Elevated Levels Of Immunoglobulin Research Articles

SENSITIVITY, SPECIFICITY, AND PREDICTIVE VALUE OF PHYSICAL EXAMINATION, CULTURE, AND OTHER LABORATORY STUDIES IN THE DIAGNOSIS DURING EARLY INFANCY OF VERTICALLY ACQUIRED HUMAN IMMUNODEFICIENCY VIRUS INFECTION

Purpose of the Study. To determine the HIV vertical transmission rate in an unselected group of infants born to HIV-infected mothers, and to examine the sensitivity, specificity, and positive and negative predictive values of physical examination and diagnostic laboratory studies (HIV culture, serum quantitative immunoglobulins and HIV-1 p24 antigen) in the diagnosis of HIV infection. Study Population. A group of 142 infants referred solely because they were born to HIV-infected mothers were selected for this study. Methods. Epidemiological and clinical data were obtained retrospectively from the Baylor Pediatric AIDS Clinical Trials Group HIV Infection Registry and medical records. The information recorded included results of physical examination and diagnostic laboratory tests (HIV culture, serum quantitative immunoglobulins, and HIV-1 p24 antigen). HIV cultures were performed according to a consensus protocol developed for the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Results. Of 142 infants whose HIV infection status was known at the time of the study, 17 (20%) had confirmed infection, and 68 (80%) had seroreverted with no evidence of infection. All HIV-infected infants were at least 3 months old when abnormal physical exam findings became apparent (lymphadenopathy and hepatosplenomegaly), but similar findings were noted in an equal number of HIV-uninfected infants. All infected infants available were HIV culture positive by 6 months of age (16/16). There was no positive cultures reported in the infants who seroreverted (32/32). Elevated immunoglobulins (IgG, IgA, IgM) were present by 6 months of age in a high percentage of infected infants. Nearly one-half of the uninfected infants had elevated immunoglobulin levels during the first 6 months of life, but in 50% of the cases it was IgG alone.

Elevated production of interleukin-4 and interleukin-5 by T cells in a child with idiopathic hypereosinophilic syndrome

The idiopathic hypereosinophilic syndrome (IHES) is characterized by persistent eosinophilia of more than 1500/mm 3 and a variety of resultant organ damage, and these parameters allow classification of patients into four clinical categories. This syndrome is extremely rare in children. The most common immunologic abnormality in patients with IHES is an elevated serum immunoglobulin level (IgG, IgM, and/or IgE). However, no consistent abnormality has been detected in T-cell function. 1 We describe a child with IHES whose T cells produced elevated levels of interleukin (IL)-4 and IL-5.

Elevated levels of total and Puumala virus-specific immunoglobulin E in the Scandinavian type of hemorrhagic fever with renal syndrome.

In a previous study, it was reported that the total immunoglobulin E (IgE) level was increased in patients with hemorrhagic fever with renal syndrome (HFRS). The aim of the present study was to investigate whether specific IgE is synthesized during the course of the disease. For this purpose, an epsilon-capture enzyme-linked immunosorbent assay was developed. A total of 72 patients with HFRS caused by Puumala virus were studied. Three different control groups were included: 20 blood donors, 20 patients with other viral diseases (influenza A and B virus, acute Epstein-Barr virus, and acute cytomegalovirus infections), and 5 subjects with high levels of total IgE (median, 1,070 kU/liter; range, 773 to 5,740 kU/liter). The levels of total IgE were significantly higher during the acute phase of HFRS than those of blood donors (P < 0.01) and of patients with other viral diseases (P < 0.001). All patients developed a specific IgE response (median, 55 arbitrary units; range 24 to 123 arbitrary units) in the acute phase of the disease, whereas in the different control groups no specific IgE was detectable. Both total and specific IgE levels decreased during convalescence compared with those during the acute phase of HFRS (P < 0.001 and P < 0.001, respectively). In conclusion, we have shown that both total and specific IgE levels are increased in patients with HFRS compared with levels in patients with other viral diseases. The possible pathogenetic role of the specific IgE response in HFRS is discussed.

