RESUMO
Epidemiologic studies conducted in the past 30 years to investigate the protective functions of human milk strongly support the notion that breastfeeding prevents infantile infections, particularly those affecting the gastrointestinal and respiratory tracts. However, more recent clinical and experimental observations also suggest that human milk not only provides passive protection, but also can directly modulate the immunological development of the recipient infant. The study of this remarkable defense system in human milk has been difficult because of its biochemical complexity, the small concentration of certain bioactive components, the compartmentalization of some of these agents, the dynamic quantitative and qualitative changes of milk during lactation, and the lack of specific reagents to quantify these agents. However, a host of bioactive substances, including hormones, growth factors, and immunological factors such as cytokines, have been identified in human milk. Cytokines are pluripotent polypeptides that act in autocrine/paracrine fashions by binding to specific cellular receptors. They operate in networks and orchestrate the development and functions of immune system. Several different cytokines and chemokines have been discovered in human milk in the past years, and the list is growing very rapidly. This article will review the current knowledge about the increasingly complex network of chemoattractants, activators, and anti-inflammatory cytokines present in human milk and their potential role in compensating for the developmental delay of the neonate immune system.
Assuntos
Citocinas/imunologia , Leite Humano/imunologia , Animais , Quimiocinas/imunologia , Quimiocinas/fisiologia , Fatores Estimuladores de Colônias/imunologia , Fatores Estimuladores de Colônias/fisiologia , Citocinas/fisiologia , Feminino , Humanos , Recém-NascidoRESUMO
Cytokines synthesized by the uterus or placenta include those thought to be produced exclusively by, or though to act on, cells of the lymphohematopoietic system. Although many of these cytokines are protein mediators of the immune system effector phase, in the female reproductive tract their principal target cells and sites of synthesis are non-lymphohematopoietic cells. During pregnancy, uterine epithelial cells, decidual cells and trophoblast appear to be major sources of the classic lymphohematopoietic cytokines. This suggests two not necessarily exclusive alternatives: that these cells are extensions of, or are involved in, regulating the immune system, or that these factors regulate growth and differentiation of uterine and embryonic tissues. This paper analyzes the sites of synthesis, targets and possible functions of the cytokines during early pregnancy.
Assuntos
Citocinas/fisiologia , Endométrio/fisiologia , Gravidez/fisiologia , Animais , Blastocisto/fisiologia , Fatores Estimuladores de Colônias/fisiologia , Decídua/fisiologia , Desenvolvimento Embrionário , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Humanos , Interleucinas/fisiologia , Camundongos , Ratos , Fator de Crescimento Transformador beta/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Útero/fisiologiaRESUMO
The study of the direct involvement of colony stimulating factors, interleukins, and other purified factors in distinct steps of hematopoiesis has been complicated by the in vitro presence of non-hematopoietic cells which can intermediate the effects observed on hematopoietic precursors. The review covers the recent finding that the CD34 antigen is expressed on the membranes of essentially all pluripotent stem cells, but is lacking in the majority of the differentiated blood and stromal bone marrow cells. This finding allowed in vitro experiments with selected CD34+ hematopoietic precursors, and a consequent reevaluation of the participation of different factors in their differentiation. The role of interferons, tumor necrosis factors, and transforming growth factors beta in the negative regulation of hematopoiesis is also analysed.
