~~~ What the Heck is an Allergy? ~~~

Allergy - Allergic - bummer! Get that pollen grain away from me! An allergic reaction is a physiologic response by our body against: something we have swallowed; something we have inhaled; something which has touched our skin; or, something injected into us by a bite, a sting from an insect, or by a syringe needle (a "shot" administered by medical personnel.) There are several different kinds of allergies, e.g., immediate-type, delayed-type, Types I - IV, etc., and against many different things, e.g, food, pollen (see the above image), grass, chemicals, or metals. But, the one with which most of us are familiar is the allergic reaction that leads to immediate kinds of responses such as sneezing, swollen eyes, runny nose, hives, itching, and sometimes breathing difficulties. The condition known as asthma is really an allergic reaction against something which primarily affects the lungs; this one can therefore cause serious breathing difficulties - although others can as well to a greater or lesser extent. In some cases we may become sick to our stomach, or break out in a bright rash - there can be several different symptoms. And, in some instances the allergic reaction can be so severe that as a result we may go into shock (rapid loss of blood pressure - can lead to heart failure and brain shut-down) and possibly die unless we quickly obtain medical assistance. In fact, allergies are so common and cause so many medical and personal problems, that there is an entire governmental research institute devoted to the study of allergies. This institute is called the National Institute of Allergy and Infectious Diseases, or, NIAID. This particular institute is only one among many within the National Institutes of Health (NIH) that our tax dollars support and which help find cures for the many human diseases that afflict us.

Allergic responses are linked to our immune system - and specifically to antibodies - here we go again, talking about antibodies, proteins produced by our immune system which circulate in our bloodstream and help to remove any substance (toxin) or organism (virus, bacterium) which has invaded our body. In this particular instance, we are going to talk about the immediate kind of allergic reaction that we may experience and which involves a particular kind of antibody, named IgE (immunoglobulin E). This class of antibody is one of the five different classes of antibody made by our immune system (IgM, IgG, IgD, IgA, and IgE).

Each antibody molecule is capable of binding to a distinct three-dimensional molecular shape present on substances such as proteins or complex sugars, whether or not the substance is floating around freely, or whether the substance is an integral part of an organism. Thus, whenever a substance or complete organism invades our body, the immune system can respond to this intrusion by synthesis of antibodies. If we happen to make IgE-class antibody against certain things, we can be in trouble (mild or severe). Here is why:
All antibody molecules are shaped like the letter "Y." Each arm of the Y has a site which can bind to a given molecular shape, and the bottom part (the leg of the Y) can also serve to generate certain responses when something else binds to IT. The image shows one of the two binding sites of an antibody molecule (one of the two arms of the Y, called Fab - fragment, antigen binding - the heavy-chain in blue, light-chain in green, wrapping around one another to form the site, and a protein antigen in red being held within the site; the bottom part, the leg of the molecule, is not shown).

In the case of IgE, both the top and bottom parts of the antibody molecule can lead to problems for us. The bottom part of the Y-shaped IgE molecule (called the Fc for fragment-crystallizing) can interact with and be bound by a cell receptor (a protein in the membrane which can "grab" and "hold onto" a particular thing) specific for this part of the IgE molecule (and nothing else). The receptor is located in the membrane of cells named mast cells and basophils. Mast cells are all over the place within our skin, and basophils circulate within our bloodstream. As IgE circulates, it may come in contact with mast cells or basophils, and through interaction with the receptor can specifically adhere to the membrane of these cells with the arms of the Y sticking out towards the surrounding environment, and the leg part of the molecule embedded within the membrane - would be analogous to you, standing with your feet and ankles sunk into wet cement, and your arms raised above your head. Now, if the substance against which the IgE was originally made appears and bumps into a mast cell or basophil within the skin or within the bloodstream respectively, the binding sites at the end of the arms of the IgE molecule may bind and hold onto the substance. If there are two Y Y (IgE molecules) next to one another in the membrane, and each of their "hands" simultaneously binds the substance (generates a cross-link), this interaction "wiggles" the membrane and triggers the mast cell or basophil (as the case may be) to release all kinds of powerful substances.

One of the substances released by the mast cell and/or basophil is called histamine. This chemical can interact with other cell receptors specific for histamine, and trigger these cells to release other powerful substances as well. One of the things that happens when histamine is released is that nearby tissue changes - the places where red blood cells interact with tissue - called capillaries - increase in volume (called vascular dilation). The result of this increase in volume means that more blood can get to the site (is the reason why the spot will be warmer and redder than surrounding skin). Also, the amount of secretions increase (lymph fluid) - is why the area swells (edema). This increase in blood-flow, and lymph-flow to the site, can cause a raising of the skin which may itch, and which becomes red (blood near the surface of the stretched, raised, tissue) - is the rash (erythema). Now you know why we take anti-histamines to relieve these symptoms, and other chemicals to dry up our runny nose. The allergic reaction might be pretty mild - although the rash may itch like all get out - these substances must stimulate "itch" nerves... nahhh, just kidding - but - nerves are indeed stimulated in a certain way - helps let us know that something is going on. All in all though, a mild reaction can simply be just a bother, and not particularly threatening. On the other hand, if instead of the skin these very same reactions occur within the lungs or within the bloodstream, we can be in serious trouble.

