Our immune system provides several layers of protection for the body. Physical structures like the skin, mucous lining of the mouth, nose, stomach, intestines and colon provide protection from the outside onslaught. The next layer of protection is provided by mast cells that conduct surveillance of these structures of the body. Mast cells  are one  of the earliest components of the immune system to come in contact with threats or allergens.

When a pathogen, like a parasite, bacteria, virus, fungus and  allergen  comes in contact with the body, it is encountered by surface antibodies called the IgE^[1]. When bound to the pathogen, IgE antibody signals to the mast cell to activate its defensive mechanisms. The activated mast cells can kill the pathogen directly by swallowing it and destroying it by oxidative damage^[1]. In a different strategy, the mast cell releases histamine and signaling peptides (small proteins called proteases)^[1]. This strategy creates inflammatory response to help the mast cell in dealing with the threat.

Mediator of Mast cell activity:
IgE antibody[3]	This antibody is present in small amounts in the body. It binds to pathogens or allergens when they come in contact with the protective surfaces of the body. Repeated exposure causes the number of IgE’s to grow. Therefore, repeated exposure leads to larger response against the pathogen or allergen. Because antibodies create memory of pathogen exposure for the immune system, people are able to develop immunity against specific pathogens after receiving vaccines. Each time the body is exposed to an allergen, antibodies against it continue to grow in numbers. This behavior can  cause allergies to become worse over the course repeat exposures.
Histamine[2]	Histamine is released by the activated mast cells. It signals the local mast cells to become activated and release more histamine. In this way, histamine leads to localized inflammatory response to the pathogen or allergen. Histamine also travels in the bloodstream to other parts of the body. Thus, it can activate other mast cells that are located elsewhere in the body. Excessive activation by histamine can lead to problems like anaphylactic shock. Histamine also travels to the nervous system. In the nervous system, histamine serves as a neurotransmitter that signals the hypothalamus to release Stress Hormone Releasing Hormone (SHRH), which is also called Corticotropin Releasing hormone (CRH). This action activates the stress response mechanisms of the body. This activation can really worsen the susceptibility of individuals to stress induced inflammatory problems.
Signaling peptides[2]	When release by mast cells, these molecules travel in the bloodstream to all parts of the body. They work as “proteases” that modify circulating cytokines in the blood stream. The cytokines become activated and signal all other components of the immune system to become involved. This form of activation is essential for developing long term immunity against pathogen threats. However, it can also lead to delayed hypersensitivity reaction, which can cause a delayed anaphylactic shock.

Mast cells and Allergies:

Mast cells are involved in activating many aspects of the immune system, they line themselves along mucous membranes of nose, eyes, mouth, throat, intestine ete. For this reason, they are considered an important part of the “host defense” system that protects the body against infections. However, the same widespread activation of the immune components can make mast cells the basis of chronic inflammation that is related to allergies and stress. The body undergoes three stages of sensitization to allergens. These are as follows^[3]:

1. Sensitizing – the body is exposed to the allergen for the first time. If the person is genetically or physically susceptible to allergies, the “antigen” part of the allergen is picked up by the immune cells which produce antibodies against the allergen. In this way, the body becomes sensitized to the threat.
2. Early phase response – this phase begins when a person is exposed to the allergen a second time. The first antibodies bind to the allergen and activate the mast cells. If the volume of the allergen reaches critical mass, the mast cells burst open to release histamine and proteases. The activation of mast cells works like the activation a “mine field” which causes all surrounding mast cells to become activated. Pretty soon, the body is wrapped up in an inflammatory cascade that leads to symptoms like wheezing, sneezing, itchy eyes, runny nose, and shortness of breath. Mast cell response tends to subside within the day of the exposure.
3. Late phase response – activation of mast cells calls on other forms of immune cells, called eosinophils, to become activated. These cells have a slower action that prolongs the allergic response up to 1-3 days following the exposure to the allergen.

The repeat exposure to an allergenic substance continues the cycle. Continued inflammation can lead to tissue damage that is prolonged beyond the time of exposure. Because the mast cells are primarily located in the protective surfaces of the body like the skin, mucous lining of the mouth, nose, stomach, intestines and , colon; inflammation tends to destroy these tissues first. Such destruction of these defensive barriers makes the body more vulnerable to exposure from other allergens.

Mast cells and Stress:

Stress is emerging as a major trigger for mast cell activation. Mast cells have been shown to have express receptors for stress hormone releasing hormone (SHRH), which stimulates release of corticosteroids.^[2] These receptors indicate mutually cyclical relationship between the mast cells and the nervous system. Wherein, the histamine released by the mast cells travels in the bloodstream, up to the nervous system. Once in the nervous system, the histamine binds the hypothalamus, causing it to release a SHRH. This hormone then goes in the bloodstream to various parts of the body, including the adrenal gland to stimulate the release of the stress hormone, Cortisol. But, the SHRH also binds to the mast cells^[2], further activating these cells.

This relationship between stress and mast cells is becoming clear with the study of many inflammation related diseases. Acute stress to the skin causes the release of local SHRH, which binds to the mast cells. This leads to a local inflammatory action of the mast cells.^[4] In patients with rheumatoid arthritis (RA), mast cells found in the inflamed joint have been shown to have higher levels of SHRH receptors, indicating that these cells are more sensitive to stress.^5,6 These individuals tend to have great exacerbation of symptoms due to stress compared to other individuals.^5,6 Joint inflammation in RA leads to destruction of cartilage and other component of the joint, leading to pain and immobility of the joint.

