Allergies And Your Immune System - What Is An Allergic Reaction: Allergies

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Allergies and your immune system

When it comes to allergy, your immune system acts like the Incredible Hulk, senselessly following good intentions gone wrong. In allergic individuals, genetics and environment have conspired to make cells that are essential for normal immune function become overactive and respond to otherwise innocuous substances.

Key to this process are two important immune system cells: helper T cells 1 (Th1) and 2 (Th2). These white blood cells circulate in the bloodstream and alert other immune system players that the body may be under attack from invading germs. Th1 cells handle certain types of bacterial infection, while Th2 cells help in eliminating certain parasites.

In allergic diseases, this process goes awry in at least two ways. First, Th2 cells dominate (a process called immune deviation), meaning they are more likely to respond than Th1 cells. Second, the body mounts these Th2 responses to substances that are not actually harmful, such as pollen and dust mites. During the response, Th2 cells produce substances and recruit cells and molecules — mast cells and eosinophils — that lead to an allergic reaction. The proteins produced by the Th2 cell, called cytokines, orchestrate the allergic response. One of the consequences of Th2 cell activation is that another type of white blood cell, the B cell, essential to normal immune function, is stimulated to produce an antibody called immunoglobulin E (IgE).

The role of antibodies

Antibodies account for the astounding versatility of the immune system. Each antibody is programmed to recognize a particular foreign molecule or antigen. Since the immune system produces millions of antibodies, it is prepared to recognize any antigen that enters the body. Without the surveillance capability of antibodies, the human body would be devastated by disease-causing microorganisms (pathogens). Antibodies are made of a type of protein called immunoglobulin.

Although the antibody family consists of five different types of antibodies — IgA, IgD, IgE, IgG, and IgM — the majority of allergic reactions are caused by IgE. For instance, the IgE antibody that recognizes ragweed causes symptoms of hay fever in early fall. Indeed, some purists in the field say that only an IgE-mediated response should be considered to be an allergic response. However, since other allergic responses are IgG-mediated (such as serum sickness) or T cell–mediated (for instance, poison ivy), this report takes the broader position that an allergy involves an immune response — be it IgE-mediated or not.

Normally, antibodies are produced when B cells recognize an antigen on the surface of specific harmful invading pathogens, such as the bacteria that cause pneumonia. This recognition causes B cells to mature into antibody-producing plasma cells. Like a battalion of medieval archers, these plasma cells let fly their antibodies, which travel to their targets on the outer surface of harmful bacteria. After finding their mark, IgG antibodies neutralize the bacterial toxins or make the bacteria ingestible by other cells of the immune system, neutrophils and macrophages that eat and destroy the bacteria. In a similar way, IgE antibodies set in motion the events that kill and eliminate parasites.

Antibodies behaving badly

On the whole, antibodies do a stunning job at keeping bacteria and viruses at bay. However, the downside of their efficiency is what happens in an allergic response, when certain antibodies, in particular IgE, are produced inappropriately. IgE antibodies like to link up with their receptors on mast cells, specialized cells found in great numbers at points of entry into the body such as the linings of the airways, the eyes, the gut, and the dermis (one of the layers of the skin). The trouble starts when an innocuous, often inhaled, allergen meets up with the IgE on a mast cell.

From this moment, the mast cell prompts an allergic reaction by releasing histamine and other chemicals such as leukotrienes and prostaglandins, which within minutes trigger sneezing, runny nose, itchy eyes and skin, and wheezing. One of the reasons the response is so fast is that histamine is “good to go” even before the mast cell that houses it is activated. This means that upon activation, the mast cell quickly releases histamine into the surrounding tissue like the contents of an exploding suitcase. This release is followed by leukotrienes and prostaglandins that are rapidly generated by the activated mast cell.

Allergy: A 2-step process

Even worse, when an acute allergic reaction spirals out of control, it can set in motion a life-threatening bodywide reaction called anaphylaxis or allergic shock, which requires immediate action.

But that’s not the only danger. Mast cells produce other chemicals, such as proteases, that cause tissue damage. And activated mast cells produce their own cytokines that stimulate B cells to produce more IgE, which leads to more IgE on the mast cells and more opportunity to release the inflammatory chemicals. At the same time, other cytokines recruit eosinophils to the site of the allergic response, setting up local inflammation.

