio-posterior plane and the rotation which occurs in the same plane at the level of the ankles, hips and shoulders during postural sway was examined in a group of normal human subjects. Expressed as three frequency-dependent functions this relationship consists of both relative magnitude and phase components. The magnitude component indicates that the pressure centre was most sensitive to ankle rotation, less to hip and least sensitive to rotation at the level of the shoulders. The sensitivity of the pressure centre was also a function of the frequency of the rotations and this is evidenced by the presence of several resonant peaks in the relationship. It is suggested that these could be due to body inertia and transmission delays. The resonant peaks became more prominent when the subjects stood with eyes closed. The growth of resonant peaks is taken as a sign of reduced postural stability and on this basis it is argued that a distinction should probably be made between the concepts of the stability and the steadiness of stance.