Hyperimmune serum modulates allergic response to spores in a murine model of allergic aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a disease in atopic asthmatics characterized by eosinophilia and elevated levels of immunoglobulin E (IgE) and IgG antibodies to the ubiquitous fungus Aspergillus fumigatus (Af). The role of specific antibodies in the disease process is not clear. In this study, BALB/c mice were injected with hyperimmune serum from syngeneic mice exposed to soluble antigen of Af. These mice were then exposed to either Af spores or soluble antigen. Total IgE, Af-specific IgG1 (enzyme-linked immunosorbent assay) in serum, and eosinophils (eosinophil peroxidase assay) in lungs and bone marrow were measured. Histologic sections of lungs were examined for cellular infiltration and morphologic changes. Results indicate a suppression of increase in levels of antibodies and eosinophilia in mice receiving immune serum and exposed to spores compared with controls receiving phosphate-buffered saline treatment. Spores being the primary source of exposure to Af in ABPA, these results are significant in understanding the role of preexisting specific antibodies in patients.

Increased IgM B cell differentiation lymphokine production by T lymphocytes from patients with primary biliary cirrhosis

Hypergammaglobulinemia, mainly due to increased serum immunoglobulin M concentrations, is a common and distinctive feature of primary biliary cirrhosis. T-B cell cooperation plays a pivotal role in the regulation of immunoglobulin secretion. In this paper, the production of regulatory B lymphokines by T cells, as well as the functional response of B lymphocytes to these molecules, was investigated in patients with primary biliary cirrhosis. T cells from patients with primary biliary cirrhosis have an enhanced ability to produce lymphokines that regulate the proliferation of B cells and their differentiation to immunoglobulins G- and M-secreting cells. In contrast, the cellular production of lymphokines involved in the induction of immunoglobulin A-secreting cells was normal. Simultaneously, the proliferation and differentiation of purified B cells in response to stimulation with surface immunoglobulin ligands and lymphokines were normal. These results suggest that the elevated serum levels of immunoglobulins M and G found in patients with primary biliary cirrhosis could be ascribed to an enhanced lymphokine-mediated T-B cooperation.

Red cell-reactive non-specific immunoglobulins and autoantibodies in the sera of normal and anaemic dogs

The levels of red blood cell (RBC) membrane-reactive IgG were measured in sera from normal and anaemic dogs using an enzyme-linked immunosorbent assay with erythrocyte ghosts as the target antigen (g-ELISA). The anaemic dogs were classified as cases of primary autoimmune haemolytic anaemia (AIHA), other anaemias with elevated levels of RBC-bound immunoglobulin detected by a direct enzyme-linked antiglobulin test (DELAT), or DELAT-negative anaemias. The g-ELISA detected IgG capable of binding RBC membranes in all the serum samples tested, and the levels were significantly higher ( P < 0.05) in dogs with AIHA than in cases of DELAT-negative anaemia or in healthy animals. When sera were preabsorbed with RBC ghosts, g-ELISA readings were reduced in two of three AIHA cases that were tested, but not in dogs from any other group. There was no correlation between g-ELISA results and serum IgG levels in the cases of AIHA, but there was a significant relationship ( r s = 0.74, P < 0.001) between these parameters in the dogs with other DELAT-positive anaemias. When spectrin(s) from the internal RBC membrane skeleton was used as the target antigen in the s-ELISA, sera from all groups of anaemic dogs yielded a wide range of values. Although the levels of spectrin-reactive IgG were significantly higher ( P < 0.05) in AIHA cases than normal dogs, suggesting that haemolysis provoked production of anti-membrane skeleton antibodies, the highest reading was recorded in a healthy animal. It is concluded that all canine sera contain IgG non-specifically reactive with RBC membranes and that serum antibodies against the erythrocyte surface can also be detected in some dogs with primary AIHA. Distinct spectrin-reactive serum IgG antibodies can also be demonstrated in normal and AIHA positive dogs.

Anti-Pseudomonas aeruginosa IgG subclass titers in patients with cystic fibrosis: correlations with pulmonary function, neutrophil chemotaxis, and phagocytosis.

