Candida Albicans Extract Research Articles

In vivo and in vitro observation of cellular immune parameters in squamous cell carcinoma of the oral cavity and its correlation with tumor load and prognosis.

In vivo and in vitro observations of cellular immune response in 70 patients with squamous cell cancer of the oral cavity and in 40 age-matched normal controls, were made using delayed hypersensitivity responses to DNCB, PPD, and Candida albicans extract (Dermatophytin 'O'), absolute lymphocyte counts, absolute T-cell numbers, and PHA-induced lymphocyte blastogenesis reactions as parameters. The results were correlated with clinical stage, tumor size, lymph node involvement, tumor differentiation, lymphoreticular responses, and outcome during a one-year follow-up period. A significant degree of impairment of both in vivo and in vitro parameters was found in oral cancer patients compared to normal control. The impairment was more prominent in advanced stages. Lymph node involvement was associated with impaired dermal hypersensitivity to recall antigens as well as a reduced T-cell population and blastogenic response. Only delayed hypersensitivity response to DNCB, PPD, and Candida showed a correlation with histologic features such as tumor differentiation and lymphoreticular response. Although absolute lymphocyte counts and T-cell population were reduced in the primary stage of the disease, the functional capacity of isolated lymphocytes to undergo blast formation was retained. PHA-induced lymphocyte blastogenesis showed a significant impairment only when the tumor was well established and disseminated beyond its local confines. Delayed hypersensitivity responses to DNCB, higher T-cell counts, and blastogenic indices were associated with recurrence-free survival. Immunologic parameters provide prognostic information beyond the clinical stage of the disease. Therefore, it seems that a multiparametric in vivo and in vitro observation of cellular immune response may be useful as an indicator of clinical course and prognosis of patients with squamous cell cancer of the oral cavity.

Antigen presentation by human monocytes: Effects of modifying major histocompatibility complex class II antigen expression and interleukin 1 production by using recombinant interferons and corticosteroids

Lymphocyte proliferation in response to monocytes pulsed with an antigenic extract of Candida albicans was measured in vitro and the effects of modifying major histocompatibility complex (MHC) class II antigen expression at the surface of the antigen-presenting cells was investigated. The study shows that no simple correlation exists between changes in MHC class II antigen expression and changes in the effectiveness of antigen presentation. Recombinant interferon-alpha 1 (rIFN-alpha 1), rIFN-gamma and hydrocortisone were found to increase the expression of monocyte class II MHC antigens. In contrast, rIFN-alpha 2 did not increase class II antigen expression although it did increase MHC class I expression. Treatment of monocytes with rIFN-alpha 1, rIFN-alpha 2 or corticosteroids during antigen pulsing resulted in a reduction in the subsequent proliferative lymphocyte response. In all cases this inhibitory effect was restricted to antigen-specific proliferative responses since the polyclonal lymphocyte response to pokeweed mitogen-pulsed monocytes remained unaffected. Only rIFN-gamma treatment of antigen-pulsed monocytes resulted in enhancement of the subsequent specific lymphocyte proliferative response. The suppressive effects of hydrocortisone could not be attributed to its well documented inhibitory effects on arachidonic acid metabolism. The effect of C. albicans antigen, IFN and corticosteroids on interleukin 1 (IL 1) production by monocytes was also investigated. C. albicans antigen alone induced IL 1 production. So too did IFN-alpha 1 and IFN-gamma. IFN-alpha 2 did not induce IL 1 production. Addition of interferons together with C. albicans, however, resulted in the same level of IL 1 productions as with C. albicans antigen alone. Neither antigen nor IFN had any effect on IL 1 action in the thymocyte assay. Corticosteroids did not affect IL 1 production by monocytes but were potent antagonists of IL 1 in the thymocyte proliferation assay. Mitogen-induced thymocyte proliferation was also inhibited by corticosteroids. Pretreatment of monocytes with hydrocortisone followed by washing did not markedly affect their subsequent ability to produce IL 1 neither was it possible to reverse the inhibitory effects of hydrocortisone on antigen presentation by addition of exogenous IL 1. Thus, signals which alter class II MHC antigen expression influence the antigen-presenting capacity of monocytes by a mechanism independent of IL 1. No simple correlation exists between class II expression and antigen-presenting capacity.

