An Initial Identification of Parasite Specific Immune Responses in the Jird (Meriones Unguiculatus) Infected With Brugia Pahangi.

Brugia pahangi infections in the jird (Meriones unguiculatus) is an accepted experimental model for the study of human lymphatic filariasis. Initial identification of parasite specific immune responses in jirds infected with B. pahangi are reported here. Antibody reactivity in sera from singly and multiply infected jirds against different stages of B. pahangi was determined using an indirect fluorescent antibody technique. All life cycle stages of the parasite were examined. Antibodies recognizing all stages were present in all serum samples. Removal of antibody reactivity by absorption of jird sera with B. pahangi antigen coated beads indicated that the antibodies were parasite specific. The surface was not recognized as immunogenic in jirds. Temporal occurrence of stage or organ specific antibody was not observed. Antibody responses of infected jirds to a soluble somatic extract of B. pahangi were further characterized by Western blot analysis. Antibody recognition of parasite antigens appeared to be independent of ELISA antibody titlers, lymphatic lesion severity, microfilaremia levels, inoculum size or numbers of adult parasites recovered. However, antibody recognition of 37 kD, 21 kD, 17 kD and 15 kD protein bands appeared to correspond with certain parasitological and/or host interactive events. Chronological association of antibody responses to these proteins were identical in singly and multiply infected jirds. No association between antibody recognition of antigens and severity of lymphatic lesions suggests that antibody is not directly involved in the pathogenesis of lymphatic lesions. The soluble somatic extract of B. pahangi was fractionated with lectin affinity chromatography and high performance liquid chromatography, yielding a glycoprotein pool and seven HPLC fractions. Pulmonary granulomatous inflammatory and in vitro lymphocyte blastogenic responses were measured and compared. Granulomas were induced by the glycoprotein pool and three HPLC fractions. A pulmonary eosinophilic perivascular inflammatory infiltrate appeared to be associated with granuloma size. Results indicate that the fractionation methods used yielded fractions that retained antigenicity and were both qualitatively and quantitatively different. Fractions containing antigens inducing a pulmonary granulomatous response were identified. Two fractions with suppressive properties were also identified. Some correlation between in vivo granulomatous responses and in vitro blastogenesis was observed

Regional lymphatics and lymph nodes of the testis, with reference to the testis as an immunologically privileged site

Immunologically privileged sites are those in which tissue allografts survive longer than in convectional sites. Privilege is usually attributed to absence or paucity of lymphatic drainage from these sites, preventing access of alloantigens to the regional node. There is evidence that the testis is a privileged site and this thesis examined certain aspects of its regional lymphatics and lymph nodes. 1. The existence of abundant lymphatics within the parenchyma of the testis was confirmed. 2. In guinea pigs and mice the extrinsic lymphatic trunks draining the testis were found to be uniform in pattern and to be interrupted, on each side, by at least one node, before entering the cisterna chyli. In rats, the pattern of extrinsic testicular lymph trunks was found to be variable. The left testicular trunk was always interuppted by at least one node. The right trunk, in 16 out of 52 rats, was not interuppted by any node but opened directly into the cisterna chyli. While such an arrangement might account for privilege of the right testis as a graft site in some rats, it clearly cannot be involved as an explanation in guinea pig and mouse. 3. In rats, the renal lymph nodes which receive lymph from the testis (and other sites) were found to belong to the category of haemolymph nodes. A detailed re-investigation of the structure of these nodes resolved several controversial issues:- a) haemolymph nodes possess both afferent and efferent lymphatics b) the erythrocytes, which are found in abundance within the nodes, either free in the sinuses or attached as rosettes around sinus macrophages, reach the node by afferent lymphatics and not by extravasation from intra nodal blood vessels. The kidney seemed to be the major source of erythrocytes, but other possible contributors were studied. 4. Lymph nodes regional to the testis show marked histological differences from nodes draining the pinna. They are "inactive" or "quiescent", with poorly developed cortical nodules, absent germinal cantres, inconspicuous thymus dependent cortex, narrow medullary cords and sparse plasma cells. The possibility was discussed that these appearances may be due in part at least to steroids which reach the nodes via the regional lymphatics of the testis and the adrenal gland and thus these steroids may influence the animal's response to an intratesticular allograft. 5, Six weeks after vasectomy the regional testicular lymph nodes of rats showed changes suggesting the genesis of humoral and cell mediated immunity. The nodes were enlarged, germinal centres were conspicuous, thymus dependent cortex was thickened and showed many immunoblasts and the medullary cords were enlarged and packed with plasma cells. Despite these changes, histological study of the testis and epididymus showed no sign of an autoimmune response

