Most patients with autoimmune myasthenia gravis (MG) produce autoantibodies against their muscle acetylcholine receptors (AChR), causing debilitating muscle weakness. Approximately 60% of MG patients first exhibit myasthenic symptoms after the age of 40. Yet, in the C57BL/6 mouse model of MG, older mice are resistant to induction of myasthenia gravis. To understand the immunological basis for this resistance, the effects of age on the B-cell responses to AChR from Torpedo californica, the inducing antigen, were addressed. As expected, the primary B-cell response was lower in 20-month-old mice than in 2-month-old mice; the isotype profile was not altered by age. When mice were re-immunized, the anti-T-AChR titers increased in both young and old animals, suggesting that a memory response was elicited. Importantly, memory B-cells activated in young animals were largely resistant to the age-associated loss of immune function and the recall memory response was vigorous. Furthermore, the antibodies produced in re-stimulated older mice were functional, as evidenced by the appearance of MG symptoms in some of these animals. Thus, by eliciting a recall memory response, the first examples of late onset MG in mice have been generated. By analogy, late onset MG in humans may be due to re-activation of B-cell responses initiated at a younger age.
"A first immunization at young age, when sufficient naïve T cells are still present, followed by boosting at old age may improve T cell responses at older age. This approach has shown to be effective for improving Ab responses at older age in mice (Stacy et al., 2003). Activation of the innate immune system by mixing a lipophylic glycopeptide L-TMP-PE (liposyl muramyl phosphatidylethanolamine) with the vaccine, which is capable of recruiting and activating killer macrophages (Nardin et al., 2006), is another approach if T cell activation fails or as an addition to T cell activation. "
[Show abstract][Hide abstract] ABSTRACT: The incidence of cancer has increased over the last decade, mainly due to an increase in the elderly population. Vaccine therapy for cancer is less toxic than chemotherapy or radiation and could be, therefore, especially effective in older, more frail cancer patients. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger adults. This has been attributed to T cell unresponsiveness, a phenomenon also observed in cancer patients per se. This review summarizes the current knowledge of T cell unresponsiveness in cancer patients and elderly, the results of cancer vaccination in preclinical models and in clinical trials, and recent data of cancer vaccination at young and old age in preclinical models. Finally, experimental approaches will be proposed how to make cancer vaccines more effective at older age.
[Show abstract][Hide abstract] ABSTRACT: Cancer is a disease of the elderly. Since demographic trends indicate that over the next decades the number of elderly people
will increase substantially, strategies for cancer prevention and therapy need to be optimized to older patients. Immunotherapy,
either through passive or active immunization is a highly targeted type of therapy that is potentially less toxic than chemotherapy
or radiation and could, therefore, be especially effective in older, more frail cancer patients. In particular active immunization,
i.e., employing patient’s own immune system through vaccination, offers great promise since it can potentially keep cancer
permanently at bay. However, it has been shown that older individuals do not respond to vaccine therapy as well as younger
adults. This has been attributed to diminished T-cell responses, a phenomenon also observed in cancer patients per se. To
develop cancer vaccines that are effective at older age, the availability of preclinical models that can predict age effects
on cancer vaccination is critically important. In this review, current knowledge of diminished T-cell responses in cancer
patients and elderly, the results of cancer vaccination in preclinical models and human clinical trials and the impact of
aging on immunotherapy will be discussed. Finally, experimental approaches will be proposed how to make cancer vaccines more
effective at older age.
[Show abstract][Hide abstract] ABSTRACT: Reports on the creation of a development toolkit to facilitate the
simulation of an OSI network environment. This facility can then be used
to test any user-defined OSI protocol profile as well as for the testing
of any non-OSI-to-OSI protocol converter. This toolkit also permits the
generation of the layer protocol drivers required for the set-up of a
DOS-based PC network
TENCON '93. Proceedings. Computer, Communication, Control and Power Engineering.1993 IEEE Region 10 Conference on; 11/1993
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