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At least 19 recordsLinked to original sources
PubMed1979

Polymorphonuclear leukocyte-inhibitory factor of Bordetella pertussis. II. Localization in the outer membrane.

The outer and inner membranes and cytoplasm of spheroplasts of a strain of phase I B. pertussis were fractionated by density gradient centrifugation. The high density vesicles of the outer membranes isolated had the "Pili" characteristic of the bacteria and the same antigenicty as the bacterial surface. Activities for inhibition of polymorphonuclear leukocytes were also almost exclusively localized in this outer membrane fraction. The histamine-sensitizing activity was more dispersed, but its specific activity was also highest in the outer membrane fraction. These results suggest that molecules carrying these activities, which are probably different entities together with the tissue-adhesive pili, form a virulence complex on the surface of phase I organisms of B. pertussis.

Antigens, Bacterial↗
PubMed1979

Cell mediated and local immunity to spermatozoa in infertility.

The possibility of the immunological factor as an etiological cause of infertility was investigated in 50 infertile couples. Of these, 31 couples were considered as an "unexplained sterility" group, while in the other 19 couples a variety of disorders were diagnosed. In vitro, leucocyte migration inhibition test (LMIT) was used for the detection of female cell-mediated immunity against sperm antigens. Sperm immobilization test (SIT) and sperm toxicity tests (STT) were used for the detection of antisperm antibodies in the cervical mucus. Out of the 31 "unexplained sterility" cases, six revealed a positive LMIT (5.3%). In 26 couples with an abnormal postcoital test (PCT), 10 cases had a positive SIT and STT (38.5%). However, out of the group of 16 couples with a normal PCT only in one case was a positive SIT and STT found (6.2%). The potential role of immunological reactions in infertility will be discussed.

Antibody Formation↗
PubMed1979

Alterations of two parameters of cellular immunity in the aged men.

There were two parameters of cellular immunity in 46 old and 34 adult (control) individuals investigated. These reactions were delayed type hypersensitivity of the skin and the in vitro leukocyte migration inhibition test. PPD was used as antigen for both reactions. According to our investigations there was no correlation between them neither in the aged nor in the control group. But the statistical analysis of data revealed a significant difference between skin responses of aged and control groups. In spite of this we consider cellular immunity unaltered in old men, because there was no difference in migration inhibition between aged and adult men and according to our earlier experiments in guinea pigs this test is much more reliable than skin response.

Adolescent↗
PubMed1979

Determination of the human lymphokine leukocyte migration inhibitory factor (LIF) by a sensitive radioenzymatic assay. Inhibitory effect of cGMP on the esterolytic activity of highly purified LIF.

Indirect experiments using irreversible enzyme inhibitors have shown that the human lymphokine leukocyte migration inhibitory factor (LIF) is a serine esterase and protease exhibiting specific affinity towards arginine esters and amides. A sensitive assay for direct measurement of esterase activity using p-tosyl-L-arginine (3H) methyl ester (3H-TAME) as substrate is described. Esterolytic activities are demonstrated in crude supernatants of human lymphocytes stimulated with concanavalin A (LIF-rich) and, more pronounced, in supernatants of unstimulated cells (control). To follow the effects of purification procedures, the serine esterases of LIF-rich and control preparations were specifically labeled with the irreversible, active site directed agent (1,3-3H)di-isopropylphosphorofluoridate. Most of these enzymes, visualized by Sephadex chromatography, were removed by a gentle three-step procedure, allowing at least 50% of the initial LIF activity to be recovered. The resulting LIF-rich preparation, purified to contain serine esterases at a concentration corresponding to less than 1 ng per ml original supernatant, still showed estrolytic activity towards 3H-TAME. The optimal conditions for the radioenzymatic assay of purified LIF and the inhibitory effect of 10(-4) M cGMP, which on the basis of indirect experiments has been implicated as a specific regulator of LIF activity, are described.

Affinity Labels↗
PubMed1975

Immunologically specific production of interferon in cultures of rabbit blood lymphocytes: association with in vitro tests for cell-mediated immunity.