Identification and molecular weight characterization of antigens from Candida albicans that are recognized by human sera.

Antigenic components in the cytoplasmic extract of Candida albicans were examined after fractionation by concanavalin A-Sepharose and DEAE-Sephacel ion-exchange chromatography. Fractions from the DEAE column were tested by fused rocket immunoelectrophoresis for their reactivity with antibodies in the sera of 20 patients with disseminated candidiasis. Three groups of fractions (regions A, B, and C) from the DEAE column were defined by their reactivity with these sera. Immunoblot analysis with 20 human sera identified 18 antigenic components in regions A, B, and C. Region A contained nine antigens, region B contained four antigens, and region C contained five antigens. Region A contained an antigen with an apparent molecular weight of 48,000 that was recognized by 7 of 10 sera from patients with disseminated candidiasis. Immunoprecipitation experiments with labeled proteins from region A and 51 human sera also demonstrated the presence of a major antigen whose apparent molecular weight is 48,000 to 52,000. The 48- to 52-kilodalton protein is an abundant protein in region A and is the most frequently recognized protein by antibodies in the sera of patients with disseminated candidiasis. Patients with disseminated candidiasis had significantly higher levels of antibody (immunoglobulin G) (P less than 0.001) directed against the 48- to 52-kilodalton protein than did patients with noninvasive forms of candidiasis, patients with other fungal infections, or normal, healthy persons.

Immune responses and immunoregulation in relation to human schistosomiasis in Egypt. I. Effect of treatment on in vitro cellular responsiveness.

Cell mediated immune reactivity of chronic schistosomiasis patients was tested in vitro by peripheral blood mononuclear cell (PBMN) responses against phytohemagglutinin P (PHA), Candida albicans extract, soluble schistosomal antigenic preparations derived from eggs (SEA), adult worms (SWAP) and cercariae (CAP), before and after treatment of the patients with parziquantel. The patient population was from villages in the Qalyub province, Egypt, that are endemic for Schistosoma mansoni and S. haematobium. Patients were studied immediately before, and at 1, 3, 6, and 9 months after chemotherapy. Egg counts were done on stool and urine specimens taken simultaneously with blood samples. There was a significant increase in PBMN responses to SWAP and CAP but not to SEA, PHA or C. albicans in 27 patients (age 8-65) 1 month after treatment. Eleven patients treated 1.5 years previously did not show such elevated responses 1 month after re-treatment. Three months after treatment higher mean responses were observed to SWAP, CAP, SEA, and PHA, but not to C. albicans in 24 patients (age 6-26). Significant increases in PBMN responses to SWAP and CAP, but not to SEA, PHA or C. albicans were obtained at 6 months after treatment in 12 patients (age 6-30). By 9 months after treatment in a group of 11 patients (age 8-25) SWAP and CAP responses were still elevated as were SEA and C. albicans induced reactivities. The PBMN responses of 10 patients were followed longitudinally at pretreatment, 3-, 6-, and 9-month post-treatment times. In general, elevated responses were maintained throughout this period to the schistosomal preparations. Unrelated responses occasionally fluctuated but were not consistently altered over time.

Lymphocyte transformation in vitro in acute dermatophytosis: a follow-up study

Sixteen patients with recently acquired (= nonchronic) dermatophytosis were studied clinically and immunologically before, during and after treatment for 6 months. The methods applied were lymphocyte transformation in vitro (LTT) and intra-dermal test (IDT). Phytohaemagglutinin, pokeweed mitogen, purified protein derivate (PPD) and water-soluble extracts of Trichophyton (T) rubrum, T. mentagrophytes and Candida albicans were used as stimulators. In the LTT the patients in all four studies showed normal general immune responses. Compared with a control group of 22 healthy persons, lymphocytes of the patients showed significantly stronger stimulation with the T. rubrum extract (0.01 greater than p greater than 0.001) throughout the 6 months. The degree of stimulation after one month (the second study) was significantly stronger (0.05 greater than p greater than 0.01) than in the other studies. The stimulation in the last (fourth) study was the lowest (not significant). IDT showed a majority of delayed-type reactions (47-67%) in patients as compared with 7-13% in the controls, when using dermatophyte antigens. Three patients had an immediate-type reaction or mixed reactions. A correlation was found between the severity of lesions and the degree of stimulation in LTT (p less than 0.02 for T. rubrum, p less than 0.007 for T. mentagrophytes). In contrast, no relationship was found between IDT and clinical symptoms, and there was only a slight tendency toward correspondence between the results of IDT and LTT.

