Effect of Abrin on Cell-Mediated Immune Responses in Mice

Effect of abrin isolated from Abrus precatorius on the cellular immune responses was studied in normal as well as tumor-bearing animals. Administration of abrin was found to enhance the proliferation of splenocytes and thymocytes (lymphocytes in general) in responses to mitogens. Natural killer cell activity was enhanced significantly by abrin in both the normal (49.8% cell lysis on day 9) and the tumor-bearing group (51.7% cell lysis on day 9), and it was found to be earlier than the control. Antibody dependent cellular cytotoxicity was enhanced in the abrin treated tumor-bearing group on the ninth day (44% cell lysis). An early antibody dependent complement mediated cytotoxicity was observed in the abrin treated group on day 15 (27.6% cell lysis). Results of our present study suggest the immunomodulatory property of abrin.     

狂犬疫苗接种诱生细胞免疫的研究

狂犬疫苗对免疫接种志愿者和免疫实验小鼠能诱导产生显著的细胞介导免疫应答。免疫接种者的外周血淋巴细胞在体外经刀豆球蛋白Ａ刺激呈很强的增殖反应，增殖指数（ＳＩ）达８．５％－１５．４％；在ＨｐＢＬ的ＣｏｎＡ培养上清中可测及白细胞介素２（ＩＬ－２）活性明显升高。在接种者的血清中还可测及高水平干扰素。免疫试验小鼠其脾淋巴细胞在体外用不同狂犬病毒株抗原进行刺激亦呈显著的特异性增殖反应，ＳＩ达７．４％－１８．３     

Immune Modulatory Effects of Immunoglobulins on Cell-Mediated Immune Responses In Vitro

Intravenous Immunoglobulin (IVIG) at a concentration of 5 mg/ml, significantly inhibited mitogenic responses to phytohaemagglutinin (PHA), concanavalin A (conA) and pokeweed mitogen (PWM) by peripheral blood cells from healthy donors. No difference in inhibition by IVIG was seen when stimulating different T-lymphocyte cell subsets. Inhibition by IVIG was dose-dependent. An increased response was observed when IVIG was added more than 12 h after PHA compared to adding 1 h before [p= 0·05]. Intravenous immunoglobulin added to mixed lymphocyte cultures (MLC), reduced the median response by more than 60% (range 14–89%; P= 0·03) and almost completely abrogated the lymphocyte response to Staphylococcus aureus protein A (SPA), whose median inhibition was 94% (range 90–99%; P= 0·02). When comparing 12 different commercial IVIG preparations at a concentration of 2.5 mg/ml, the median inhibition of the PHA stimulation ranged from 4% to 35% and the MLC response from 0% to 66%. In the presence of IVIG the lymphocyte response to different herpes virus antigens was reduced by <50%. No difference in inhibitory effect was seen when comparing IVIG and cytomegalovirus (CMV) hyper Ig, but CMV negative Ig resulted in lower inhibition (P= 0·05]. Three out of five IgG preparations (2.5 mg/ml) made from single donors inhibited PHA stimulation signifiantly more than commercial IVIG [P<0·05]. Mean inhibition was 61% compared to 35% Inhibition by pooled IgG from five donors was 56%. F(ab‘)₂ fragments of IVIG inhibited the MLC response by more than 50% (range 34–75%), SPA stimulation by 97% (83–104%) and PHA stimulation by more than 30% (26–37%). One of two Fe preparations tested had an inhibitory effect, but the inhibition was less than that obtained with the F(ab')₂ fragments [P= 0.04]. These results further strengthen the notion that IVIG exerts its immune modulatory effect by binding to leukocyte surface receptors. A clear inhibition was obtained with concentrations corresponding to the serum levels obtained when IVIG is given 250–500 mg/kg bodyweight. F(ab')₂ fragments have the same inhibitory effect as intact IgG molecules but the role of Fc fragments still remains unclear. Differences in the immunosuppressivc effect of various IVIG preparations may be associated with the method of preparation.     

Effect of Biophytum sensitivum on Cell-Mediated Immune Response in Mice

Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum.     

