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PubMed1987

Characterization of helper T cells induced by the type 2 antigen polyvinylpyrrolidone.

Type 2 antigens are usually unable to prime for IgG memory responses or to activate helper T cells (TH) necessary for memory B cell generation. Previous studies from this laboratory have established that low doses (0.0025 microgram) of polyvinylpyrrolidone (PVP) or a T-dependent form of PVP, PVP-coupled horse red blood cells (PVP-HRBC) can activate PVP-specific TH. The present study was undertaken in order to determine some of the characteristics of the TH activated by PVP and to compare their properties with those of classical TH1 and of TH2 cells described in many T-dependent systems. TH activated with either 0.0025 microgram of PVP or PVP-HRBC were characterized with respect to cell surface antigens, Igh restriction and generation in mice expressing an X-linked immune defect (xid mice). PVP-specific TH are similar to TH1 cells in that they are required for the production of IgG subclasses absent in primary responses and have the Lyt-1+, L3T4+, I-J-surface phenotype. These TH may not be identical with TH1 cells, however, since they are I-A+ and Igh restricted. PVP-specific TH can be generated in xid mice which do not produce antibody in a primary anti-PVP response and do not develop a memory response to PVP, regardless of whether it is presented as a type 2 or T-dependent antigen.

Animals↗
PubMed1987

Synergistic effects of the xid gene in X chromosome congenic mice. I. Inability of C3.CBA/N mice to respond to thymus-dependent antigens in adoptive transfer assays.

The xid gene, which causes a B lymphocyte immune defect in CBA/N mice, has been bred onto the C3H/HeN background. The resulting X chromosome congenic mice (C3.CBA/N) exhibit immunologic defects that are much more profound than the defect exhibited by CBA/N mice; thus, the B cells from C3.CBA/N mice not only fail to respond to thymus-independent (TI) type 2 antigens such as TNP-Ficoll, but they fail to respond in vitro to TI-type 1 antigens such as TNP-Brucella abortus (BA) and B cell mitogens such as LPS and Nocardia water-soluble mitogen. In this paper we show that the synergistic defect seen in C3.CBA/N B cells is also elicited in adoptive transfer assays to thymus-dependent (TD) antigens such as TNP-KLH and PC-KLH, antigens to which both parental strains respond. Thus, the secondary adoptive transfer response of C3.CBA/N spleen cells is generally less than 5% of the immune response produced by CBA/N or C3H/HeN spleen cells. This synergistic defect is restricted to the C3.CBA/N B cells, since C3.CBA/N T cells can provide help to CBA/N B cells that is equivalent to the help obtained with CBA/N T cells. The low responsiveness of C3.CBA/N spleen cells to TD antigens, which is elicited in adoptive transfer assays, is not seen when the intact animal is immunized with antigen in CFA; this, intact C3.CBA/N mice produce anti-PC-KLH and anti-TNP-KLH responses only slightly lower than the responses of CBA/N mice to these same antigens. In contrast, when these mice are immunized with phenol-extracted LPS, a TI-type 1 antigen, their antibody responses are severely depressed. These data suggest that under conditions in which T cell help may be limiting or in which the intact physiology of the T and B cells has been disrupted, C3.CBA/N B cells demonstrate profound immunologic impairment; however, when adequate T cell help is available and the splenic architecture is not disrupted, their immune responses appear to progress in a normal fashion.

Animals↗
PubMed1988

[Diagnostic studies in patients suspected of having an immunodeficiency disorder].

Knowledge of the normal structure and function of the human immunological defence system, as well as of its disorders has increased considerably during recent decades. On the basis of this an operational classification of immunodeficiency diseases can be made. In this contribution patterns of infection and associated symptoms, characterizing the different types of primary immunodeficiency diseases, are described. Also a protocol for the assessment of the immunological competence is proposed. A characteristic feature of this protocol is a graduation in stages of tests with increasing complexity. The aim of such a grouping is to tackle the presenting problem in a systematic manner, as well as to avoid needless burden to the patient and excessive costs. However, this does not obviate the need for expert knowledge of and experience with immunodeficiency diseases, in order to be able to ask for the appropriate laboratory tests, to judge the results of these tests and to appreciate their relevance for the clinical problem.

