RESUMO
These studies compared the ability of specific secretory IgA (sIgA) and IgG antibodies to promote phagocytosis of viable pseudomonas aeruginosa by human alveolar macrophages. Macrophages were obtained by lung lavage of normal adult smoker and nonsmoker volunteers and were maintained as in vitro cell monolayers. Both immune sIgA and IgG agglutinating antibodies were demonstrated to coat and opsonize viable bacteria, whereas similar nonimmune immunoglobulin preparations did not. When alveolar macrophages were challenged with viable opsonized 14C-labeled Pseudomonas IgG-reacted bacteria were ingested better and killed more readily than sIgA-opsonized organisms. Phagocytic responses were not significantly different between macrophages obtained from smokers and nonsmokers. Although sIgA and IgG antibodies can be found in respiratory secretions and both are undoubtedly important in pulmonary host defense, IgG opsonic antibody was superior in enhancing the uptake of Pseudomonas by in vitro-cultured alveolar macrophages. It may be the more important respiratory antibody for certain bacterial infections.
Assuntos
Imunoglobulina A , Imunoglobulina G , Macrófagos/imunologia , Proteínas Opsonizantes , Fagocitose , Pseudomonas aeruginosa/imunologia , Adulto , Bioensaio , Humanos , Soros Imunes , Técnicas In Vitro , Contagem de Leucócitos , Pulmão/imunologia , Pulmão/metabolismo , Linfócitos , Macrófagos/análise , FumarRESUMO
Immunization with Pseudomonas lipopolysaccharide induced both cellular and humoral immunity in rabbits, particularly in the respiratory tract after intranasal immunization. Either parenteral (i.m.) or intranasal immunization elicited an IgG antibody response in respiratory secretions, but only intranasal immunization produced secretory IgA antibody. Immunization by both routes stimulated serum IgM and IgG agglutinative antibodies. Because both methods of immunization produced skin test reactivity which had components of both Arthus and tuberculin-like reactions, cellular immunity was more readily assessed by the measurement of migration inhibitory factor (MIF) released from immune lymphocytes in respiratory and spleen cell suspensions after challenge with the lipopolysaccharide antigen. After intranasal vaccination, MIF activity was detected in the respiratory tract by direct assay; in contrast, i.m. immunized rabbits did not produce respiratory MIF. Both modes of immunization resulted in splenic MIF activity. However, lymphocytes were only capable of producing MIF for short periods after primary immunization had ended, apparently losing this function in about 2-3 wk. Therefore, it was concluded that cellular immunity by in vitro assay was transient after primary immunization with this Pseudomonas antigen in contrast to the more persistent humoral immunity. The biological significance of immune lymphocytes as part of the coordinated host defense of the lung needs further evaluation.
Assuntos
Antígenos de Bactérias/farmacologia , Imunidade Celular , Imunidade , Lipopolissacarídeos/farmacologia , Polissacarídeos Bacterianos/farmacologia , Sistema Respiratório/imunologia , Animais , Formação de Anticorpos , Imunoglobulina G , Injeções , Injeções Intramusculares , Lipopolissacarídeos/administração & dosagem , Fatores Inibidores da Migração de Macrófagos , Nariz , Polissacarídeos Bacterianos/administração & dosagem , Pseudomonas aeruginosa/imunologia , Coelhos/imunologia , Baço/imunologiaRESUMO
Approximately 4 h after an initial bronchoalveolar lavage (BAL) of a primate's lung, an appreciable number of polymorphonuclear leukocytes (PMNs) were noted to accumulate in respiratory fluids when lavage was repeated. Whereas, alveolar macrophages (90%) and lymphocytes (7%) were the principal respiratory cells recovered initially from lavage fluid, later samples contained 45-90% PMNs To explain the observed ingress of PMNs into lung fluids, concentrated BAL fluid was tested for chemoattractant activity. Such fluid obtained 4 and 24 h after an initial lavage contained material that produced directed migration (chemotaxis) for PMNs and mononuclear cells isolated from peripheral blood of normal donors. Gel filtration chromatography of BAL disclosed two peaks of chemotactic activity in the effluent fractions. Material from the column with an estimated molecular weight of 15,000 daltons was chemotactic for both PMNs and mononuclear cells. Because it was susceptible to inactivation with antiserum against the fifth component of complement, resistant to heating, and unaffected by antiserum against C3, this factor was considered analogous to the cleavage product of the fifth component of complement. C5a. In addition chemotactic activity for PMNs only was contained in an effluent peak having a molecular weight of about 5,000 daltons. This material was heat labile but unaffected by antisera to complement components. To locate the possible source of these factors in respiratory fluid, in vitro cultures of alveolar macrophages were established. These cells, whether stimulated by phagocytosis of opsonized bacteria or merely by attachment to a glass surface, produced chemotactic material which had physical characteristics similar to the small molecular weight material in BAL. Moreover, it induced preferential chemotaxis for PMNs. Thus, in primate lungs, at least two chemotactic substances may generate an inflammatory response; one which is a fragment of the complement component C5 and another small molecular weight factor which is released from alveolar macrophages.