Effects of reduced temperature on the components of human lymphocyte transformation responses to antigens.

The present studies were designed to determine the site at which reduced temperature, such as that found at the skin surface, affects the lymphocyte transformation response to an antigenic stimulus. Extracts of Candida albicans and Pityrosporum orbiculare were used as antigens since most normal subjects demonstrate positive lymphocyte responses to both. Total lymphocyte transformation responses to both antigens were reduced and delayed at 34.5 as compared with 37 degrees C. The former temperature did not significantly affect the numbers of antigen-responsive cells, as estimated by limiting dilution analysis. However, the response of first-generation lymphocytes to both antigens was significantly reduced at the lower temperature. There did not seem to be any significant differences between the two antigens with respect to the effects of the reduced temperature on the resulting lymphocyte transformation response or its components. Therefore, the present data suggest that reduced temperature suppresses antigen-stimulated lymphocyte transformation by affecting the later stages of this response.

In vitro lymphocyte proliferation in response to polyclonal activators and microbial antigens, and production of immunoglobulins stimulating thyroid adenylate cyclase in Graves' disease.

Cultures of blood lymphocytes from 16 patients with Graves' disease (GD) and 14 matched controls were studied. Incorporation of [14C]thymidine was significantly increased in unstimulated cultures of GD lymphocytes, while the incorporation after stimulation with polyclonal activators (concanavalin A, pokeweed mitogen, phytohaemagglutinin), microbial antigens (E. coli, Candida albicans extract, purified protein derivative of tuberculin, Yersinia enterocolitica serotype 3) and subcellular fractions of human thyroid antigens did not differ from the controls. Due to the increased incorporation in unstimulated cultures, stimulation index is not suitable as an indicator of lymphocyte sensitization. After polyclonal activation or stimulation with thyroid antigens the lymphocytes were cultured for up to 21 days, and the supernatants were investigated for thyroid adenylate cyclase stimulating immunoglobulins (TACSI). No TACSI were demonstrated in supernatants of the lymphocyte cultures neither afer polyclonal activation nor after specific stimulation with several thyroid antigens.

Effects of experimental hyper- and hypothyroidism on numbers of blood mononuclear cells and immune function in rats and guinea-pigs.

A possible effect of thyroid hormones on numbers of mononuclear cells and immune reactivity has been studied in hyperthyroid and hypothyroid guinea-pigs and rats. There were no major changes in populations of blood mononuclear cells in hyperthyroid or hypothyroid animals compared with populations in euthyroid animals. Although there was some evidence for depressed cell-mediated responses to an extract of Candida (monilia) albicans in hyperthyroid rats as assessed by skin tests, this was minor, and responses in tuberculin purified protein derivative (PPD) were normal in all groups, whilst production of macrophage migration inhibition factor in response to PPD and Candida was similar in the three groups of animals. Antibody responses to sheep red blood cells, a thymic-dependent antigen, tended to be depressed in hyperthyroid and hypothyroid rats and increased in hyperthyroid and hypothyroid guinea-pigs, although this was significant only for hyper-thyroid guinea-pigs 16 days after immunization. Responses to trinitrophenol-Ficoll, a thymic-independent antigen, were similar to the three groups of guinea-pigs. Thus, a major effect of excess or deficiency of thyroid hormone on immune responses to foreign antigens has not been demonstrated, although it is possible that immune reactions against thyroid antigens may be more sensitive to the effect of thyroid hormones than responses to foreign antigens.