Antibody Formation↗
PubMed1988

[The significance of determining humoral defense factors: Ig isotypes, specific antibodies and complement].

The diagnosis of an immunodeficiency is made after detailed clinical and laboratory investigations. To guide these investigations the Dutch Working Group on Immunodeficiencies had made a protocol for evaluating the functioning of the immune system of patients. The protocol is based on the report 'Immunodeficiency' from a WHO scientific group. This paper discusses the value of laboratory investigations on the following aspects of the immune system: immunoglobulins and their subclasses, primary and secondary antibody responses in vivo, and the complement system. The evaluation of these components of the defense system can firmly establish possibly occurring severe immunodeficiency states. Some cases of chronic and/or recurrent infections, however, remain enigmas that have to be resolved by future investigations on the interactions of infectious agents with the immune system.

Antibodies↗
PubMed1987

Molecular analysis of heavy and light chains used by primary and secondary anti-(T,G)-A--L antibodies produced by normal and xid mice.

The primary (1 degree) antibody response to (T,G)-A--L shows limited heterogeneity, consisting mostly of side chain-specific antibodies that bind GT and that express the TGB5 idiotype (Id). The secondary (2 degrees) response is very diverse: antibodies that bind the backbone A--L constitute a third of the response, and a high proportion of the side chain-specific antibodies do not bind GT and are TGB5 Id-. To provide a molecular basis for understanding this difference in repertoire expression, we analyzed the Ig genes used by heavy and light chains of 1 degree and 2 degrees side chain-specific anti-(T,G)-A--L hybridoma antibodies (HP). Southern blot restriction analysis and nucleotide sequence analysis of the expressed genes used by three TGB5 Id+ 2 degrees HP showed usage of three different VH genes in two VH gene families (36-60 and J558), different D segments, and two different Vk1 genes (the Vk1A and Vk1C subgroups). Thus, antibody heterogeneity in the 2 degrees response is contributed by combinatorial diversity of distinct germ-line genes. Nucleotide sequence analysis of the expressed genes used by TGB5 Id+ 1 degree HP showed use of highly homologous VH genes in the J558 VH gene family and highly homologous Vk1A genes. The majority of TGB5 Id+ 1 degree HP from different donors gave similar heavy and similar light chain gene rearrangements by Southern blot restriction analysis, after correction for known or potential J region differences. The combined nucleotide sequence and Southern blot restriction analysis data suggest that most 1 degree B cells use the same or very similar VH and Vk genes, i.e., the 1 degree response is paucigenic. Different D segments were used by the TGB5 Id+ 1 degree and 2 degrees HP that were sequenced, and there was no apparent correlation between TGB5 idiotypy and VH, D gene, or JH gene usage. However, all TGB5 Id+ HP sequenced used highly homologous genes from the Vk1 group. Expression of a Vk1 light chain correlates with, but is not sufficient for, TGB5 idiotypy, because one GT-binding, TGB5 Id- HP was found to use a Vk1C subgroup light chain. By Southern blot and nucleotide sequence analysis, the Vk genes used by two TGB5 Id+ 2 degrees HP from xid mice are highly homologous, if not identical to the Vk1A gene(s) used by 1 degree and 2 degrees Id+ HP from wild-type mice.

Amino Acid Sequence↗
PubMed1977

Alterations in host responsiveness in patients with prostatic cancer following cryosurgery or transurethral resection.

Anesthesia, stress, trauma or the operation per se have been reported to result in alterations of host resistance in a wide range of diseases. The effect of such changes on the thymolymphatic system of patients with prostatic cancer is not known. While evaluating in vitro parameters of cellular immunologic responsiveness in patients with prostatic cancer, we have observed a depression two to seven days following cryosurgery or transurethral resection (TUR) of the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBL). Contrary to the reduced proliferation of PBL cultured in autologous and homologous serum from patients receiving TUR, patients receiving cryosurgery, while also showing reduction in autologous serum, showed increased responsiveness when cultured in homologous serum. Although transient, depression of lymphocyte proliferation, particularly if involving tumor-cloned T-cells, may provide reduced surveillance to potential metastatic tumor cells leading to an alteration of tumor-host homeostasis. The potential of reduced surveillance, at least in the case of TUR, appears to be supported by observations that patients dying from prostatic cancer at our institution had an antecedent TUR. Identifying those patients with changes in responsiveness before surgery, as well as those prone to develop or undergo further reductions in responsiveness after surgery, would appear to be relevant in the management of patient with prostatic as well as other malignancies. Pre- and/or postoperative immunotherapy in such patients may be indicated.

