ELECTRON MICROSCOPY OF SERUM SICKNESS NEPHRITIS

The renal lesions of serum sickness were studied with the electron microscope. The most prominent change was a marked swelling and proliferation of glomernlar endothelial cells causing obliteration of the capillary lumen. The basement membrane also showed focal thickenings and excrescences. Deposits of electron-dense material blended into the basement membrane. On the extracapillary side epithelial foot processes were reduced in number and replaced by broad sheets of cytoplasm which were closely applied to the basement membrane. From a comparison of electron and fluorescent microscopic studies of the glomerulus in serum sickness, it would seem that antigen-antibody complexes initiated injury in endothelial cells, although the possibility of the primary reaction occurring on basement membrane cannot be excluded

CYTOLOGY OF IMMUNOLOGIC MEMORY : A MORPHOLOGIC STUDY OF LYMPHOID CELLS DURING THE ANAMNESTIC RESPONSE

Pairs of rats were immunized with keyhole limpet hemocyanin (KLH) and simultaneously labeled with thymidine-methyl-3H or 5-iodo-2'-deoxyuridine-125I. From 10–50 days later, their lymphoid organs were examined 3 days after anamnestic stimulation with KLH or after primary injection of BGG. Light and electron microscopic study of the labeled cells revealed that immunologic memory resided in the mature resting monoribosomal lymphocyte which, upon stimulation, transformed to an immature polyribosomal lymphocyte and mitotically active blast cell. These latter elements differentiated into plasma cells directly or after mitosis

RENAL HOMOTRANSPLANTATION IN RATS : I. ALLOGENEIC RECIPIENTS

Within 3–6 hr after the reestablishment of the circulation, a characteristic pathology developed in renal homotransplants. Blood monocytes and lymphocytes adhered to large thin-walled vessels of the septa carrying interlobular arteries, traversed their walls, and aggregated in the connective tissue spaces around them. Within 3 days, the number and size of the extravascular cells markedly increased, filling the septa completely and spreading from them centrifugally to occupy the intertubular spaces throughout the cortex. The composition of these aggregates at first was a mixture of lymphocytes and monocytes, and later consisted of large blast cells, macrophages, a few plasma cells, and polymorphonuclear leukocytes. Mitotic activity was seen 2 days after surgery among the large blast cells and increased to a maximal level a day later. Coevally with these changes, the thin-walled septal vessels, intertubular veins and capillaries, and finally, arteries and arterioles, in that order, were damaged. Focal injury of tubules was slight 24 hr after homografting; widespread cortical necrosis had developed 5–7 days later. At no time up to 7 days were concentrations of immunoglobulins detected by fluorescence microscopy in the transplanted kidneys. The morphologic manifestations and temporal sequences of renal homograft destruction suggested that several mechanisms acted synergistically to eliminate the transplant. The initial injury appeared to be the result of an interaction between host lymphoid cells and target endothelium, a phenomenon akin to allogeneic inhibition; followed by spreading ischemia; additional contact injury to tubules; and nonspecific inflammation associated with necrobiotic tissue

QUANTITATION OF TRANSPLANTATION IMMUNITY : I. METHOD

A technique for in vivo quantitation of transplantation immunity has been presented. Known numbers of H3-thymidine-labeled lymphoid cells were injected intravenously into isologous or homologous recipients. The total radioactivity in host spleens was counted at different time intervals. The rate of isotope disappearance from the spleen was exponential to 0.5 per cent of the dose or less. In isologous recipients, the calculated half-life of labeled cells was 82 hours; in homologous recipients it was 40 hours; and in presensitized homologous hosts it was 18 hours. The technique is a highly reproducible, precise, and sensitive measure of transplantation immunity

