Monday, October 24, 2011

The Role of the Human Immune System in Obesity

Human immunity has developed, over evolutionary time, into a complex system that impacts a great deal of human biology.  It is for this reason that it often a key player in the cause of many ailments.  It has recently been implicated in human obesity, insulin resistance and type 2 diabetes – these three conditions constitute the so-called metabolic syndrome.  Immune responses are potent reactions to bodily insults and, therefore, must be tightly regulated.  These responses are activated and suppressed by a large family of small regulatory proteins referred to as interleukins.

The white blood cells (WBC) that are found circulating in human blood are, in fact, comprised of a complex mixture of cell types that all perform unique immunological roles.  Eosinophils are a particular WBC type that is classically involved in combating helminth (parasitic worm) infections and allergies.  In addition, macrophages are a subtype of WBC that is characterized by its large size and ability to respond to a wide range of human infections. 

Extensive studies of obesity using animal models led by Dr. Davina Wu at the Howard Hughes Medical Institute at the University of California in San Francisco have implicated Eosinophils and a particular subtype of macrophage referred to as alternatively activated macrophages (AAMs) in the maintenance of glucose balance in fat (Adipose) tissue.  It appears that the role of eosinophils in this process involves the secretion of a type of Interleukin called Interleukin-4 (IL-4).  When eosinophils are not present in adipose tissue, the level of glucose is no longer subject to regulation.

Doctor Wu and colleagues, working with the mouse model, have shown that the macrophages resident in the adipose tissue of obese subjects are actively involved in an inflammatory response while the macrophages in the adipose tissue of lean mice are not.

This study reinforces the established relationship between metabolism and immunity.  Furthermore, these findings support the connection between obesity and the enrichment of those genes involved in inflammatory and immune responses in humans – a strong indication of the health dangers posed by obesity. 

Saturday, October 1, 2011

A New Approach to Immunization Against the Flu Virus

Influenza – the flu – continues to infect millions of individuals each year and cause thousands of deaths.  In addition, the economic losses associated with this illness are considerable.  Although immunizations against this virus exist, their effectiveness is diminished by the fact that this virus mutates readily and produces a variety of strains that evade the immunization strategy.  These vaccines provide only limited protection against these strains.  In order to more fully understand the nature of the global health problems posed by the influenza virus, we will examine the nature of its action.


The influenza virus is essentially spherical in shape.  Its outer layer is, in fact, a lipid membrane that it has acquired from the host cell that it has previously infected.  Embedded in this outer layer are proteins that are characteristic of the strain of the virus.  It is these proteins that are potential targets for antibodies used in various vaccine regimens.   The virus – like all viruses – is essentially inert outside of living cells.  Once it effectively infects a target tissue – usually in the respiratory system –the virus delivers the infective material directly into the target cell.  The influenza virus belongs to a class of viruses called Ribonucleic acid (RNA) viruses; because, RNA is the infective agent.  Once the viral RNA enters the cell, it commandeers the cell machinery to produce more viruses and eventually kill the cell.  The dead cell releases its contents including many copies of the virus and each of these goes on to infect neighboring cells.

The strategy behind the development of vaccines against this virus is to discover an identifying protein on the virus' surface that persists (highly conserved) over a wide variety of subtypes.  This has proved to be a very elusive quest.   However, there has been a recent discovery of what is referred to as VH1-69 antibodies that knock out almost all type A Group 1 viruses.  This is an exciting development in its own right, since it is the type A virus that represents the most virulent strain.

One of the major surface proteins on the Influenza virus is Hemagglutinin (HA).   Antibodies that target HA, for example, bind with a unique part of the protein referred to as an antigenic determinant or epitope.  Doctor Damian C. Ekiert and his colleagues from the Department of Molecular Biology at the Scripps Research Institute in LaJolla California have isolated and characterized a human monoclonal antibody called CR8020 that has been shown to have broad reactivity to most group Type A 2 viruses.  It seems quite possible that a cocktail containing these two antibodies -  VH1-69  and CR8020 - may produce an effective universal flu vaccine.  This would be an exciting development from the global public health perspective.