A longitudinal study of cell-mediated immunity in human pregnancy

Studies of cell-mediated immunity, comprising delayed hypersensitivity skin testing with four antigens, PHA and antigen-induced lymphocyte transformation and detection of the lymphokine, monocyte chemotactic factor, were undertaken in 14 women during pregnancy and in the post-natal period. Skin test reaction sizes to SKSD, PPD, Candida albicans extract and tetanus toxoid were not significantly different during pregnancy. In vitro lymphocyte transformation induced by PHA, SKSD and Candida albicans was enhanced during pregnancy. Monocyte chemotactic factor production was not significantly different during pregnancy. These in vitro tests were performed in the absence of autologous sera. These studies indicate that cell-mediated immune responses are normal during human pregnancy.

Immune Responses during Human Schistosomiasis Mansoni

The lymphocyte blastogenic responses of chronic schistosomiasis mansoni patients were tested in vitro in medium supplemented with either normal human serum or patients' serum (either autologous or third party). As expected, when patients' lymphocytes were cultured in patient sera, many of them (75--78%) displayed reduced responsiveness to schistosome antigens (derived from either the cercariae, adult worms or eggs of Schistosoma mansoni), but not to Candida albicans extract. For decreased blastogenesis to be manifest, a combination of both suppressive sera and suppressible cells was required; however, some patients had nonsuppressible cells and not all sera were suppressive. In an attempt at classification, four categories of patient responsiveness concerning serosuppression are proposed. The categories depend on the suppressive capabilities of patient sera and the response of patient lymphocytes to suppressive sera. By individually testing the capabilities of each patient's lymphocytes and sera in relationship to each antigenic preparation, we were able to assign the majority of patient responses to a given category. It is hoped that by using these categories, a better understanding of the mechanisms concerning serosuppression will be obtained.

Suppressive action of cytoplasmic and metabolite extracts of Candida albicans on the immune response in guinea pigs.

This study investigated the possibility that Candida albicans components exert a suppressive effect on the immune response of guinea pigs (GP), similar to that of live C. albicans organisms as was previously shown. Hartley GP were inoculated with C. albicans crude cytoplasmic or metabolite (culture filtrate) extracts (containing most of the organism's cell contents or its metabolite and degradation products, respectively). Their immunological responses towards sheep red blood cells (SRBC) were compared with those of GP inoculated with SRBC alone or with SRBC together with live C. albicans organisms. The immunological responses were measured by: 1) rosette formation (RF) of SRBC with peritoneal macrophages, 2) haemolytic plaque formation (PFC) with lymph node-cells, 3) haemagglutination and 4) haemolysis tests. According to the RF tests, inoculation of GP with either cytoplasmic or metabolite extracts resulted in decreased RF as compared to GP inoculated with SRBC only; the decrease was correlated with the protein concentration of the extracts. Inoculation with metabolite extract led to a more diminished RF than with cytoplasmic extract, but less than with live C. albicans organisms. Inoculation of cytoplasmic extracts did not affect the haemagglutinin and haemolysin titers, while that of metabolite extracts resulted in a slight decrease of these titers. The assays for PFC were not conclusive enough to point to a suppressive effect of C. albicans extracts. In summary, it appears that both the cytoplasmic and metabolite extracts of C. albicans exert a partial suppressive effect on the immune response in GP, as judged primarily on the basis of the RF results.

Experimental Candida‐Induced Arteritis in Mice

An extract of Candida albicans isolated from a patient with typical mucocutaneous lymph node syndrome (MCLS) can produce coronary arteritis in a mouse when injected intraperitoneally. An unusual feature of this arteritis is that it is granulomatous, shows no fibrinoid change and is confined to the coronary arteries. These characteristics are quite similar to those found in patients with MCLS.

