Immune resistance and malnutrition.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R A Good.
Explore the source record for details and available documents.
The immune functions of neonatally thymectomized C3Hf mice exposed only temporarily to thymus function show a progressive decay with time in the absence of the thymus. The immune responses studied at different ages in the range of 100-600 days were: first-set rejection of H-2-compatible and incompatible skin allografts, second-set rejection of skin allografts, capacity of spleen cells to produce graft-versus-host reactions in F(1) hybrids, resistance to infection with mouse hepatitis virus, and response of spleen cells to phytohemagglutinin in vitro. These long-term studies had the purpose of determining the duration of the restoration induced by thymus function when the mice were exposed only temporarily to it. Different models were used but the two basic ones were: (a) mice grafted intraperitoneally at 15 days of age with a syngeneic thymus that was removed surgically at 10, 20, or 30 days after grafting, and (b) mice grafted at 15 days of age with allogeneic strain A thymoma or C57BL thymus, these representing situations in which there is spontaneous rejection of the restoring graft. In all the experimental models used, the animals were restored when tested at 100 days of age, but progressively became immunologically incapacitated at 200-300 days of age. From the more controlled experiments in which the restoring thymus graft was removed surgically, the following conclusions can be drawn. (a) A short exposure to a thymus graft can produce restoration of immune functions in neonatally thymectomized mice, but this restoration is not self-sustaining in the absence of the thymus and declines progressively with age. The decline usually starts at 200-300 days of age. (b) This was especially clear in experiments in which the same animal was tested twice in its lifetime for capacity to produce graft-versus-host reactions; these animals were competent at 100 days and became incompetent at 400 days of age. (c) The shortest period of thymic exposure studied was 10 days; if vascularization of the graft is taken into account, 2-3 days of thymic function are sufficient to produce restoration. (d) The immune decay observed in the thymectomized animals exposed temporarily to thymus was more profound than the physiological decay of immunity observed in control animals of similar age. (e) Of all the tests studied, the response of spleen cells to phytohemagglutinin was to be preserved the longest in animals exposed only temporarily to thymic function. The present results were interpreted in accordance with our previous findings indicating that a population of postthymic cells can be developed by temporary exposure of neonatally thymectomized animals to thymic function, but that this population is not self-sustaining in the absence of thymus and progressively decays by physiological attrition.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We have developed a new micromethod for testing phytohemagglutinin stimulation of human lymphocytes. 50 mul of peripheral blood is incubated at 37 degrees C directly, without cell separation, with 50 mul of tissue culture medium containing 50mug of phytohemagglutinin for 24 hr. Then, 0.5 muCi of tritiated thymidine in 50 mul of tissue culture medium is added and incubated for an additional 16 hr. After incubation, erythrocytes are selectively lysed in distilled water, and white blood cells are trapped quickly on a Millipore filter. The radioactivity of the filter is then assessed by a scintillation counter. The requirement of extremely small amounts of blood and a short incubation time are advantages. Further, this method provides a most useful evaluation of thymusdependent cell populations in man and experimental animals and, for the first time, this method provides the possibility of quantitating the deficiency of thymus-dependent cells.
A higher incidence of malignancy as well as greater susceptibility to infection has been found to be associated with primary immunodeficiencies. An increased incidence of leukemia has been associated with X-linked infantile agammaglobulinemia-an isolated defect of humoral immunities. An increased frequency of a wide variety of malignancies have been found to accompany several different forms of primary immunodeficiency. Secondary immunodeficiencies produced by immunosuppressant therapy to facilitate renal transplantation have also been found to have far too much cancer to be explained by chance assocaition. Many experimental associations between immunity and malignancy have also been encountered, indicating that these two adaptive processes have an essential relationship that must be elucidated.
Skin fibroblasts were cultured from 15 patients with primary immunodeficiency diseases associated with a high cancer risk, including sex-linked agammaglobulinemia, IgA deficiency, variable immunodeficiency, ataxia-telangiectasia (cerebellar malfunction and abnormalities of blood vessels and immune response), Wiskott-Aldrich syndrome (low platelet count, eczema, and abnormal immune mechanism), and severe combined system (cellular and humoral) immunodeficiency. Fourteen of 15 cell strains were found to have low or regular susceptibility to transformation with the tumor virus, simian virus 40. The data are consistent with the view that the frequent occurrence of malignancy in patients with primary immunodeficiency is due to abnormalities of the immunologic surveillance mechanism.
The disparity index is an expression of histocompatibility difference between two siblings with identical human leukocyte antigen (HL-A) type who are nonreactive in mixed leukocyte culture (MLC) test. This index is derived from a third-party MLC test. The disparity index was found to be correlated with the severity of graft-versus-host reaction in bone marrow transplantation between HL-A-identical siblings. The disparity index may prove to be a useful means of predicting the severity of graft-versus-host reaction and the outcome of bone marrow graft when HL-A- and MLC-matched sibling donors are studied. The third-party MLC test is offered as a new method of histocompatibility testing. It may provide a useful model for the study of immunogenetics relative to so-called weaker histocompatibility determinants in man and experimental animals.
Explore the source record for details and available documents.
Natural hemagglutinin activity against vertebrate erythrocytes is present in the hemolymph of the cockroach Blabarus craniifer. The hemagglutinin titer against rabbit erythrocytes is high, whereas sheep and horse red cells agglutinate weakly. Hemagglutinin activity was depressed by the complement inhibitor, cobra venom factor. Cockroach hemagglutinin is heat-labile; all activity is destroyed by heating at 56 C for 1 hr. A humoral factor similar to the complement component 3 proactivator is also present in cockroach hemolymph. The formation of the cobra venom factor-hemolymph "complex" is dependent on the presence of divalent cations and will not proceed at 56 C. The hemolytic intermediate formed after treatment of cockroach hemolymph with cobra venom factor was active in the presence of serum treated with ethylenediaminetetraacetic acid to inactivate the early complement components.
Evidence that the bactericidal ability and the stimulated oxidative metabolism of leukocytes appear in parallel during fetal development of the Minnesota Miniature pig has been obtained by application of the techniques applied to studies of human cells. It was demonstrated that leukocytes from 87- to 90-day fetuses were fully capable of ingesting Staphylococcus aureus but greatly diminished in bactericidal capacity as compared to leukocytes of older fetuses and adults. Although resting levels of oxygen consumption and hexose monophosphate pathway activity of leukocytes from the younger fetuses compared well with those of leukocytes from older animals, the phagocytosis-stimulated increments of metabolism were much less at 87 to 90 days of gestation than at later developmental stages. Both bactericidal capacity and increased metabolism of leukocytes reach adult levels by 100 days of gestation (normal gestation period of 115 to 120 days). Acrylamide gels stained for reduced nicotinamide adenine dinucleotide (NADH) and NADH phosphate (NADPH) diaphorase activity after disc electrophoresis of leukocyte extracts revealed normal mobility and intensity of NADH diaphorase bands. Three NADPH diaphorase bands were present in adult leukocyte extracts. Only the fast-migrating NADPH diaphorase band of 87- to 90-day cells stained with decreased intensity. This "deficiency" was no longer present at the later fetal period. The fast-migrating NADPH diaphorase band may represent an electron transfer protein which functions in cyanide-insensitive respiration of the leukocytes of the pig.
Lymphocytes derived from 72- to 90-day-old fetal piglet thymuses respond in vitro to phytohemagglutinin quantitatively greater than do spleen cell lymphocytes.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.