5 replies to this topic

[Mind]

Here is an article desrcibing a theory of why the immune system is gets less effective with age. Apparently, T-cell diversity declines with age, thus making a person more susceptible to disease. My question is: what is the root of the problem? I am guessing that accumulated damage in the lymph nodes or bone marrow results in less production of t-cells with age....just like other bodily systems and organs decline with age.

Read the full article here

VGTI RESEARCHERS HELP UNCOVER WHY AGING REDUCES IMMUNE SYSTEM FUNCTION
The current flu vaccine shortage demonstrates the importance of better protecting the elderly against disease

PORTLAND, Ore. -- Scientists at the Vaccine and Gene Therapy Institute at Oregon Health & Science University have made a discovery that helps explain why our immune system worsens with age. The work was led by Janko Nikolich-Zugich, M.D., Ph.D., a senior scientist at the VGTI. The scientists hope this new information can be used to better protect the elderly from infectious diseases by finding ways to slow or stop the degradation of the immune system. The research results are printed in the current edition of the Journal of Experimental Medicine.

"One of the major components of the immune system are T cells, a form of white blood cell. These cells are programmed to look for certain kinds of disease-causing pathogens, then destroy them and the cells infected by them," said Nikolich-Zugich who also serves as a professor of molecular microbiology and immunology in the OHSU School of Medicine, and is a senior scientist at the OHSU Oregon National Primate Research Center. "Throughout our lives, we have a very diverse population of T cells in our bodies. However, late in life this T cell population becomes less diverse, potentially resulting in a higher level of susceptibility to disease. We think we have found one of the key reasons behind this age-related susceptibility."

Specifically, in old age, the number of CD8 T cells diminishes. CD8 T cells have two functions: to recognize and destroy abnormal or infected cells, and to suppress the activity of other white blood cells to protect normal tissue. The scientists believe that late in life a different kind of CD8 T cell is increasingly produced by the body. These cells, called T cell clonal expansions (TCE), are less effective in fighting disease They also have the ability to accumulate quickly as they have a prolonged lifespan and can avoid normal elimination in the organism.

In the end, these TCE cells can grow to become more than 80 percent of the total CD8 population. The accumulation of this one type of cell takes away valuable space from other cells, resulting in an immune system that is less diverse and thus less capable in effectively locating and eliminating pathogens.

To conduct the research, scientists at the VGTI studied mice, which have immune system function very similar to humans. The scientists found the aging mice to have greater TCE levels than normal mice, a less diverse population of CD8 T cells and reduced ability to fight disease. In addition, the scientists were able to show that increasing TCE cells in a normal, healthy mouse reduces that animal's ability to fight disease.

[kevin]

I had read that an additional contributing factor to aging immune systems is the recurring exposure to the same pathogens, both in the environment and those viruses which are transiently expressed after stowing away in our genomes. Recurring stimulation of the immune system by the same agents is supposed to cause a skewing of the population of T cells resulting in a decline in diversity.

There also hasn't been a lot of research done on them yet either, but I think that 'regulatory' or 'suppressor' T cells may be involved in preventing a more normal response because of problems which may arise in that population. A lack of suppressor cells might have a role to play in increased inflammation and the autoimmunity issues that seem to increase as we age.

[manofsan]

Well, don't all these immune cells come from some progenitor cells? Or do they simply replicate themselves to maintain their population?

If the latter's the case, then I can see how the population would get skewed. If so, would you cure that thru some external monoclonal technique to replenish the low-count cells?

Since most of our growth occurs during our formative years, I wonder how the immune systems of people who had lots of illnesses during childhood compare to those with disease-free childhoods?

[kevin]

Single T-cells (and B cells) undergo clonal expansion upon stimulation lby particular pathogens. After successful clearing of the 'invader' most of the cels undergo apoptosis but a significant number become 'memory' cells which are sentinels left to fight the same pathogen on the next encounter. This is the 'adaptive' part of the immune response that eventually skews the population.

I understand that IL-7 can be used to rebuild the immune system but I'm not quite sure the exact mechanism.

They've shown that robust immune systems are built by allowing pretty free exposure to the environment as children. Children sheltered tend to turn into adults who have immune dysfunction, allergies and autoimmune disorders, if they are genetically predisposed to such. The education of an immune system is one of the most complicated parts of our biology as it involves so many different cell types, organs, and needs to be system wide. There even seems to be some link between nerves and their adaptability and immune cells variability.