To explore possible mechanisms for the association between elevated immunoglobulin levels and lower pulmonary function in cystic fibrosis patients, we measured serum IgG subclass levels and anti-P. aeruginosa IgG subclass titers and correlated levels with neutrophil phagocytosis and chemotaxis. Serum was obtained from 13 cystic fibrosis patients colonized with the same serotype of P. aeruginosa, 12 noncolonized patients, and 12 normal volunteers. All anti-P. aeruginosa IgG subclass titers were elevated in serum from colonized patients. IgG3 level and anti-P. aeruginosa IgG3 titer were inversely correlated with pulmonary function. Phagocytosis of P. aeruginosa by neutrophils correlated with serum IgG3 level and was increased by opsonization with serum from colonized patients. Chemotactic index was increased in serum from colonized patients and inversely correlated with pulmonary function chest roentgenogram score. Chemotactic index directly correlated with anti-P. aeruginosa IgG3 titer and serum IgG3. These data demonstrate that cystic fibrosis patients with increased IgG3 levels are in poorer clinical condition and that their serum enhances neutrophil function. Such patients may have increased pulmonary inflammation with subsequent lung damage.

Red cell-bound immunoglobulins and complement measured by an enzyme-linked antiglobulin test in dogs with autoimmune haemolysis or other anaemias

A direct enzyme-linked antiglobulin test ( DELAT) was used to measure IgG, IgM, IgA and C 3 bound to the red blood cells ( RBC) of anaemic dogs. One or more of these parameters was raised in 78 per cent of the cases tested, and elevated levels of bound IgG, IgM, IgA and C 3 was the most common pattern recorded. When the DELAT-positive animals were divided into two groups on the basis of clinical findings, the two categories differed serologically. Cases diagnosed clinically as primary autoimmune haemolytic anaemia ( AIHA) were typified by the demonstration of specific antibody binding to RBC, had significantly higher levels of RBC-bound IgG (P<0·001) and IgM (P<0·02) and included a significantly (P<0·01) higher proportion of the dogs with at least three DELAT parameters raised. The second group comprised the DELAT-positive dogs with other diseases. In most of these cases, RBC-specific antibody was not detectable and there was a significant (r s=0·62, P<0·001) relationship between RBC-bound and serum IgG levels, suggesting that the immunoglobulin was reacting with the RBC non-specifically in a concentration-dependent manner. It is concluded that elevated levels of RBC-bound immunoglobulin and, or, complement are detectable with the DELAT in most anaemic dogs, but that this finding is not necessarily associated with autoimmune haemolysis.

Stiff man syndrome: clinical and laboratory findings in eight patients.

The clinical, biochemical, neuroimaging and neurophysiological findings of eight patients with stiff man syndromes (SMS) [four of six being tested with autoantibodies against glutamic acid decarboxylase (GAD)] are presented. In two patients (one GAD-positive, one GAD-negative), transient oculomotor disturbances suggested progressive encephalomyelitis with rigidity and myoclonus (PERM) as differential diagnosis. The catalogue of characteristic clinical symptoms of SMS is extended by three new symptoms: (1) an aura-like feeling reported by five patients to precede spontaneous spasmodic attacks; (2) a stereotyped motor pattern seen in seven patients during spasmodic jerks, consisting of brief opisthotonos, stiffening of the slightly abducted legs and inversion of the plantar-flexed feet; (3) a paroxysmal fear when crossing a free space unaided, or even thinking of it. Clinical findings did not enable us to discriminate between patients tested GAD-positive or GAD-negative. Cerebrospinal fluid contained elevated immunoglobulin levels or cell counts, or both, in the majority of patients. Autopsy of one patient revealed scattered lymphocyte cuffs around leptomeningeal, intracerebral and particularly intraspinal vessels, suggesting a mild inflammatory process. Whether SMS and PERM are closely related is discussed; they are possibly both manifestations of a spectrum of encephalomyelopathies having autoimmunity against GABAergic neurons in common.

The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis.