Assuntos
Líquidos Corporais/análise , Brônquios/metabolismo , Quimiotaxia , Neutrófilos , Alvéolos Pulmonares/metabolismo , Animais , Contagem de Células , Complemento C5 , Cicloeximida/farmacologia , Feminino , Haplorrinos , Técnicas In Vitro , Inflamação/imunologia , Macaca mulatta , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Irrigação TerapêuticaRESUMO
Pseudomonas aeruginosa infection plays a primary pathogenetic role in the chronic respiratory tract disease of cystic fibrosis (CF) patients. Despite pronounced humoral immune responses, reflected by high levels of antibodies against Pseudomonas in serum and in sputum, the antibodies do not eliminate this bacterium. In the present study we have used affinity chromatography with a lipopolysaccharide substituted immunoadsorbent gel to isolate high titers (meanCF = 1:256) of immunotype specific Pseudomonas IgG antibodies from the sera of nine CF subjects, and have evaluated the functional ability of these antibodies to promote phagocytosis and intracellular killing of P. aeruginosa in an in vitro human alveolar macrophage culture system. The phagocytic and intracellular bactericidal kinetics revealed that CF IgG antibodies function in an inhibitory fashion. Both the rate of phagocytosis (rateCF = 204 cpm/unit time) and absolute bacterial uptakes maximal at 120 min (uptakeCF = 18 x 10(3) 14C cpm) were inhibited compared with appropriate positive controls (hyperimmune serum, HIS; [rateHIS = 399; uptakeHIS = 29 x 10(3), P less than 0.005]). The ability of such CF-derived opsonins to potentiate macrophage intracellular bactericidal processes was mildly impaired (bacterial survivalCF = 15 x 10(3) colony forming units (CFU)/min, survivalHIS = 9 x 10(3)). Further characterization of this defect, assessed with functional studies of the Fab and Fc portions of the immunoglobulin molecule, revealed an impairment in the attachment of these specific antibodies to the alveolar macrophage membrane Fc gamma receptors. Preliminary studies of the physical-chemical properties of these immunoglobulins were normal. The expression of this inhibitory activity in vivo may facilitate Pseudomonas colonization and the subsequent established infections in the respiratory tracts of CF subjects.