In patient with asthma, involvement either environmental or emotional stress can trigger asthmatic episodes. Mast cells located in the lung tissues of these individual have higher numbers of SHRH receptors. This indicates increase sensitivity of mast cells to stress. In a Finnish study of over 10,000 college students between the age of 18-25 years, the occurrence of asthmatic episodes and other allergic diseases was increased in response to stressful events like disease, family conflict, or death of a close family member.^[7]

Activity of mast cells have also been indicated in  occurrence of heart disease. The mechanism is similar to other stress-related mast cell activation. Either environmental or emotional stress that activates the mast cells can cause cardiac damage. Mast cells have been shown to participate in development of plaque in blood vessels, coronary inflammation, and cardiac ischemia^[8] – which is deprivation of blood from the heart muscle. These mast cells present at the site of the coronary arterial plaque are believed to contribute to erosion or rupture of the plaque, leading to a heart attack.^[9]

Protecting against over activation of mast cells:

Environmental and emotional stress can be very difficult to control. For individuals who are susceptible to reactivity, this can be a challenging circumstance. Therefore, conventional therapy has been focused on using histamine blockers, mast cell stabilizers, and immune suppressive drugs. Often these drugs are very effective at doing their jobs, but they also tend to block the body’s natural immune activity. This puts the individual in a different kind of danger.

Natural agents derived from Ayurvedic herbs Guduchi, Pippali, Vasaka, and many more provide a great alternative to using drugs. Using these herbs in combination with cleansing diet, regular physical activity, breathing exercises ( pranayama) and removal of stressors helps has great potential for controlling allergic response, while maintaining natural responsiveness of the body’s immune system. Let’s take a look at how these herbs help:

Tinospora cordifolia (Guduchi)

Traditionally, Guduchi is also called “amrita” which means ambrosia, indicating the wide-range of health benefits that derive from this herb. In animal studies, Guduchi has been shown to curb histamine-induced edema and anaphylactic reaction.^[10] Use of this herb seems to block the release of histamine from the mast cells by stabilizing the cells. This activity makes the mast cells less likely to burst open and generate an inflammatory cascade. Additionally, use of Guduchi also lessened the impact of oxidative damage in the tissues^[10]; thus, protecting from inflammatory destruction of tissue. In a clinical study on allergic symptoms, use of Guduchi showed complete resolution sneezing in 83%, nasal discharge in 69%, nasal obstruction in 61%, and itching in 71% of people^[11]. Additionally, Guduchi has also been shown to be stress reducing, while improving learning and memorizing capacity.^[12]

Piper longum (Pippli)

Pippli, which is more commonly known as long pepper and its relative Piper nigrum (black pepper) both provide similar medicinal qualities that protect the individual. Both herbs are culinary spices that have been traditionally described as having warming and drying effect on the body. Experimental studies on animal models of Type 1 allergy have been performed to test the effect to the plants. Both herbs were shown to improve stability mast cells, preventing them from bursting and releasing histamine.^13,14 Though specific mechanisms of the stabilizing is not understood, it is clear that these herbs do not suppress the immune system in any way. Therefore, these herbs allow normal function of the immune system while effectively reducing allergic response mediated by mast cells.

Adhatoda vasica (Vasaka)

Vasaka has a long history of documented use in Ayurvedic and Unani medicine.^[15] Like Guduchi, Vasaka also has a wide range of beneficial effects on the body that nurture the health of the individual. In research studies, Vasaka has been proven to be an effect anti-allergy medicine among several animal models.^[16] In another study, Vasaka also demonstrated anti-allergy and anti-asthmatic effect on guinea pigs.^[17] A polyherbal formula containing Vasaka and Pippli was studied for effectiveness. The formula showed dose dependent benefit with the most effective dose demonstrating 66% better stabilization of the mast cells.^[18] Other mechanisms of benefit from Vasaka are its anti-inflammatory and antioxidant activities. The combination of these activities have proven effective in managing the symptoms of airway inflammation associated with Asthma in animal models.^[19] Thus, Vasaka effectively cleans up any damage created by inflammatory and oxidative processes in the body.

Ayurvedic herbs are excellent tools to help control allergic response and related inflammatory symptoms. However, overcoming allergies is a matter of fortifying the health of the individual. In Ayurvedic medicine, this practice of fortifying one’s health is called Swasthavritta. Here, “Swastha” means health, and “vritta” means circle. This “circle of health” is created by infusion of healthy activities into daily life. As compared with the western concept of strict healthy hygiene practices that involves creating a pathogen-free environment. However, sterile environments might do more harm than good. People living in sterile environment are more likely to develop immune system imbalance that leads to allergies^[20]. On the other hand, research has shown that natural, mild exposure to pathogens can help to develop immune system that is less sensitive to allergen.^[21] The Ayurvedic concepts of Swasthavritta outlines activities that supports natural assimilation of the person in their environment, while promoting optimal function of physiology.  These activities include:

• Yoga and breathing exercises
• Regular exercise
• Use of neti pot for nasal cleaning
• Gardening, other outside activities
• Right amount of sleep
• Healthy food from healthy sources
• Living in an hygienic and clean environment
• Effective stress management
• Cultivation of a Spiritual practice

Incorporating these activities into the daily routine forms the foundation of health that helps to prevent diseases in the long run.

RESEARCH AND WRITING ASSISTANCE FOR THIS ARTICLE WAS PROVIDED BY DR. ANUP MULAKALURI, ND