What is inflammation? Doctors first described inflammation as painful, hot, red swelling of tissues in the body such as that seen around a boil or an insect bite. These early physicians used the Latin words rubor (red), calor (heat), dolor (pain), and tumor (swelling) to describe inflammation. We now know that inflammation that lasts for hours or days represents white blood cells trying to fight off an invading pathogen or deal with a foreign body such as a splinter. Over time, the process leads to lasting damage with formation of scar tissue as the body attempts to heal itself. When today’s physicians see the characteristic cellular changes of inflammation under a microscope, they call it “inflammation” without needing to see the classic signs (redness, heat, pain, swelling) originally described by the early physicians.

The cascade effect

Meanwhile, the allergen continues to stimulate the Th2 cells, stirring up more production of IgE and inflammation and fueling the allergic reaction even further. In other words, a cascade effect is now in motion that, unless stopped, may lead to what are called late-phase reactions, typically peaking six to nine hours after exposure to the allergen. Left unchecked and with repeated encounters with the allergen, this perpetuating cycle can lead to continual allergic reactions, which over time may cause lasting tissue damage.

Mast cells, which are so instrumental in most allergic attacks, are something of a mystery. For quite a while, their purpose was unclear. But evidence suggests that they not only fight parasites but also help the body deal with harmful bacteria. So although mast cells seem to do more harm than good by setting off annoying allergic reactions, they probably play an important role in protecting the body against unwelcome parasitic and bacterial guests.

The mast cells’ protective function explains why they are positioned so close to where any microorganism might get into the body, for example, in the membranes lining the digestive and respiratory tracts. Packed as they are with chemicals, mast cells are designed to respond fast — within minutes. Mast cells activated in the digestive tract can cause abdominal pain, diarrhea, and vomiting; in the airways, the effect can be congestion and blockage that cause wheezing, coughing, and mucus; and their effect on blood vessels is to increase blood flow, which increases fluid in the surrounding tissues — the cause of swelling and, when severe, anaphylaxis. Mast cells are aided by eosinophils, another type of immune system cell that plays an important role in inflammation.

Delayed hypersensitivity

So far, we have focused on IgE and its role in allergic reactions. We also indicated that a broader use of the word “allergy” includes other immunological hypersensitivity reactions that are not IgE-mediated. For example, a reaction called contact hypersensitivity or delayed hypersensitivity is the mechanism of contact dermatitis, a type of rash caused by certain chemicals, such as those found in poison ivy. The process begins in much the same way as in many other immunological processes, with the chemical substance being taken up by immune cells in the skin, called dendritic cells, that “present” the chemical to T cells, rather like a host introducing an arriving guest to family members. The T cell population recognizes the chemical and increases its numbers, creating a new population of cells called memory T cells. The next time you come into contact with the chemical, these “primed” memory T cells are ready to react to the chemical and generate an inflammatory response as though they were fighting off an infection. This reaction is not immediate like that generated by mast cells and IgE, but takes 48–72 hours to reach its peak; hence the term delayed hypersensitivity. If you’ve ever had poison ivy, you’ll remember that the rash didn’t appear immediately but emerged a day or two later.

Serum sickness

A third type of reaction is serum sickness. This is a reaction due to IgG antibodies rather than IgE antibodies. IgG, or immunoglobulin G, is the main type of antibody produced by the body. Some people make large and inappropriate quantities of IgG antibodies to medications they receive. When these people receive those medications a second time, the antibodies attach to the medication as though it were an invading microorganism, forming very large molecule complexes of antigen (the medication) and antibody. These molecules get stuck in the bloodstream, where they activate another part of the body’s defense system, a group of proteins called a complement. The complement system is another part of the body’s defense against microorganisms. When activated, it initiates an inflammatory response, recruiting cells that eat and kill the invading bugs. The upshot is serum sickness, marked by widespread signs of inflammation with a rash, enlarged lymph nodes, and damage to the kidneys. Serum sickness was first described in individuals who received horse serum as part of their treatment for pneumococcal pneumonia. While penicillin can cause allergic reactions because of mast cells and IgE, it can also cause serum sickness.

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Last updated:	August 21, 2006
Reviewed By:	Faculty of Harvard Medical School

Medical content reviewed by the Faculty of the Harvard Medical School. Harvard Health Publications, Copyright © 2007 by President and Fellows of Harvard College. All rights reserved. Used with permission of StayWell.

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