The magnitude and regulation of antibody responses to antigens injected into the central nervous system

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The Regulation of Pulmonary Immunity

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.No evidence has emerged which suggests that the principles of immunity derived from studies on cells from other body sites are contradicted in the lung and its associated lymphoid tissue. What is clear, however, is that the environment dictates the types of cells, their relationship to one another, and what perturbing events will set in motion either the development of an "active" immune response or tolerance. Investigating mechanisms for the development of lung immunity has increased our understanding of how human diseases develop and is continuing to suggest new ways to manipulate pulmonary immune responses. Demonstration that lung cells regulate both nonspecific inflammation and immunity through the expression of adhesion molecules and the secretion of cytokines offers hope for ways to design more effective vaccines, enhance microbial clearance in immunosuppressed hosts, and to suppress manifestations of immunologically mediated lung disease. Important lung diseases targeted for intensive research efforts in the immediate future are tuberculosis, asthma, and fibrotic lung disease. Perhaps even the common cold might be conquered. Considering the pace of current research on lung immunity, it may not be too ambitious to predict that these diseases may be conquered in the next decade

The Distribution of plasma and other cells containing immunoglobin in the respiratory tract of normal man, and the alterations found in subjects with chronic bronchitis

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Inflammatory Responses of the Jird to Brugia Pahangi: Parasite Stage Specificity and Role of the Macrophage.

The host systemic and peritoneal inflammatory responses against different stages of Brugia pahangi were compared in intraperitoneally infected-jirds. Systemic inflammatory responses were assessed by measuring the pulmonary granulomatous response to B. pahangi antigen-coated beads (PGRN). Peritoneal inflammation was characterized by enumeration of different cell types in peritoneal exudates following infection. Further, the toxoplasmacidal activity and TNF-$\alpha$-like production of peritoneal macrophages were also characterized. Infection with L3, L4, male worms, female worms, microfilariae (MF) or dead adult worms induced a rapid PGRN. This response decreased to levels of controls in jirds inoculated with living parasites at the chronic time period, indicating that viable worms are needed to downmodulate the PGRN, but MF are not required. Large numbers of female worms induced greater downmodulation of the PGRN than low numbers, and adult worm infection resulted in greater downmodulation of the PGRN than MF inoculation. These observations suggest that parasite burden is important in filarial-induced PGRN decrease. The greatest peritoneal inflammatory response was found in infections that resulted in MF production, and this response did not correspond to the level of PGRN indicating that MF act as potent inflammatory stimulus when compartmentalization occurs. Gamma radiation inhibited the development and decreased the survival of B. pahangi L3. This effect was inversely related to the radiation dose used. Downmodulation of the PGRN occurred in infections with normal L3 or L3 irradiated with 15 krads, but not in infections of L3 irradiated with more than 15 krads, supporting the importance of the adult stage in the PGRN downmodulation in absence of MF. The PGRN decrease occurred at the time period when the molt to adult worms had just occurred, suggesting that larval stages are also involved in the downregulation phenomenon. Macrophages from jirds inoculated with male or female B. pahangi were activated to kill Toxoplasma at 15 DPI coinciding with the peak of PGRN. TNF production peaked at 56 DPI and decreased markedly at 135 DPI. Absence of toxoplasmacidal activity was found in macrophages after 56 DPI corresponding to PGRN decrease. These data suggest that filaria-specific hyporesponsiveness may be associated with a downmodulation of macrophage function.* ftn*Originally published in DAI Volume 57, No. 7. Reprinted here with corrected text