The Immune Response to a Schistosomacide, Amoscanate Ii. Cell-Mediated Immune Responses

A potent antischistosomal drug, Amoscanate, was found to induce vigorous serum antibody responses when either fed or administered parenterally as a drug-protein conugate. Because of preliminary evidence that the drug could bind covalently to proteins in vivo, we decided to investigate the possibility that the drug could act as a contact sensitizing agent like DNCB. It was found that Amoscanate could induce a delayed-type hypersensitivity (DTH) response when painted on the shaved skin of guinea pigs. Moreover, the type of DTH response elicited was found to be cutaneous basophilic hypersensitivity (CBH). The significance of these findings are discussed.     

Role of Mononuclear Phagocyte System in Hemopoiesis Regulation in AKR/JY Mice during Preleukemic Period

Feeder activity of bone marrow adherent cells and peritoneal macrophages is decreased and colony-stimulating and erythropoietic activity of unfractionated bone marrow increased in highly leukemic AKR/JY mice in comparison with CBA/CaLac mice. At the same time maturation of hemopoietic precursor cells in AKR/JY mice is delayed compared to controls. This indicates compensatory activation of nonadherent elements of the hemopoiesis-inducing microenvironment against the background of suppressed activity of adherent elements. Hence, leukemogenic virus produced a systemic damage to target cells (e.g. mononuclear phagocyte system), which probably represent a mechanism of leukemic transformation in AKR/JY mice.     

Effect of Biophytum sensitivum on Cell-Mediated Immune Response in Mice

Effect of Biophytum sensitivum on cell-mediated immune response was studied in normal as well as Ehrlich ascites tumor bearing BALB/c mice. Administration of Biophytum sensitivum significantly enhanced the proliferation of splenocytes, thymocytes and bone marrow cells by stimulating the mitogenic potential of various mitogens such as Lipopolysaccharide (LPS), Concanavalin A (Con A), Phytohaemagglutinin (PHA) and Poke Weed Mitogen (PWM). Natural killer (NK) cell activity was enhanced significantly by Biophytum sensitivum in both the normal (43.6% cell lysis on day 5) and the tumor bearing group (48.2% cell lysis on day 5), and it was found to be earlier than tumor bearing control animals (maximum of 13.4% cell lysis on day 9). Antibody dependent cellular cytotoxicity (ADCC) was also enhanced significantly in both Biophytum treated normal (35% cell lysis on day 7) as well as tumor bearing animals (40.2% cell lysis on day 7) compared to untreated control tumor bearing animals (maximum of 12.3% cell lysis on day 11). An early antibody dependent complement mediated cytotoxicity (ACC) was also observed in the Biophytum treated normal (22.6% cell lysis, on day 15) and tumor bearing animals (26.4% cell lysis, on day 15). Results of our present study suggest the immunomodulatory property of Biophytum sensitivum.     

Humoral and Cell-Mediated Immune Responses to Fractions of Birch Pollen Extract

IgE and IgG antibodies (ab) and lymphocyte transformation (LT) were studied in untreated and hyposensitized birch pollen allergic subjects and in non-atopic controls using whole extract and fractions obtained by gel filtration of birch pollen extract. All the allergic subjects had positive IgE ab, IgG ab and LT responses to the whole extract. Both the untreated and the hyposensitized subjects had peak IgE ab and LT responses against the allergenic fractions of the extract, while negative responses were obtained in the non-atopic controls. Only hyposensitized subjects had developed high IgG ab responses to the allergenic fractions. Most of the treated and untreated subjects showed IgG ab and LT responses to the high molecular weight fractions with low allergenic activity. Significantly higher IgE ab responses to these fractions were observed in the treated subjects than in the untreated ones, indicating potentiation of IgE ab responses against some antigens during immunotherapy. Some of the allergic subjects also responded to the fractions of low molecular size (mol.wt. 2000-5000) with low allergenic activity. Both IgE ab, IgG ab and LT responses to these fractions were observed.     

