Why do some individuals produce autoreactive antibodies against receptors and/or their ligands? A possible answer to the question. A review with implications.
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Age Factors↗
Biomedical subjects
B L Hansen
Publications and source records attributed to B L Hansen.
[Iron poisoning as a risk in the treatment of nephrogenic anemia].
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Adolescent↗
[Captopril in the treatment of hypertension in patients with renal insufficiency].
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Adolescent↗
Immunocytochemical demonstration of mammalian lutropin-like material in the pituitary of the lungfish, Lepidosiren paradoxa.
The presence of lutropin (LH)-like material in the pituitary gland of the South-American lungfish, Lepidosiren paradoxa, has been demonstrated by means of the unlabeled antibody-enzyme method, by use of rabbit anti-ovine LH as first antibody. The LH-like substance was revealed in a single PAS-positive cell type primarily located in the anterior part of the distal lobe. Dot blot tests as well as conventional liquid-phase absorption experiments indicate that the anti-ovine LH antibodies possess specificity against the oLH beta subunit. These observations indicate that dipnoans (Lepidosiren) share a number of antigenic determinants with those of mammalian LH beta and support the concept that mammalian LH beta, or part of it, was established early in evolution. The exact nature and physiological function of the substance detected remains to be defined.
Animals↗
Autoantibodies in sera from patients with multiple sclerosis directed against antigenic determinants in pituitary growth hormone-producing cells and in structures containing vasopressin/oxytocin.
We have reported previously that autoantibodies in sera from patients with multiple sclerosis (MS) were reactive with rat brain, including pituitary, and with swine pituitary in areas thought to contain peptides of the somatotropin family and/or vasopressin/oxytocin. We have now tested the same patient sera for their specificity to antigenic determinants which are common to animal and human peptides. Localization of the binding sites of the MS sera was demonstrated in rat pituitaries and brains using the double immunofluorescence staining method, employing anti-bovine somatotropin (STH), anti-ovine prolactin (PRL), anti-neurophysin I and II, anti-somatostatin, and anti-vasopressin as reference antibodies. In the pituitary, the positive MS sera reacted specifically with cells which were also reactive with anti-bSTH. In the brain, positivity of MS sera was mainly localized in structures reactive with anti-neurophysin I and II and anti-vasopressin. Absorption experiments, immunocytochemical model assays, and radioimmunoassays, however, did not show specific binding of the MS sera to any of the above-mentioned peptides. Therefore, while these data present additional evidence on the localization of the immunocytochemical reaction sites of the MS autoantibodies, they do not enable us to identify the specificity of these antibodies.
Animals↗
High-dose survival in the lymphocytic choriomeningitis virus infection is accompanied by suppressed DTH but unaffected T-cell cytotoxicity.
Provided that intracerebral inoculation is applied, an increase in the virus dose from 10(2) to 10(4) LD50 of lymphocytic choriomeningitis virus (LCMV) leads to strikingly reduced mortality. To analyse the background for this autointerference, we measured several virologic and immunologic variables in mice infected with these doses of virus. In the high-dose mice we found generally higher organ virus titres and serum interferon titres than in the low-dose mice. Since we could demonstrate that virus-specific T-cell cytotoxicity in spleen, peripheral blood, and meningeal exudate was similar after intracerebral infection with large and small virus doses, and since the LCMV infection in the brain qualitatively and quantitatively was independent of the size of virus inoculum, the explanation for the survival of the high-dose animals is obviously not lack of possibilities for interaction between cytotoxic T cells and infected sensitive targets in the central nervous system. On the other hand, high doses of virus caused a clear suppression of the LCMV-specific delayed-type hypersensitivity (DTH). In addition, when splenocytes from high-dose animals were transferred either intravenously or locally into the footpad of newly virus-challenged mice, DTH was markedly suppressed as compared with the response after transfer of spleen cells from low-dose mice. We therefore conclude that autointerference in the LCMV infection is due to a selective suppression of Td function. Large amounts of persistent virus late after infection with high doses of virus suggest a central role for Td function also in virus clearance. Finally, our results indicate the existence of two subsets of K,D region-restricted T cells, one mediating cytotoxicity and the other mediating DTH. This possibility is discussed.
