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At least 667 records · Page 37Linked to original sources
PubMed2003

Mimotopes of tumor-associated T-cell epitopes for cancer vaccines determined with combinatorial peptide libraries.

Cytotoxic T-cells are the most important effector cells in immune responses against tumors. The identification of tumor-associated epitopes for these cells, therefore, has become a key aspect of the development of cancer vaccines. Here, we describe a new approach to the determination of tumor-associated T-cell epitopes which employs combinatorial peptide libraries with singly defined sequence positions in a randomized context. The analysis of the responses of a T-cell clone to these libraries yields the amino acid constituents of the epitope which can be combined to obtain mimotopes that are suitable as vaccine antigens for the induction of tumor-specific responses.

Amino Acid Sequence↗
PubMed2005

Pediatric heart transplantation across ABO blood type barriers: a case study.

Heart transplantation with ABO blood type-incompatible donors has historically been contraindicated because of the high risk of an immediate hyperacute humoral graft rejection. The immature neonatal immune system presents an immunologic window that allows for breaching the ABO barrier before the natural development of anti-ABO antibodies. Information from a small series of neonates has demonstrated similar survival rates and posttransplant outcomes compared to ABO-compatible transplantations. In the posttransplant period, particular attention is placed on the surveillance of graft-specific antibody production and monitoring for immunologic signs and symptoms of early graft vasculopathy. This article presents a case study of a neonate with congenital heart disease who underwent one of the first successful ABO-incompatible heart transplantations in the United States.

ABO Blood-Group System↗
PubMed1984

Homogeneous luminescence immunoassay for total estrogens in urine.

We describe an homogeneous luminescence immunoassay for "total" estrogens in enzymically hydrolyzed urine from nonpregnant women. The antiserum, raised against estriol-16,17- dihemisuccinate conjugated to bovine serum albumin, specifically bound the C-19 steroids carrying the estrogen-characteristic phenolic group. 17 beta-Estradiol conjugated with aminobutylethyl isoluminol was used to monitor the immunological reaction; this conjugate was stable for at least two years. Because binding to the antiserum markedly enhances the light-producing efficiency of the tracer, no separation of bound and free antigen is necessary. Results (microgram/24 h) by this method (y) correlated well (r = 0.958) with those by a conventional fluorometric (x) method (y = 2. 51x - 2.83). The sensitivity (detection limit) is 4 micrograms/L and the precision compares well with that of commonly used RIA methods. The method appears suited to large numbers of samples, as in menstrual cycle monitoring.

Cross Reactions↗
PubMed2002

Regulation of CD1d expression by murine tumor cells: escape from immunosurveillance or alternate target molecules?

alpha beta+ TCR T cells recognize peptide fragments displayed by MHC-class I or -class II molecules. Recently, additional mechanisms of antigen recognition by T cells have been identified, including CD1-mediated presentation of nonpeptide antigens. Only a limited number of CD1 antigens is retained in the mouse, i.e., the group II CD1 antigens, which are split into CD1D1 and CD1d2. Several T cell subsets have been shown to interact with murine CD1 antigens, including NK cells or "natural T cells" with the invariant V alpha 14 J alpha 281 TCR chain. Even if TAP defects may prevent classical endogenous antigen presentation in tumor cell lines, antigen presentation via CD1 is still functional. Therefore, CD1-mediated recognition of transformed cells by NK cells or "natural T cells" may represent an alternative way for immune surveillance. CD1 cell surface expression in murine tumor cell lines of different histology, including the B cell lymphoma A20, macrophage cell lines J774 and P388D1, mastocytoma P815, thymoma EL-4, melanoma B16, colon adenocarcinoma MC-38 and renal carcinoma Renca is regulated by Th1- (IFN-gamma), Th2- (IL-4, IL-10 and vIL-10) or GM-CSF (Th1/Th2) cytokines, depending on the tumor histology. In order to distinguish between CD1D1 and CD1d2 molecules, we examined differential expression of these CD1 isoforms by ratio RT-PCR: A20, EL-4, P815 and MC-38 cells exclusively express CD1D1 transcripts but not CD1D2 mRNA independent of cytokine treatment. Decreased CD1d expression leads to reduced immune recognition of CD1d+ tumor cells by freshly isolated NK1.1(+) effector cells as defined by cytolysis and IFN-gamma release. Thus, modulation of CD1 expression on tumor cells by cytokines may be advantageous to drive cellular anti-tumor antigen directed immune responses directed against TAP-independent, non-classical MHC restricting molecules.

