Showing papers on "Antibody published in 1969"

The influence of immunologically committed lymphoid cells on macrophage activity in vivo

Abstract: It has been shown that the immune response of mice to infection with L. monocytogenes gives rise to a population of immunologically committed lymphoid cells which have the capacity to confer protection and a proportionate level of delayed-type hypersensitivity upon normal recipients. The cells were most numerous in the spleen on the 6th or 7th day of infection, but persisted for at least 20 days. Further study revealed that the immune cells must be alive in order to confer protection, and free to multiply in the tissues of the recipient if they are to provide maximum resistance to a challenge infection. The antibacterial resistance conferred with immune lymphoid cells is not due to antibacterial antibody; it is mediated indirectly through the macrophages of the recipient. These become activated by a process which appears to depend upon some form of specific interaction between the immune lymphoid cells and the infecting organism. This was deduced from the finding that immune lymphoid cells from BCG-immunized donors, which were highly but nonspecifically resistant to Listeria, failed to protect normal recipients against a Listeria challenge unless the recipients were also injected with an eliciting dose of BCG. The peritoneal macrophages of animals so treated developed the morphology and microbicidal features of activated macrophages. It is inferred that acquired resistance depends upon the activation of host macrophages through a product resulting from specific interaction between sensitized lymphoid cells and the organism or or its antigenic products. Discussion is also made of the possibility that activation of macrophages could be dependent upon antigenic stimulation of macrophages sensitized by a cytophilic antibody.

Metabolism of Immunoglobulins

Abstract: Publisher Summary Techniques for the study of immunoglobulin metabolism using purified radioiodinated serum proteins helps define the factors controlling the rates of immunoglobulin synthesis, catabolism, and transport. These techniques are important in studying the pathogenesis of the abnormalities of immunoglobulin levels seen in various immunodeficiency diseases. These techniques are of value in the differential diagnosis of immunodeficiency states and in addition provide the information necessary for the rational use of γ-globulin or its subunits as therapeutic tools. The disorders of immunoglobulin pool size and concentration occur secondary to a variety of pathophysiological mechanisms that are associated with a variety of different patterns of immunoglobulin metabolism. At one end of the metabolic processes are the disorders characterized by decreased immunoglobulin synthesis, while on the other end of the metabolic process are disorders characterized by a short survival of immunoglobulin. This short immunoglobulin survival may be caused by excessive loss of immunoglobulins into the urinary or gastrointestinal tracts. Hypogammaglobulinemia may be caused by a disorder of endogenous catabolic pathways that affect a single immunoglobulin class or all immunoglobulin classes.

Cell selection by antigen in the immune response.

Abstract: Publisher Summary This chapter discusses the essential features of the antibody with respect to the interaction of antigen with preformed, cell-bound, antibody-like receptors. The effect of this interaction on individual cells is determined by the affinity of the antigen cell-bound antibody combination and results in the recruitment or selection of cells and their activation. The chapter also describes certain basic phenomena that are characteristic of the immune response and analyzes their mechanism at both the cellular and the molecular levels. These phenomena are an attempt to formulate a unified concept of the immune response as an antigen-driven proliferation and selection of specific cells that are committed to the synthesis of specific immunoglobulin molecules prior to the contact with antigen. This process, describable in thermodynamic terms, is the central biological event that can explain or predict such features of the antibody response as the progressive increase in average binding affinity of antibody produced, the effect of antigen dose on amount and affinity of antibody, the mechanism of action of adjuvants, the essential role of specific cell proliferation stimulated by antigen, the interference of humoral antibody with antigenic selection of cells, the phenomenon of “original antigenic sin,” and the induction of tolerance.

Characterization of a Soluble Cytoplasmic Antigen Reactive with Sera from Patients with Systemic Lupus Erythmatosus

Abstract: Summary A tissue antigen reactive with sera from SLE patients has been partially characterized. The antigen is a soluble cytoplasmic component which is present in a variety of human tissues and is distinct from known nuclear antigens. It is an acidic macromolecule which has the electrophoretic mobility of an α 1 globulin and is resistant to most proteolytic enzymes including trypsin, pepsin and chymotrypsin. Antigenicity is destroyed by 0.02 M periodate and by 0.001 M parahydroxy mercuribenzoate. Antibodies to this antigen have been found in 40% of unselected LE sera and were absent from a large number of sera from normal persons and from the sera of patients with other connective tissue disorders.