When IgE sticking from mast cells in the lung tissue binds to an invading (inhaled) substance like pollen grains, all of those substances just mentioned are released. The resultant increase in lymph-secretion in the lungs can cause the lungs to fill with fluid. Now, I know that you know that liquids cannot be compressed - cannot be squeezed down into a smaller volume - no matter how much pressure you place upon them - is why hydraulic fluid works - so, if the lungs fill with fluid, our muscles are not strong enough to squeeze our lungs properly, and we are then unable to breathe. Too, the allergic response chemicals can lead to swelling of the tissue - decreasing the diameter of our airway pipes (bronchial tubes). Also, the slow-reacting substance of anaphylaxis (SRA) causes the breathing muscles to become constricted which squeezes the bronchial tubes (airways), making it yet more difficult to breathe. This condition would be an asthmatic condition - a scary, uncomfortable, and sometimes dangerous condition. If the reactions occur within the bloodstream via IgE bound to basophils, we can be in yet deeper trouble.

The chemicals released by the basophil will rapidly circulate all over the body - there will be blood-flow and lymph-flow increases all over the place. This rapid loss of blood into tissues via the capillary beds will result in a rapid drop in blood pressure. The brain will not receive proper oxygen flow; the heart will strain to function; the lungs will fill with fluid; the airways will become severely restricted - breathing muscles become severely constricted - these things together are called anaphylactic shock. If a person does not receive help, the person can die. It is for this reason that a person allergic to bee/wasp venom can be at significant risk. If a bee or wasp stings a person, the venom enters the bloodstream directly, and circulates within minutes all over the body. The allergic reactions also occur within minutes, and a person can be in serious difficulty in a very short time. It is for this reason that if you are about to receive an injection of any kind from your health care provider, that you are asked if you are allergic to so-and-so. Examples are: receiving anesthetics of any kind (prior to dental work or surgery); receiving injections of or swallowing antibiotics (penicillin); receiving a flu shot (egg protein - the virus is grown in chicken eggs); receiving any vaccination. Sometimes a person will not know whether or not they are allergic to something - it is for this reason that after you receive a vaccination that you are asked to wait around in the physician's office for awhile - just in case. If you are at the dentist or are about to undergo surgery, you'll have to wait, anyway.....

How do we prevent these reactions - or at least - how do we overcome an allergic reaction? The easiest way to prevent allergies is to avoid coming into contact with the substance against which you are allergic (the allergen). In some instances, avoiding exposure is difficult. As it turns out, we have natural responses of our own, some pretty neat physiologic things that happen automatically - but sometimes our automatic responses are overwhelmed and we need outside assistance. Let's say that you are experiencing an asthma attack. You will begin to have trouble breathing - this result will frighten you - the fright you feel causes the brain to send "fright-response" substances out and about, which bind to specific receptors for these things on the cells of the adrenal glands located on your kidneys. The adrenal gland cells in turn release the substance adrenalin (epinephrine) which has several powerful effects. One important effect is to stimulate an enzyme to breakdown glycogen - a glucose-sugar storage polymer in liver and muscles - into individual glucose molecules. These glucose molecules are rapidly "burned" by cells and the energy released speeds-up all kinds of metabolic activity - including the destruction of already-released histamine and the other allergic-response substances - this response is known as the fight and flight response - your muscles may even quiver with all of the energy available - your strength will increase - sometimes astonishingly - allows you to run like heck to get away from danger. The heart will beat faster, and stronger too. Also, adrenalin begins almost immediately to reverse the effects of histamine, by causing basophils and mast cells to stop releasing this chemical. Consequently, the stopping of histamine release and the increased metabolic activity which destroys histamine quicker than normal, both result in the lowering of the amount of histamine throughout the body. This lowering of the amounts of allergic-response chemicals, results in decreased tissue swelling, decreased fluid accumulation, etc - and blood-pressure rises, breathing returns to normal, and rashes and the like gradually go away. Now, sometimes there just isn't enough adrenalin produced in time to reverse the reactions quickly enough - in this instance one may need outside assistance by receiving an injection of adrenalin along with other substances in liquid, tablet, or injection form which cause swelling to go down, lung-associated muscle constriction to ease, airways to open, and fluid accumulation to stop. People who are severely allergic to bee/wasp venom usually carry around a little syringe filled with adrenalin when they are in the woods, camping, or somewhere far from a medical facility or phone.

Why do we even make IgE in the first place if all we seem to get is trouble? Well, actually, we aren't sure - but- there is pretty strong evidence that IgE is really good at protecting us from parasitic infections. Those darn scallywag mast cells and basophils, if connected to a parasite via the IgE bridges (become the "hands" of the basophil and mast cells) release a bunch of things - and 'though these things if released around and about within our body cause us trouble, these same things are deadly to a parasite. So apparently like everything else in life, under some circumstances actions are helpful, and under different circumstances these very same actions can get us into trouble. Apparently, the trick is to be able to recognize the circumstance!

Book: Don't Touch That Doorknob!

Copyright John C. Brown, 1995
[ Top of Page | What the Heck?? | "Bugs" | My HomePage | KU Microbiology ]