Control of the Immune Response: Role of Macrophages in Regulation of Antibody-and Cell-Mediated Immune Responses

The ability of peritoneal macrophage subpopulations, separated into different classes according to their size, to reconstitute antibody or cellular immune responses in macrophage-depleted spleen cells has been investigated. Data are presented to show that whether reconstitution is by 'normal' or 'activated' macrophages, be they syngeneic or allogeneic to the lymphocyte source, different populations reconstitute antibody and cellular immunity. Reconstitution is in general by two classes of macrophages, small and large. The former seem to reconstitute only if syngeneic to the responding lymphocyte pool, whereas large macrophages reconstitute immune responses from allogeneic lymphocytes as well as syngeneic lymphocytes. Evidence is also presented to show that syngeneic large macrophages can determine the type of immune response reconstituted; that is, with greater numbers of large cells only cytotoxic responses (and not T-dependent antibody formation) were reconstituted and vice versa.     

Effects of Carbon Dust Inhalation on the Cell-Mediated Immune Response in Mice

The effects of carbon dust inhalation on the bone marrow-derived (B) and thymus-derived (T) lymphocyte populations of spleen and mediastinal lymph node (MLN) cultures were examined. The concanavalin A (Con A)-responsive cell population (T cells) in the spleen was found to be depressed after 7 days of pre-exposure to carbon dust. However, this effect was transient, and after 14, 21, and 28 days of pre-exposure to carbon dust, the Con A-responsive cells exhibited a 30 to 40% enhancement over control group responses. Conversely, Con A-responsive cells in the pooled MLN cultures exhibited depression, ranging from 22 to 33% below control group values, after 7, 14, and 28 days of pre-exposure to carbon dust. The lipopolysaccharide (LPS)-responsive cell population (B cells) in the spleens of carbon-exposed mice was found not to differ significantly from control group values after all times of pre-exposure. LPS-responsive cells in the MLN cultures exhibited enhancement, ranging from 49 to 74% above control values, after 14, 21, and 28 days of pre-exposure to carbon dust. The ability of carbon spleen cell cultures from carbon-exposed mice to undergo antigen induced blast transformation after sensitization with Mycobacterium tuberculosis H37Ra was also determined. Mice exposed to carbon dust inhalation 2 weeks before and 3 weeks after aerosol or subcutaneous immunization exhibited significantly enhanced ratios of transformation upon culture of their spleen lymphocytes with purified protein derivative of tuberculin.     

Bartonella henselae-Specific Cell-Mediated Immune Responses Display a Predominantly Th1 Phenotype in Experimentally Infected C57BL/6 Mice

Immune responses of the immunocompetent host to Bartonella henselae infection were investigated in the murine infection model using C57BL/6 mice. Following intraperitoneal infection with human-derived B. henselae strain Berlin-1, viable bacteria could be recovered from livers and spleens during the first week postinfection, while Bartonella DNA remained detectable by PCR in the liver for up to 12 weeks after infection. Granulomatous lesions developed in livers of infected mice, reached maximal density at 12 weeks after infection, and persisted for up to 20 weeks, indicating that B. henselae induced a chronic granulomatous hepatitis in the immunocompetent murine host. T-cell-mediated immune responses were analyzed in vitro by means of spleen cell proliferation and cytokine release assays as well as analysis of immunoglobulin G (IgG) isotypes. Spleen cells from infected mice proliferated specifically upon stimulation with heat-killed Bartonella antigen. Proliferative responses were mainly mediated by CD4+ T cells, increased during the course of infection, peaked at 8 weeks postinfection, and decreased thereafter. Gamma interferon, but not interleukin-4, was produced in vitro by spleen cells from infected animals upon stimulation with Bartonella antigens. Bartonella-specific IgG was detectable in serum of infected mice by 2 weeks, and the antibody concentration peaked at 12 weeks postinfection. IgG2b was the prominent isotype among the Bartonella-specific serum IgG antibodies. These data indicate that B. henselae induces cell-mediated immune responses with a Th1 phenotype in immunocompetent C57BL/6 mice.     