Animals↗
PubMed1991

Sequential interleukin 2 and interleukin 2 receptor levels distinguish rejection from cyclosporine toxicity in liver allograft recipients.

Previous studies of renal transplant recipients have demonstrated that allograft rejection is accompanied by an increase in plasma and urinary levels of interleukin 2 and its soluble receptor before the development of clinical symptoms. After measuring interleukin 2 and interleukin 2 receptor levels in the plasma, bile, and urine of liver transplant recipients, we found that rejection is preceded by elevation of plasma and biliary levels of both substances, that cyclosporine toxicity did not affect either of these levels, and that urinary levels of the substances are unaffected in either condition. Levels of interleukin 2 and interleukin 2 receptors increased in bile earlier than in plasma, and interleukin 2 levels did not overlap among stable patients and those experiencing rejection, whereas levels of interleukin 2 receptors did. Serial measurements of interleukin 2 levels, particularly in the product of the transplanted organ, provide a reliable assessment of the immunologic status of the allograft.

Bile↗
PubMed1992

[The immunologic studies on experimental heterogeneous penetrating keratoplasty].

Using the experimental model of chicken-rabbit penetrating corneal grafting, micro-whole-blood 3H-TdR incorporation and ELISA the authors dynamically observed the functional state of cellular and humoral immunities for 10 weeks after operation. The results showed, (1) In both the homogroup and the hetero-group, the transformational degree of lymphocytes in peripheral blood increased, most obviously in the 3rd or 4th week postoperatively. (2) In the hetero-group, specific anti-corneal antibody appeared obviously in the serum during 2-8 weeks postoperatively. Combined with morphologic observation, it has proved that: (1) The immune rejection is mainly cellular mediated immunoresponse, meanwhile, the humoral immunoresponse also participates in it, and the humoral immunoresponse participates in the heterokeratoplasty more obviously. (2) Applying the micro-whole-blood 3H-TdR incorporation is capable of determining the immunologic state of the body after corneal transplantation. (3) Attention should be focused on the 3-4 week period postoperatively when immunosuppressive-agent is administered.

Animals↗
PubMed2006

The relationship between migraine and atopic disorders-the contribution of pulmonary function tests and immunological screening.

This cross-sectional clinical study was conducted in order to explore the relationship between atopic disorders and migraine. We evaluated 186 consecutive patients with migraine. Patients with a history of atopic disorders were compared with the others during headache-free intervals, for their headache characteristics, pulmonary test (PFT) performances and immunological screenings, through appropriate statistical methods. Of the patients with migraine, 77 (41.4%) reported at least one atopic disorder. PFT screening showed a general decreased pulmonary capacity and an important correlation between a positive history of atopic disorders and both increased eosinophil and IgE levels in headache-free periods. It should be discussed whether screening with PFT or immunological tests helps in early detection of progressive lung disease which might develop in these patients.

Adolescent↗
PubMedDate not supplied

Phenotypic and functional analysis of peripheral blood lymphocytes during interferon-alpha 2b therapy in multiple myeloma patients with low tumor mass.

