Mechanisms of Hypersensitivity

I am always fascinated by my clients and their eagerness to better understand their bodies. It inspires me to dig deeper into the literature and think more critically about what I already know and have yet to comprehend or appreciate. Immunity and inflammation would maybe have been a chapter I would have skimmed previously because I can’t say that I’ve ever had a particular attraction to that aspect of medicine; however, the more functional medicine pulls at me, the more I recognize the importance of truly grasping the basic concepts of self-defense are to helping my clients. The immune system is a finely tuned network, complex as hell, and brilliant beyond human comprehension. It protects the host from foreign antigens, most often infectious agents, but at times there are break downs in the network, or miscommunications, even misrepresentations and more than ever before, our bodies are beginning to attack themselves.


Disease or damage to our bodies in someway can create a hypersensitivity. We understand this to be an allergy or autoimmunity, or even alloimmunity for some. Autoimmunity is essentially our body becoming intolerant to itself and in conventional medicine, physicians wait for this attack to mount to the point of full blown disease prior to intervention. Functional medicine providers seek to correct the underlying cause that originally initiated the attack in effort to remove the trigger and bring the body back to optimal health. Many clinical disorders are associated with autoimmunity and are collectively referred to as autoimmune diseases.

Have you ever seen a pharmaceutical commercial state, “if diet and exercise hasn’t worked for you, try our magic pill.” We’re the ones actually doing the diet and exercise part, and addressing additional lifestyle modifications, rather than skipping this vital step and immediately offering surgery or a medicine required for the rest of your life. Conventional physicians know diet and exercise work. They know its the safest route with the best outcomes, they just don’t have time to teach you about it and lack resources in how to help you implement this into your life. They’ve lost faith that you can do this on your own, so they’ve given up. Physicians also recognize that autoimmune diseases are the result of environmental exposures, infections, and underlying genetics (well, except that one endocrinologist that told my client her diet had nothing to do with her diabetes).

Mechanisms of Hypersensitivity

I hear my office staff explaining the facets of hypersensitivity reactions daily and its such a joyful sound because it demonstrates how much good they have seen result from this therapy within our clientele base. Even my administrative staff is totally on board and teaching clients about their immune system.

Like all other areas of our bodies, the immune system is complex and not easily compartmentalized into distinct sections because our systems work together like a master orchestra. For the purposes of this post though, lets break it down a bit. The first type of reaction in our body is IgE-mediated, the second is tissue specific, the third is immune complex-mediated, and the fourth is cell-mediated. In all sensitivity reactions, our body first require an initial exposure. During this first exposure, we create antibodies to the foreign substance and then on second exposure, our defenses are prepared for attack. Some individuals can mount a very quick response, after a single exposure, but more often we need more frequent exposures even over years to acquire sensitivity.

When Ruby was born, as many of you know, my bladder took a major hit requiring four hours of surgical repair. My urologist described it as wet kleenex held together with a bird’s nest of suture. My bladder is “not normal” as the radiologist describes it as it leaks urine within its walls. For this reason, I had an indwelling catheter for several weeks after her birth. On top of healing from my cesarean section after four long days of labor, I was fighting off infection, bladder spasms and simultaneously caring for my infant daughter. My body was addressing every attack with great fortitude and after a month of long nights as a new single mommy, I woke up and apathetically took a look at myself in the mirror. I was in the midst of a full blown allergic response to my catheter! Hives covered my body, my eyes were nearly swollen shut, and I could hardly even see. Begging my urologist to appreciate my immune reaction when his primary concern was my failing bladder was a challenge, and my obstetrician had already abandoned ship feeling too incompetent to even write a prescription for antibiotics when my culture came back with greater than 100,000 colonies of bacteria! Out with the catheter and my body found healing, although my urologist and obstetrician still shudder with anticipation of my total collapse. They haven’t sufficient appreciation for how giving proper attention to step one can bring a body back to optimal health. Reduce your toxic load, avoid your inflammatory agents, sleep well, get sun on your face, put your feet in the soil, and laugh often. Kissing on Ruby is quite beneficial as well.

Antibody Mediated verses Cell Mediated Hypersensitivity

The first three hypersensitivity reactions are in response to antibodies. The initial exposure created a target for a secondary response whether from environmental exposures or a specific cell or tissue under attack. The first and last I will talk about here, as these are more common to our clients and help them understand their sensitivities when working through addressing the underlying cause of their autoimmune disease.