Animals↗
Recovery of kidney function after cessation of graft function or prolonged dialysis treatment.
The occurrence of recovery of kidney function after cessation of graft function or prolonged dialysis treatment has been studied retrospectively, and the frequency was found to be roughly 1%, inasmuch as 8 of approximately 750 patients could dispense with dialysis after 10-131 weeks of treatment. The causes of recovery of kidney function are discussed, as the importance of keeping this possibility in mind.
Adult↗
Autoantibodies against pituitary peptides in sera from patients with multiple sclerosis.
Autoantibodies against pituitary peptides were demonstrated in sera from multiple sclerosis (MS) patients. Ten patients with lupus erythematosus disseminatus (SLE) and 97 healthy blood donors served as controls. The sera were used as primary antibodies in the indirect immuno-enzyme cytochemical (IEC) method, with fixed, paraffin-embedded rat brains and rat and hog pituitaries as antigen substrates. Eleven of the 33 MS sera reacted with peptides in the neural lobe/hypothalamic nuclei or distal lobe. The MS had a significantly higher incidence of peptide antibodies than sera from controls (11/33 vs 9/97). The mean antibody titers were significantly different (1577 vs 333). Comparison with rabbit reference antibodies specific to each of the 6 distal lobe hormones showed that the 9 distal lobe-positive MS sera reacted with cells harboring peptides of the somatotropin family. The presence of peptide autoantibodies was not related to clinical status or medical treatment. No antibodies against pituitary peptides were found in the SLE sera. One of the 11 positive MS sera showed antibodies against gastric parietal cells. None of the 11 sera showed antibodies against muscle, mitochondria, thyroid, adrenal, or parotid antigens. We propose that in a proportion of patients with MS, these autoantibodies might be involved in the demyelinization process by interfering with the peptide/receptor interplay, thus placing MS as a disease in analogy with myasthenia gravis. Alternatively, these autoantibodies might be involved in the altered immunoregulation of MS or be secondary to the disease.
Adult↗
Demonstration of autoantibodies against ACTH in serum from a patient with cancer of unknown origin.
We report the presence of autoantibodies against ACTH in plasma from a 46 year old man with poorly differentiated adenocarcinoma of unknown origin. There was no evidence of Cushing's syndrome. By radioimmunoassay and immunocytochemical technique the antibodies were found to possess specificity against the 13-24 aminoacid sequence of ACTH. This sequence includes the biologically active site. On the basis of our findings it is discussed whether the presence of the autoantibodies could reflect a fundamental immunological disturbance primarily or secondarily related to cancer.
Adenocarcinoma↗
Immunocytochemical demonstration of somatotropin-like and prolactin-like activity in the brain of Calamoichthys calabaricus (Actinopterygii).
Cellular binding of anti-bSTH and anti-oPRL IgG is demonstrated in the brain and the pituitary gland of the African freshwater fish Calamoichthys calabaricus by means of the unlabeled antibody enzyme method at the light microscopic level. In the brain, somatotropin and prolactin are demonstrated in separate neurons in the preoptic area. The somatotropinergic and prolactinergic perikarya are distinct from those of the hypothalamic-hypophysial neurosecretory neurons, i.e., those stainable with aldehyde fuchsin presumed to be vasotocinergic and isotocinergic. The somatotropinergic and prolactinergic neuronal perikarya give rise to separate beaded axons which pass either ventroposteriorly into the infundibulum, terminating in the neurohypophysis, or ventro-laterally through the wall of the preoptic recess, terminating near the superficial capillary bed covering this part of the brain surface. Moreover, coarse dendrite-like processes of both kinds of immuno-reactive neurons extend towards, and end in, the third ventricle. Binding sites in the brain to antisera against hLH beta, hFSH beta, hTSH beta and anti-(1-24) ACTH IgG, all reactive in the pituitary, are not observed in the neurons confined to the preoptic area.
Animals↗
Immunoreactive material resembling vertebrate neuropeptides in the corpus cardiacum and corpus allatum of the insect Leucophaea maderae.