Immune Responses During Human Schistosomiasis Mansoni

Abstract Peripheral blood mononuclear cells (PBMN) from chronically infected schistosomiasis mansoni patients responded poorly in vitro to a soluble schistosomal egg antigen preparation (SEA) and moderately well to either soluble worm (SWAP) or soluble cercarial (CAP) antigenic preparations. The responses induced by SWAP or CAP were dramatically increased, in 84 and 92%, respectively, of the 24 chronically infected patients tested, upon removal of adherent/phagocytic (A/P) cells from the original cell populations. In contrast, removal of A/P cells from the PBMN of treated patients, transiently infected patients, and uninfected control subjects did not result in enhanced reactivity to these antigens. Overall, SEA-induced responsiveness of chronically infected patients' cells remained low in spite of A/P cell removal. Lymphocyte transformation induced by phytohemagglutinin-P and Candida albicans extract was not significantly altered by removal of A/P cells in any of the groups tested. The expression of another regulatory system concerned with a nonspecific suppressive influence exerted by SEA was also unaffected by the presence or absence of A/P cells. The previously reported, in vitro, schistosome antigen-specific, serosuppression mediated by sera from most chronically infected patients was effective in the presence or absence of A/P cells. However, serosuppression and A/P cells combined to exert maximum suppression of both the SWAP- and CAP-induced responses of chronically infected patients' cells. The enhanced responses observed after A/P cell depletion represented actual increases in blastogenesis, as determined morphologically, as well as increased incorporation of tritiated thymidine. These studies have demonstrated the presence of immunoregulatory A/P cells in the PBMN cells of chronically infected schistosomiasis mansoni patients which have the capability to suppress lymphocyte blastogenesis induced by the antigenic preparations derived from adult worms and the infectious, cercarial, larval stage of the parasite Schistosoma mansoni.

Increasing the predictive value positive of the precipitin test for the diagnosis of deep-seated candidiasis.

Three hundred fifty human sera were tested by double immunodiffusion, crossed-line electrophoresis, and crossed immuno-affinoelectrophoresis with a concanavalin A intermediate gel for precipitating antibodies to antigens present in cytoplasmic extracts of Candida albicans. Sera from 48 of 287 hospitalized patients at risk of invasive candidiasis contained precipitating antibodies to Candida antigens. Of these 48 sera, 27 had precipitating antibodies only to cell-wall antigens present in the cytoplasmic extract, and 21 sera had precipitating antibodies to both cytoplasmic and cell-wall antigens. The latter sera came from patients who were 2.5 times as likely to have deep-seated candidiasis as those patients with precipitins exclusively to cell-wall antigens. Sera from seven of 22 patients with vaginal candidiasis and 10 of 41 patients with other fungal infections had precipitating antibodies to C. albicans cell-wall antigens; only two of these sera also contained precipitating antibodies to the cytoplasmic antigens. Crossed immunoaffinoelectrophoresis with concanavalin A reduced the number of false-positive results and increased the predictive value positive of the precipitin test for deep-seated candidiasis from 31% to 71%.

Ichthyosiform sarcoidosis

A 31-year-old black woman had acquired ichthyosis. Histologic examination of her skin revealed a sarcoidal reaction in the dermis. The diagnosis of sarcoidosis was supported by negative tuberculin (intermediate strength purified protein derivative) and Candida albicans extract intradermal skin tests; by a positive Kveim test; and by roentgenographic evidence of bilateral hilar adenopathy, paratracheal node enlargement, and diffuse pulmonary parenchymal changes. Sarcoidosis must be considered when acquired ichthyosis develops in a patient.

Cell wall antigens in soluble cytoplasmic extracts of Candida albicans as demonstrated by crossed immuno-affinoelectrophoresis with Concanavalin A

Crossed immuno-affinoelectrophoresis with Concanavalin A precipitated four antigens from soluble extracts of the yeast and mycelial phases of Candida albicans. Two of these antigens were also present in spheroplast preparations. One of the Concanavalin A precipitated antigens was destroyed by periodate and none were digested by pronase. Sequential treatment with pronase and periodate destroyed two of the remaining three antigens. The Concanavalin A precipitated antigens appear to be glycoproteins, two of which are associated with the cell wall of C. albicans.