Aged↗
PubMedDate not supplied

[Evaluation of thymic hormone and E-rosettes in patients with IgA deficiency].

We have investigated lymphocyte subpopulations and T cell functions, in particular E rosettes and serum level of thymic factor in ten young patients (aged 6 to 20) with partial and selective IgA deficiency. The control group included ten age-matched healthy subjects. Significantly depressed levels of serum thymic factor were found in six patients. These results were correlated with the decreased number of E rosettes found in five of them, and support a T-cell involvement in IgA deficiency.

Adolescent↗
PubMed1977

Phagocytosis. Clinical disorders of recognition and ingestion.

Tentative conclusions concerning the role of recognition and ingestion of microorganisms by phagocytes in host defense and the consequences of disorders of phagocytosis can be derived by correlating a) knowledge about recognition and ingestion derived from studies in vitro, b) investigations of the clearance of particulate matter from the circulation of animals and man, and c) analyses of the behavior of phagocytes in patients susceptible to recurrent pyogenic infections. Deficiency of the major serum recognition-conferring (immunoglobulins and complement proteins that deposit a fragment of C3 on microbes) prevents the optimal clearance of virulent encapsulated pathogens by fixed mononuclear phagocytes. Confrontation of phagocytes with particulate matter appearing in pathologic states (viruses, immune complexes, damaged erythrocytes in sickle cell anemia and other hemoglobinopathies) diverts them from their normal task of clearing opsonized encapsulated microorganisms. Corticosteroids impair the phagocytic capacity by an unknown mechanism. Major impediments to progress in this field are inadequate assays for phagocytosis and the difficulty in measuring phagocytosis in the intact organism.

Anemia, Sickle Cell↗
PubMed1987

Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells.

Little is known of the role of T-cell mediated immune responses in the clearance and pathogenesis of respiratory syncytial virus (RSV) infection. In this study, we established persistent pulmonary RSV infections in athymic nu/nu BALB/c mice or immunodeficient irradiated BALB/c mice, and examined the patterns of virus clearance following adoptive transfer of splenic memory T cells. Primed T cells transferred between Day 5 and Day 8 of infection will clear lung RSV from both nu/nu mice and irradiated mice within 10 days of transfer. Partially purified Lyt 2+ T cells are more effective than L3T4+-selected T cells. No RSV-specific serum antibody could be detected, suggesting that clearance is by an antibody-independent mechanism. In contrast, delayed (Day 14) transfer of primed L3T4+-selected cells clears lung RSV from nu/nu mice, and this correlates with RSV-specific serum antibody production. Clearance is not seen following Day 14 transfer of total primed T cells or T cells selected for the Lyt 2+ subset.

Animals↗
PubMed1986

Treatment of congenital immune deficiencies with a thymic hormone--thymic humoral factor.

Five infants with congenital immune defects are presented. Three had various combined immune deficiencies (CID) and two had thymic deficiencies only. As bone marrow or thymus transplantations were not feasible in these patients, we attempted treatment with thymic humoral factor (THF), a thymic hormone, by daily i.m. injections during biweekly courses. In one CID patient, a partial improvement in immune indices and temporary clinical improvement were achieved. In the other two, THF did not arrest the patients' demise. The two patients with thymic dysplasia benefitted repeatedly from THF treatment, as exemplified by the disappearance of wasting, diarrhea and infections and by reconstitution of T cell parameters. Nevertheless, the patients relapsed after prolonged periods without THF administration. We therefore propose the administration of long-term, continuous or intermittent thymic hormone replacement therapy in infants with congenital thymic defects. Early diagnosis and immediate institution of treatment will probably improve prognosis.

Female↗