Assuntos
Anticorpos Antibacterianos , Fibrose Cística/imunologia , Proteínas Opsonizantes , Infecções por Pseudomonas/imunologia , Anticorpos Antibacterianos/isolamento & purificação , Atividade Bactericida do Sangue , Fibrose Cística/complicações , Humanos , Macrófagos/imunologia , Fagocitose , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/imunologia , Receptores Fc/imunologiaRESUMO
Alveolar macrophages are the initial phagocytic cells that encounter foreign material and particulates deposited in the terminal airways. We have examined a mechanism by which these cells, after phagocytic challenge, may control or amplify the inflammatory response in lung parenchyma. Normal human alveolar macrophages (AM) were studied from eight subjects. With in vitro culture, AM produced and released two substances into culture media which have potent chemoattractant activity for blood polymorphonuclear granulocytes (PMN) and negligible activity for mononuclear cells. Release of these factors is maximally stimulated by aggregated human immunoglobulin (Ig)G or zymosan particles; however, simple adhesion of the macrophages to plastic surfaces is also sufficient to stimulate release of these chemotactic substances. The larger substance (10,000 daltons) is immunologically distinct from C5a and interacts with a different PMN membrane receptor than that known to exist for formyl-methionyl-leucyl-phenylalanine. Its chemotactic activity is sensitive to the enzymatic effect of trypsin. Although producing a single elution peak on gelfiltration chromatography, electrofocusing in polyacrylamide gels yielded five peaks of radioactivity. Chemotactic activity was localized to a fraction with a pI = 5.0. The smaller molecular weight substance has been less well characterized. Thus, the human AM can produce at least two factors which attract PMN and this capability may augment the local inflammatory response in the lung.
Assuntos
Fatores Quimiotáticos/biossíntese , Macrófagos/metabolismo , Alvéolos Pulmonares/metabolismo , Células Cultivadas , Fatores Quimiotáticos/farmacologia , Feminino , Granulócitos/efeitos dos fármacos , Humanos , Imunoglobulina G/administração & dosagem , Técnicas In Vitro , Cinética , Leucócitos/efeitos dos fármacos , Masculino , Peso Molecular , Fumar/fisiopatologia , Zimosan/farmacologiaRESUMO
Pseudomonas pneumonia was produced in dogs with radiation-induced leukopenia. Treatment of this infection with either gentamicin alone or gentamicin plus daily granulocyte transfusion was compared in a randomized controlled trail. The dogs receiving granulocytes plus gentamicin survived significantly longer than those treated with gentamicin alone (P < 0.05). The Pseudomonas immunotype which was inoculated into the dogs were recovered at autopsy from none of the granulocyte-transfused dogs, whereas seven or eight of the dogs treated with gentamicin alone had the inoculated Pseudomonas immunotype in the area of induced pneumonia at autopsy. As measured by the limulus test, the granulocyte-transfused dogs also did not have endotoxemia as frequently as the dogs given only gentamicin (P < 0.05). This controlled study establishes that transfused granulocytes can favorably alter the course of experimental Pseudomonas pneumonia and suggests that granulocyte transfusion may be a useful therapy in serious bacterial infections of leukopenic subjects.
Assuntos
Transfusão de Sangue , Leucócitos , Pneumonia/terapia , Infecções por Pseudomonas/terapia , Animais , Plaquetas , Modelos Animais de Doenças , Cães , Gentamicinas/uso terapêutico , Contagem de Leucócitos , Leucopenia/etiologia , Neutrófilos , Pneumonia/tratamento farmacológico , Pneumonia/imunologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Lesões Experimentais por RadiaçãoRESUMO
To evaluate cellular and protein components in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP), limited broncho-alveolar lavage was done in 58 patients (19 IPF, 7 CHP, and 32 controls). Analysis of the cells and protein in the lavage fluids from patients with IPF revealed an inflammatory and eosinophilic response and a significant elevation of IgG in the lungs. With corticosteroid therapy, inflammation diminished but eosinophils remained. Lavage fluid from patients with CHP also had eosinophils and elevated levels of IgG. However, in contrast to IPF, lavage fluid from CHP patients contained IgM, fewer inflammatory cells, and a strikingly increased number (38-74%) of lymphocytes. Identification of lavage lymphocytes in CHP showed that T lymphocytes were significantly elevated and B lymphocytes were decreased compared to peripheral blood. These studies suggest nthat the lung in IPF and CHP may function as a relatively independent immune organ, and that analysis of cells and proteins in broncho-alveolar lavage fluid may be of diagnostic, therapeutic, and investigative value in evaluating patients with fibrotic lung disease.