Tumour-specific Antibodies in Human Malignant Melanoma and their Relationship to the Extent of the Disease

Abstract: Biopsy specimens and sera were obtained from 103 melanoma patients. Autoantibodies were demonstrated by (1) complement-dependent cytotoxicity of autologous melanoma cells in short-term culture; (2) complement-dependent inhibition of ribonucleic acid synthesis; (3) immunofluorescent staining of the cytoplasm of killed melanoma cells and of the surface membrane of viable melanoma cells. Over one-third of the sera studied had antibodies to autologous melanoma cells. Although for technical reasons all three tests could not be performed with the cells from every melanoma, whenever multiple testing was possible there was complete concordance. The autoantibodies were virtually confined to patients in whom the disease was not widely disseminated, and over 80% of such patients had positive sera. In a limited number of patients who have been followed autoantibodies disappeared as the disease progressed to become widely disseminated. Two patients with generalized disease developed autoantibodies following inoculation by their own irradiated tumour cells. Two types of autoantibodies were recognized: one, active against antigen(s) in the cell surface membrane, was specific for each tumour—that is, only the autologous serum reacted—and was concerned in the cytotoxic activity; the other reacted with cytoplasmic antigens which appeared to be present in most or all melanoma cells.

Regulation of the immune response i. reduction in ability of specific antibody to inhibit long-lasting igg immunological priming after removal of the fc fragment

Abstract: The ability of 7S and F(ab')2 antibody fragments to suppress priming with low doses of antigen was compared. The 7S preparation was approximately 100–1000 times more potent than the F(ab')2 preparation when the agglutinin titers of the two preparations were the same. The presence of any ability to suppress priming in the F(ab')2 preparation may reflect an inherent capacity of the F(ab')2 antibody or contamination with small amounts of 7S antibody. The difference between 7S and F(ab')2 antibody in ability to suppress priming is attributed to the lack of the Fc portion on the F(ab')2 antibody. The Fc portion may be needed to prevent rapid excretion of antibody from the body, to induce rapid phagocytosis of antigen-antibody complexes with consequent breakdown and elimination of antigen, or to inactivate or suppress the antigen-sensitive cells from reacting to antigenic determinants. More detailed studies will permit a better assessment of the importance of these three possible regulatory roles of the Fc portion of the immunoglobulin in the immune response.

Cell separation on antigen-coated columns. Elimination of high rate antibody-forming cells and immunological memory cells.

Abstract: Glass and plastic bead columns coated with antigenic protein molecules were used as an immunological filter for cell populations containing immune cells of relevant specificity. A selective elimination of these immune cells from the passing cell suspension was regularly noted and it approached, in some experiments, complete abolition of the specific immune reactivity of the filtered cell population. This specific retention of immune cells by antigenic columns could be selectively blocked by the presence of free antigen molecules in the medium during filtration. The results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody. Using the present bead column system, results were obtained indicating that this receptor was an active product of the immune cells and not any passively adsorbed, cytophilic antibody. Antigenic bead columns may very well constitute a tool for the production in vitro of cell populations being specifically deprived of immune reactivity and allow detailed analysis of the characteristics of the cell-associated antibody of immune cells.

Blood group isoantibody stimulation in man by feeding blood group-active bacteria

Abstract: It was investigated whether or not the human blood group isoantibodies A and B could be induced by immunogenic stimuli via natural routes with a kind of antigenic substance to which all humans are commonly exposed, or if the appearance of these antibodies is independent of antigenic stimuli as has long been believed. Escherichia coli O86, which possess high human blood group B and faint A activity in vitro, were fed to healthy humans and those with intestinal disorders. 80% of the sick individuals of blood group O and A responded with a significant rise of anti-B antibodies which was frequently de novo in infants; significant increase of anti-A isoantibodies among blood group O individuals was less frequent. Over one-third of the healthy individuals also had a significant isoantibody increase. Intestinal lesions favor isoantibody stimulation by intestinal bacteria; this view was supported by the study of control infants. Persons of blood group A responded more frequently with anti-B and anti-E. coli O86 antibody production than those of blood group O. Isoantibody increase was accompanied with antibody rise against E. coli O86. Inhalation of E. coli O86 or blood group AH(O)-specific hog mucin also evoked isoantibodies. The induced isoantibodies were specifically inhibited by small amounts of human blood group substances. E. coli O86-induced anti-blood group antibodies in germ-free chickens and preexisting blood group antibodies in ordinary chickens were neutralized by intravenous injection of E. coli O86 lipopolysaccharide. This study demonstrates that human isoantibodies A and B are readily elicited via physiological routes, by blood group-active E. coli, provided the genetically determined apparatus of the host is responsive. Antibodies against a person's own blood group were not formed. Interpretation of these results permits some careful generalizations as to the origin of so-called natural antibodies.