Cell-Mediated Immune Responses in Four-Year-Old Children after Primary Immunization with Acellular Pertussis Vaccines

Cell-mediated immune (CMI) responses to Bordetella pertussis antigens (pertussis toxin [PT], pertactin [PRN], and filamentous hemagglutinin [FHA]) were assessed in 48-month-old recipients of acellular pertussis [aP] vaccines (either from Chiron-Biocine [aP-CB] or from SmithKline Beecham [aP-SB]) and compared to CMI responses to the same antigens at 7 months of age, i.e., 1 month after completion of the primary immunization cycle. None of the children enrolled in this study received any booster of pertussis vaccines or was affected by pertussis during the whole follow-up period. Overall, around 75% of 4-year-old children showed a CMI-positive response to at least one B. pertussis antigen, independently of the type of aP vaccine received, and the proportion of CMI responders were at least equal at 48 and 7 months of age. However, longitudinal examination of individual responses showed that from 20 (against PT) to 37% (against FHA) of CMI responders after primary immunization became negative at 48 months of age. This loss was more than compensated for by conversion to positive CMI responses, ranging from 36% against FHA to 69% against PRN, in other children who were CMI negative at 7 months of age. In 60 to 80% of these CMI converters, a lack of decline or even marked elevation of antibody (Ab) titers against B. pertussis antigens also occurred between 20 and 48 months of age. In particular, the frequency of seropositivity to PRN and FHA (but not to PT) was roughly three times higher in CMI converters than in nonconverters. The acquisition of CMI response to B. pertussis antigens in 48-month-old children was not associated with a greater frequency of coughing episodes lasting >/=7 days and was characterized by a prevalent type 1 cytokine profile, with high gamma interferon and low or no production of interleukin-5, reminiscent of cytokine patterns following immunization with whole-cell pertussis vaccine or natural infection. Our data imply that vaccination-induced systemic CMI may wane by 4 years of age but may be acquired or naturally boosted by symptomless or minor clinical infection by B. pertussis. This might explain, at least in part, the persistence of protection against typical pertussis in aP vaccine recipients despite a substantial waning of both Ab and CMI responses induced by the primary immunization.     

Humoral and Cell-Mediated Immune Responses to Dog Dander and Hair in Asthmatic Children

Dog dander and hair (DDH) specific IgA, IgG and IgE antibodies from serum samples Of 202 asthmatic children, and in nasal secretion from 4 to 15 years were measured by enzyme-linked immunosorbent assay. The results were compared with clinical history, and with allergy test (skin prick test, provocation test and RAST) using the same DDH extract. A blood sample for the in vitro lymphocyte stimulation test was obtained from 40 children, and a nasal secretion sample for analysis of the local DDH-specific IgA, IgG and IgE antibody levels was collected form 35 of them. In children of dog-keeping families, higher serum levels of DDH-specific antibodies, especially IgE antibodies, were observed if the dog had been in the home already during the first years of the child's life. The serum levels of DDH-specific antibodies, however, did not correlate with the degree of the present exposure to dogs. The serum levels of DDH-specific or total IgE, or with the results of skin prick or provocation test. The serum levels of DDH-specific IgA were highest in children who were subjectively most sensitive to dogs. Nasal levels of DDH-specific IgE correlated positively with serum specific IgE levels. The correlation was weaker between nasal and serum titers of specific IgG, and not significant between nasal and serum IgA antibody levels, Specific IgE antibody levels were higher, while specific IgA and IgG antibody levels were lower, in nasal secretion form subjects with nasal symptoms on contact with dogs, when compared with subjects with other complaints (asthma, conjunctival or skin reactions). DDH-specific IgG levels correlated negatively with specific IgE level in the nasal secretion from subjects with a positive provocation test result, while the correlation was positive in subjects with a negative provocation test. The in vitro lymphocyte response to DDH did not correlate with the results of allergy test, or with the levels of DDH-specific antibodies in serum or in nasal secretion.     