Correlation of Cutaneous Hypersensitivity with Lymphocytic Response to Candida albicans

The relationship between delayed cutaneous hypersensitivity to Candida albicans and in-vitro lymphocytic proliferative response using a highly sensitive micro-technic was studied in 26 healthy adult subjects and six children with chronic mucocutaneous candidiasis. The maximum in-vitro lymphocytic proliferative response in adult subjects with cutaneous hypersensitivity, 18.94 +/- 4.16 (SE), was significantly greater than that in those without cutaneous reactions, 2.49 +/- 0.45 (SE) (P less than 0.005). A close correlation was found between cutaneous hypersensitivity (mean diameter of induration at 48 hours) and in-vitro lymphocytic proliferative response (r = 0.73, P less than 0.001). A cutaneous reaction of 5 mm or more of induration after injection of 0.1 ml of 1:100 Candida albicans extract corresponded to an in-vitro lymphocytic proliferative index of 5 or more (P less than 0.005), which supports the previously empiric use of 5 mm of induration as an indicator of intact cellular immunity in clinical practice. In the children with chronic mucocutaneous candidiasis, no consistent relationship between cutaneous hypersensitivity and lymphocytic proliferative response was found. Administration of Levamisole resulted in increased lymphocytic proliferation in vitro, and the development of cutaneous hypersensitivity, suggesting potentiation of cellular immune function.

Immune Responses During Human Schistosomiasis Mansoni

Abstract The in vitro lymphocyte blastogenesis capabilities of patients with schistosomiasis mansoni were tested against phytohemagglutinin (PHA), Candida albicans extract, and soluble preparations of schistosome eggs (SEA), adult worms (SWAP), or cercariae (CAP). When patients' lymphocytes were cultured in medium which contained 5% human (homologous) normal (uninfected) serum, they responded well to PHA and Candida extract. The responses induced by SEA were maximal in patients with early Schistosoma mansoni infections, while reactivity against SWAP and CAP increased during chronic infection. These responses, induced by the schistosome-derived antigenic preparations, were suppressed if the homologous-normal serum supplement of the culture medium was replaced with either the patient's own (autologous) serum, or that of another S. mansoni patient. All sera were heat-inactivated (56°C/30 min) prior to use. In contrast, responses against the non-specific mitogen (PHA) and the unrelated antigen (Candida extract), were not altered by these changes of the serum supplementation of the media. The degree of suppression by patient serum was not changed by increasing the serum percentage in the medium from 5% to 25%. The suppressive effects of patient sera on responses induced by SEA and SWAP were increased in relationship to the duration of the serum donor's S. mansoni infection. Preincubation of lymphocytes in suppressive patient sera for 30 min at 37°C did not reduce the expected level of responsiveness if the cells were subsequently cultured in homologous-normal serum supplemented medium. The data indicate that during S. mansoni infection patients develop serum component(s) which specifically interfere with the responsiveness of their lymphocytes in regard to certain schistosome-derived antigenic preparations. The immunoregulatory events described could participate in the modulation of immunopathology, the maintenance of chronic adult worm survival, and the prevention of full expression of protective immune responses.

A comparison of different extracts of Candida albicans in agar gel double diffusion techniques

A preliminary comparative study, by 4 independent groups, of certain extracts of Candida albicans, showed variation in their antigenicity. Different agar gel double diffusion tests were used by each group; two groups used micro-methods and two used macro-methods. The number of positive precipitin reactions detected by these methods was shown to vary greatly.

Separation and some characterizations of NADPH-enoyl CoA reductase(s) from Candida albicans.

Two fractions containing NADPH-enoyl CoA reductase activities were isolated from crude extracts of Candida albicans. One fraction (Type-I) having larger molecular weight utilizes 5-hydroxyundec-cis-2-enoyl CoA, oct-cis-2-enoyl CoA and oct-trans-2-enoyl CoA as substrates with Km values of 2.5×10-6M, 1.1×10-6M and 5.0×10-7M, respectively, while another fraction (Type-II) having smaller molecular weight utilizes these substrates with Km values of 3.0×10-6M, 5.3×10-5M and 1.0×10-5M, respectively. This indicates that there exist comparable differences between these two in their affinities especially for the latter two substrates. Some characterizations, such as, effects of pH and of heat treatment on the activities of these reductase preparations were also investigated.