Pathogenesis of chronic disease associated with persistent lymphocytic choriomeningitis viral infection. I. Relationship of antibody production to disease in neonatally infected mice.

Abstract: Mice infected shortly after birth with lymphocytic choriomeningitis (LCM) virus are not immunologically tolerant, although they carry the virus throughout life. These LCM carrier mice make anti-LCM antibody, which apparently complexes with viral antigen in the circulation and these complexes accumulate in the glomeruli. LCM carrier mice of different strains vary significantly as to concentration of detectable infectious virus in their tissue, amount and time of appearance of anti-LCM antibody, and development of an associated chronic disease. The chronic disease consists primarily of glomerulonephritis, focal hepatic necrosis, and disseminated lymphoid infiltrations. LCM carriers of the SWR/J strain contain high tissue concentrations of virus, considerable anti-LCM antibody detectable in the glomeruli by 3 wk to 2 months of age and develop chronic disease within the first 2–3 months of life. In contrast, C3H strain LCM carriers contain 1/1000 as much infectious virus, less detectable anti-LCM antibody, and have not, over a 24 month observation period, developed any detectable disease. B10D2 old and new carrier mice with intermediate amounts of virus develop chronic disease during the latter half of the first year of life. The pathogenesis of the glomerulonephritis of chronic LCM disease is apparently related to the formation of circulating virus-antibody complexes which are trapped in the glomerular filter. There is no evidence for direct glomerular injury by the virus nor for any autoimmune response by the host.

Virus-like antigen, antibody, and antigen-antibody complexes in hepatitis measured by complement fixation.

Abstract: Complement fixation techniques are described for measuring a virus-like antigen associated with viral hepatitis Antigen was found in the blood of 98 percent of 130 patients, with the serum form of hepatitis, from whom multiple samples were obtained Antibodies arising during hepatitis are usually combined with antigen and cause anticomplementary activity in the serum, which is reversible with excess antigen or antibody Tests for antigen and specific anticomplementary activity can be used diagnostically and to screen blood donors for hepatitis carriers

An in vitro reaction between labelled flagellin or haemocyanin and lymphocyte-like cells from normal animals.

Abstract: Labelled bacterial flagellin and haemocyanin reacted with lymphocyte-like cells from several rat and mouse tissues. This reaction occurred at low temperatures and in the presence of sodium azide, conditions which inhibited uptake of labelled proteins by phagocytic cells. The reactive cells took up at least 40,000 molecules of labelled flagellin, and appeared to have a much greater capacity, since pretreatment with 10,000 times this amount of flagellin was required to inhibit the reaction. The flagellin and haemocyanin were firmly bound to the cells, possibly to immunoglobulin at the cell surface, since prior treatment with antisera directed against mouse immunoglobulin inhibited the reaction with lymphocytes from mouse spleen and peritoneal exudate. The number of reactive cells in spleen was proportional to the concentration of labelled protein. At a given concentration of labelled protein, however, the number of reactive lymphocytes was characteristic of each tissue. Spleen, lymph node and thoracic duct lymph contained a similar proportion of reactive lymphocyte-like cells, peritoneal exudate contained more, and thymus contained few if any such cells. Bone marrow contained a high proportion of reactive lymphoid cells which apparently reacted in a non-specific manner, since the uptake of labelled protein by these cells was not inhibited by anti-immunoglobulin serum.

