No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Principles of Immunology
Abstract
The immune system, composed of innate and acquired immunity, allows an organism to fight off foreign pathogens. Healthy immunity accomplishes four essential principles: (1) ability to detect and fight off infection; (2) ability to recognize a host's own cells as "self," thereby protecting them from attack; (3) a memory from previous foreign infections; and (4) ability to limit the response after the pathogen has been removed. In an unaltered state, the intricate network of immunologic organs and cells creates an environment for proper host defense. Without adequate execution of immunologic mechanisms, a host is rendered defenseless against pathogens. Conversely, an unchecked immune response can be self-destructive. As a result of either of these untoward sequelae, immune dysfunction can elicit disease states in the host. The goal of this review is to elucidate the characteristics of a healthy immune system, focusing on the principles of immunity and the cells that participate in host protection. We also briefly discuss the clinical ramifications of immune dysfunction.
... Defense against a viral infection begins with the non-specific innate immune response followed by activation of the virus-specific adaptive immune response, which may be cell-mediated (T cell), or antibodymediated (B cell). Many common viral infections can be cleared by these host defense mechanisms before clinically apparent symptoms develop [40][41][42][43] (Figure 3). ...
... APCs display the digested viral peptides on their cell surface and migrate to local lymph nodes to present them to the adaptive immune cells (T and B cells) in order to produce a cell or antibody-mediated response, respectively. Both responses target the specific virus against which they are generated and usually have no effect against other types of viruses [40][41][42][43]. ...
... A small subset of these virus-specific CD8 + T cells become long-lived memory cells and may be called back into service at a later time to prevent disease caused by the same virus. Vaccines rely on the use of pathogen-derived antigens to generate memory responses that provide specific recognition of infected cells and their elimination by CD8 + T cells [40][41][42][43]. ...
Pathogenic viruses cause many human, animal, and plant diseases that are associated with substantial morbidity, mortality and socio-economic impact. Although effective strategies for combatting virus transmission and associated disease are available, global outbreaks of viral pathogens such as the virus responsible for the COVID-19 pandemic demonstrate that there is still a critical need for new approaches that can be used to interrupt the chain of viral infection and mitigate virus-associated pathogenesis. Recent studies point to non-thermal plasma (NTP), a partly ionized gas comprised of a complex mixture of reactive oxygen and nitrogen species along with physical effectors, as the potential foundation for new antiviral approaches. A more thorough understanding of the antiviral properties and safety of NTP has stimulated explorations of NTP as the basis for treatments of viral diseases. The recently described immunomodulatory properties of NTP are also being evaluated for potential use in immunotherapies of viral diseases as well as in antiviral vaccination strategies. In this review, we present the current state-of-the-art in addition to compelling arguments that NTP merits further exploration for use in the prevention and management of viral infections and associated diseases.
... En las últimas décadas del siglo pasado se produce un incremento en un grupo de enfermedades infecciosas, algunas aparentemente ya controladas y otras de nueva aparición (1) . La más temible, por el número de afectados, extensión y aparente imposibilidad para su control, es la inmunodeficiencia adquirida causada por el retrovirus VIH (virus de la inmunodeficiencia humana ), causa de una afección en la cual el individuo, hasta entonces sano y competente, como consecuencia a la afectación selectiva de las células TCD4, macrófagos y células dendríticas, comienza paulatinamente a perder sus capacidades defensivas y sucumbe habitualmente presa de afecciones oportunistas y ciertos tipos de cáncer (2) . ...
... Un sistema inmune competente defiende al organismo de las proteínas extrañas que se le presentan en forma de antígenos, ofreciendo una respuesta armónica, graduada y limitada para así conservar la homeostasis. Las acciones integradas de sus componentes constitutivos son fundamentales para la vida, sin esta red intricada de chequeos y balances el organismo termina por sucumbir a la infección, al cáncer y a las disfunciones auto inmunes (2,11) . ...
... Los órganos generadores son la medula ósea y el timo, dentro de la medula ósea se distinguen 2 líneas celulares originados de una célula progenitora o tronco: la línea de la serie mieloide y la línea de la serie linfoide. A partir de la línea mieloide se originan los hematíes y las plaquetas, células que no forman parte del sistema defensivo como tal, y los monocitos y granulócitos o polimorfonucleares, con su subdivisión en neutrófilos, basófilos y eosinófilos , formaciones que si forman parte del sistema inmune (2) . ...