The presence and differential distribution of substances antigenically related to known vertebrate neuropeptides demonstrated within the corpus cardiacum of the insect Leucophaea are as follows: Of ten mammalian antisera tested, six yielded substantial immunoreactive deposits resembling oxytocin, somatostatin, Substance P, met-enkephalin, bombesin, and neurotensin, respectively. In the remaining four, the reaction was moderate (vasopressin, beta-endorphin) or marginal (LH-RF, calcitonin). With regard to their regional distribution, these biochemically distinct reaction products seem to fall into two groups: (1) Materials resembling oxytocin, vasopressin, met-enkephalin, beta-endorphin (and presumably also neurotensin and LH-RF) predominate in the central release area of the organ and are considered to be of extrinsic (cerebral) origin. (2) Substances localized primarily in areas rich in intrinsic glandular cells of the corpus cardiacum, and revealed by antisera raised against somatostatin, Substance P, and bombesin, are judge to be synthesized and stored within this organ. In peptidergic fibers entering ther adjacent corpora allata, thus far Substance P-, beta-endorphin-, and LH-RF-like immunoreactivities have been demonstrated. Some of these "new" neuropeptides may be contained in classical neurosecretory neurons, formerly identified by less specific methods, others must be assigned to additional peptidergic neurons heretofore unknown.
Animals↗
Immunoreactive material resembling ovine prolactin in perikarya and nerve terminals of the rat hypothalamus.
The presence of prolactin (PRL)-like material is demonstrated in the brain of rats with the aid of anti-ovine PRL (oPRL) IgG as primary antibody in the unlabeled antibody-enzyme method. Immunoreactive deposits are visualized as an intraneuronal constituent with a widespread distribution in the hypothalamus and neural lobe of the pituitary. Dense networks of reactive nerve terminals derived from two prominent fibre tracts, a ventral (VHT) and a dorsal hypothalamo-neurohypophysial tract (DHT) are seen. The VHT is confined to the median eminence and pars oralis tuberis, the DHT to the pars caudalis tuberis. Both fibre tracts pass through the infundibular stalk into the neural lobe. The origin of the immunoreactive nerve terminals can be elucidated only to some extent. The VHT gives off beaded fibres entering the ependymal and glandular layer of the median eminence. Immunoreactive perikarya are observed in the supraoptic nucleus, the paraventricular nucleus, the anterior hypothalamic nucleus, the anterior commissural nucleus, the preoptic nucleus and the interstitial nucleus of the stria terminalis. A few of the immunoreactive perikarya are observed in close connection with brain vessels and the ependymal cells of the third ventricle. The results indicate that the anti-oPRL has a unique region specificity implying that only a segment of the mammalian PRL molecule is present in these nuclei of the brain. Fragments of PRL may function as neuromodulators or neurotransmitters in the rat brain.
Animals↗
[Abdominal pregnancy resulting in a live-born infant].
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Abnormalities, Multiple↗
Comparative immunocytochemical localization of prolactin and somatotropin in the pituitaries of Lepidosiren paradoxa, Rana temporaria and Ambystoma mexicanum.
The cellular binding sites of anti-oPRL IgG and anti-bSTH IgG were demonstrated in the pituitary glands of Lepidosiren paradoxa, Rana temporaria and Ambystoma mexicanum by means of the unlabeled antibody enzyme method by light and electron microscopy (the latter only in Lepidosiren). With the light microscope PRL or PRL-like substances and STH or STH-like substances were revealed in two different cell types in the distal lobe corresponding to the acidophils. However, as a result of the insufficient differentiation of the acidophils in Lepidosiren after staining with Brookes' procedure it was not possible to distinguish the two types of acidophils in this animal. Treatment with low dilutions of both anti-oPRL and anti-bSTH IgG revealed simultaneous immunocytochemical staining in both types of acidophils in Lepidosiren and in Rana. These results, indicating that there is antigenic cross-reaction between anti-oPRL and anti-bSTH IgG and both PRL and STH in these animals, are discussed. The electron microscopic investigations of Lepidosiren revealed that the specific anti-oPRL IgG reactive cells contain granules ranging in size from 200 to 300 nm, while the specific anti-bSTH IgG reactive cells contain smaller immunoreactive granules ranging from 80 to 160 nm.