PASSIVE TRANSFER OF TRANSPLANTATION IMMUNITY : III. INBRED GUINEA PIGS

Passive transfer of transplantation immunity was accomplished in inbred guinea pigs with tritiated thymidine-labeled lymphoid cells sensitized to homologous tissues. Autoradiographs of the homologous skin graft sites disclosed the presence of relatively few or no labeled cells at the site of rejection. Passive transfer of transplantation immunity was also accomplished with sensitized lymphoid cells enclosed in cell-impenetrable Millipore chambers. Previous studies with passive transfer of tuberculin sensitivity in guinea pigs revealed that the specifically sensitized cells could be easily found at the site of challenge in the presence of specific antigen and were ineffective when enclosed in Millipore chambers. It appeared, then, that the homograft reaction and delayed sensitivity of tuberculin type were achieved by different immunologic mechanisms within the same species

THE ROLE OF THYMUS AND BONE MARROW CELLS IN DELAYED HYPERSENSITIVITY

Adoptive transfer experiments were performed to define the immunological role of thymus and bone marrow cells in the induction of delayed hypersensitivity (DH). The results indicated the following, (a) Bone marrow from immune donors contained cells capable of being stimulated by antigen to initiate the expression of DH. (b) Bone marrow from nonimmune or tolerant donors contained cells that were needed to complete the expression of DH after the infusion of immune lymph node cells. (c) Normal bone marrow and thymus cells cooperated in the irradiated recipient to induce the most vigorous skin reactions to specific antigen; these reactions were seen only when the recipients were stimulated by antigen. Either cell type alone was ineffective. (d) In the presence of tolerant bone marrow cells, thymus cells from immune donors gave a more vigorous response than did thymus cells from normal or tolerant donors. (e) There was suggestive evidence that thymus cells were the source of trigger elements that initiated DH. (f) Antigen in the irradiated recipient was necessary to induce DH after infusion of bone marrow cells alone, or bone marrow and thymus cells together

PASSIVE TRANSFER OF TUBERCULIN SENSITIVITY BY TRITIATED THYMIDINE-LABELED LYMPHOID CELLS

Passive transfer of tritiated thymidine-labeled BCG sensitized lymphoid cells into homologous guinea pigs resulted in positive tuberculin skin reactions 24 hours after testing with PPD. Labeled cells were found specifically attracted to these sites. Labeled non-sensitized lymphoid cells did not appear at PPD injection sites, nor did labeled sensitized cells accumulate in non-specific inflammatory lesions. The specifically reacting tritiated cells were small, medium, and large lymphocytes and stem or immature cells of the lymphoid series. In the homologous system employed, positive skin tests were either minimal or absent 3 days after transfusion of activated cells. The injected labeled sensitized cells were rapidly cleared from the circulating blood and lodged in the lungs, spleen, and lymph nodes. Upon application of specific antigen they reappeared at the skin test site at 6 hours and then increased in number for the next 18 hours

PASSIVE TRANSFER OF CONTACT SENSITIVITY BY TRITIATED THYMIDINE-LABELED LYMPHOID CELLS

Passive transfer of tritiated thymidine-labeled lymphoid cells sensitized to the simple chemical DNFB into homologous guinea pigs resulted in positive contact skin reactions 24 hours after skin testing with DNFB. Labeled sensitized cells were found to accumulate at these sites, whereas, labeled nonsensitized lymphoid cells did not appear non-specifically in contact skin reaction sites. The labeled cells were small and large lymphocytes and immature cells of the lymphoid series. The maximum reactions were obtained at 24 hours, with an average of 3.4 per cent of the infiltrating mononuclear cells showing a label. At 48 hours, the macro- and microscopic reactions were similar to the 24 hour reactions but diminished in intensity, and the number of labeled cells in the infiltrates had decreased to 1 per cent of the total infiltrating mononuclear cells. ¼ to ⅓ of the labeled cells were found within the epidermis in the test skin sites. These data have indicated that contact sensitivity, like tuberculin sensitivity, required the sensitized cell to initiate the skin reaction and that the majority of the cellular infiltrate was the result of non-specific host response to injury