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Biomedical subjects

R S Geha

Publications and source records attributed to R S Geha.

At least 253 records · Page 14Linked to original sources
PubMed1983

Presence of circulating anti-idiotype-bearing cells after booster immunization with tetanus toxoid (TT) and inhibition of anti-TT antibody synthesis by auto-anti-idiotypic antibody.

We have previously documented the appearance of auto-anti-idiotypic (anti-Id) antibody in the serum of normal subjects after booster immunization with tetanus toxoid (TT) antigen. In the present study circulating auto-anti-Id-bearing cells and the regulatory role of auto-anti-Id antibody on anti-TT antibody synthesis were examined. Two adult volunteers were boosted with TT antigen, and IgG (Fab')2 anti-TT was prepared from plasma obtained 7 and 10 days after boosting. Auto-anti-Id antibody directed against autologous IgG (Fab')2 anti-TT became detectable in the serum starting 2 wk and up to 4 mo after booster immunization with TT. Circulating cells capable of specifically binding fluorescein-conjugated autologous IgG (Fab')2 anti-TT were identified starting 3 wk after immunization and throughout the 3- to 4-mo study period. Auto-anti-Id-bearing cells were predominantly B cells and secreted auto-anti-Id antibody after stimulation with pokeweed mitogen (PWM) in vitro. When added to cultures of peripheral blood lymphocytes (PBL) obtained 10 days after immunization, serum auto-anti-Id antibody inhibited the PWM-induced synthesis of IgG anti-TT. This inhibition was idiotype specific and affected predominantly the synthesis of anti-TT idiotypes recognized by the auto-anti-Id antibody. Auto-anti-Id antibody did not affect the synthesis of IgG anti-TT by PBL that co-circulated with the auto-anti-Id antibody. These results suggest that auto-anti-Id antibodies play a role in the regulation of the normal human immune response.

Adult↗
PubMed1983

Morphology of human T lymphocyte clones.

Six human T lymphocyte clones, characterized as to cytolytic activities and several surface markers, were investigated for possible morphologic correlates of function. Cytotoxic T lymphocyte clones and natural killer-like clones had basically similar morphology, but cytotoxic T lymphocytes tended to cluster in groups and had many more lipid bodies, whereas natural killer-like cells had fewer intercellular contacts and had more and larger electron-dense bodies. Dense bodies were also quite prominent in noncytotoxic clones. The latter were distinctive in having a minority of very large cells (10 to 16 microns) with many microvilli, scattered among the majority of 5- to 8-microns diameter cells.

Antibodies, Monoclonal↗
PubMed1983

Chronic urticaria in childhood: natural course and etiology.

We retrospectively studied 94 children with urticaria longer than six weeks in duration. The disease was equally distributed among the sexes and the following age subgroups (0-3.9 years, 4.0-7.9 years, 8.0-11.9 years and 12.0-15.9 years). A cause of the urticaria was identified or suspected in 15 of the patients. These included eight patients with cold urticaria, two with infection (hepatitis, sinusitis), two with food allergy, one patient with juvenile rheumatoid arthritis, one with arthralgia associated with a positive ANA and one with a low level of total hemolytic complement (CH50). Follow-up of a year of more on 52 patients revealed a median duration of urticarial symptoms of 16.0 months, with 58% of children becoming symptom free for six months or more, whereas the remaining 42% continued to have recurrent symptoms but without the development of an underlying serious illness. Results of the present study indicate that the etiology of chronic urticaria in childhood remains mostly undetermined but that the prognosis is generally favorable. However, one must consider an underlying infection or autoimmune disease as a potential etiology.

Adolescent↗
PubMed1982

Elicitation of the prausnitz-kustner reaction by antiidiotypic antibodies.

Rabbit antiidiotypic IgG directed against IgG F(ab')2 anti-tetanus toxoid (TT) antibodies ("idiotype") elicited a Prausnitz-Kustner reaction in normal skin sites sensitized 48 h earlier with the serum of the idiotype donor that contained IgE anti-TT antibodies. The serum moiety that caused the sensitization was heat sensitive (56 degrees C, 1 h), and was specifically removed by passage over immunosorbents containing rabbit antihuman IgE or TT antigen. The data obtained indicate that human IgG and IgE antibodies share idiotypic determinants and raise the possibility that idiotypic interactions may play a role in the regulation of the IgE antibody response in man.

Adult↗
PubMed1982

Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus B lymphoblastoid cells.

T cell proliferation in response to antigen requires the presence of an antigen-presenting accessory cell. The accessory cell most commonly associated with antigen presentation has been the macrophage (Mo). This study demonstrates that B cells in the form of Epstein Barr virus-transformed B lymphoblasts (EBV-B) are able to present tetanus toxoid (TT) to human T cells and induce proliferation of these cells. T cells freshly isolated from peripheral blood were shown to undergo blast transformation and proliferation in response to TT and irradiated EBV-B cells. Furthermore, TT-reactive T cell blasts were shown to proliferate in the presence of EBV-B cells and TT, but not with other antigens. There was a progressive increase to a plateau in T blast proliferation with increasing numbers of EBV-B cells added to the culture. The concentration of TT required for optimal antigen presentation was similar for EBV-B cells and for Mo. TT-specific cloned T cells also proliferated in response to TT and EBV-B cells and could be continuously grown in culture with TT, interleukin 2-containing supernatant, and EBV-B cells in place of autologous Mo. EBV-B cells pulsed with TT could also act as antigen-presenting cells. The proliferative response of T cell clones to TT in the presence of EBV-B cells was inhibited by antiserum to human p29,34 glycoprotein but not by anti-beta 2-microglobulin. This inhibition was shown to result from interaction with Ia-like determinants on EBV-B cells. These results indicate that B lymphoblastoid cells in man are able, like Mo, to present antigen to T cells in the context of Ia-like determinants.

