Changes in Natural (Innate) Immunity

The components of natural immunity are dendritic cells, macrophages, natural killer cells, and the complement system.

Dendritic cells: These are the antigen-presenting cells for CD4⁺ T-helper lymphocytes, a crucial step in initiation of the immune response. They take up and process antigen into small peptides, which then complex with newly synthesized class II major histocompatibility complex (MHC) proteins. Whether dendritic cells or other antigen-presenting cells (eg, macrophages) display the class I MHC-peptide complex to CD8⁺ lymphocytes is unclear. These cells also require the help of CD4⁺ lymphocytes to proliferate and develop their cytotoxic activity.

The antigen-MHC complex is transported to and displayed on the cytoplasmic membrane of the dendritic cell. This complex delivers the first activation signal to CD4⁺ T-helper lymphocytes. Optimal T-lymphocyte activation also requires signals from other molecules expressed on dendritic cells.

Few studies have examined the effects of aging on dendritic cells. In general, elderly persons have fewer dendritic cells than do younger persons. However, even in the elderly, these cells appear to retain their antigen-presenting capacities: ie, expressing surface molecules and inducing the activation and proliferation of T lymphocytes.

Macrophages: Macrophages are among the first cells that pathogens encounter after traversing the epithelial barrier. Macrophages specialize in phagocytosis and intracellular killing of microorganisms. They demonstrate tumor cytotoxicity and are efficient antigen-presenting cells. Bacteria trigger macrophages to produce numerous chemicals and cytokines, which initiate the acute-phase response, enhance their own microbicidal activity, stimulate the production of cytokines by other cells, and promote the activation of T-helper lymphocytes.

In the elderly, macrophages usually support a normal T-lymphocyte response to specific antigens. The production of cytokines and expression of surface molecules by macrophages are similar in elderly and younger persons. However, the rate of antigen clearance by macrophages decreases notably with age. Also, in elderly persons, the toxicity of macrophages against tumor cells is low, which may contribute to increased cancer susceptibility in this population.

Natural killer (NK) cells: These cells can kill target cells spontaneously (in the absence of any obvious prior activation) and are involved in host resistance to various tumors and infectious diseases.

With age, NK cell activity remains unchanged or increases. Increased activity is usually associated with an increased proportion of cells expressing the NK phenotype.

Complement: The complement system consists of interacting plasma proteins constituting a triggered enzyme system; it appears to be the main soluble effector of natural immunity. Through cytolysis, opsonization, and activation of inflammation, complement efficiently defends against microorganisms.

Healthy elderly persons appear to have slightly lower levels of complement components than do younger persons. Age-related differences are more apparent during the course of bacterial infection: Complement levels increase dramatically in younger persons with acute bacteremia but do not significantly do so in elderly persons.