Cell-Mediated Immune Responses and Protective Efficacy against Infection with Mycobacterium tuberculosis Induced by Hsp65 and hIL-2 Fusion Protein in Mice

Heat shock protein 65 (Hsp65) is an important immunodominant antigen against tuberculosis (TB), and interleukin-2 (IL-2) plays an important role in the regulation of antimycobacteria immune responses. In order to further increase the immunogenicity of Hsp65 against infection caused by Mycobacterium tuberculosis (MTB), we expressed MTB Hsp65 and human IL-2 fusion protein, Hsp65-hIL-2, in Escherichia coli. The expression of Hsp65-hIL-2 was confirmed by Western blotting using anti-Hsp65 MoAb and anti-hIL-2 MoAb, respectively. Hsp65-IL-2 and Hsp65 were then purified by Ni-NTA affinity chromatography. Mice were immunized with purified Hsp65-hIL-2 or Hsp65 emulsified in the adjuvant combination dimethyl dioctadecylammonium bromide and monophosphoryl lipid A. Eight weeks after immunization, there was significant proliferation of spleen lymphocytes in response to both Hsp65 and Hsp65-hIL-2 proteins. Interestingly, Hsp65-hIL-2 fusion protein elicited significantly higher levels of IFN-γ and IL-2 in the lymphocytes culture supernatant than that of the BCG (Denmark strain) immunized group and Hsp65 group ( P  < 0.05). After challenging the immunized mice with MTB, the bacteria loads in the spleens and lungs of mice immunized with the fusion protein were significantly lower than Hsp65 alone group, reaching an equivalent level as BCG immunization group. Our results suggest that the Hsp65 and hIL-2 fusion protein may serve as an alternative vaccine candidate against MTB infection.     

Effects of Antithymocyte Sera and Antimacrophage Sera on Cell-Mediated Immune Reactions in Listeria-Infected Mice

The cell-mediated immune responses of allograft rejection, delayed hypersensitivity, and resistance to Listeria monocytogenes were suppressed by injections of antithymocyte serum (ATS), but the immune responses were not significantly altered by antimacrophage serum (AMS) or normal rabbit serum (NRS). Antisera were prepared in rabbits against purified mouse thymocytes and purified peritoneal macrophages. When mice were injected with ATS near the time of skin grafting, allografts survived significantly longer. Similar administration of AMS or NRS failed to alter the course of graft rejection. Decreased footpad swelling indicated the suppression of delayed hypersensitivity in mice injected with ATS 6 days after a sublethal inoculation of Listeria cells. None of the serum treatments affected the ultimate survival of mice infected with a small number of bacteria. Either ATS or NRS was injected into immunized mice 1 day before and 2 days after a challenge inoculation of Listeria cells. Pronounced suppression of delayed hypersensitivity was found in the ATS-treated groups, along with extensive mortalities that reached 100% in the group receiving the largest dose of ATS. All control animals survived and demonstrated strong delayed hypersensitivity reactions. Antimacrophage serum had no significant effect on the three mechanisms of cell-mediated immunity that were tested. The lymphoid cells which mediate delayed hypersensitivity, antimicrobial cellular immunity, and allograft rejection possess antigenic determinants in common with thymocytes.     

Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans

Protective antigen (PA)-specific antibody and cell-mediated immune (CMI) responses to annual and alternate booster schedules of anthrax vaccine adsorbed (AVA; BioThrax) were characterized in humans over 43 months. Study participants received 1 of 6 vaccination schedules: a 3-dose intramuscular (IM) priming series (0, 1, and 6 months) with a single booster at 42 months (4-IM); 3-dose IM priming with boosters at 18 and 42 months (5-IM); 3-dose IM priming with boosters at 12, 18, 30, and 42 months (7-IM); the 1970 licensed priming series of 6 doses (0, 0.5, 1, 6, 12, and 18 months) and two annual boosters (30 and 42 months) administered either subcutaneously (SQ) (8-SQ) or IM (8-IM); or saline placebo control at all eight time points. Antibody response profiles included serum anti-PA IgG levels, subclass distributions, avidity, and lethal toxin neutralization activity (TNA). CMI profiles included frequencies of gamma interferon (IFN-γ)- and interleukin 4 (IL-4)-secreting cells and memory B cells (MBCs), lymphocyte stimulation indices (SI), and induction of IFN-γ, IL-2, IL-4, IL-6, IL-1β, and tumor necrosis factor alpha (TNF-α) mRNA. All active schedules elicited high-avidity PA-specific IgG, TNA, MBCs, and T cell responses with a mixed Th1-Th2 profile and Th2 dominance. Anti-PA IgG and TNA were highly correlated (e.g., month 7, r² = 0.86, P < 0.0001, log₁₀ transformed) and declined in the absence of boosters. Boosters administered IM generated the highest antibody responses. Increasing time intervals between boosters generated antibody responses that were faster than and superior to those obtained with the final month 42 vaccination. CMI responses to the 3-dose IM priming remained elevated up to 43 months. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT00119067","term_id":"NCT00119067"}}NCT00119067.)     