Assuntos
Alveolite Alérgica Extrínseca/metabolismo , Líquidos Corporais/análise , Brônquios/análise , Alvéolos Pulmonares/análise , Fibrose Pulmonar/metabolismo , Idoso , Doença Crônica , Proteínas do Sistema Complemento/análise , Eosinófilos/análise , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina E/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Linfócitos/análise , Macrófagos/análise , Masculino , Pessoa de Meia-Idade , Neutrófilos/análise , Fumar , Irrigação TerapêuticaRESUMO
In the disease cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a common clinical complication that determines most morbidity and almost all excess mortality. We postulated that in this disease a defect in Pseudomonas-reactive IgG antibodies may contribute to chronic Pseudomonas infections. Bronchoalveolar lavages were performed upon 13 patients with CF, 7 patients with chronic bronchitis characterized by recurrent Pseudomonas infections, and 4 normal volunteers. The levels of various proteins important to host defenses and proteases were determined; enzyme inhibition studies were performed. CF respiratory immunoglobulin levels were significantly elevated when compared with both normals and patients with chronic bronchitis (P less than 0.05). Albumin and transferrin levels were decreased in the CF lung fluids. CF elastolytic activity was strikingly elevated (means = 6.02 micrograms/mg total protein) and the inhibitory profile suggested such activity resembled a serine-proteinase. Alpha-1-antitrypsin antigenic levels were not altered in CF respiratory fluids. There was a tendency for the lavage IgG to fall as elastase levels rose (r = -0.29). IgG opsonins for two Pseudomonas immunotypes were isolated with affinity chromatography for functional and immunochemical studies. Bacterial phagocytic rates in the presence of these Pseudomonas-reactive IgG opsonins derived from CF lavage fluid were depressed (0.3% uptake/unit time) when compared with similarly titered positive controls (uptake = 1.3%/unit time, P less than 0.001). Additionally, normal pulmonary macrophage intracellular killing of Pseudomonas was severely altered in the presence of opsonins derived from CF respiratory fluids. At some time points, less than 30% of the bacteria were killed. CF IgG opsonins contain a cleavage fragment (100,000 D, 5S sedimentation coefficient) with antigenic determinants similar to the Fab portion of IgG. The presence of such a fragment was inversely correlated with phagocytic functional activity. Intact IgG comprised as little as 18% of the CF lavage fluid specimens. Aliquots of intact human IgG, when mixed with the CF opsonins, augmented Pseudomonas uptake and improved intracellular killing. Conversely, peptide fragments of IgG opsonins, which are proteolytically derived in vitro, duplicated in our system the defect observed with opsonins derived from CF lung fluids; bacterial uptake was inversely related to the concentration of F(ab')2 and to a greater degree, to Fc present in the opsonic mixture. We concluded that IgG respiratory opsonins are fragmented, inhibiting phagocytosis and serving a permissive role in the chronic Pseudomonas pulmonary infection in the disease CF.
Assuntos
Brônquios/imunologia , Fibrose Cística/imunologia , Imunoglobulina G/análise , Imunoglobulinas/análise , Proteínas Opsonizantes/análise , Alvéolos Pulmonares/imunologia , Adulto , Formação de Anticorpos , Bronquite/imunologia , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Imunoeletroforese/métodos , Masculino , Pessoa de Meia-Idade , Elastase Pancreática/análise , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/imunologia , Valores de ReferênciaRESUMO
Potent, mono-specific anti-Pseudomonas immunoglobulins were isolated from serum and lung lavage fluid from patients with cystic fibrosis using immunotype specific Pseudomonas aeruginosa lipopolysaccharide (LPS) substituted immunoadsorbent gel. Iodinated monovalent Pseudomonas LPS somatic antigens, Fisher immunotypes, were used as ligands for two different insoluble gel matrices. LPS iodination, using the water insoluble chloroglycoluril reagent, permitted quantitation of the percent LPS bound as a ligand. The coupling efficiencies of epoxy-activated and cyanogen bromide-activated Sepharose matrices for various Pseudomonas immunotype specific LPS preparations were compared. Although each of the 7 LPS somatic antigens produced an equivalent amount of coupling, higher percentages of coupling were found using the cyanogen bromide-activated gel when compared to the epoxy-activated gel. IgG fractions prepared from cystic fibrosis sera and lung lavage fluid were passed through the LPS affinity gels, and Pseudomonas LPS immunotype specific antibodies were eluted. The presence of specific antibody activity against individual Pseudomonas immunotypes was determined with a passive micro-hemagglutination assay. Bronchial lavage fluid seemed to be as effective as serum as a source of Pseudomonas specific antibody. Use of such a LPS substituted gel permits direct recovery of Pseudomonas monospecific antibodies suitable for physical-chemical analyses and for biologic functional assays.
