In my last post, I looked at the causes and consequences of chronic inflammation. One common cause of inflammation is allergy. The term allergy refers to an immune reaction in which a specific type of antibody, IgE, is created by the immune system against an inappropriate target such as pollen, house dust, cat fur, peanuts, latex…and many more. The symptoms can occur in the form of runny nose and sore eyes as seen in hay fever or rhinitis, skin reactions as seen in eczema, hives or contact dermatitis, the lungs as in asthma or in the gut as in food allergies.

 

Fast reactions

If you suffer from allergies, you’ll know that your symptoms can come on super-fast when exposed to your trigger. This is because, in allergies, the specialised IgE antibodies attach themselves to an immune cell called a mast cell that act as sentinel cells and hang out in the lungs, nose, gut, and skin on alert to react to any invader. When the antibodies on the mast cell encounter the allergen (say pollen), they immediately release histamine. Histamine causes the allergic symptoms such as itchy eyes, sneezing, runny nose etc. Histamine also recruits other immune system cells to the site and creates inflammation. These cells once recruited release enzymes, toxic proteins and more cytokines leading to more inflammation. If very large amounts of histamine are released by mast cells, a drop in blood pressure may occur and the bronchial tubes may swell and restrict breathing severely so as to be life-threatening, as happens in severe allergy such as some people have to peanuts (or in my case, penicillin).

Sensitisation to an allergen occurs as described in my immune system primer and you may not experience a noticeable reaction. However, once the antibodies are formed and have attached themselves to the mast cells, the reaction is very rapid.

 

An anti-parasite reaction gone wrong

The IgE antibodies that are typical of allergic reactions have evolved as the body’s way of attacking internal parasites like worms, so why would the body treat, for example, grass pollen like a worm? It seems that certain protein patterns (antigens) found on grass pollen (and other substances that trigger allergic reactions in susceptible people) are so similar to those found on parasites that the immune system reacts inappropriately. (This concept of similar-looking proteins triggering an immune response is called “molecular mimicry” and crops up in another situation in which the immune system goes wrong: autoimmunity.)

The link between parasites and allergies was nicely demonstrated by a group of scientists who compared 2712 proteins known to cause allergies with more than 70,000 proteins from 31 species of parasites. They were able to identify 2445 parasite proteins that are very similar to allergenic proteins. For instance, they found a protein in the worm Schistosoma mansoni that closely resembles one in birch pollen that can cause hayfever. What is not yet clear, though, is why people who have never been infected with worms would develop antibodies to birch pollen.

 

Can you be too clean?

A theory that was just coming to the fore when I did my PhD in the late 1980s was that if the immune system does not encounter sufficient parasites and other infections in early childhood, it can develop a tendency to react to harmless substances instead: the immune system being like an angry young man spoiling for a fight! This theory came about when it was discovered that children who grow up on farms and are (presumably) exposed to more dirt than those living in sanitised city accommodation have lower rates of asthma. Further, children from large families were also less likely to have allergies: it was thought that they were exposed to more infections from their siblings than singletons might be. As you might guess, it turned out to be more complicated than that. More recently it has become clear that it is exposure to friendly bacteria that colonise our skin, gut and lungs (our microbiome) that is important. Early exposure to a wide range of these friendly microbes is needed to train our immune systems to react appropriately to stimuli. Excessive hygiene such as very frequent washing, using antibacterial soap and cleaners can kill off friendly as well as unfriendly bacteria, so there is some element of truth that you can be too clean.

 

How is the immune system trained to understand the difference between friend and foe?

Without a system to differentiate between friends and foes, our immune systems would be reacting to everything we breathe in, we eat and even to the proteins in our own bodies! We could not survive such an onslaught. Thus, a sophisticated system has evolved to train our armies of immune cells to fight only real enemies. The immune system learns to differentiate between what is part of the body (“self”) from what is foreign (“non-self”) and then if it is foreign to differentiate between a harmless foreigner and a dangerous foreigner.  Immune tolerance as this mechanism is termed, starts while we are developing in the womb and continues in early childhood. There are different ways in which tolerance is created.

1.     Central: this is the system that ensures that if the antibodies to self proteins are ever created (and the system does do this occasionally in everyone) the B cells producing them are destroyed (see here for how antibodies are created). Similarly, if T cells bearing antibodies to self proteins are produced, they are deleted.

2.     Peripheral: if any B or T cells escape the central tolerance mechanism, specialised T cells (called T regulator cells, or Tregs), whose job is to calm down the immune system come into play.