Lymphocytes of animals with delayed hypersensitivity produce mediators of cellular immunity when challenged in vitro with specific antigen. Among these are macrophage migration inhibitory factor (MIF) and interferon (IF). Nonspecific mitogens also induce the production of these lymphokines. In the following study leukocytes and column-purified lymphocytes of the same peripheral blood sample from tuberculin (purified protein derivatives [PPD])-sensitive rabbits were concurrently cultured in medium alone or with PPD. Supernatants of 1- and 4-day lymphocyte cultures were assayed for MIF. Supernatants of 1-, 2- to 4- and 5- to 7-day leukocyte cultures were assayed for IF by inhibition of cytopathic effect of vesicular stomatitis virus on rabbit kidney cultures. In the presence of PPD, normal lymphocytes did not produce MIF, but lymphocytes from sensitized animals did (8/8 animals), after 1 and 4 days of culture. Leukocytes from normal animals produced little or no IF when cultured with or without PPD. Leukocytes from sensitized animals cultured in medium alone produced little IF. However, when cultured with PPD they produced significant amounts of IF on day-1 (6/8 animals) and day-2 to day-4 (4/8) animals. There was no correlation between relative amounts of MIF and IF produced by cultures of respective cells from individual animals. Rabbit IF produced or released in vitro appeared in significant and maximum amounts by 24 h coincident with the time release of significant amounts of another mediator of cellular immunity, MIF.

Animals↗
PubMed1978

An in-vitro immunological assay for diagnosis of coeliac disease.

Production of leucocyte-migration-inhibition factor (L.I.F.) by peripheral-blood lymphocytes in response to challenge with gluten fractions was studied in 55 patients with coeliac disease and in 32 controls. 96% of the patients with coeliac disease demonstrated significant L.I.F. reaction in response to gluten fractions irrespective of their dietary status. Only 2 out of 32 controls had a positive reaction. This was in response to the B2 or B3 fraction, but never to both. The agarose microdroplet method of L.I.F. assay is reliable and technically simple enough for use in most clinical laboratories. The assay of L.I.F. production by peripheral-blood lymphocytes in response to gluten fractions, would be a useful adjunct in the diagnosis of gluten-sensitive enteropathy.

Adolescent↗
PubMed1978

Effects of cyclophosphamide on the expression and induction of delayed hypersensitivity.

Erythematous delayed reactions without induration, presumably assigned to Jones-Mote type, were characterized by the resistance to treatment with cyclophosphamide (CY) before elicitation or immunization in guinea pigs immunized with BGG in IFA or CFA. CY-treatment before elicitation converted delayed erythematous reactions from negative to positive at late intervals after immunization with BGG in IFA. Such a treatment augmented erythematous delayed reactions in animals immunized with BGG in CFA, but abolished induration at the reaction sites. CY-treatment before elicitation or immunization reduced the numbers of basophils at the reaction sites, although erythematous delayed reactions were augmented. Effector T cells responsible for delayed erythematous reaction without induration appear to persist for a long period of time after immunization in the presence of antibody production or tuberculin hypersensitivity and the expression of their function may be inhibited by suppressive mechanisms.

Animals↗
PubMed1976

Some physicochemical properties of human leucocyte migration inhibitory factor (LIF).

Leucocyte migration inhibitory factor (LIF) obtained from human lymphocytes stimulated with concanavalin A was consistently and irreversibly blocked by the serine-esterase inhibitor phenyl-methyl sulphonylfuoride (PMSF). This effect was not due to fluoride ions, hydrolysis products of PMSF or to impurities. PMSF pulse treatment of human buffy coat cells did not affect cell migration under agarose. LIF was also irreversibly destroyed by treatment with L-cysteine and 2-mercapto-ethanol, suggesting that the molecule contains disulphide linkage groups decisive for its configuration and biological activity. Di-sodium EDTA completely inhibited LIF activity but only if present during the entire migration period. Removal of EDTA before LIF assay restored LIF activity. Leucotye migration was neighter influenced by L-cysteine nor by EDTA. LIF activity was slightly diminished after treatment at 56 degrees C for 1 h and completely lost at 80 degrees C for 1/2 h. Furthermore, LIF appeared rather stable when treated at pH values between 4 and 11. These findings suggest, but do not prove, an esterase or a protease nature of human LIF.

Concanavalin A↗
PubMed1975

Properties and activities of transfer factor.

