Cellular mechanisms that may impact immune functions in the elderly discovered

American College of Allergy, Asthma and ImmunologyNov 9 2009

Investigators discover cellular mechanisms that may impact the decline of both innate and adaptive immune functions that increase the susceptibility to various infectious agents, cancer and diseases in the elderly say experts at the annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Miami Beach, Fla.

"Our ultimate challenge studying the immune system throughout the human life span is to identify antecedents of adult end stage disease during early development. It may be possible to intervene when these conditions are still reversible to prevent the long term disease progression by appropriate therapeutic interventions, such as anti-inflammatory modulation and immunotherapy," said Joseph A. Bellanti, M.D., professor of pediatrics & microbiology-immunology, director, Immunology Center, Georgetown University Medical Center, Washington, D.C.

The older concept of the function of the immune system to recognize "self" from "non-self" has been broadened said Dr. Bellanti, whereby danger signals or invading organisms activate pattern recognition receptors and drive the inflammatory response.

There is emerging evidence that early microbial exposure resulting in colonization of skin and GI tract are crucial events for maturation of the neonatal immune system. "The young have vigorous responses to initial and subsequent contact with antigen. The elderly have poor or limited ability to respond to new antigens, but good recall to antigens seen previously. For example, the novel influenza A (H1N1) 2009 virus vaccine is not recommended for persons age 65 and over because of prior exposure to other flu strains and presumed good memory cell pools," Dr. Bellanti said.

Nan-ping Weng, M.D., Ph.D., senior investigator, Laboratory of Immunology, National Institute on Aging of the National Institute of Health in Baltimore, Md., defines immune aging or senescence as "a reduced capacity to mount a robust immune response, thereby increasing the susceptibility to various infectious agents, cancer and diseases in the elderly."

Age-associated increase in CD28- T-cells have been observed including a decrease in thymic output, a decrease in diversity and an increase in the number of memory and effector/memory cells. Investigators are working to develop methods to sustain or activate CD28 expression in T-cells.

Telomere is a specialized structure at the end of a chromosome involved in cellular replication and stability that erodes with aging.

"Cells, including lymphocytes, with significantly shortened telomeres are incapable of undergoing further cell division. It has been shown that the telomere lengths of blood lymphocytes are often shorter in old than in young adults. The significance of such changes in the elderly is currently under intensive studies." Dr. Weng said. The future direction is to "understand the role of telomere and telomerase in lymphocyte function in vivo with aging, and develop strategies to maintain telomere length or even lengthen telomere under certain circumstances."