Direct flow cytometric measurement of nucleic acid content in individual platelets is possible using the fluorescent dye Thiazole Orange (Becton-Dickinson, San Jose, CA). When applied to studies of thrombocytopenic patients, platelets with elevated nucleic acid content ("reticulated platelets") can be identified and quantitated. Labeling of these platelets is saturable and is abolished by treatment with RNAse. It has been suggested that, similar to the erythrocyte reticulocyte response to anemia, the number of these platelets appearing in the circulation may provide an estimate of the rate of thrombopoiesis. The authors studied 229 thrombocytopenic patients, measuring both reticulated platelets and platelet-associated immunoglobulin. The results show that for the subset of patients with normal levels of platelet-associated immunoglobulin, the average absolute number of reticulated platelets is independent of platelet count and remains in the normal range. For those with elevated levels of platelet-associated immunoglobulin, the absolute number of reticulated platelets increases in patients who are moderately thrombocytopenic (60 to 100 x 10(9)/L) but decreases to normal or subnormal levels as thrombocytopenia worsens. The latter finding has been duplicated in studies of mice made thrombocytopenic by injection of anti-platelet antiserum. These results are consistent with the hypothesis that reticulated platelets are subject to peripheral destruction at the same rate as mature platelets, and that in the severely thrombocytopenic patient their level may decrease despite an appropriate marrow thrombopoietic response.

Familial pulmonary nodular lymphoid hyperplasia

We describe three persons in one family with diffuse lung infiltrates, digital clubbing, and chronic hypoxia. Elevated immunoglobulin levels and antinuclear antibodies were found in all patients; pathologic findings included hyperplastic lymphoid follicles infiltrating the epithelium of the small airways. These cases may represent a familial systemic autoimmune disorder seen primarily with pulmonary compromise.

Human peripheral blood leukocytes transplanted on CB17 scid-scid mice are transferred to their offspring.

Severe combined immunodeficient (scid) mice are deficient in functional T cells and B cells. Hence, scid mice reconstituted with human peripheral blood leukocytes (scid-huPBL) provide an excellent model for analysis of the human immune response under in vivo conditions. We have investigated this model further by analyzing human immune responses in the progeny of scid-huPBL (termed scid-humo). We find markedly elevated levels of human immunoglobulins (Ig) in the serum of scid-humo for more than 12 weeks indicating materno-fetal transfer of human B lymphocytes. Consistent with this finding we obtained evidence for the existence of human lymphocytes in scid-humo. Murine Ig levels in scid-humo were also elevated and surface Ig-expressing cells (probably B cells) were demonstrable. In this respect scid-humo resembled "leaky" scid. In contrast to "leaky" scid, scid-humo accepted transfer of human blood leukocytes. Not only leukocytes from autologous but also those from heterologous donors were accepted. Human Ig levels in scid-humo increased more rapidly as compared to normal scid mice. Thus, despite these increased B cell activities in scid-humo, transferred human leukocytes were not affected indicating that materno-fetal transfer of human cells had caused tolerization or conditioning. This is in contrast to scid mice in which elevated Ig levels correlate with increased failure rates of reconstitution with human blood leukocytes. We propose that scid-humo provide an improved model for studying the human immune responses in an in vivo setting.

Identification and immunochemical characterization of IgA in sera of patients with mammary tumors

It has been reported that several types of human cancer are associated with elevated levels of class-A immunoglobulins (Ig) and IgA-containing immune complexes. Moreover, most previous work has come up against the lack of IgA reactivity for chemically defined antigen (Ag). To overcome this, we first evaluated possible immunological binding in sera of patients with mammary tumors or malignant hematologic diseases and controls on a mouse monoclonal anti-idiotypic antibody (Ab2), internal image of conjugated benzo(a)pyrene (BP) coated on well plates. Using this indirect ELISA, a statistically highly significant immunological binding was found in sera of patients with mammary tumors of every grade, type and size. This immunological binding was linked to the IgA isotype. Second, we performed competition experiments between a BP conjugate coated on well-plates and anti-anti-"BP-like" antibodies (Ab) previously incubated with rabbit idiotypic antibodies (Ab1) directed against conjugated BP. A part of these anti-anti-BP-like Ab, raised in rabbits immunized with human IgA of patients with mammary tumors, recognized the Ag-combining site of polyclonal Ab1, previously developed in a rabbit immunized with BP conjugates. It appears that part of the human Ig from sera of patients with mammary tumors shares common idiotopes with rabbit polyclonal Ab1 raised against conjugated BP.