Specific Inactivation of Antigen-reactive Cells with 125I-Labelled Antigen

Abstract: A QUESTION of current interest is whether the initial stages of an immune response—either the induction of antibody formation or of specific tolerance—may involve the reaction of an antigen with a specific lymphocyte. Naor and Sulitzeanu1 have demonstrated, both in vivo and in vitro, a reaction of 125I-labelled bovine serum albumin with a small proportion (about 1/5,000) of mouse spleen lymphocytes. We have since shown2 that both flagellin and polymerized flagellin (Salmonella adelaide) and haemocyanin (Jasus lalandii) labelled with 125I or 131I react in vitro with certain cells from spleens of rats and mice. Of the strongly reactive cells, almost all are mononuclear with a high nuclear/cytoplasmic ratio and 7–12 microns in diameter and, for any one antigen, comprise about 1/5,000 of the total cell population. These reactive cells adsorb between 4,000–40,000 molecules of labelled protein when allowed to react at 0° C with labelled protein (about 3 × 1012 molecules/ml.) in 10 per cent foetal calf serum. A similar proportion of such reactive cells was observed in cell suspensions from lymph nodes and thoracic duct lymph, while peritoneal exudate contained a higher proportion and thymus a lower proportion of these cells2. The reaction was not inhibited by concentrations of sodium azide which restricted the uptake of labelled antigen by macrophages but was inhibited, using mouse cells, by rabbit anti-mouse globulin serum. Spleen cells from germ-free and conventional mice reacted equally well with 131I-labelled flagellin2. We wished to know whether the ability of these cells to react with antigen was immunologically significant. Experiments were devised to distinguish between the following possibilities: that the reactive cells were (1) cells present because of a prior experience of the animal with a related antigen, (2) antigen-reactive cells3,4 which had not had prior antigenic experience but which were capable of contributing to a specific immune response such as formation and secretion of antibody, and (3) cells coated non-specifically with cytophilic antibody.

ANTIBODIES OF THE IgA TYPE IN INTESTINAL PLASMA CELLS OF GERMFREE MICE AFTER ORAL OR PARENTERAL IMMUNIZATION WITH FERRITIN

Abstract: In adult germfree C3H mice immunized with horse spleen ferritin, either subcutaneously or intraperitoneally, plasma cells containing specific antibodies were found in lymph nodes and spleen and, in smaller numbers, also in the lamina propria of the intestine. In extraintestinal sites, these antiferritin-containing plasma cells were mainly of the IgM class after a single stimulation, and of the IgG1 class after repeated stimulation. In the intestine, all the anti-ferritin-containing cells appeared to be of the IgA class. Circulating antibodies, after repeated stimulation, were for the major part IgG1 and IgG2. In germfree mice given ferritin in their drinking water, antiferritin-containing cells were abundant in the intestinal mucosa, much less numerous in the mesenteric lymph nodes, and extremely scarce in other lymphoid tissues. All these cells, whatever their location, appeared to belong exclusively to the IgA class. Similarly, all the circulating antibody in these animals was found to be IgA. These findings illustrate the role of the gut as a site of antibody synthesis, as well as its selective commitment to the production of antibodies of the IgA class.

The IgG receptor: an immunological marker for the characterization of mononuclear cells

Abstract: Using red cells sensitized with an IgG anti-Rh0 antibody, an IgG receptor was demonstrable on human monocytes, hepatic macrophage and splenic macrophage preparations. The receptor was uniformly lacking on lymphocytes, lymphoid cell lines and lymphocytes stimulated with phytomitogens in vitro. The integrity of this receptor was demonstrated on monocytes obtained from patients with `acquired' agammaglobulinaemia, chronic granulomatous disease and acute monocytic leukaemia. There was no direct correlation between the presence of the receptor and the fine structure of the cells studied. It is proposed that this receptor is an immunological marker for identification of mononuclear cells.

Use of erythrocytes sensitized with purified pneumococcal polysaccharides for the assay of antibody and antibody-producing cells.

Abstract: A method was described for the sensitization of erythrocytes with purified type-specific pneumococcal polysaccharide antigens using chromium chloride as a coupling agent. Erythrocytes so sensitized can be used in routine passive hemagglutination and hemolysis tests as well as in the technique of localized hemolysis-in-gel for the detection of specific antibody and specific antibody-producing cells, respectively.

Cell interactions in the primary immune response in vitro: a requirement for specific cell clusters

Abstract: Mouse spleen cells were found to associate in cell clusters during the primary immune response to sheep erythrocytes in vitro. About 10% of the cell clusters had the following unique properties; (a) they contained most, if not all, antibody-forming cells, (b) they contained only cells forming antibody to one antigen when cell cultures were immunized with two antigens, (c) the cells in clusters reaggregated specifically after dispersion, and (d) the specific reaggregation of clusters appeared to be blocked by antibody to the antigen. The integrity of cell clusters was required for the proliferation of antibody-forming cells, and prevention of clustering by mechanical means or by excess antibody blocked the immune response. Antibody and antigenic determinants on the surfaces of cells probably provide the basis for interaction. The unique microenvironment of cell clusters was essential for the primary immune response in vitro.

