Death From Simple Infections: Disorders of Neutrophils

White blood cells (WBC) are made in our bone marrow and are absolutely imperative to fight infection. Without WBCs, we would succumb to even the most benign viruses and bacteria (i.e. germs) in our environment and die at a very early age. Once WBCs are made, they are released into the blood to mix with the RBCs (cells that carry oxygen) and circulate around our body. Stem cells in the bone marrow give rise to multiple WBC types, namely lymphocytes (T cells and B cells), neutrophils, basophils, eosinophils, and monocytes. Each type of WBC has a specific function. Eosinophils, for example, are important when fighting parasitic infectious. Many people are familiar with the Human Immunodeficiency virus (HIV), a disorder of T cells which impairs the body's ability to fight life-threatening bacterial and fungal infections. Neutrophils play a major function in our first line of defense against bacteria and fungi, and problems with them can carry grave consequences.

Neutrophils are typically first to the scene of an infection or traumatic injury. They are very quick, and their lifespan is only a few days. They follow chemical trails left behind by inflammation and, when they arrive, they suck bacteria into the center of their cell where some sanitizing then takes place- trapped bacteria are basically bathed in hydrogen peroxide. Two things can go wrong in this fight against the bacteria: either the neutrophils fail to work correctly, or the numbers of neutrophils are far too low to overpower invaders. Mildly low levels lead to oral/vaginal/rectal ulcers, ear infections, and skin abscesses. Severely low levels lead to overwhelming infection and death.

Disorders of the FUNCTION of neutrophils:
Congenital Leukocyte Adhesion Deficiency 1. Neutrophil movement is affected, so they are slow and fail to arrive to the scene of the infection. Newborn infants have delayed separation of their umbilical cord or infection where the cord meets the belly (omphalitis)

Chronic Granulomatous Disease. The release of the hydrogen peroxide inside the cell ("respiratory burst") doesn't work properly. Children need lifetime antibiotics (bactrim)

Hyperimmunoglobulin E Syndrome. The neutrophils don't follow the chemical trail to the site of infection like they are supposed to. Levels of an immune globulin called IgE are very high, and children have recurrent "cold" (non-red, non-tender) staph abscesses.

Chediak-Higashi Syndrome. There is a problem bringing the bacteria into the cell to sanitize them. Children also have albinism and their condition is worsened by infection with Epstein-Barr virus (EBV)


Disorders of the NUMBER of neutrophils:
External factors. Neutropenia caused by viruses (some viruses "shock" the stem cells and cause them to stop functioning for a period of time) or cancer chemotherapy

Autoimmune disorders. Neonatal Isoimmune Neutropenia occurs briefly in infants, whereby their mothers release antibodies that cross the placenta and attack their neutrophils. The disorder will resolve in less than 3 months. After 3 months, the baby can make their own antibodies against neutrophils leading to autoimmune neutropenia of infancy or chronic benign neutropenia.

Genetic syndromes. Shwachman-Diamond and Kostman Syndrome are characterized by low levels of neutrophils. Another interesting disorder is termed cyclic neutropenia, characterized by 3 day periods of neutropenia occurring every 21 days.

New Antibody Discovered Highly Effective Against HIV

A recent article in the Journal of Immunology highlighted a groundbreaking discovery in the fight against the human immunodeficiency virus (HIV). Funded by the National Institute of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID), Dr. Mark Connors and his team discovered an antibody named N6 that appeared to neutralize over 98 percent of the HIV isolates tested. What is particularly promising was the ability to eradicate even the known resistant strains.

To date, the discovery of a vaccine has been difficult due to the rapidly changing structure of the proteins on the surface of the virus. The N6 antibody, however, is particularly adept at binding a more consistent portion of the virus called the CD4 binding site, which allows it to attach to human cells.

The N6 antibody joins the ranks of the VRC01 antibody, which was discovered in 2010 and is in clinical trials, but it's effectiveness is far greater. This may translate to a vaccine that will finally prevent HIV from evading our immune system, saving countless lives and cutting healthcare costs.