3.     Oral tolerance: refers to the ability of the immune system to be tolerant towards foods. Approximately 30kg of food proteins reach the human intestine during a year, and 130–190g of these proteins are absorbed daily in the gut. The epithelium (lining) of the gastrointestinal tract is roughly the size of a tennis court. It is just a single cell thick and just underneath this layer, and with tentacles poking through it, are the immune sentinel cells called dendritic cells. Indeed, around 80% of the entire human immune system is situated within the gut, in and below the epithelium. The dendritic cells are key in creating immune tolerance to food proteins. It is they who “decide” whether to tell the immune system to react or not. Under their direction, Tregs may be increased to prevent an immune reaction, or other T cells which promote inflammation may be increased instead. The dendritic cells constantly “sample” what is passing through the gastrointestinal tract and decide whether or not it is a threat…this will include sampling foods as well as friendly and not so friendly bacteria.

4.     Similar mechanisms occur in the lungs. My PhD work showed that the sentinel cells in the lungs of people with asthma produce more cytokines and hence trigger an inflammatory reaction more easily compared with people without asthma.

 

Allergies: a failure to develop tolerance

Development of allergies may involve many factors:

• Proper maturation of the immune system in early life

• Over-enthusiastic hygiene measures or other environmental aspects which deplete our friendly bacteria: on the skin, in the lungs and in the gut.

• A genetic tendency to create IgE antibodies in response to non threats

• A healthy gut

 

Perhaps most important is the role of a healthy gut. As explained above, most of the immune system is focussed around the gut and depends on proper functioning of the sentinel cells within the context of a strong barrier (that is to say the integrity of the one-cell-thick epithelial layer). If food proteins or gut bacteria can penetrate through the gut barrier and bypass the monitoring of the sentinel cells which keep the immune system quiet, these proteins can trigger an immune response.

 

What to do

If you suffer from allergies there are many things that you can do to help your immune system to be properly balanced: this means to help it to react to things it should and not to react to things it should not.

1.       Gut health: there are strong links between gut health and eczema and other allergies as well as the more obvious one with food allergies. Looking after your gut is always the first step to improving immune function! Eat a rainbow of fresh or frozen vegetables every day! Vegetables will provide essential fibre that feeds your gut bacteria and a myriad of essential vitamins, minerals and phytonutrients. Each colour of vegetable will vary in the nutrients it provides hence the importance of eating the rainbow. Avoid junk food containing emulsifiers and artificial sweeteners which are known to damage the gut bacteria.

2.       Hygiene and toxic chemicals: while handwashing is essential to prevent spread of coronavirus and other pathogens, excess showering, use of antibacterial toothpaste and mouthwashes, additives in junk food, pesticide residues, certain preservatives in skin creams and frequent showering can adversely affect the friendly bacteria that live in your gut, in your mouth and nose and on your skin. Think about what you are putting on your skin, inhaling into your lungs and eating in your food. When gardening, be very careful if using pesticides or weed killers; when cleaning your house: what chemicals are you potentially inhaling or getting on your skin?

3.       Encouraging production of Treg cells. As mentioned above, a particular immune cell, the Treg has the job of preventing an over-enthusiastic immune system. One of the biggest causes of low numbers of Treg cells is stress. Low vitamin D is also linked with low Treg numbers and so if you can stress bust by getting outdoors and topping up your vitamin D from the sun at the same time, that would be a great move! Green tea can increase the number of Tregs

4.     Reduce histamine production. Histamine is the body chemical that is responsible for most allergy symptoms. Vitamin C is a key nutrient which helps reduce histamine levels and also encourages an appropriate immune response. Quercetin is a natural anti-histamine which is found in black grapes, raspberries, green leafy vegetables, and also in broccoli, red onions, peppers, apples, and black or green tea.

5.    Naturally, avoiding exposure to any trigger foods or other substances will also be a good idea. If you are not sure what things may make your allergy symptoms worse, it is worth keeping a detailed food and lifestyle diary where you note what you have eaten, how bad your symptoms are and any other relevant factors such as stress, pollen count etc. If you would like a template food and symptom diary, get in touch and I can send you one.

To read in more detail about practical things you can do for allergies and hayfever in particular, read my blog post from last year on pollen allergies: How to survive the pollen season.

If you’re struggling with allergy symptoms, do get in touch to find out how I can help you overcome them and rebalance your immune system.