Assuntos
Anticorpos Antibacterianos/isolamento & purificação , Técnicas de Imunoadsorção , Pseudomonas aeruginosa/imunologia , Líquidos Corporais/imunologia , Fibrose Cística/imunologia , Humanos , Imunoglobulina G/imunologia , Lipopolissacarídeos/imunologia , Pulmão/imunologiaRESUMO
A heptavalent lipopolysaccharide Pseudomonas vaccine was evaluated in 22 patients with acute leukemia and 12 patients with cystic fibrosis during an 18 month interval at the Clinical Center of the National Institutes of Health. Of the 34 patients, 32 had an excellent serum hemagglutinating (HA) antibody response to immunization. In comparison to the patients with cystic fibrosis, the patients with leukemia had a smaller HA antibody response, which lasted a shorter period of time, and also experienced greater toxicity from the vaccine. The mixing of adrenal corticosteroids with vaccine greatly decreased side reactions among the patients with leukemia without significantly inhibiting antibody production. Previous antineoplastic chemotherapy had little influence on antibody response in patients with leukemia, with the exception of methortrexate. Vaccinated patients with leukemia had 1 Pseudomonas infection of 14 bacterial or fungal infections, whereas 2 pseudomonas infections of 5 bacterial or fungal infections occurred in a control group of 20 patients with acute leukemia. Of the 12 patients with cystic fibrosis, 4 had a Pseudomonas infection after vaccination.
Assuntos
Vacinas Bacterianas , Leucemia/imunologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/imunologia , Adolescente , Adulto , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/efeitos adversos , Criança , Ensaios Clínicos como Assunto , Fibrose Cística/imunologia , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-IdadeRESUMO
Immunoglobulin G--which can be subdivided into four classes, each with different functional characteristics--is an important component of the host defense system of the respiratory tract. An excessive amount can be produced or can accumulate after airway irritation (exposure to cigarette smoke) or from immunologic stimulus of B-lymphocyte-plasma cells in types of hypersensitivity and interstitial lung diseases. Specific antibody activity can be identified in organic dust-induced hypersensitivity pneumonitis and asthma that contributes to disease pathogenesis. The availability of opsonic antimicrobial antibodies is essential for optimal function of phagocytes in uptake and containment of bacteria. With an absolute or functional deficiency of IgG, recurrent and chronic types of sinopulmonary infections occur. These extremes of IgG availability, either high levels (presumably excessive) or deficient, are discussed in this review.
Assuntos
Imunoglobulina G/fisiologia , Sistema Respiratório/imunologia , Infecções Respiratórias/imunologia , Síndrome da Imunodeficiência Adquirida/imunologia , Asma/imunologia , Líquido da Lavagem Broncoalveolar/análise , Humanos , Deficiência de IgG , Imunoglobulina G/análise , Imunoglobulina G/classificação , Pneumonia Pneumocócica/imunologia , Polissacarídeos Bacterianos/imunologia , Fibrose Pulmonar/imunologia , Sistema Respiratório/análise , Fumar/imunologiaRESUMO
The mucosal surface of the respiratory tract has an operable immune system, specially designed for producing immunoglobulins (antibodies); however, it has not been harnessed effectively yet to provide local, immunospecific protection against many microbes that enter. Respiratory host responses in humans have been used in this review where possible. New research approaches seem necessary to manipulate the physical and immunologic barriers in the respiratory tract and this may require different antigen preparations, better and more specific vehicles for delivery and selective enhancement of cytokines and interleukins in the mucosa. The immunologic tools are available and need to be explored more in the human model.