Suppression of Humoral and Cell-Mediated Immune Responses in Vitro by Benzo (A) Pyrene

Abstract

The effect of benzo(a)pyrene (BaP) at different molar (MI concentrations on the in vitro anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFCI response and the one-way mixed lymphocyte response (MLR) was tested. Inhibition of the PFC response and the MLR occurred when spleen cells were exposed to a wide range of BaP concentrations from 10^–4 m to 10^–8 m. Maximum depression of the responses occurred at 10^–5 M for PFC production (47% of controls) and for the MLR (19% of controls) as measured by a stimulation index. No significant loss in cell viability was observed at this or lower molar concentrations of BaP. The non-carcinogenic analog of BaP, benzo(e)pyrene, did not suppress PFC responses at comparable concentrations. This in vitro system will facilitate manipulations of T and B lymphocytes and macrophages (adherent cells) in a controlled culture environment for precisely characterizing the sensitivity of these cells and their subpopu-lations on exposure to BaP.     

Suppression of Humoral and Cell-Mediated Immune Responses in Vitro by Benzo (A) Pyrene

The effect of benzo(a)pyrene (BaP) at different molar (MI concentrations on the in vitro anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFCI response and the one-way mixed lymphocyte response (MLR) was tested. Inhibition of the PFC response and the MLR occurred when spleen cells were exposed to a wide range of BaP concentrations from 10^-4 m to 10^-8 m. Maximum depression of the responses occurred at 10^-5 M for PFC production (47% of controls) and for the MLR (19% of controls) as measured by a stimulation index. No significant loss in cell viability was observed at this or lower molar concentrations of BaP. The non-carcinogenic analog of BaP, benzo(e)pyrene, did not suppress PFC responses at comparable concentrations. This in vitro system will facilitate manipulations of T and B lymphocytes and macrophages (adherent cells) in a controlled culture environment for precisely characterizing the sensitivity of these cells and their subpopu-lations on exposure to BaP.     

Immune Responses to Candida albicans in Genetically Distinct Mice

Mice from six genetically distinct strains were examined for their immune responses to Candida albicans in in vitro and in vivo assays, and naive mice and mice immunized with the fungus were challenged intravenously with three different doses of C. albicans to determine differences in susceptibility. Naive mice from the six groups showed substantial differences in resistance to challenge based on mortalities and quantitative cultures of kidneys, with mice from strains C57BL/6J and BALB/cByJ showing the most resistance; mice from strains A/J, C3H/HeJ, and CBA/J showing moderate susceptibility; and mice from strain DBA/2J showing the highest degree of susceptibility to challenge. Unimmunized mice from strains C57BL/6J and BALB/cByJ did not produce detectable levels of Candida-specific antibody by the end of the 28-day observation period when challenged intravenously, but the other strains did. Immunized mice showed a degree of protection to challenge, with all groups except mice from strain BALB/cByJ showing a reduction of two to three log units in the level of colonization in their kidneys and all strains producing significant levels of antibody. Additionally, the immunized mice of all strains developed substantial levels of delayed-type hypersensitivity and demonstrated nearly identical lymphocyte proliferative responses to Candida antigens. The results indicate that resistance to systemic candidiasis is dependent upon a combination of innate factors, predominately an intact complement system, and the acquisition of an immune response, most likely of a cell-mediated type. Additionally, the findings suggest that genetic control of acquired resistance to C. albicans may not be associated with the H-2 complex.