Antigen complex of Coccidioides immitis which elicits a precipitin antibody response in patients

The occurrence in patients of elevated levels of immunoglobulin M (IgM) precipitin antibody to Coccidioides immitis antigens, which are commonly detected by the immunodiffusion-tube precipitin (TP) assay, is suggestive of primary nondisseminating coccidioidomycosis. We previously demonstrated that the concanavalin A-bound mycelial culture filtrate plus lysate preparation is a source of at least two TP antibody-reactive antigens (TP-Ags), which were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis as 120- and 110-kDa fractions. Evidence is presented here that the crude filtrate plus lysate preparation contains additional lectin-bound, TP antibody-reactive fractions as well as a component which elicits a complement fixation antibody response in patients. The 120- and 110-kDa fractions were isolated from the antigen complex and further characterized in this paper. Both TP-Ags are glycoproteins and have been shown by immunoelectron microscopy to be colocalized within cytoplasmic vesicles and the wall of spherules. Deglycosylation of these TP-Ags by sodium periodate treatment resulted in a loss in patients of 82 to 95% of IgM adsorption to the antigens as detected by the enzyme-linked immunosorbent assay (ELISA). Comparison of their carbohydrate compositions revealed that mannose and glucose are the predominant monosaccharides of both TP-Ags but only the 120-kDa fraction contained 3-O-methylmannose, a sugar which appears to be unique to C. immitis among the systemic fungal pathogens. We previously showed that 3-O-methylmannose is at least partly responsible for the reactivity of IgM antibody with the 120-kDa TP-Ag. Good correlation was shown between results of immunodiffusion-TP assays and ELISAs of IgM response to both the 120- and 110-kDa fractions by using 70 serum samples from patients with proved coccidioidomycosis. However, only 2.8% (3 of 109) of the serum samples from patients with other mycoses and nonmycotic infections showed IgM adsorption to the 120-kDa TP-Ag as detected by the ELISA, while 21.1% (23 of 109) showed IgM adsorption to the 110-kDa TP-Ag. The 120-kDa TP-Ag is a potentially valuable serodiagnostic reagent for detection of specific IgM by ELISA in patients with primary coccidioidomycosis.

A current perspective on the role of eosinophils in dermatologic diseases

Eosinophils are frequently observed in cutaneous inflammation, but little is known of their significance in the pathophysiology of cutaneous disease. Recent studies of the structure, content, and activities of the eosinophil have shown that it has potent toxic proteins with the potential to mediate tissue damage. Furthermore, immunofluorescent localization of eosinophil granule proteins has shown that eosinophils disrupt in tissue and deposit toxic granule proteins. The deposition of granule proteins in several diseases is vastly out of proportion to the number of identifiable cells and indicates that eosinophil involvement in cutaneous disease cannot be judged by the number of intact eosinophils in the tissue. Specifically, deposition of eosinophil granule proteins outside of eosinophils has been observed in eczematous lichenified disorders with elevated serum levels of immunoglobulin E, in urticarial and an-gioedematous disorders, and in bullous diseases, The structural, compositional, and functional characteristics of eosinophils are reviewed, and evidence of eosinophil degranulation in cutaneous diseases is presented. Mechanisms whereby eosinophil degranulation may mediate pathophysiologic effects are also discussed.

Gaucher's disease: lack of antibody response in 12 patients following repeated intravenous infusions of mannose terminal glucocerebrosidase

An amplified ELISA has been employed for monitoring the safety of repeated intravenous infusions of modified human placental glucocerebrosidase. The enzyme infusions consisted of biweekly injections of macrophage targeted glucocerebrosidase over a 6 month duration. Serum samples collected throughout the study were assayed by use of an ELISA using alkaline phosphatase coupled to alcohol dehydrogenase for amplification. Using this protocol, 0.2-5 ng affinity purified immunoglobulin specific for glucocerebrosidase can be detected. Occasional false positives necessitate multiple repeat assays over time to accurately assess immunogenic response. Blinded ELISAs were performed on sera from both infused patients with Gaucher's disease and uninfused control patients and compared with apparent immunoglobulin concentration in 54 normal control sera. Although several samples showed apparently elevated immunoglobulin levels, repeat analyses failed to demonstrate high levels reproducibly. Furthermore, these sera were unable to neutralize enzyme or to precipitate radiolabelled enzyme, confirming the absence of antibody. Problems with high sensitivity ELISA formats are discussed.

Elevated levels of immunoglobulin A to Giardia lamblia during a waterborne outbreak of gastroenteritis.