Luego de realizar un esbozo de la constitución y funciones del sistema inmunitario, enfatizando en sus estrechas relaciones con la función alimentaria- nutricional, y de detallar algunos aspectos históricos en el desarrollo de los diversos tipos de inmunodeficiencia, especialmente la adquirida infecciosa y de la evaluación nutricional en general, se presenta un estudio comparativo del estado nutritivo que utiliza indicadores clínicos, bioquímicos, inmunológicos, antropométricos y dietéticos, de tipo descriptivo y corte transversal, realizado en un grupo de 42 personas adultas no ingresadas de ambos sexos, con diagnóstico VIH/sida, residentes en el populoso municipio de Centro Habana en la capital cubana, 20 de ellas clasificadas casos sida y 22 asintomáticos, según el criterio del CDC 1993. Los promedios en los indicadores bioquímicos e inmunológicos se encontraron en niveles aceptables, aunque el 38% de estas personas tenía anemia. Integrando el índice de masa corporal, área muscular y área grasa del brazo se encontró en los individuos asintomáticos un 41% en valores aceptables, 30% y 40% sobrepesos y obesos, respectivamente dentro de los casos sida. Se encontró un mayor consumo de macronutrientes en los casos sida y, en los dos grupos, un déficit en la ingesta de riboflavina, hierro y zinc. A destacar en la investigación -que nos permitió acceder al título de Master en Nutrición y Salud Pública- se resalta la extensa revisión bibliográfica, la exposición de aspectos revolucionarios en la terapéutica integral, y en especial la nutricional, de tales personas inmunodeficientes, con apoyo en todos los mecanismos de autosanación fisiológica y simbiótica del hospedero con su microbiota, además de diversas consideraciones y experiencias del uso del selenio en el combate de esta temible epidemia.
... The immune system is composed of an integrated network of organs, tissues, cells and molecules that work together to resist infection, but maintain tolerance to harmless factors such as "self", antigens, and allergens [113]. When a challenge is detected (e.g., an allergen or pathogen), cell signaling between immune cells produces a coordinated immune response involving the release of cytokines and eicosanoids, which under normal circumstances allows cells to communicate with each other to neutralize and eliminate the challenge [114,115]. ...
Arachidonic acid (ARA, 20:4n-6) is an n-6 polyunsaturated 20-carbon fatty acid formed by the biosynthesis from linoleic acid (LA, 18:2n-6). This review considers the essential role that ARA plays in infant development. ARA is always present in human milk at a relatively fixed level and is accumulated in tissues throughout the body where it serves several important functions. Without the provision of preformed ARA in human milk or infant formula the growing infant cannot maintain ARA levels from synthetic pathways alone that are sufficient to meet metabolic demand. During late infancy and early childhood the amount of dietary ARA provided by solid foods is low. ARA serves as a precursor to leukotrienes, prostaglandins, and thromboxanes, collectively known as eicosanoids which are important for immunity and immune response. There is strong evidence based on animal and human studies that ARA is critical for infant growth, brain development, and health. These studies also demonstrate the importance of balancing the amounts of ARA and DHA as too much DHA may suppress the benefits provided by ARA. Both ARA and DHA have been added to infant formulas and follow-on formulas for more than two decades. The amounts and ratios of ARA and DHA needed in infant formula are discussed based on an in depth review of the available scientific evidence.
Les cellules souches mésenchymateuses (CSM) issues de la gelée de Wharton (GW) du cordon ombilical sont immuno-privilégiées et immunosuppressives. Dans le cadre d’une utilisation en ingénierie vasculaire, la persistance de ces propriétés après différenciation endothéliale a été explorée. La différenciation a été induite par ensemencement des CSM-GW sur des films multicouches de polyélectrolytes en présence du milieu EGM-2. L’immunogénicité des cellules endothéliales-« like » (CEL) a été vérifiée en évaluant l’expression de 2 marqueurs immunologiques HLA-DR et CD86. Afin d’évaluer l’effet immunosuppresseur des CSM-GW avant et après différenciation, celles-ci ont été cultivées en premier lieu en présence de cellules mononucléées stimulées en contact cellulaire direct ou séparées, puis avec des cellules Natural Killer (NK) et lymphocytes T (LT). Les résultats ont montré que les CEL expriment les marqueurs endothéliaux, n’expriment pas HLA-DR et CD86 et qu’elles inhibent la prolifération des différentes populations immunitaires selon un mécanisme dépendant de facteurs solubles tels que IDO, les IL-6 et -1[bêta] et de la PGE2, et de contacts cellulaires. La co-culture de LT avec les CEL a induit l’apparition d’une population de LT régulateurs de manière similaire aux CSM-GW. La co-culture des cellules NK en présence de CEL a induit une diminution du récepteur activateur NKG2D et a aussi induit un transfert du CD73 à leur surface, suggérant leur capacité à produire de l’adénosine, un puissant immunosuppresseur. Les CEL maintiennent le caractère immunoprivilégié et immunosuppresseur des CSM-GW, suggérant leur possible utilisation en ingénierie vasculaire
The Athenian epidemic of 430-426 BC, at the outbreak of the Peloponnesian War, caused the death of the great statesman, Pericles, decimated the population and contributed significantly to the decline and fall of classical Greece. In his remarkable documentation of the epidemic, Thucydides (who survived the disease) not only left us a clear clinical picture of the pestilence but also identified its infectious nature and the fact that it conferred at least partial immunity on survivors. As confirmed by a large number of scholars who studied the subject, Thucydides' description does not accurately fit any existing disease, but we suggest that analysis of the signs and symptoms, considered in conjunction with significant epidemiological evidence, narrows down the many possibilities to epidemic typhus, plague, arboviral disease (e.g. Rift Valley fever) and smallpox. Typhus and smallpox fit best, but we favour the latter for reasons given. Unless further primary sources of information become available (and this seems most unlikely), productive speculation as to the cause of Thucydides' epidemic has probably reached the end of the road.
