allergy Every spring and summer, many people suffer from hay fever, a very common form of allergy. The symptoms include itchy eyes, sneezing, and congested nostrils. Most of these symptoms can be controlled by antihistamine or steroid nasal spray. Unfortunately, in some forms of allergy, violent reactions may take place leading to serious or even fatal consequences —
anaphylactic shock — as seen in allergies to seafood, nuts, or certain drugs such as penicillin.
In the realm of immunology, substances that cause immune responses or allergic reactions are known as antigens. Specific antigens that provoke an allergic reaction are called allergens. Typical allergens include pollens, house-dust mites, animal dander, bacteria, foods, drugs, and chemicals. At present, we do not know why, in similar amounts and circumstances, these substances are harmless to most people but can cause health hazards in others. Avoidance of known allergens is the best protection against such reactions.
In the
immune system several mechanisms have been evolved to protect the body against antigens. Prominent among these are the lymphocytes, white blood cells that are specialized to react to specific antigens. There are two kinds of lymphocytes — B cells and T cells. B cells produce antibodies, which are proteins that bind to and destroy or neutralize antigens. T cells do not produce antibodies; instead, they produce
cytokines — soluble molecules mediating interaction between cells. T cells also bind directly to an antigen and initiate an attack on it by ‘presenting’ parts of it to B cells, to stimulate antibody production.
Allergic reactions
Depending on whether the antigen triggers a response by B cells or T cells, allergic (
hypersensitivity) reactions can have immediate or delayed effects. They are classified as Type I, II, III, and IV. Type I, II, and III allergic reactions are the products of B cell stimulation, and, as a result of antibody–antigen responses, these reactions take immediate effect. Different types of reaction may occur together — for example, in asthma, bronchial reactions to allergens show both an immediate and a late-phase response.
Type I reactions;
which include hay fever and insect venom allergy, involve the class of antibodies known as
immunoglobulin E (IgE). IgE molecules are bound to
mast cells, which are found in connective tissue. When enough antigen has bound with the IgE antibodies, the mast cells release granules of histamine and heparin and produce other substances that cause inflammation. These potent chemicals dilate blood vessels and constrict bronchial air passages. Histamine is responsible for the visible symptoms of an allergic attack, such as running nose, wheezing, and tissue swelling. Antihistamines or steroid nasal spray are often used to give temporary relief. An alternative treatment is desensitization, in which increasing amounts of the antigen are injected over a period of time until the sufferer no longer experiences an allergic response.
In severe allergic reactions, ‘complement’ fragments (
anaphylatoxins) — proteins circulating in the blood — stimulate a more massive release of substances from mast cells which dilate blood vessels and constrict bronchioles. This sequence of events results in the collapse of the circulatory system, together with respiratory symptoms, leading to a potentially fatal reaction — anaphylactic shock.
Drug allergy is a hypersensitivity reaction to therapeutic agents. It occurs occasionally on second exposure to a drug against which an individual has already produced antibodies. It remains to be established why some drugs rarely cause allergic reactions (e.g. tetracyclines, digitalis), while others frequently provoke them (e.g. penicillin, phenytoin).
The mechanisms of immune activation in drug allergy are similar to antibody responses to foreign molecules, especially proteins, that enter the body. Although drug molecules are too small to be antigenic by themselves, they can conjugate to body proteins and elicit an immune response. Symptoms vary with the drug and the sensitivity of the affected person, but include, as separate reactions, hives (urticaria), serum sickness, and, sometimes, anaphylaxis. Several drugs can successfully counteract these allergic symptoms (antihistamines, cromolyn, and corticosteroids) — but at present, the best way to combat drug allergy is to identify the offending drug and to observe a lifelong avoidance of that particular compound and its derivatives.
Type II reactions
involve different immunoglobulins, known as IgG or IgM, which are antibodies against antigens on the surface of certain ‘target’ cells or in their immediate environment. These antigens may be natural components of healthy cells, or they may be extrinsic components induced by drugs or infectious microbes. The resulting antigen–antibody complex activates the complement system: a series of potent enzymes that destroy the target cell. An example of Type II reactions is
autoimmune haemolytic anaemia. In patients with this condition, antibodies destroy their own red blood cells, leading to anaemia.
Type III reactions
result when the antigen– antibody complexes (
immune complexes) become deposited on the walls of the small blood vessels. Normally,
phagocytes remove immune complexes effectively. However, if this mechanism is overloaded, the immune complexes persist and are eventually deposited in a range of tissues and organs. These complexes then trigger the complement system, resulting in damage to blood vessels and inflammation; an example is
glomerulonephritis, when the ‘filtering’ components of the kidneys are affected.
Type IV
allergic reactions are the only ones that involve delayed hypersensitivity. These reactions are caused by the actions of T cells. Here the antigens are trapped inside
macrophages and cannot be cleared. T cells are then activated to produce cytokines, which mediate a range of inflammatory responses. In contrast to the rapid responses mediated by B-cell antibodies, T cells take longer to accumulate at the site where the antigen is present. Thus the allergic responses are delayed and appear 12 to 24 hours or more after exposure to an appropriate antigen. Contact dermatitis is one example, in which the skin responds to allergens such as nickel and rubber accelerators. These substances penetrate the skin and become linked to a carrier protein, capable of producing allergic reactions.
Hypersensitivity involving T-cell-mediated immunity occurs also in some chronic diseases due to infectious agents such as the mycobacteria that cause leprosy and tuberculosis, and parasitic worms such as schistosomiasis.
Organ
transplantation (of kidney, heart, or lungs, respectively) is increasingly used to save patients with renal failure, cardiac failure, or cystic fibrosis. Unfortunately, T cells of the recipients can recognize and respond to foreign antigens of the grafts, leading to their eventual destruction. Immunosuppressive drugs such as steroids and cyclosporin are successful in preventing rejection. However, these drugs do not work specifically against the particular unwanted functions of macrophages or T-cells, and may reduce the patients' resistance to infections.
Tai-Ping Fan
See also
autoimmune disease;
phagocytes;
thymus.