A complement-fixation test for measuring Australia antigen and antibody.

Abstract: The role of Australia antigen (Au) in serum hepatitis is ill-defined, but there is growing evidence that the antigen may be the virus of serum hepatitis or a virus-associated protein [1-3]. Au antigen has been measured in the sera of persons with acute or chronic hepatitis; antibody to Au antigen (anti-Au) has been studied less well but is known to occur in sera from a proportion of hemophiliacs [3] and other persons receiving multiple transfusions [4]. Until now Au and anti-Au have been detected primarily by agar gel diffusion (AGD) techniques. In only a few reported studies has the antigen or the antibody been quantitated. The present study describes a complement-fixation (CF) test for the measurement of Au and anti-Au, the relative sensitivity and specificity of the test, and its use in detecting, quantitating, and serologically comparing Au and anti-Au.

The adherence of leucocytes and platelets induced by fixed IgG antibody or complement.

Abstract: Human, rabbit and guinea-pig neutrophils and rabbit and guinea-pig macrophages were shown to adhere to sheep erythrocytes sensitized with isologous IgG antibody (EAIgG). IgM antibody, however, was less active and use of rabbit IgM antibody to fix complement from different species allowed the examination of neutrophil, macrophage and platelet adherence to alexinated erythrocytes (EAIgMC′). Complement from twelve mammalian species induced the adherence of isologous neutrophils. On the other hand, platelets showed some variability. Ox, goat, sheep and pig platelets, like those from man and the baboon, did not adhere to EAIgMC′, although adherence of platelets from the rabbit, guinea-pig, rat, mouse, horse and cat was observed. C′3 was the complement component implicated in these reactions. Treatment of the leucocytes with trypsin prevented the adherence to EAIgMC′ but not to EAIgG. Chelation of free magnesium with EDTA inhibited the adherence of rabbit neutrophils, but not of human neutrophils, to EAIgMC′. EDTA had no effect on the adherence to EAIgG. Rabbit and guinea-pig neutrophils exhibited some species specificity towards the antibody and complement which would induce their adherence. This was not shown by human neutrophils or by rabbit and guinea-pig macrophages. The adherence of particles to phagocytes comprises the first stage of phagocytosis and the role of antibody and complement in this process is discussed.

EARLY STAGES OF INTESTINAL ABSORPTION OF SPECIFIC ANTIBODIES IN THE NEWBORN : An Ultrastructural, Cytochemical, and Immunological Study in the Pig, Rat, and Rabbit

Abstract: In mammals, passive immunity is transferred from mother to offspring by transplacental passage or by intestinal absorption. The rabbit receives antibodies exclusively across the placenta, whereas intestinal absorption is the principal source of antibodies for the new-born pig. In the rat, passive immunity is transferred by both pathways. The role of the jejunal absorptive cells was investigated in these three species, by the use of specific immune globulins as tracers of protein absorption. Rabbit anti-peroxidase and anti-ferritin antibodies were injected into the jejunum of newborn pigs, rats, and rabbits, and absorption was studied over the first 2 hr. The specific antibodies were detected in glutaraldehyde-fixed tissues after in vitro treatment with the antigens, and in sera by immunological methods. Intact antibodies are transferred into the circulation of the pig and the rat, but not into that of the rabbit. In the three species, the jejunal absorptive cells take up antibodies by endocytosis. In the pig, the antibodies are transported across the epithelium in vacuoles. In the rabbit, the endocytosis of antibodies triggers a lysosomal response and all absorbed antibodies are trapped in lysosomes. In the rat, both situations are found; there is no evidence of transfer of antibody fragments into the circulation.

The pathogenesis of autoimmunity in new zealand mice, i. induction of antinucleic acid antibodies by polyinosinic·polycytidylic acid

Abstract: Antibodies to DNA and RNA were induced in young NZB/NZW F(1) (B/W) female mice following multiple injections of the interferon-inducer polyinosinic.polycytidylic acid (poly I.poly C). Despite serum concentrations of interferon adequate to inhibit the C-type murine leukemia viruses, there was an acceleration of the autoimmune disease in these animals. Anti-RNA, but not anti-DNA antibodies, were induced in B/W male mice, as well as in NZB and NZW mice. Anti-RNA antibodies were also found in 50 per cent of female B/W mice who had never received poly I.poly C and in 8 of 24 sera from patients with systemic lupus erythematosus. These results suggest that double-stranded RNA functions as a potent antigen in New Zealand mice. Naturally occurring nucleic acids (e.g., viruses) probably act as stimuli to a genetically hyperreactive immune system. According to this hypothesis, the unusual feature in this disease is not a unique virus, but rather the unique genetic susceptibility of the B/W (particularly female) host to immunization with nucleic acids. A similar pathogenetic mechanism may be operative in some humans with systemic lupus erythematosus.

