Recently during a Functional Medicine Study group discussion on autoimmunity, a question was raised as one doctor was attempting to establish a connection between the Paleo diet and a reduction in TPO antibodies.
While there may be references in regards to the benefits of a gluten-free diet, of which Paleo definitely is. The general assumption was that the immune system is functionally “normal” during autoimmune conditions. Thus labs tests should report “normal” immune responses after following the Paleo diet for some time.
But really, when it comes down to it, I was taught that looking for changes in thyroid anti-bodies is worthless. Once autoimmune, always autoimmune; which doesn’t really answer the question. Just because post testing shows antibodies in normal ranges, doens’t mean the patient is not autoimmune. An immunosuppressed or immunocompromised individual may not be able to mount an immune response and thus TPO antibodies would be low. But if the immune system was somehow provoked just prior to the test being done may show high TPO antibodies. I have had many patients ask how one test can show just that. There is a simple answer.
You can’t assume normal immune function in an autoimmune patient.
The reason a person suffers from an autoimmune condition is because their immune system is not functioning in a normal healthy manner. In order to better understand the immune system, one should first know how it should function. From there, it becomes easier to spot the areas that are not behaving properly.
Read Part Two of the Series: Autoimmune Disease: The Immune System Lead A Stray
The Human Immune system
The human immune is extremely complex. It has evolved over hundreds of millions of years to respond to invasion by the pathogenic microbes that regularly attempt to infect our bodies, and invasion by the microbes that tried to infect our genetic ancestors.
The immune system does not rely on one single mechanism to deter invaders, but instead uses many strategies, the most important of which are detailed below. The main division between the strategies is that between Innate immunity, which does not require previous exposure to the invading microbe, and Acquired immunity, whereby the immune system “remembers” how to deal with a microbe that it has dealt with before.
Phagocytes are the soldiers of the immune system, and provide innate immunity. They are responsible for swallowing, killing and digesting invading microbes. The process of swallowing microbes is known as phagocytosis. There are two main types of phagocyte
- Microphages. These cells are also known as Polymorphonuclear Leucocytes, PMNs and Polymorphs. Blood test results report these as neutrophils, basophils and eosinophils. These cells start life in the bone marrow. They are constantly circulating in the blood. They cannot replicate, and live for only a few days. The bone marrow contains large reserves of microphages.
- Macrophages. These cells start out life as monocytes, which originate in the stem cells in the bone marrow, but when they are first called into action, they turn into macrophages. Blood test results report these as lymphocytes and monocytes. Macrophages are not as numerous as microphages, and there are no large reserves of them, but they are longer lived than microphages. Macrophages are stationed at strategic locations throughout the body, usually in places that are not otherwise well defended. These areas include the alveoli of the lungs, the abdominal (peritoneal) and chest (pleural) cavities, under the top layer of the skin and the intestines. Macrophages are the front line of defense against microbial invasion in these areas.
As mentioned above, the process of swallowing of microbes by the phagocytes is known as phagocytosis. After the invading microbe has been ingested, the next task for the phagocyte is to kill the microbe. This is achieved in two main ways.
- Aerobically, i.e. using oxygen. The phagocytes produce oxygen based chemicals that are highly disruptive to the swallowed microbe. Oxygen is highly chemically reactive, and these oxygen based chemicals “tear” the microbe apart. This process is known as the oxidative burst, or the respiratory burst.
- Anaerobically, i.e. without using oxygen. One way to kill the microbe without oxygen is by using a chemical that deprives the microbe of iron, thus preventing it from metabolizing. Another way is to increase the acidity of the internal environment of the phagocyte.
When these tasks are complete, the Macrophages have one further task to complete. They return to the lymph nodes, displaying the remnants of the destroyed invader on their surface. This has the effect of stimulating the cells of the Acquired immunity system into action.
The Complement System
The complement provides innate immunity. It is comprised of a collection of proteins that “recognize” corresponding proteins on the cell walls of invading microbes. When such invading microbes have been recognized, the following actions are taken
- The “alarm” is sounded. Chemicals, known as chemotaxins, that attract phagocytes are emitted. This process is known as chemotaxis. The phagocytes follow the trail of chemotaxins to arrive at the site of invasion.