Assuntos
Sistema Respiratório/imunologia , Formação de Anticorpos , Antígenos/administração & dosagem , Aderência Bacteriana/imunologia , Citocinas/fisiologia , Humanos , Imunização , Memória Imunológica , Linfócitos/imunologia , Macrófagos Alveolares/imunologia , Mucosa/anatomia & histologia , Mucosa/imunologia , Mucosa/fisiologia , Fenômenos Fisiológicos Respiratórios , Sistema Respiratório/anatomia & histologiaRESUMO
Patients with diffuse interstitial lung diseases (DILD) are challenging to treat. Many patients with DILD have inadequate information about the disease process, an imprecise diagnosis, unsatisfactory treatment or unacceptable side effects associated with therapy, and poorly controlled symptoms of progressive illness. Establishing an accurate diagnosis is necessary so that the patient and his/her family can be provided with reasonable expectations about prognosis and outcome from therapy. A pragmatic approach is presented that emphasizes diagnostic strategies and plans for therapy that are effective and resource efficient and that will help maintain patient satisfaction.
Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Anti-Inflamatórios/uso terapêutico , Biópsia , Lavagem Broncoalveolar , Humanos , Imunossupressores/uso terapêutico , Oxigenoterapia , Radiografia Torácica , Reprodutibilidade dos Testes , Testes de Função Respiratória , Toracoscopia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
To assess the impact of bronchoalveolar lavage (BAL) on clinicians' diagnostic reasoning, we administered serial telephone questionnaires to all pulmonary physicians submitting BAL specimens to our laboratory from nonimmunocompromised patients with diffuse interstitial lung disease. Questionnaires were completed when the lavage specimens were first submitted and again after the results were reported to referring physicians. We recorded the clinicians' ordered list of likeliest diagnoses for the patient, a level of confidence in each diagnosis mentioned, and any proximate plans for further diagnostic tests. Of 78 patients in the study, information from the BAL fluid cell analysis caused clinicians to change their diagnostic thinking in 46 (59 percent). These changes were far more frequently appropriate (52 percent) than not (9 percent), and clinically impressive changes did occur but were infrequent (3 of 78 [4 percent]) in this series. Specifically, BAL permitted the unexpected diagnosis of Pneumocystis carinii in a patient not previously suspected to have acquired immune deficiency syndrome (AIDS) and appropriately encouraged clinicians to avert planned surgical biopsies in two patients subsequently found to have sarcoidosis. These findings suggest that when used to evaluate nonimmunocompromised patients, BAL fluid cell analysis can have an important impact on clinicians' diagnostic reasoning about their patients' interstitial lung diseases.
Assuntos
Líquido da Lavagem Broncoalveolar/citologia , Fibrose Pulmonar/diagnóstico , Biópsia , Contagem de Células , Humanos , Pulmão/patologia , Pneumopatias/diagnóstico , Sarcoidose/diagnósticoRESUMO
The application of the method of bronchoalveolar lavage to an increasing array of pulmonary diseases was evident, and the use of sophisticated technology to study cells and measure minute amounts of protein and other components in bronchoalveolar lavage fluid indicated that more meaningful information may be gained about diseased airways and alveolar spaces than suspected. That new techniques are being developed to make assays more sensitive and specific was evident. The popularity of this research approach was underscored by the interest and participation of colleagues in the United States and especially in Europe (notably France, England, Italy, and West Germany) and in Japan. This meeting was an opportune time to reflect on what bronchoalveolar lavage analysis has contributed to date and to focus attention on new applications that will be forthcoming and will improve our understanding of immunopathogenic mechanisms in an expanding number of pulmonary diseases.
