Immunosenescence: participation of T lymphocytes and myeloid-derived suppressor cells in aging-related immune response changes / Imunosenescência: participação de linfócitos T e células mieloides supressoras nas alterações da resposta imune relacionadas ao envelhecimento

ABSTRACT Healthy aging is partly related to appropriate function of the immune system. As already reported, some changes in this system are observed, including reduced number and repertoire of T cells due to thymic involution, accumulation of memory T cells by chronic infections, homeostatic proliferation compensating for the number of naïve T cells, decreased proliferation of T cells against a stimulus, telomere shortening, replicative senescence of the T cells, and inflammaging, besides the accumulation of myeloid-derived suppressor cells. The purpose of this article is to clarify each of these changes, aiming to minimize limitations of immunosenescence. If such associations can be established, these cells may be used as early and less invasive markers of aging-related diseases, as well as to indicate interventions, evaluate the efficacy of interventions and be a tool to achieve longevity with quality of life.

RESUMO O envelhecimento saudável está relacionado, pelo menos em parte, com a função adequada do sistema imunológico. Isso porque já foi relatado que, com o envelhecimento, algumas mudanças desse sistema são observadas, como a diminuição da percentagem e do repertório de células T pela involução tímica, acúmulo de células T de memória por infecções crônicas, compensação do número de células T naïve por proliferação homeostática, diminuição da capacidade de proliferação das células T frente a um estímulo, encurtamento dos telômeros, senescência replicativa das células T, e inflammaging, além do acúmulo de células mieloides supressoras. Este artigo visa esclarecer cada uma das mudanças, mencionadas, com o intuito de buscar meios de minimizar as limitações da imunosenescência. Caso seja possível estabelecer tais relações, essas células podem ser utilizadas como marcadores precoces e pouco invasivos de doenças relacionadas ao envelhecimento, além da possibilidade de serem utilizadas para indicar intervenções, avaliar a eficácia das intervenções e como ferramenta para alcance da longevidade com qualidade de vida.

The remarkable journey of adaptation of the Plasmodium falciparum malaria parasite to New World anopheline mosquitoes

Plasmodium falciparum originated in Africa, dispersed around the world as a result of human migration and had to adapt to several different indigenous anopheline mosquitoes. Anophelines from the New World are evolutionary distant form African ones and this probably resulted in a more stringent selection of Plasmodium as it adapted to these vectors. It is thought that Plasmodium has been genetically selected by some anopheline species through unknown mechanisms. The mosquito immune system can greatly limit infection and P. falciparum evolved a strategy to evade these responses, at least in part mediated by Pfs47, a highly polymorphic gene. We propose that adaptation of P. falciparum to new vectors may require evasion of their immune system. Parasites with a Pfs47 haplotype compatible with the indigenous mosquito vector would be able to survive and be transmitted. The mosquito antiplasmodial response could be an important determinant of P. falciparum population structure and could affect malaria transmission in the Americas.

Consideraciones sobre la evolución de la respuesta inmunitaria Th2 y sus posibles relaciones con parasitosis y alergia / The evolution of the Th2 immune responses and its relationships with parasitic diseases and allergy

Hay diversos vínculos entre las parasitosis, especialmente las helmintiasis, y las enfermedades alérgicas, ambas condiciones de importancia epidemiológica en las regiones tropicales. Mientras que se ha especulado con frecuencia los efectos de las enfermedades parasitarias sobre la evolución del sistema inmunitario, no se conocen las fuerzas selectivas que han moldeado la respuesta alérgica y pensamos que incluyen mecanismos evolutivos distintos a los tradicionalmente divulgados. Los helmintos, fuente infecciosa y antigénica inductora de una respuesta parecida a la alérgica, se establecieron como parásitos en huéspedes que ya tenían grupos celulares de inmunidad de tipo 2. Hoy sabemos que un componente esencial en la relación de parasitismo entre los helmintos y sus huéspedes es la inmunosupresión que los primeros inducen, al crear una especie de equilibrio que permite la supervivencia de ambos. El desarrollo de este equilibrio debió incluir adaptaciones de ambos organismos y la supervivencia del parásito podría ser el resultado de la adquisición de mecanismos supresores de la respuesta defensiva, la selección de los huéspedes con menor intensidad de la respuesta de tipo 2, o ambas. Esto, a su vez, sugiere que aunque las infecciones helmínticas hayan influido en la conformación de la inmunidad de tipo 2, no han sido una fuerza selectiva importante en el caso particular de la respuesta alérgica que, a su vez, está más ligada a una exagerada respuesta Th2/IgE.