- The invading bacteria are “marked” with chemicals that make them stand out. These chemicals are known as opsonins, from the Latin word opsonium, meaning “sauce”. This “marking” greatly increases the chances of the invading bacteria being phagocytosed.
- Chemicals are released which promote the inflammatory response. More on the inflammatory response later.
The acquired immunity system comprises B Cells and T Cells. Together, these cells, which provide acquired immunity, are known as Lymphocytes. The acquired immunity system further divides into two parts, humoral immunity and Cell Mediated Immunity (CMI).
B Cells provide “Humoral Immunity”. Each B cell secretes a unique antibody, which acts against a particular antigen. An antigen is a chemical feature (a protein), which is unique to any given type of invading organism. When B cells meet an invading organism for which they have the antibody, they do one of two things.
- They may turn into antibody factories and start manufacturing as many copies of their antibody as they can.
- They may clone themselves, thus increasing the numbers of antibody factories, which results in an increased immune response to the target organism.
The precursor to B-lymphocytes and T-lymphocytes are the same but they perform completely different functions. T-lymphocytes are made in the bone marrow but need to be sensitized in the thymus in order to work (hence the name T-lymphocytes). When stimulated with an antigen, they don’t make antibodies but instead produce cytotoxins, chemicals in our body that kill foreign cells. The T-lymphocytes divide themselves up into killer T-cells, helper T-cells and megakaryocytes, all that have a specific function in the destruction of foreign agents.
T Cells provide “Cell Mediated Immunity”, often referred to as “CMI”. T cells have several functions. They can be:-
- Helper T cells, which control other cells, such as B cells or Macrophages, directing them to carry out their task.
- Suppressor T cells, which dampen down the immune response when it is no longer needed.
- Cytotoxic T cells, which destroy host cells that have become infected with the invading organism.
Cytokines are the last element of the immune system, which I shall discuss here. Cytokines (meaning “cell movers”) are the messengers of the immune system. There are two types of cytokines: inflammatory and anti-inflammatory. The inflammatory cytokines stimulate inflammation, which is needed to do simple repairs like a cut on your skin or to defend against invading microbes. The anti-inflammatory cytokines inform the body the repair has been completed or the all-clear that the invaders are under control.
The measurement of multiple cytokines will present the CAM practitioner with a broader picture of the patient’s inflammatory condition, and thereby would be useful in fitting a therapeutic intervention on an individual basis. – Vojani
The above-mentioned elements of the immune system (Complement, Phagocytes, Lymphocytes) do not work separately, but all work together in cooperative fashion. If they are to work effectively, they need a good system for communicating messages. This system is provided by the cytokines. Among the cytokines are the Interleukins, of which there are known to be at least twelve, Gamma-Interferon, Lymphotoxin, and Tumor Necrosis Factor.
Depending on which T cell subset prevails during an immune response, different constellations of cytokines predominate. Several cytokines have the capacity to shift the balance of an immune response to a particular T cell subset. In addition to cytokines and growth factors, the immune response is governed by a large family of chemotactic cytokines (chemokines), including IL-8 (CXCL8), MCP-1 (CCL2), and MIP-1β (CCL4), function to recruit white blood cells and direct their trafficking patterns through normal and inflamed tissues.
Dendritic cells are present in small quantities in tissues that are in contact with the external environment, mainly the skin (where there is a specialized dendritic cell type called Langerhans cells) and the inner lining of the nose, lungs, stomach and intestines. They can also be found in an immature state in the blood.
Although there are several distinct subtypes of DCs, they all share these features:
- They are actively motile.
- They continuously sample their surroundings — ingesting antigens by endocytosis (using phagocytosis, receptor-mediated endocytosis, and pinocytosis).
- Many of these antigens are “self” antigens, e.g., dead cells, proteins in the extracellular fluid.
- But the antigens can also be foreign antigens, for example, bacteria that are resident in the body (e.g., in the colon) or that invade the body.
Dendritic cells are known as the most efficient antigen-presenting cell type with the ability to interact with T cells and initiate an immune response. Dendritic cells are receiving increasing scientific and clinical interest due to their key role in the immune response and potential role in the gastrointestinal tract.
Read Part Two of the Series: Autoimmune Disease: The Immune System Lead A Stray
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