Although there is agreement that transfer factor endows skin test-negative subjects with the ability to develop the delayed allergic responses of the transfer factor donors, there is little direct information on the mechanism of this phenomenon or on the nature of the active components (s). This report reviews some of the known effects of transfer factor or immune responses and inflammation. It is concluded that transfer factor has multiple sites of action, including effects on the thymus, on lymphocyte-monocyte and/or lymphocyte-lymphocyte interactions, as well as direct effects on cells in inflammatory sites. It is also suggested that the "specificity" of transfer factor is determined by the immunologic status of the recipient rather than by informational molecules in the dialysates. Finally, it is proposed that many effects of transfer factor may be due to changes in intracellular cyclic nucleotide content, especially accumulation of cGMP, in immunologically reactive cells.

Antibody Formation↗
PubMed1978

The indirect assay for leukocyte migration inhibitory factor (LIF)--standardization and the effect of pH.

In the indirect assay for leukocyte migration inhibitory factor (LIF), lymphokine-rich supernatants were obtained by culture of stimulated lymphocytes and then tested for LIF activity in agarose plates using purified granulocytes as target cells. Studies on the standardization of the conditions under which LIF acts on the target cells are described, with emphasis on the use of "standard" supernatants of known LIF activity and the influence of pH on the action of LIF and the sensitivity of the assay. The observation that LIF activity is reduced when the ambient pH falls below 7.2 is suggested as an explanation firstly for the "escape" phenomenon seen particularly in capillary tube assays for LIF, and secondly for the reduced sensitivity of the capillarly tube assay in comparison with the corresponding agarose plate assay.

Granulocytes↗
PubMed2026

MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma.

Immune checkpoint inhibitors show insufficient efficacy against pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment (TME) has a remarkable influence on responsiveness to cancer immunotherapy. The aim of this study was to investigate immunosuppressive characteristics of TME in PDAC tissues. The flow cytometry (FCM) of PDAC surgical specimens revealed that the profile of tumor-infiltrating leukocytes was classified into myeloid cell- and T-cell-dominant subtypes; the myeloid subtype was associated with poorer patient outcomes. Myeloid-derived suppressor cells (MDSCs) showed the highest hazard ratio among various myeloid cell types. Single-cell RNA sequencing and FCM revealed that most MDSCs, but not lymphocytes, in PDAC tissues characteristically express CD74. Macrophage migration inhibitory factor (MIF), a CD74 ligand, was highly expressed in cancer-associated fibroblasts (CAFs) and cancer cells. Spatial transcriptomics demonstrated that the MIF-CD74+ myeloid cell interaction was recognized in CAF-dominant areas in PDAC tissue. CAFs expressing immune suppressor molecules such as MFAP5 and LRRC15 were consistent with MIF+ CAFs. Furthermore, MIF+ CAFs enhanced the migratory activity of MDSCs and promoted MDSC induction and activation. In the murine model, MDSCs were significantly increased in MIF-expressing PDAC tumors, as were CD74+ M-MDSCs per M-MDSC, confirming in vivo interaction between CD74 and MIF. MDSCs play a crucial role in creating an immunosuppressive TME in PDAC; the MIF-CD74 axis drives interactions between MDSCs and CAFs.

Humans↗
PubMed1979

Abrogation of cell-mediated immunity by a serum blocking factor isolated from patients with infectious mononucleosis.

Lymphocytes from 80% of patients with infectious mononucleosis in this study failed to produce macrophage migration-inhibition factor in response to partially purified early antigen of Epstein-Barr virus or to tetanus toxoid, whereas lymphocytes from normal subjects did produce this lymphokine. Subsequent analysis of serum from the patients with infectious mononucleosis revealed a serum factor that completely abrogated antigen-specific inhibition of migration by human leukocytes as well as lymphocyte blastogenesis. The serum blocking factor was present in sera from 11 (73%) of 15 patients with infectious mononucleos but only in sera from two (13%) of 15 normal subjects. Samples of serum from five of the patients with infectious mononucleosis and five normal subjects were fractionated with use of Sephadex G-200 gel filtration, and the eluants were assayed for several substances known to inhibit cell-mediated immunity. Serum blocking factor activity could be demonstrated only in fractionated sera from patients with infectious mononucleosis. The serum blocking factor is postulated to be either a soluble immune complex or some as yet unidentified immunoregulatory globulin contained in the IgG fraction of human serum.

Antigen-Antibody Complex↗