During an outbreak of diarrheal illness among residents of a trailer park in rural Vermont, 37 (30%) of 122 residents met the case definition of outbreak-related giardiasis. Convalescent-phase sera from 24 residents and 20 nonresident control subjects were tested by enzyme-linked immunosorbent assay for immunoglobulin G (IgG), IgM, and IgA antibodies to Giardia lamblia. Residents showed higher levels of parasite-specific antibody than did nonresident controls for IgG and IgA but not IgM. Nine residents with giardiasis had a higher median level of G. lamblia-specific IgA but not IgG or IgM than 15 healthy residents (0.61 versus 0.16 optical density units; P = 0.004). Moreover, parasite-specific IgA levels were higher in those consuming tap water than in those who did not (0.31 versus 0.08 optical density units; P = 0.03) and increased with increasing water consumption. Levels of serum antibody to G. lamblia, particularly IgA, may be useful in determining exposure to G. lamblia-contaminated water and illness from G. lamblia during waterborne outbreaks of diarrheal illness.

Immunologic dysregulation in a patient with familial hemophagocytic lymphohistiocytosis

A 6-year-old Jewish Iranian girl with familial hemophagocytic lymphohistiocytosis (FHLH) is described. The course of the disease fluctuated with partial initial response to antibiotics, steroids, and supportive treatment. Subsequent cytotoxic treatment, including VP-16, Velban (vinblastine sulfate), and methotrexate (MTX) controlled the disease for a few months but the child died with a clinical picture of meningocephalitis 1.5 years later. Benign-looking lymphohistiocytic infiltrates with varying degrees of hemophagocytosis were present in the bone marrow, pleural effusion, cerebrospinal fluid (CSF), liver, and brain. Clinical and laboratory evidence of immunologic dysregulation during the disease could be demonstrated. Frequent and intense viral and bacterial infectious diseases were encountered. The laboratory examination most consistently found was the absence of natural killer (NK) cell activity against K562 target cells. The impaired activity of NK cells persisted during all stages of the disease including remission, although NK cell numbers, determined morphologically and immunophenotypically (by Leu-11, Leu-7), were normal. Natural killer activity could not be restored by interferon. Moreover, the interferon system appeared to be intact. Impaired monokin interleukin 1 (IL-I) production by peripheral blood monocytes was found and could not be restored by indomethacin. Lymphopenia, a mild decrease in T4 numbers, and subsequently, decreased proliferative response to mitogens was noted. Elevated immunoglobulin levels were found during exacerbations and viral episodes, at times accompanied by the presence of auto-antibodies. The exaggerated fatal lymphohistiocytic response typical for FHLH could be attributed to a underlying genetic pathologic dysregulation of the various immunological response pathways.

Significance of anticentromere antibody in idiopathic Raynaud's syndrome

Fifty-eight patients with Raynaud's syndrome who had no evidence of definite underlying connective tissue disease had serum analyzed for the presence of anticentromere antibody using indirect immunofluorescence techniques on HEp-2 cell lines. Eighteen patients (31 percent) were anticentromere antibody-positive. The anticentromere antibody-positive group demonstrated significantly more frequent digital telangiectases, digital edema, elevated levels of immunoglobulins, and low C4 values. Photoplethysmography revealed significantly diminished blood flow in the anticentromere antibody-positive group. Capillary microscopy revealed significantly increased avascularity and number of dilated loops in the anticentromere antibody-positive group. Giant loops were seen exclusively in the anticentromere antibody-positive group. The clinical findings in the anticentromere antibody-positive group are suggestive of a transition to a connective tissue disease with features of the CREST syndrome.

Experimental American Leishmaniasis in the Brazilian Squirrel Monkey (Saimiri sciureus): Lesions, Hematology, Cellular, and Humoral Immune Responses

Unulcerated cutaneous lesions appeared and persisted in squirrel monkeys experimentally infected with Leishmania braziliensis braziliensis or L. b. panamensis. Peripheral blood mononuclear cell (PBMC) numbers increased following infection, and cultured PBMCs from infected monkeys proliferated in response to parasite antigens. The responses of PBMCs to mitogens were not suppressed in infected monkeys. Elevated levels of leishmania-specific immunoglobulins M and G were also observed. Thus, the squirrel monkey is susceptible to American leishmaniasis and is capable of responding to the infection with measurable cellular and humoral immunity.