Action of malarial antibody in vitro.

Abstract: In the presence of immune serum, malaria parasites inside red blood cells grow and differentiate, but re-invasion of erythrocytes is prevented and the succeeding cycle of parasite development is completely inhibited.

General methods for the study of cells and serum during the immune response: the response to dinitrophenyl in mice.

Abstract: Two new methods for antibody assay are reported: one for antibody in solution, the other for individual cells releasing antibody. They depend on the use of an immunoabsorbent-bound antigen to absorb the antibody, and radioactively-labelled anti-immunoglobulin antibody (anti-Ig) for its detection. In the first method immunoabsorbent was added to the solution containing antibody, washed free of serum components other than the bound antibody, treated with [131I]anti-Ig, and the uptake of radioactivity assessed by γ-ray counting. This method was standardized for anti-DNP antibody by comparison with results of equilibrium dialysis. It was shown to be independent of affinity, down to K0 = 106 1/M. It would detect 0·1 ng antibody. For the study of lymphoid cells releasing antibody the cells and immunoabsorbent were dispersed in agarose gel on microscope slides, incubated at 37°C in the presence of [125I]anti-Ig, washed, and autoradiographed. Antibody released by a cell could then be visualized as a circular area (`spot') of silver grains. When sheep red blood cells were used as the antigen, the number of spots approximated to the number of lytic plaques obtained by the addition of complement. The methods were shown to be generally useful for a number of antigens. Both methods were used in a study of the course of the primary immune response to dinitrophenyl in mice. Cells releasing anti-DNP antibody were detected from 2 days after immunization and rose to a peak number at 9 days of 2 × 105 in the lymph nodes local to the site of injection.

Additional specificities of Australia antigen and the possible identification of hepatitis carriers.

Abstract: IN 1964 (ref 1), we identified an antibody which is common in the blood of transfused haemophiliacs and which reacts with an antigen (first identified in an Australian aborigine, thus “Australia antigen”) found in some human sera2 Australia antigen, Au(1), is found transiently in the sera of many patients with acute viral hepatitis3–6 (13 per cent in infectious hepatitis, 34 per cent of post transfusion hepatitis7–9) This association with hepatitis has been confirmed by other workers using reference antisera from our laboratory (refs 10 and 11, and unpublished results of Vierucci) Okochi and Murakami10 used an anti-Australia antiserum from a transfused patient which seems to be identical with reference sera we have exchanged The “SH antigen” recently described by Prince is identical with Australia antigen11 In addition to its presence in acute viral hepatitis, Australia antigen is found in patients with some forms of leukaemia2 and Down's syndrome (who have chronic anicteric hepatitis)2,3,12,13 It is also found in 5–20 per cent of apparently normal populations in the tropics and south-east Asia2,9,14, who may be hepatitis carriers10

Immunological Relationship between Herpes Simplex and Varicella-zoster Viruses Demonstrated by Complement-fixation, Neutralization and Fluorescent Antibody Tests

Abstract: Summary The antigenic relationship between the viruses of varicella-zoster and herpes simplex was studied by complement-fixation, fluorescent antibody staining and neutralization tests. Twenty-three of 75 patients with herpes simplex infections showed significant heterologous increases in complement-fixing antibody titre to varicella-zoster virus. These heterologous increases occurred in patients with serological evidence of a prior infection with varicella-zoster virus, and the greatest proportion occurred in patients in the younger age groups who had probably experienced the most recent varicella-zoster virus infections. Five of 42 patients with varicella-zoster infections showed heterologous complement-fixing antibody responses to herpes simplex virus; all were patients with serological evidence of a prior herpes simplex virus infection. The patients with herpes simplex infection who showed heterologous complement-fixing antibody responses to varicella-zoster virus also showed marked increases in neutralizing antibody and antibody demonstrable by immunofluorescent staining. However, none of the patients with varicella-zoster infection who showed heterologous increases in complement-fixing antibody titre to herpes simplex virus had significant increases in neutralizing antibody.