Assuntos
Citocinas/fisiologia , Hematopoese/fisiologia , Medula Óssea/fisiologia , Fatores Estimuladores de Colônias/fisiologia , Técnicas In Vitro , Interferons/fisiologia , Interleucina-1/fisiologia , Interleucina-4/fisiologia , Interleucinas/fisiologia , Fatores de Crescimento Transformadores/fisiologia , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
El queratinocito es una celula inmunologica que participa activamente en la respuesta inflamatoria e inmunologica. Se efectua una revision de los conocimientos sobre las multiples funciones de esta celula epitelial
Assuntos
Humanos , Animais , Ratos , Queratinócitos/fisiologia , Interleucina-1/fisiologia , Pele/imunologia , Queratinócitos/imunologia , Fatores de Crescimento Transformadores , Fator de Necrose Tumoral alfa/fisiologia , Fatores Estimuladores de Colônias/fisiologia , Inflamação/fisiopatologia , Fator de Crescimento Epidérmico/fisiologiaRESUMO
El queratinocito es una celula inmunologica que participa activamente en la respuesta inflamatoria e inmunologica. Se efectua una revision de los conocimientos sobre las multiples funciones de esta celula epitelial
Assuntos
Humanos , Animais , Ratos , Interleucina-1/fisiologia , Queratinócitos/fisiologia , Pele/imunologia , Fatores Estimuladores de Colônias/fisiologia , Fator de Crescimento Epidérmico/fisiologia , Inflamação/fisiopatologia , Queratinócitos/imunologia , Fatores de Crescimento Transformadores , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
We have recently demonstrated that polyclonal T-cell activation induced by PHA defines an activation pathway which is resistant to blockade by barium (Ba2+) ions. Other modes of T-cell activation, including ConA-induced responses, are completely blocked by Ba2+, which seems to affect an early Ca2+-dependent step of T-cell activation, as determined by kinetic and competition experiments. In the present study, we have analysed the lymphokine requirements of Ba2+-resistant pathway of PHA-induced T-cell activation by means of functional blocking experiments with monoclonal antibodies (mAbs) directed against mouse IL-2 (mAb S4B6) and against mouse IL-4 (mAb 11B11). We found that Ba2+-resistant T-cell activation can be blocked by either S4B6 or 11B11. Thus, both IL-2 and IL-4 participate in Ba2+-resistant T-cell growth induced by PHA. In addition, we found that cyclosporin A (CsA) completely blocks T-cell activation induced by either ConA or by PHA plus Ba2+, but not T-cell activation induced by PHA in the absence of Ba2+, which is reduced by less than 50% in most experiments. This CsA-resistant proliferative component of the PHA response is, thus, distinct from the Ba2+-resistant response, and is carried out by proliferating T-cells. Although mAbs S4B6 and 11B11 are potent blockers of ConA-induced responses, they failed to block CsA-resistant T-cell growth induced by PHA. At the doses of CsA employed, no IL-2 and/or IL-4 activity could be detected in the supernatants of CsA-treated, PHA-stimulated T-cell cultures. The data indicate that this CsA-resistant pathway is both IL-2 and IL-4-independent. The lymphokine involved in this T-cell activation pathway remains to be identified.
Assuntos
Bário/farmacologia , Ciclosporinas/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfocinas/fisiologia , Fito-Hemaglutininas/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Fatores Estimuladores de Colônias/fisiologia , Concanavalina A/farmacologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Substâncias de Crescimento/fisiologia , Interleucina-2/fisiologia , Interleucina-4 , Interleucinas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CAssuntos
Fatores Estimuladores de Colônias/fisiologia , Substâncias de Crescimento/fisiologia , Leishmaniose/etiologia , Animais , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Leishmaniose/imunologia , Leishmaniose/fisiopatologia , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos BALB CRESUMO
A child with repeated infections was immunologically normal but was found to have neutropenia with periodic elevations of the absolute mature polymorphonuclear count at 21-day intervals. Immediately following the PMN rise, bone marrow morphology and in vitro cultures demonstrated a maturation arrest at the myelocyte stage with an increase in proliferative capacity. His cycle was not altered by infusions of normal plasma or by injections of epinephrine or typhoid vaccine. Infusion of 10 ml/kg of "stimulated" plasma from donors reactive to TV, obtained 60 minutes following immunization, resulted in an out-of-phase rise in PMN cells and clinical improvement. In vitro assays, using normal or patient marrow, detected high levels of colony-stimulating activity only in those plasma samples that were effective in the patient. These observations support a role of CSA as a physiologic regulator of granulopoiesis in man.