Recent experience with a novel influenza virus shows that young, healthy individuals may have a higher risk for severe disease than the typical at-risk populations.
The elderly and the very young are usually at greatest risk of death from infections with influenza. Ostensibly, people in these age groups have less efficient immune systems and are therefore more likely to succumb to the initial viral pneumonia caused by seasonal flu; they are also less likely to survive the secondary bacterial infections that sometimes accompany influenza.
Some influenza viruses, however - the 1918 “Spanish flu” strain, H5N1 (otherwise known as “avian flu”), and now, apparently, 2009 H1N1 - elicit a hyperimmune response that places those with exuberant immune systems at greater risk for severe disease and death.
Health experts have coined the phrase “cytokine storm” to describe this exaggerated immune reaction.
A basic grasp of immune system function is useful for understanding this abnormally aggressive immune response.
The Biology of the Immune System
The immune system is a collection of cells, tissues, organs, and molecules that is designed to distinguish what is “us” from what is “not us.” Its job is to eliminate potentially harmful molecules, microbes, and cells from the body.
Healthy immunity consists of three phases:
Activation
- When a foreign invader (virus, bacterium, fungus, cancer cell, etc.) enters the body, it is recognized by circulating antibodies or by receptors on immune cells (natural killer cells, Langerhans’ cells, etc.).
- The invader (antigen) may become coated with antibodies or specialized molecules called complement (“immune butter”) that make the antigen more “palatable” to immune cells.
- The antigen is then phagocytosed (eaten) by patrolling immune cells and is either killed outright (a vital function of the innate, or nonspecific, immune response) or carried to other sites - such as lymph nodes - where the antigen is presented to more specialized immune cells like T helper cells. These specialized cells then initiate the acquired, or learned, immune response.
- Whenever an antigen interacts with immune cells, the cells produce cytokines that act as messenger molecules for other immune cells.
- Cytokines (interferons, tumor necrosis factors, interleukins, etc.) are a critical means by which one immune cell communicates with another. Depending on their assigned roles, cytokines promote inflammation, recruit antibody-producing cells, enable the destruction of abnormal cells, down-regulate the immune response, or initiate tissue healing.
Regulation
- Whenever the immune response is allowed to proceed unchecked, significant damage to normal tissues - indeed, to the entire host organism - can result. This is what occurs in anaphylactic shock or autoimmune diseases, such as scleroderma or lupus.
- As the response to a foreign antigen unfolds, specialized white cells (T suppressor cells) secrete their own cytokines (e.g., interleukin-10, transforming growth factor, transfer factors, etc.) that dampen the immune response and help to prevent runaway inflammation.
Resolution and Immune Memory
- Once a foreign antigen is sequestered or eliminated from the body, the activated immune cells no longer receive cytokine-mediated messages. Most of these cells then enter a stage of senescence and are themselves consumed by other immune cells.
- If the antigen was novel to the immune system - that is, if it had never entered the body before - some T and B lymphocytes that were involved in the immune response remain in the tissues, ready to quickly respond should that antigen reenter the body in the future. These lymphocytes become part of immune “memory.”
(Adapted from Biology of the Immune System in The Merck Manual, 18th Edition. 2006:1320-30)
Influenza and the Cytokine Storm
Whenever a particularly virulent organism enters the body (one that the immune system recognizes as exceptionally deadly or that possesses certain molecular characteristics) an abnormally vigorous response may ensue.
As this exuberant, all-or-none immune reaction proceeds, an outpouring of inflammatory cytokines occurs, and any tissues surrounding the “field of battle” experience collateral damage before regulatory mechanisms commence.
Because damaged tissues themselves are recognized by the immune system as foreign invaders, a cascading cycle of immune cell response, cytokine production, and immune cell recruitment begins.
If uncontrolled, such a cytokine storm occurring in vital organs can lead to organ failure and death.
Although medications and medical support are useful for dealing with the cytokine storm associated with infections by virulent organisms, the human immune system normally presents a very efficient challenge to foreign antigens. It is the immune system, after all, that allows humans to survive in a veritable soup of microorganisms that would otherwise reduce us to compost in short order.
Alas, the immune system can sometimes be indiscriminate in its efforts to eliminate perceived enemies. The cytokine storm is simply one manifestation of an unbridled immune response.