The limitations of currently available treatment for severe respiratory infection are demonstrated by the relatively fixed mortality associated with these infections despite advances in nutrition, vaccines, antibiotics, and critical care. This might be due in part to the changing spectrum of pathogens and development of drug resistance. Cytokines are potent molecules that function as growth factors and orchestrate both innate and adaptive immune responses. Several of these factors have entered the clinical arena to support or augment the immune response. Moreover, the use of cytokines has recently been expanded to patients without an overtly defective immune system but who have either significant infection or infection with drug resistant organisms. The use of cytokines as adjuvants in the treatment of respiratory infections is reviewed.
Our understanding of host defense has exploded during the past two decades. It is temping to take advantage of this knowledge by considering the modulation and control of these mechanisms as therapeutic options. In intensive care medicine, the aim is usually to block an overwhelming inflammatory response, which represents the "bad" side of the double-edged sword of host defense. The obvious danger of such treatment strategies is that impairing the inflammatory reaction means impairing host defense in patients exposed to infectious agents. The alternative approach, i.e., strengthening or supplementing favorable host defense mechanism, has so far been little explored clinically. Granulocyte colony-stimulating factor, the granulocyte colony-stimulating factor, combines the unique properties of an anti-infectious and an anti-inflammatory factor. This attractive profile has led us to various approaches to exploit these immunomodulatory activities. In a recently terminated, placebo-controlled, randomized study, we investigated if prophylactic treatment with rh granulocyte colony-stimulating factor (Filgrastim), at the time a risk can be anticipated such as before an operation, may offer protection from immunoinflammatory dyshomeostasis and thus lower the incidence of postoperative sepsis. Perioperative rh granulocyte colony-stimulating factor administration, compared with placebo treatment, resulted in the prevention of postoperative monocyte deactivation, conservation of an adequate Th1/Th2 ratio, as well as a considerable alleviation of the acute phase response. In parallel, there was a clear tendency toward lowering the rate of postoperative septic complications under the administration of Filgrastim.
One of the most consistent defects in the neonate's host defense system is in the ability of polymorphonuclear leukocytes
(PMNL) to move in a unidirectional fashion towards a chemotactic stimulus. Such impaired chemotaxis can be an important contributor
to life-threatening neonatal infection. In vitro studies suggest that preincubation ofPMNL from neonates with recombinant
human interferon-γ (rIFN-γ) can enhance chemotactic responses. No other recombinant human cytokine except granulocyte colony-stimulating
factor improved chemotaxis of PMNL from neonates. Similarly, pretreatment with rIFN-γ has been shown to improve in vitro neutrophil
chemotaxis in cells obtained from patients with hyperimmunoglobulinemia E (Job's) syndrome. These results suggest the need
for controlled trials of rIFN-γ in pediatric patients who are uniquely susceptible to tissue and pulmonary infections.
The growth and progression of solid tumours is dependent on several biological factors, such as tumour angiogenesis, appearance of new genetic alterations and/or the failure of the immune defences of the host. Physicians have dreamed of treating cancer with vaccines since the first vaccines against infectious diseases were developed. The identification and availability of tumour-associated antigens now allows the possibility of eliciting humoral (antibody-mediated) and cell-mediated immunity to be tested, which may result in direct or indirect tumour destruction. Thus cancer vaccines have been constructed in order to activate and amplify the patient's immune reaction against tumour-associated antigens. Recent progress in defining the immunogenic epitopes of tumour antigens and in augmenting their immunogenicity (that is their ability to be recognised by and stimulate the immune system of the host), along with the new information on the mechanisms of tumour antigen presentation, has revolutionised the field of cancer vaccines, initially based on non-specific approaches. This review will briefly focus on the biological basis of the development and the clinical application of a wide spectrum of tumour vaccines.
In the past 5 y, the 28 d mortality in patients with sepsis syndrome has decreased somewhat but still ranges from 30% to 40%; mortality in those patients with septic shock and multiple organ failure is higher. This high mortality is observed despite intensive care units that deliver hemodynamic, metabolic, ventilatory, and renal support. Clearly some patients survive the ordeal but it remains frustrating not being able to stop the downhill course leading to multiple organ failure and death in these patients. New therapies have been sought and tested, including those preventing the biologic activity of two pro-inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF). Based on animal studies, anti-TNF and IL-1 therapy has been used to "rescue" the patient who continues to deteriorate in the face of considerable support efforts. Unfortunately, these anticytokine therapies have not dramatically reduced 28 d mortality in double-blind, placebo-controlled trials involving nearly 10000 patients, although there is a consistent but statistically nonsignificant decrease in mortality associated with anticytokine therapies. On the other hand, the same anti-TNF and IL-1-based therapies have made a dramatic improvement in the local inflammation and progression of rheumatoid arthritis. It appears that systemic inflammation of sepsis requires more than anticytokine monotherapy to significantly reduce mortality.