EGID and Immunology
The following is an article written by Kimberly Risma MD, PhD, and Marc E Rothenberg MD, PhD, at the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children's Hospital Medical Center.
As printed in the October 2005 American Partnership for Eosinophilic Disorders (APFED) EoSolutions newsletter.
When considering the causes of EGID, it is important to think about the whole immune system since eosinophils are interacting with the full range of immune cells and their components. As such, working up the immune system is often part of the evaluation of patients suffering from EGID, especially in those people with recurrent infections. Based on this, we have put together this short review about the immune system.
The immune system has two primary roles: fighting infections and limiting inflammation. This requires the coordination of many different cells, primarily found in the blood, lymph nodes, and in the tissues. The most important immune cells are the white blood cells, of which there are many different kinds. The first type of white blood cells to consider are lymphocytes, of which there are subtypes referred to as B cells, T cells, and NK cells. Lymphocytes are particularly important in EGID because they regulate eosinophils by making eosinophil directed proteins like the eosinophil growth factors interleukin-5 (IL-5).
B cells respond to stimuli such as viruses, bacteria, or vaccines by making proteins in the blood called antibodies. The most abundant antibody is IgG. If a child gets a vaccine, the immunologist can determine if the vaccine "worked" by checking for an IgG response specific to that vaccine, also called a titer. Immunologists who see children with recurrent infections will check for B cell function by looking at the total numbers of B cells and the titers to one or more vaccines. B cells also make three other types of antibodies: IgM, IgA, and IgE. IgM is the first antibody that the body learns how to make. IgA is made at the surface of the gut and lungs and is important for local immunity; however, many people have IgA deficiency and have no increase in infections at all. Finally, allergic individuals produce IgE against triggers such as foods, pollens, dust, molds, or animal danders. This sensitivity may be tested by skin testing or by a blood test referred to as IgE RAST.
T and NK cells also respond to infectious agents and vaccines. To evaluate T cell function, the immunologist will look at the total numbers of T cells by the subtypes, CD4 and CD8 cells. CD4 T cells are also called helper cells, as they assist B cells to make antibodies and other white blood cells to fight infection; and CD8 cells are called cytotoxic T cells as they may kill foreign invaders (infections, tumor cells) directly. The function of T cells can be measured indirectly in the blood, by their ability to multiply to a variety of chemical or protein triggers. The number of NK cells can also be measured and the function of NK and CD8 T cells can be measured by a blood test that determines the level of killing against a foreign cell. The activation of T and NK lymphocytes in the blood may be evaluated by various markers noted on the surface or in granules of these cells.
There are two other white blood cells in the blood evaluated by the immunologist. The first is the neutrophil, a cell that is primarily important for fighting infections. The number of neutrophils is determined by a complete blood count, but the function of neutrophils rarely needs to be tested. Eosinophil counts are also noted on a complete blood count, but their function is not tested. Eosinophils are involved in the inflammatory response to parasite infections, although these infections are not very common in the Western world. Therefore, we typically think of eosinophils as markers of an allergic reaction as their numbers can be elevated in the blood in individuals with food allergies, eczema, environmental allergies, asthma, and other allergic diseases like EGID. They are also seen in the gut in non-allergic inflammatory conditions such as inflammatory bowel disease. Finally, their elevation in the blood can be idiopathic, meaning the etiology is unknown.
The function of the immune system can be "deficient," generally presenting with recurrent infections. Primary immune deficiency generally presents in childhood and may be marked by recurrent bacterial and viral infections, failure to thrive, and specific symptoms related to low white blood cell numbers or function. A good resource for families considering whether their child needs an immune work up for immune deficiency is the 10 warning signs listed at the web site of the Jeffrey Modell Foundation (www.jmfworld.com) and National Primary Immunodeficiency Resource Center (www.info4pi.org).
The function of the immune system may also be "dysregulated." This means that the immune system does not normally control the inflammatory response to either dangerous or benign stimuli. There are many different examples of immune dysregulation. Food allergy may be considered an abnormal inflammatory response to a protein that the immune system of most individuals ignores or tolerates. Autoimmune disease constitutes an abnormal inflammatory response to "self" proteins. Rheumatic fever is an abnormal inflammatory response to a bacterial infection, "Strep throat." In each instance, there is evidence of abnormal accumulation and activation of white blood cells that causes injury to the individual. There are numerous methods to measure immune dysregulation, depending on the clinical scenario, but most involve looking for non-specific markers of inflammation and evidence of specific activation of white blood cells. This is an emerging field in the study of eosinophil-based disorders, as the immunologist seeks to understand the mechanism for the accumulation of eosinophils in the blood or tissues of individuals.