BACKGROUND: IFN-alpha has recently been shown to prolong the remission phase in MM patients with low tumor mass. So far, it is not known whether IFN-alpha exerts its effect directly on the myeloma cells or is mediated by modulation of the host response. METHODS: The immune status of 12 multiple myeloma patients with low tumor mass (10 in remission phase, 2 with stage IA disease) was investigated by phenotypic and functional analyses before, after 3, and after 6 months of recombinant interferon-alpha 2b (IFN-alpha) therapy. RESULTS: Phenotyping of peripheral blood lymphocytes (PBL) revealed a significant decrease of HLA-DR+ (P = 0.01) and CD20+ (P = 0.04) cells after 6 months of therapy. Two-color phenotyping of purified T cell populations (PBT) showed a significant increase of CD4+ CD11b+ cells (P = 0.01) after 6 months of therapy. Functional analyses were carried out on PBL (NK cell-mediated cytotoxicity) and PBT (alloreactive cytotoxicity, CTL; IL2-induced cytotoxicity, LAK activity). NK and CTL activities were poorly influenced by IFN-alpha treatment, whereas LAK activity showed a significant increase (P = 0.007). Any significant association between these immunological changes and the disease status was questioned by the lack of differences between MM in relapse and MM with stable disease at the sixth month of IFN-alpha therapy. CONCLUSIONS: i) IFN-alpha in MM with low tumor mass may exert its therapeutic activity by directly acting on the tumor cells; ii) the parameters which have been used in this study are not appropriate to monitor the immunological effects (if any) of IFN-alpha therapy.

Antigens, CD↗
PubMed1992

Autotransplanted jejunum in patients with carcinomas of the head and neck: transport of immunosurveillance against tumor cells?

Autologous jejunum, transplanted as a functional replacement immediately after radical dissection of advanced stages of squamous cell carcinomas of the head and neck and subsequently irradiated, was examined by immunohistochemistry (APAAP/PAP-technique). Biopsies from 9 patients were taken at the time of transplantation and up to 24 months thereafter (group 1) and from 5 patients only once after transplantation (group 2). Twenty-six monoclonal antibodies (mAbs) were used as surface markers to give an overview about phenotypical changes with respect to T-, B- and M phi-antigens. 1) B cells: a general increase of CR2+ (CD21, p less than 0.01) could be noticed after transplantation, immunoglobulin positive cells remained unchanged expect for a significant decrease of IgM+ (p less than 0.01) and IgA1+ (p less than 0.01) cells. 2) The number of T cells (CD3+) showed no significant differences although TcR gamma/delta+ cells decreased (p less than 0.01) in the autotransplant. ICAM-1 (CD54) and IL-2R (CD25) were found on a significant (p less than 0.01) higher number of cells after transplantation. 3) Cells with M/M phi morphology showed increased expression of the Fc gamma receptors (CD64, p less than 0.001; CD32, n.s.; CD16, p less than 0.001), of the complement receptors CR1 (CD35, (p less than 0.001) and CR3 (CD11b, p less than 0.02), of HLA-DQ (p less than 0.01), and of the antigens 25F9 (mature M phi; p less than 0.01) and CD4 (p less than 0.02). Correlation analyses of data obtained from the biopsies of the 14 autotransplanted jejunum cases revealed a CD35+ and a 25F9+ subpopulation of M/M phi. Our findings indicate that despite irradiation autotransplanted jejunum contained cells with immunological capacities. Therefore, the replacement of larynx by autologous jejunum may facilitate not only mechanical but also immunological functions.

Adult↗
PubMed1979

Leishmanial excreted factor: protein-bound and free forms from promastigote cultures of Leishmania tropica and Leishmania donovani.

Leishmania spp. growing in culture produce an immunologically active substance called excreted factor (EF), which precipitates antibodies raised against intact cells and has been implicated as the conditioning agent for parasite infection of host macrophages. An improved method for isolation of the material is described, based on Sephadex column chromatography of growth medium which had been boiled at pH 5.0. This procedure allows the detection of differences among the EF molecules of different species, and it overcomes previous shortcomings through the monitoring of immunological activity throughout. Analysis of the products of this procedure revealed that EFs from Leishmania tropica and Leishmania donovani share a common carrier protein, identified as rabbit serum albumin, and are chemically quite similar. Growth medium from L. tropica boiled at acidic pH contains primarily an EF-albumin complex of 75,000 molecular weight. Treated growth medium from L. donovani, on the other hand, contains both the albumin complex and a smaller molecule (less than 27,000 molecular weight) that is not associated with rabbit protein. This material accounts for nearly 20% of the EF of one L. donovani strain, but constitutes only a minute fraction of L. tropica EF. Treatment of the EF-albumin complex with trichloroacetic acid separates the molecule into two major subunits, one having a molecular weight of about 61,000 (without anti-Leishmania activity) and the other having a molecular weight of about 18,000 (with no anti-rabbit activity). The protein-free EF of L. tropica differs from that released by trichloroacetic acid extraction in that it is capable of precipitating antisera of nonhomologous serotypes, whereas the albumin complex and the trichloroacetic acid-treated EF fragment are not. EFs from both species display pH-dependent affinity for certain lectins.