Antigens↗
PubMed1982

Presence of auto-anti-idiotypic antibody during the normal human immune response to tetanus toxoid antigen.

Auto-anti-idiotypic antibodies were searched for in the serum of two individuals who received booster immunization with tetanus toxoid (TT) antigen. IgG from serial bleeds obtained for 4 mo after immunization was studied a) for its capacity to specifically bind 125I IgG F(ab')2 anti-TT prepared from serum obtained 7 and 10 days post-booster immunization, and b) for its capacity (after its absorption with TT) to specifically inhibit the binding of 125I-radiolabeled TT to IgG obtained 7 and 10 days post-immunization and designated "peak IgG." In both individuals studied, auto-anti-Id IgG were detected in both assays as early as 2 wk post-booster immunization and remained detectable throughout the study period. Evidence for modulation of idiotypic expression on IgG F(ab')2 anti-TT after booster immunization with TT was obtained by studying a) the capacity of serial IgG samples to inhibit the binding of 125I-IgG F(ab')2 anti-TT to rabbit anti-Id antibody raised against the IgG F(ab')2 anti-TT, and b) the capacity of the rabbit anti-Id to specifically inhibit the binding of 125I-TT to serial samples of serum IgG. Both assays indicated that some idiotypic determinants present on anti-TT obtained before and shortly after booster immunization were expressed to a much lesser extent 2 wk and beyond after immunization. The decrease in the expression of these determinants coincided with the appearance of auto-anti-Id antibody and remained evident throughout the 4-mo study period. The results obtained indicate that auto-anti-Id antibodies arise in normal human subjects after a secondary challenge with antigen and suggest that these antibodies may play a role in the modulation of idiotypic expression that is observed after booster immunization with antigen.

Animals↗
PubMed1981

Deficiency of T helper cells in transient hypogammaglobulinemia of infancy.

We studied 17 patients with transient hypogammaglobulinemia of infancy to define the immunologic defect responsible for this disorder. The number of circulating B cells in these patients was normal, as was the ability of the B cells to synthesize immunoglobulins when stimulated with Epstein-Barr virus, a direct B-cell activator. However, the capacity of the B cells to synthesize IgG in response to pokeweed mitogen, a T-cell-dependent B-cell activator, was depressed. Experiments with cultured lymphocytes indicated that excess suppressor-cell activity was not present in these patients, but that their T cells were deficient in providing help to B cells from their normal parents. A numerical deficiency in T4-positive (T4+) helper cells was found. Patients who had recovered from the disorder had a normal number of T4+ helper cells. Our results indicate that a numerical, as well as a functional, deficiency in helper T cells underlies the deficiency in IgG production in transient hypogammaglobulinemia of infancy.

Adolescent↗
PubMed1981

Nature of the immunogenic moiety recognized by the human T cell proliferating in response to tetanus toxoid antigen.

This study was undertaken to investigate the nature of the immunogenic moiety recognized by the human T cell which proliferates in response to tetanus toxoid (TT) antigen. Immunosorbent-purified anti-TT IgG antibodies failed, even when added in great excess, to inhibit T cell proliferation in response to TT. Urea-denatured (UD) TT antigen containing less than 1% native TT, as assessed by its reactivity with antibodies raised against native TT, triggered proliferation in T cells to an extent equal to that seen with native TT. The proliferative response to UDTT was seen only in T cells obtained from donors immune to TT and was inhibited by antisera to DRw antigens of the cell donor. T cells responding to TT and to UDTT essentially overlapped because exposure to 5'-bromo-2-deoxyuridine and light of T cells prestimulated with TT or UDTT abolished the specific response to both forms of the TT antigen but not to phytohemagglutinin or to Monilia antigen. It is concluded that proliferating human T cells recognize determinants which differ from those that elicit an antibody response and which may arise as a result of antigen processing by macrophages. The implications of these present results on the nature of the human T cell receptor for antigen are discussed.

Animals↗
PubMed1981

Macrophage T-cell interaction in man: handling of tetanus toxoid antigen by human monocytes.

An absolute requirement for monocytes was demonstrated in the T-cell proliferative response to tetanus toxoid (TT) antigen. Antigen-pulsed monocytes were shown to be effective in triggering T-cell proliferation. Using 125I-radiolabeled TT antigen, uptake by monocytes increased progressively over an 18-hr period, at which time 80-85% of the monocytes contained radiolabeled material. The ability of antigen-pulsed monocytes to trigger T-cell proliferation paralleled antigen uptake over an 18-hr period. Monocytes pulsed with antigen, then washed, lost their ability to trigger T-cell proliferation following a 24- to 48-hr culture period. Metabolic inhibitors blocked antigen uptake by monocytes and monocyte triggering of T-cell proliferation. Trypsin treatment of TT-pulsed monocytes did not affect the amount of antigen associated with monocytes or T-cell triggering by monocytes. Anti HLA-DR alloantibodies, which when added during antigen pulsing of monocytes inhibit the capacity of these monocytes to trigger T-cell proliferation, did not interfere with antigen uptake. These results indicate that human monocytes present antigen to T cells via an active process and in association with Dr determinants, and that the immunogenic moiety of antigen does not remain indefinitely available to the T cell.

Antigens↗