Learn the basics of PI

In 2013, an international consortium classified over 200 primary immunodeficiencies. Last year, that number increased to more than 400. That rise, which shows no signs of stopping, is the perfect example of the intricacy of the immune system and the discoveries that have yet to happen concerning its operations.

“The immune system is incredibly complex and we are learning so much about the immune system, almost on a daily basis,” said Dr. Tyler Yates, Assistant Professor of Pediatric Allergy and Immunology for Oregon Health and Sciences University.

At an IDF forum on September 1 entitled, “PI: The Basics,” Dr. Yates provided participants with a broad overview of the immune system, or, as he described, as a “30,000-foot view” of the immune system. During his discussion, Dr. Yates covered the major categories of the immune system, what they are responsible for, and why we might be looking at those areas in bloodwork.

“As an immunologist, I always tell my patients I want to make sure you have all the working parts, and the parts work correctly,” explained Dr. Yates. “It’s really important to know. A lot of the different diseases, you may be missing a component of your immune system or it may be there but it may not function well.”

Dr. Yates described the immune system as a biological system that is responsible for defense against infectious organisms.

“The immune system does a whole lot of things. Most of you are familiar with the immune system in that it is responsible for defense against infectious organisms, and if our immune system isn’t functioning properly, depending on which arm of the immune system we are discussing, you may be more likely to come down with a bacterial infection, a viral infection, a fungal infection, maybe a little of both,” said Dr. Yates.

“This is how most patients with a primary immunodeficiency are going to present. They’re going to present with either a lot of infections or maybe some strange infections.”

But preventing infection is not the only role of the immune system, said Dr. Yates. It prevents autoimmune diseases, and acts as surveillance for cancer cells.

“You may have been told with whatever immune deficiency that you were diagnosed that you have an increased risk of developing autoimmune diseases or certain cancers, like lymphomas, maybe skin cancers, or GI cancers, it changes a little bit depending on the immune deficiency, but that’s where this comes from, it comes from the idea that the immune system is really important in fighting infections preventing autoimmune disease and for fighting off cancer,” said Dr. Yates.

The immune system can be divided into two main branches – the innate immune system and the adaptive immune system.

The innate system is the initial response that happens very quickly, minutes to hours after being exposed to a bacteria or virus, said Dr. Yates. It’s not specific and it doesn’t care about the type of infection and has no memory of the germ. Some people with PI may have innate defects or disorders.

Some of the key players in the innate system are:

• Neutrophils – They are a type of white blood cell that is a first responder to infection and is a key component of pus. Some disorders associated with neutrophils are chronic granulomatous disease and leukocyte adhesion deficiency disorder.
• Natural Killer cells – These cells are very important for protection against viruses and killing cancer cells. Persons with some forms of severe combined immunodeficiency may have defects in their Natural Killer cells.
• Complement System – These are very small proteins and their job is to help your antibodies function. There are a wide range of disorders associated with the complement system, because people may be missing different parts of the system.
• Macrophages – These are white blood cells that eat bacteria. If you have a defect in your macrophages, you may get a lot of infections, such as tuberculosis, from micro-bacteria.

Different from the innate immune system, the adaptive immune system, explained Dr. Yates, is a delayed response to infection and it takes days to work and has a very specific response to specific organism. It also has memory, unlike the innate system, so that if you’re exposed to the same organism subsequent times, you can have a quicker response.

The adaptive immune system produces B cells which are important for producing antibodies or immunoglobulins. Immunoglobulins are very important for our defense against bacteria, as well as viruses, and fungi, but they work very closely with helper T cells.

“I’m willing to bet that the majority of people here have some type of antibody deficiency,” said Dr. Yates.

There’s a pretty wide spectrum of B cell deficits but for the most part they all present similarly, he said, with sinopulmonary infections such as pneumonia, ear infections, sinus infections, and perhaps gastro-intestinal infections. If you have a hard time producing antibodies, this may result in common variable immune deficiency or selective IgA deficiency. Or you may have normal or low numbers of IgG, which is your most abundant antibody, but may not be able to respond specifically to different organisms and that’s called specific antibody deficiency.

So what are the kinds of immunoglobulin? They are:

IgA – This is an antibody found in your mucosal tissues that line your GI track, sinuses, ears, and lungs. Most people with IgA deficiency are asymptomatic, but about 10 to 15 percent of people have sinopulmonary and GI problems.

• IgG - This is the most abundant in the bloodstream and it goes everywhere to fight infections. It’s also the type is given during plasma donation, so it’s really the most important one, said Dr. Yates.
• IgM – These are the first responders when you get an infection and can be problematic in conditions like Hyper IgM.
• IgE – This type of immunoglobulin that is most often implicated in allergies. You may have Hyper IgE in which you are more susceptible to allergies, autoimmune diseases, and infections.
• IgD – This is not a well understood immunoglobulin.

Along with the B cell, the T cells are also key players in the adaptive immune system. They start their journey in the bone marrow and travel to an organ called the thymus, which sits above the heart, explained Dr. Yates. A colleague of Dr. Yates’ describes the thymus as the schoolhouse where the T cells go to get educated to fight infections and to learn not to attack your cells.

The mature T cells are important for fighting viruses and fungal infections and assisting other cells to fight bacteria. They are also very important for fighting cancer cells. The types of T cells include Helper T cells, which work with B cells to fight infection; Killer T cells, which directly kill cells infected with virus or cancer; and regulatory cells, which help prevent autoimmunity.

Dr. Yates wrapped up his presentation discussing combined immune deficiencies, those that involve more than one part of the immune system. Some types of those are SCID, Wiskott-Aldrich Syndrome, and Hyper IgE Syndrome.

After answering some questions from the audience, Dr. Yates left the audience with these parting words of advice.

“Wear your masks. Wash your hands. Don’t be around anyone who is coughing, and do your best to help all of us get through this thing as safely as possible."

To listen to the full presentation of the IDF Forum “PI: The Basics,” click here.