Carrier Proteins↗
PubMed2002

The use of immunoglobulins in the treatment of human epilepsy.

The use of immunoglobulin (IVIg) in intractable epilepsy is one of its oldest applications in medicine, starting from the empirical observation of its beneficial effect on seizures. Immune system dysfunction may play a role in epilepsy by triggering, maintaining or, unexpectedly, improving intractable seizures. Several laboratory and clinical investigations are in favor of an immunological basis for different forms of experimental and human epilepsies. A wide range of immune abnormalities have been reported, suggesting the existence of different subtypes of epileptic syndromes with different abnormalities of the immune system. In this view, IVIg with its broad immunomodulatory mechanism of action could be effective in different forms of immune-dysregulated intractable epilepsies. Non-immunological mechanisms of action have been also suggested, based either on human epilepsy data or on animal experimental data. The possible anticonvulsant properties and the ability of IVIg to interfere with the final common pathway of seizures at a cellular level, with a significant increase in seizure threshold, have been demonstrated in different experimental epilepsy model. Although IVIg may represent a valuable resource in some drug-refractory epilepsies and its effectiveness has important pathogenetic implications, controlled studies with the systematic monitoring of immunological markers are needed to define more precise indications and to optimize the administration protocols.

Blood-Brain Barrier↗
PubMed1994

Circulating serum levels of soluble CD23 (sCD23) after renal transplantation.

In the present study the role of sCD23 determination in the management of renal graft recipients during the early postoperative period has been evaluated. In the majority of patients, increases in sCD23 serum levels were observed up to 3 days before the manifestation of an acute rejection (in 82% of cases) or infection episode (in 73% of cases), but no discrimination between these two clinical events was possible. This rise in sCD23 levels was significantly more pronounced than fluctuations observed in patients with uncomplicated courses or with graft dysfunction due to acute tubular necrosis. Serum levels of sCD23 were not influenced by excretory kidney function. These findings indicate that, in addition to its reflecting B-cell function, sCD23 may also play a role in immunological processes involving T cells and/or monocytes, thus indicating a broader range of activity of this cytokine-like molecule than has been previously assumed.

Adolescent↗
PubMed1980

[Theoretical Basis of Hyposensitization. (author's transl.)].

Hyposensitization was introduced in 1911 and after nearly 70 years of this kind of immunotherapy the mechanisms involved are still obscure. Although some results may be conflicting, there is much evidence from many placebo-controlled studies that hyposensitization has a beneficial effect in patients with allergic diseases. A critical view of the immunological effects shows that increased local and systemic tolerance to the injected allergens seems to be caused by many mechanisms. The injection treatment apparently triggers the synthesis of so-called blocking antibodies, reduces IgE production and may influence the mode of macrophage presentation of allergenic determinants to the immunocompetent lymphocyte and/or the stimulation of T suppressor cells. Considering these assumptions, the understanding and probably the future of hyposensitization depends on the production of better characterized allergen extracts and on the development of simple methods for the monitoring of immunologic effects during therapy.

Antibody Formation↗
PubMed2006

Cellular pharmacodynamics of immunosuppressive drugs for individualized medicine.