Assuntos
Brônquios/patologia , Alvéolos Pulmonares/patologia , Asma/patologia , Humanos , Pneumopatias/patologia , Lesão Pulmonar , Doenças Profissionais/patologia , Fibrose Pulmonar/patologia , Fumar , Irrigação TerapêuticaRESUMO
Colonization of the lower respiratory tract by enteric Gram-negative bacilli (EGNB) has been a frequent finding in patients with long-term tracheostomies; however, the association of hospitalization and certain features of serious illness with this phenomenon has not been clearly established. Because such factors can render the oropharynx more susceptible to EGNB colonization, we sought to discover whether they can also have this effect on the tracheobronchial tree and its microflora. Thus, we collected serial paired culture samples from these two mucosal sites in 15 subjects with long-term tracheostomies and examined patterns and rates of colonization and related these findings to clinical parameters. In 49 sets of cultures, we found that EGNB (especially Pseudomonas species) were present in significantly fewer upper-airway cultures (36.7 percent) than lower-airway cultures (75.5 percent) (p = 0.009). At the tracheobronchial site, seven subjects had persistent EGNB colonization, all with Pseudomonas species, while only one subject had this finding at the oropharyngeal site (p = 0.015). Patients with persistent tracheobronchial colonization were more ill than those without this finding. They were treated with higher doses of prednisone (p = 0.06), received antibiotics more often, and developed purulent tracheobronchitis more often (100 percent vs 25 percent) than patients without persistent colonization. In addition, in the month following the culture survey, four subjects developed pneumonia, and three of these had previous persistent tracheobronchial colonization.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Infecções por Enterobacteriaceae/etiologia , Infecções por Pseudomonas/etiologia , Infecções Respiratórias/etiologia , Traqueotomia/efeitos adversos , Adulto , Idoso , Brônquios/microbiologia , Bronquite/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orofaringe/microbiologia , Pneumonia/etiologia , Risco , Fatores de Tempo , Traqueia/microbiologia , Traqueíte/etiologiaRESUMO
It is surprising that forms of hypersensitivity pneumonitis do not occur more frequently, given the variety of biologic dusts and airborne antigens that have been found to cause disease. Exposure is almost universal in some occupations that involve handling animals or feed products, and development of humoral immunity occurs in most; however, overt respiratory illness is relatively infrequent or not easily recognized by the subject. What differs between symptomatic and asymptomatic subjects is not certain, but unique host resistance or susceptibility, as the case may be, appears to be a factor. This may have a genetic basis, but this has not been investigated vigorously. With repeated airborne exposure to appropriate antigens, a humoral and a local respiratory antibody response occur but perhaps with little disease consequence, as most subjects so immunized remain clinically asymptomatic. So far as is known, there is no other route of antigenic exposure except through the respiratory tract, but contact with the antigens could occur on the skin or on mucosal surfaces such as the conjunctiva, or antigens could be ingested by swallowing nasopharyngeal secretions. Except for serum antibodies, however, there is little documentation that other systemic organs are affected, as may occur with sarcoidosis. Of course there is great variability in the age of the subjects and the dosage of antigen to which the subject is exposed, and the frequency and duration of exposure can vary considerably. All of these would seem to be easily tested, however, in an animal model where most of the variables could be independently controlled and varied at will. Even the genetic and aging factors, which are the most difficult parameters to control in humans, could be investigated. Yet, it has been very difficult and perplexing not to have created a more faithful model of hypersensitivity pneumonitis in the laboratory. It is virtually impossible to cause predictable lung disease without the use of an adjuvant that will induce some measure of delayed or cellular hyperreactivity. The acute lung disease caused by antigen-antibody reactions seems too explosive and severe, for its acute disease counterpart of hypersensitivity pneumonitis in humans and the persistence of histologic changes in lung tissue is brief and is usually resolved within 1-2 weeks. A chronic model producing granulomas and fibrosis has been difficult to construct, although the work reported by Fulmer and colleagues is very encouraging.