IgE-Mediated Hypersensitivity Reactions

Most of you are well familiar with IgE-mediated reactions. These are our allergic responses to bees, peanuts, fish, pollen – environmental antigens. This association to allergy is so prominent that most healthcare providers use the term allergy to indicate only IgE-mediated reactions, but IgE can contribute to a few autoimmune all alloimmune diseases, and many common allergies, such as poison ivy, are not IgE-mediated (Rote & McCance, 2015).

IgE responses are typically quick after initial exposure and short-lived. Histamine mediates this response and is the cause of our signs and symptoms, such as edema, shortness of breath, and gut reactions.

Cell-Mediated Hypersensitivity Reactions

This fourth reaction is mediated by T lymphocytes and do not involve antibodies. These T cells may attack directly or they may call up friends, most often macrophages, to assist in their attack. You may know these friends as “T helper cells.” It is this same response that causes rejection of grafts and allergic reactions resulting from contact with poison ivy and metals. Some autoimmune diseases are the result of cell-mediated response, such as rheumatoid arthritis and Hashimoto disease and diabetes mellitus.

Antigen Targets

Allergies are a hypersensitivity against an environmental antigen – foreign invader. Most all are type one responses, through IgE mechanisms, but any of the other three mechanisms can cause allergic responses. Pollens, molds, fungi, mild, eggs, fish, cat dander, dog dander, cigarette smoke, dust mites, and almost anything else we might encounter in our environment is typical of this response. Allergens that typically elicit the fourth mechanism of response, or cell-mediated response, is plant resin such as poison ivy, metals like nickel and chromium, acetylates, and chemicals in rubber, cosmetics, detergents, and topical antibiotics. The second and third allergic hypersensitivities are super rare but may include antibiotics and soluble antigens by infectious agents such as hepatitis B (Rote & McCance, 2015).

Genetics make some more vulnerable to these responses, particularly the first variety. When one parent has an allergy, allergies develop in about 40% of their offspring, but if both parents have allergies, the incidence of offspring may be as high as 80%. These individuals are referred to as “atopic.” They produce more IgE and have more receptors to reading IgE on their mast cells. Their airways and skin is more responsive to a wide variety of both specific and nonspecific stimuli than those of non-atopic individuals. Multiple genes have been associated with the atopic state, including polymorphisms in a large variety of cytokines that regulate IgE synthesis and cellular receptors (Rote & McCance, 2015, p 271).

Clinical Symptoms

Those responding to type one reactions are mostly the result of histamine. The tissues most sensitive to histamine are found in the gut, skin, and respiratory tract. The symptoms also tend to reflect the main portal of entry for the allergen. For instance, pollens and other airborne allergens usually cause respiratory problems. Conjunctivitis, rhinitis, asthma, angioedema, urticaria, bronchospasm, dysrhythmias, hypotension, gastrointestinal cramps, and malabsorption are all symptoms of this hypersensitivity response.

When symptoms are primarily in the gut, typically food or medicines are the cause. We have seen malabsorption in our practice. Your certainly familiar with elimination diets because milk, chocolate, citrus fruits, eggs, wheat, nuts, peanut butter, and fish are often culprits. Sometimes it isn’t even the whole food, but a product of the food breakdown by your digestive enzymes.


As our practice grows in functional practice and even primary healthcare, we are seeing more and more clients with hives. Again, this is a hypersensitivity reaction and the underlying mechanism is histamine. It does not have to be allergic however, or even immunologic based. Sometimes it is related to cold temperatures, sometimes emotional stress or medications. Other times it may be a sign of underlying disease or hyperthyroidism. It may even be related to malignancies, such as lymphomas.

Atopic and Contact Dermatitis

These are type four cell-mediated responses and fairly easy to differentiate based on the area of lesions. For example, immediate hypersensitivity reactions, termed atopic dermatitis, are usually characterized by widely distributed lesions, where as contact dermatitis consists of lesions only at the site of contact, such as with jewelry or poison ivy.

Understanding Your Insensitivities

Our practice offers a number of services with regards to discerning your sensitive to foods, chemicals and dyes. Responses can come from a number of different pathways as I’ve discussed above, and sometimes there are underlying issues like a histamine intolerance which is less about the exposure and more about your body’s response to histamine itself. Our staff can assist you in understanding the complex nature of food sensitivity testing. It is a bit more complex than IgG food testing or even elimination diets which can be overly restricting and not necessary for your individual needs. Give our office a call. We’d be happy to help you and it is rather incredible how better our clients feel when they learn what their specific needs are. My own findings for example really surprised me! Apples and goat’s cheese were my highest inflammatory foods!

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