The therapeutic effects of immunosuppressive drugs are known to deviate largely between patients, but efficient strategies for the differentiation of patients who show clinical resistance to immunosuppressive therapies have not been established. Accordingly, a considerable number of patients receive treatment with immunosuppressive drugs despite the onset of serious side effects and poor responses. Cellular pharmacodynamics of immunosuppressive drugs in vitro using peripheral lymphocytes derived from each patient, an attractive way to distinguish resistant patients, is respected and has been applied to the carrying out of individualized immunosuppressive therapy. In this article, I summarize experimental procedures for assaying immune cell responses to immunosuppressive drugs in vitro, and highlight the relationship between cellular sensitivity to immunosuppressive drugs and the therapeutic efficacy of drugs in organ transplantation and several immunological disorders. I will also overview the molecular mechanisms and genetic bases for cellular and clinical resistance to immunosuppressive drugs. Lastly, the future clinical prospects for the application of in vitro drug sensitivity tests for "patient-tailored" immunosuppressive therapies are discussed.

Cells, Cultured↗
PubMed1993

Langerhans cells, immunomodulation and skin lesions. A quantitative, morphological and clinical study.

The epidermal Langerhans cell (LC) plays an important role in contact hypersensitivity reactions by presenting the antigens to T lymphocytes. LCs may also play a role in defence mechanisms against neo-antigens in skin tumours. Some studies have indicated that the LC population declines with age. Ultraviolet radiation induces a significant reduction in the number of epidermal LCs and most immunosuppressive drugs decrease the number and function of LCs as well. Such alterations in LCs might predispose to the development of skin tumours. To evaluate the importance of LCs in immunosurveillance of skin tumours, the number and the morphology of LCs was investigated in unaffected skin of patients with cutaneous tumours and in immunosuppressed patients. LCs within basal cell carcinoma (BCC) were examined as well. ATPase and CD1a staining was used to visualise LCs. The inflammatory response around BCC was estimated by the expression of HLA-DR+, CD3+ and ICAM-1+ cells. The prevalence of skin tumours was studied in renal transplant recipients on different immunosuppressive treatments such as azathioprine (Aza) and prednisolone (P), cyclosporin (CyA), azathioprine and prednisolone or cyclosporin and prednisolone. We found no difference in LC populations in patients treated with PUVA (psoralen and UVA-radiation) or in patients with skin tumours as compared with controls and no age-related reduction in LC numbers. However, immunosuppressed patients showed a reduced number of LCs, especially those who had received triple drug therapy (CyA+Aza+P). Patients treated with azathioprine and prednisolone (10-25 years) had a high prevalence of multiple warts (40%) and skin tumours (29%). In contrast, warts and skin tumours were not common in patients treated for 5 years with CyA+Aza+P or with CyA+P. Thus, the duration of immunosuppressive treatment seems crucial for the development of warts and skin tumours. However, the reduction in LC numbers was not more pronounced with time or in patients with skin lesions as compared with those without lesions. In the epidermis overlying basal cell carcinoma (BCC) the number of LCs was decreased and their morphology changed as compared with LCs in perilesional skin. These alterations were documented in horizontal sheets as well as in vertical sections of the epidermis analysed by light microscopy and with confocal laser scanning microscopy (CLSM). The latter technique permits a quantitative and morphological analysis of LCs in the same tissue volume. In vertical sections, numerous LCs were observed in the dermis surrounding BCC nests.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphatases↗
PubMed1991

In vitro study of immunologic changes in long-term cytapheresis donors.

Several in vitro measurements of immune function were examined retrospectively in a population of active long-term cytapheresis donors (group I; n = 50) and the results were compared to age- and sex-matched controls (group II; n = 50) who had donated only whole blood. In group I, significantly different mean absolute lymphocyte counts (P = .0025), total T-cells (P = .0026) and T-helper cells (P less than .0001), and helper-to-suppressor ratios (P = .0279) were present. No differences were noted between the two groups for peripheral blood mean B-cell count, T-suppressor numbers, lymphocyte responsiveness to mitogens or alloantigen, and serum immunoglobulin level. The reduced mean absolute lymphocyte count in group I was due to the reduction in T-helper cell numbers and accounted for the imbalance in the helper-to-suppressor ratio. These disturbances are currently unexplained and, while no clinical consequences have so far become evident, there is a need to continuously monitor the immunologic status of cytapheresis donors. It is also important to determine whether reversal of the defects occurs and, if so, over what time interval.

Adult↗