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Alveolite Alérgica Extrínseca/etiologia , Pulmão/imunologia , Doença Aguda , Alveolite Alérgica Extrínseca/imunologia , Alveolite Alérgica Extrínseca/patologia , Animais , Pulmão do Criador de Aves/etiologia , Pulmão do Criador de Aves/imunologia , Pulmão do Criador de Aves/patologia , Doença Crônica , Modelos Animais de Doenças , Poeira/efeitos adversos , Pulmão de Fazendeiro/etiologia , Pulmão de Fazendeiro/imunologia , Pulmão de Fazendeiro/patologia , Cobaias , Humanos , Imunização/métodos , Pulmão/patologia , Macaca mulatta , Alvéolos Pulmonares/imunologia , Alvéolos Pulmonares/patologia , Coelhos , Linfócitos T/imunologiaRESUMO
Host defense mechanisms spaced along the respiratory tree and in the alveolar spaces effectively remove or contend with micro-organisms that enter the airways, so serious lung infections occur rarely in healthy people. Special circumstances, such as virgin exposure to a virulent microbe or a large innoculum of a pathogen, can result in illness, but usually routine surveillance host defenses are protective and suffice to keep colonizing airway flora in check. When pneumonia develops or recurrent sinopulmonary infection exists, however, some element of the normal defense apparatus may have failed or is inadequate. This review highlights several components of the apparatus, that is immunoglobulins IgG and IgA and the interaction of alveolar macrophages and lymphocytes, and examines deficiencies in their function that may result in infection. Along the conducting airways, poor mucociliary clearance and/or deficiencies in certain IgG subclass antibodies or destruction of IgA may predispose to sinopulmonary infections; these may be a manifestation of a hereditary disease. In pneumonia the alveolar macrophage is positioned as the central cell which must respond in several directions. This scavenger phagocyte first intercepts the microbe and either can kill or contain it or must call in some other phagocytic cell or inflammatory mediator(s) for assistance. Opsonic antibodies (IgG) and other nonimmune opsonins (complement and surfactant or fibronectin fragments) facilitate phagocytosis, but an absence of antibody may permit infection to develop with encapsulated bacteria (pneumococcus). Insufficient bone marrow reserves of PMNs or a paucity of chemotactic factors to attract them into the alveoli is a situation that may permit gram-negative bacilli and fungal organisms to flourish. Inability of immune T-lymphocytes to energize macrophages, through soluble cellular mediators that provide cell-mediated immunity and activation, makes containment of certain intracellular microbes impossible for these phagocytes (Legionella or mycobacteria). Likewise, concomitant infection of macrophages with viruses (human immunodeficiency virus, and cytomegalovirus or herpes viruses) plus an excessive T-lymphocyte suppressor cell influence may make P. carinii and common bacterial and fungal organisms difficult to contain in the lungs of AIDS patients. Consideration about what the lung host deficiency might be can make therapy more specific through immunization to develop special antibodies, replacement of certain immunoglobulins (IgG subclasses), or selective administration of cell mediators (gamma-interferon or interleukins).
Assuntos
Síndromes de Imunodeficiência/complicações , Infecções Respiratórias/etiologia , Formação de Anticorpos , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Humanos , Imunidade Celular , Imunoglobulinas/análise , Mucosa Nasal/metabolismo , Infecções Respiratórias/imunologiaRESUMO
A sophisticated system of pulmonary host defense strives to maintain the functional integrity of the lung against the threats of infections, toxins, and malignancy. Congenital and acquired defects in the immune mechanisms of this host defense are associated with a variety of pulmonary disorders that include infections with usual or opportunistic organisms; inflammatory disorders; and malignancies. The age of the patient, associated abnormalities, family history, and the type of pulmonary and systemic diseases that are present provide clues to the specific underlying disorder. Laboratory tests including immunoglobulin levels, lymphocyte subset enumeration, and tests of lymphocyte function can help to confirm the clinical impression. Determination of the specific disorder allows the physician to anticipate possible complications, initiate appropriate prophylactic measures, and, in an increasing number of diseases, offer specific therapy.