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Influenza is caused by a constantly varying segmented RNA virus that necessitates yearly review of vaccine composition. Humans over the age of 65 years are considered at high risk from influenza; during influenza epidemics the rate of hospitalization in the elderly is very high and up to 90% mortality can occur. Vaccination of the elderly has been shown to be efficacious and cost effective but immunological...
Changes in the B-cell repertoire during aging include a shift in antibody specificities from foreign to autologous antigens associated with a decline in the activity of conventional B2 compared to B1 lymphocytes. The age-associated increase in B1 lymphocyte number and activity contribute to the increased serum concentration of autoantibodies and the B-cell clonal expansions that develop with age....
Aging is associated with the progressive increase of T cells that lack expression of the CD28 costimulatory molecule. Because CD28/B7 signal transduction is required for proliferation, T cells lacking CD28 gene expression are incapable of clonal expansion. To determine whether CD28- T cells are a separate lineage or, alternatively, are the progeny of formerly CD28+ T cells, we performed cell culture...
Dendritic cells (DC) are powerful antigen presenting cells, which have the unique capacity to stimulate naive T cells. In spite of the well-known decline of T cell function in old age, little information is available on whether DC are also affected by the aging process. This is mainly due to problems with the isolation and purification of DC. Rapid progress in the characterization of DC has been made...
In this study, we investigated a role of apoptosis in lymphopenia and progressive cell-mediated immunodeficiency associated with aging. We examined two major signaling pathways of apoptosis in lymphocytes from aged humans and compared them with lymphocytes from young subjects. Both CD4+ and CD8+ T cell subsets from aged subjects demonstrated increased sensitivity to TNFR-mediated and Fas-mediated...
Pneumococcal proteins, alone, in combination with each other, or in combination with capsular polysaccharide-protein conjugates may be useful pneumococcal vaccine components. Four proteins with a potential for use in vaccines are PspA, pneumolysin, PsaA, and PspC. In a mouse model of carriage, PsaA and PspC were the most efficacious vaccine proteins. Of these, PsaA was the best at eliciting protection...
Community-residing elderly were immunized twice intranasally three weeks apart with a new inactivated whole influenza vaccine. A control group was immunized intramuscularly with conventional influenza vaccine. Local antibody response was detected in about 50% of intranasally immunized subjects compared to about 20% of intramuscularly immunized subjects, to the three viral strains.Increasing the incidence...
Many genes have been shown to be involved in the decline in immune function of the elderly. However, normal numbers of myeloid and lymphoid colonies can be grown from elderly bone marrow under optimal conditions and some thymic function is preserved well into adult life. It may also be possible to reverse partially declining thymic function by IL-7 treatment. Peripheral B and T cells show evidence...
The thymus represents the major site of lymphopoiesis of T-cell receptor (TCR) αβ T-cells. Age-related involution may affect its potential to reconstitute T-cells that are lost during HIV infection, chemotherapy, and bone marrow transplantation. However, there is mounting evidence that the age-related changes in the thymus are quantitative, not qualitative, and recent data suggest that the adult thymus...
Inactivated influenza vaccine (Ivac) has had an important impact on reducing attack rates of influenza and reducing the severity of illness amongst the vaccinees who still acquire infection. Ivac is most efficacious amongst young, otherwise healthy subjects and least effective against elderly at high risk. This is in part because Ivac does not appear to significantly reduce infection rates and in...
Our studies in mice show that DNA vaccines, initially designed to prevent infection, can have a dramatic therapeutic action too. In heavily infected mice, simply by giving DNA vaccination, the immune response can be caused to switch from one that is relatively inefficient and gives bacterial stasis to one that kills the bacteria, and persistent bacteria can be eliminated. Adoptive transfer of protection...
Maximum life span is controlled by genes that regulate molecular mechanisms accounting for the synchrony of structural and functional changes in different cells and tissues of each member of a given species. The role of immune response genes was investigated in aging mice genetically selected for high (H) or low (L) antibody response (Biozzi mice). Results from genetic selection of over 1000 mice...
Age related deterioration in the function of the immune system has been recognised in many species. The clinical presentations of such immune dysfunction are an age-related increased susceptibility to certain infections, and an increased incidence of autoimmune disease and certain cancers. Laboratory investigations reveal a reduced ability of the cells from older individuals, compared with younger...
Natural killer (NK) cells are cytotoxic cells that play a critical role in the innate immune response against infections and tumors. Recent studies on NK cell biology have demonstrated that besides their cytotoxic function, NK cells express cytokine and chemokine receptors and also that they secrete other immunoregulatory cytokines and chemokines, supporting their relevance in the regulation of the...
Several age-related alterations occurring in the immune system, especially in T cells and in B cells, may account for an increased susceptibility to infections, autoimmune diseases, and malignancies. In particular, the adaptive immune response has been shown to lose part of its diversity and its memory in old mice. However, whether dendritic cells, which play a central role in the initiation of the...
To develop a mucosal vaccine strategy for the elderly, we have compared mucosal and systemic immune responses between aged (12-14 months) and young adult (8-12 weeks) mice. Both aged and young mice were immunized weekly with three oral doses of 1<space>mg of ovalbumin (OVA) and 10<space>μg of cholera toxin as adjuvant. Although elevated levels of OVA-specific systemic IgG and mucosal IgA...
Active immunization of women against human chorionic gonadotropin (hCG) has been considered as a promising option for contraception. However, prototype hCG vaccines based on natural sources of antigen are expected to be costlier for use by common people. In the present report, a functionally active, cost-effective antigen of bacterial origin has been described. Sulfonation of thiol groups of the protein,...
The potential utility of using DNA vaccination to protect mice from the microbial neurotoxin, botulinum toxin type A, was evaluated. A synthetically derived gene encoding a carboxyl-terminal 50 kDa fragment of the toxin was placed in two sites in the DNA inoculation vehicle pCMVint-BL (Vical), one predicted to lead to MHC I processing (pJT-1 construct) and the other to direct MHC II processing (pJT-2...
Utilizing a plasmid DNA encoding a single cytotoxic T lymphocyte (CTL) epitope and that encoding ovalbumin (OVA), we compared the reproducibility in the induction of immune responses by gene gun and intramuscular immunization. As compared to intramuscular inoculation, gene gun DNA immunization appeared to bring about highly reproducible and reliable results in the induction of specific CTL and IFN-γ...
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