A variety of links occur between parasites, particularly helminths, and allergic diseases--both common conditions of epidemiological importance in tropical regions. Although speculations are often made about the effects of parasitic diseases on the evolution of the immune system, the selective forces that have shaped the allergic response are unknown and probably include evolutionary mechanisms different to those traditionally reported. Helminths, infectious and antigenic sources that induce allergic-like responses, established themselves as parasites in organisms that already had cell groups related to the type 2 immunity. An essential component in the relationship between helminths and their hosts is that the former induce immunosuppression, creating a kind of balance that allows the survival of both. The development of this equilibrium undoubtedly includes adaptations in both organisms, and the survival of the parasite is the result of (a) acquiring immune suppressor mechanisms and (b) finding hosts with lower intensity of the type 2 response. This in turn suggests that although helminth infections have influenced the formation of type 2 immunity, they have not been an important selective force in the particular case of allergic response. The latter is more related to an exaggerated Th2/IgE response.

Coadaptation and malaria control

Malaria emerges from a disequilibrium of the system 'human-plasmodium-mosquito' (HPM). If the equilibrium is maintained, malaria does not ensue and the result is asymptomatic plasmodium infection. The relationships among the components of the system involve coadaptive linkages that lead to equilibrium. A vast body of evidence supports this assumption, including the strategies involved in the relationships between plasmodium and human and mosquito immune systems, and the emergence of resistance of plasmodia to antimalarial drugs and of mosquitoes to insecticides. Coadaptive strategies for malaria control are based on the following principles: (1) the system HPM is composed of three highly complex and dynamic components, whose interplay involves coadaptive linkages that tend to maintain the equilibrium of the system; (2) human and mosquito immune systems play a central role in the coadaptive interplay with plasmodium, and hence, in the mainten-ance of the system's equilibrium; the under- or overfunction of human immune system may result in malaria and influence its severity; (3) coadaptation depends on genetic and epigenetic phenomena occurring at the interfaces of the components of the system, and may involve exchange of infectrons (genes or gene fragments) between the partners; (4) plasmodia and mosquitoes have been submitted to selective pressures, leading to adaptation, for an extremely long while and are, therefore, endowed with the capacity to circumvent both natural (immunity) and artificial (drugs, insecticides, vaccines) measures aiming at destroying them; (5) since malaria represents disequilibrium of the system HPM, its control should aim at maintaining or restoring this equilibrium; (6) the disequilibrium of integrated systems involves the disequilibrium of their components, therefore the maintenance or restoration of the system's equilibrium depend on the adoption of integrated and coordinated measures acting on all components,...

Effects of stresses on serum cortisol level in Bangladeshi people.

The present study was undertaken to estimate serum cortisol level in control experimental groups in Bangladeshi people. For this purpose a total number of 55 subjects of age range (18-55) years were selected from Mymensingh Medical College Hospital during July 2003 to June 2004. Subjects included in this study were divided in to two main groups: control (n=13) and experimental (n=42). According to different types of stress the experimental group was further divided in to four subgroups: infection, psychiatric, pre and post surgery. Blood samples were collected from all subjects with aseptic precautions at 8 AM and serum cortisol concentration was measured by Radioimmunoassay method. Statistical analyses were done by using Student's 't' test. A distinct and statistically significant increased serum cortisol level was observed in infection, psychiatric disorders and post surgical group in comparison to control group (P< 0.001). While no significant difference was observed in pre surgery when compared to that of control group.