Ambystoma↗
Production of monospecific antibodies to varicella zoster virus antigen in rabbits tolerant to human IgG and immunized with antigen immunoprecipitated with human IgG from zoster reconvalescent sera.
A method for production of antisera specific to a single antigen of a human infectious agent is described with varicella zoster virus (VZV) as a model. Microisolation of immunochemically pure antigen contained in defined immunoprecipitates was achieved by crossed immunoelectrophoresis of a crude antigenic preparation (detergent solubilized, VZV infected cells) into agarose gel containing zoster reconvalescent immunoglobulin. Immunization of rabbits made tolerant to human IgG with immunoprecipitates resulted in the production of antibodies to the antigen part of the immunoprecipitate. The method represents a short cut to the production of heterologous diagnostic antisera to defined antigens of human infectious agents.
Animals↗
The cell types in the adenohypophysis of the South-American lungfish, Lepidosiren paradoxa, with special reference to immunocytochemical identification of the corticotropin-containing cells.
The histological features and distribution of cell types in the distal lobe of Lepidosiren resemble those of Protopterus. Three "basophilic" cell types are described, whereas the identification of two acidophilic cell types is uncertain. In the intermediate lobe two cell types have been found. Anti-(1-24)ACTH IgG was used in the unlabeled antibody-enzyme method to identify corticotropin-containing cells in the adenohypophysis of Lepidosiren with light and electron microscopy. Corticotropin was demonstrated in cells of the distal lobe and the intermediate lobe. The staining reaction in the distal lobe is localized in the rostrally distributed lead-hematoxylin positive cells. At the ultrastructural level the immunoreaction in these distal lobe cells is localized on polymorphic granules ranging from 130 to 210 nm. Absorption experiments show that the immunoreactive cells in the distal lobe contain at least residues 1-3 and 14-17 of the naturally occurring corticotropin hormone, while the intermediate lobe cells contain alpha-MSH or at least residues 1-3 of ACTH. The plasma level of corticotropin was determined to be 71 ng/l by means of radioimmunoassay (RIA).
Adrenocorticotropic Hormone↗
Ultrastructural immunocytochemical localization of vitellogenin in the fat body of the blowfly, Calliphora vicina Rob.-Desv. (erythrocephala Meig.) by use of the unlabeled antibody-enzyme method.
The unlabeled antibody-enzyme method was used to demonstrate ultrastructurally the specific localization of vitellogenin in the fat body of Calliphora. In control flies the binding sites to vitellogenin were localized in secretory granules situated in the Golgi complex, and in larger bodies named composite secretory granules. These composite granules appear to be formed when a part of a Golgi complex containing secretory granules and a number of small vesicles become surrounded by a common membrane. Ovariectomized flies, which apparently do not produce secretory granules, exhibited no immunocytochemical staining. Ovariectomized flies in which the administration of ecdysterone induced formation of secretory granules, also revealed specific staining on these granules. This is the first ultrastructural evidence of: (a) the specific localization of vitellogenin in secretory granules of the fat body of an insect; (b) the relationship between the presence of the ovary, and of ecdysterone, and the synthesis of vitellogenin by the fat body.
Adipose Tissue↗
Immunoelectron microscopic localization of herpes simplex virus antigens in infected cells using the unlabeled antibody-enzyme method.
Subcellular localization of viral antigens was demonstrated during viral morphogenesis using herpes simplex virus type 1 (HSV-1) infected monolayers of rabbit cornea cells. The localization was done by immunoelectron microscopy employing the peroxidase-antiperoxidase (PAP) immunocytochemical technique and the postembedding staining method. The localization of viral antigens was followed at time intervals during infection from 2 to 19 hr. After exposure of sections to either polyspecific antibodies against total HSV-1 antigens or monospecific antibodies against HSV-1 antigen No. 8, specific immunological reaction products were identified both in the cytoplasm and nucleus after 2 hr. The distribution and quantity of reaction products varied in the infected cells during the viral morphogenesis. The present results on the subcellular distribution of the HSV-1 antigens are related to current biochemical findings.
Animals↗