The four main types of Hypersensitivity are labeled I, II, III and IV, but also have Descriptive names.
Type I, or IgE-mediated, Allergic Hypersensitivity
Type I hypersensitivity, or “immediate onset” allergy, develops in stages on repeated exposure to a specific allergen such as dust-mite feces, animal dander, foods, pollens, drugs and insect parts. The first encounter sensitizes the body and stimulates B-cells to produce IgE antibodies specific to the invading allergen.
The IgE then binds to the surfaces of mast cells in mucous membranes and to basophils in blood. The mast cells and basophils may remain sensitized with IgE on their surfaces for many months, or even years. If the same allergen again enters the body, it is hooked onto the waiting IgE antibodies, making the mast cells and basophils “degranulate” —the medical term for the explosive discharge of mediators from their granules.
The mediators, each with a different action, produce the allergic symptoms — the itching, puffiness, flushing, congestion, hives and other discomforts.
Once someone is sensitized, a type I or IgE-mediated allergy — as the name “immediate-onset” implies — usually surfaces within minutes or seconds of exposure to the allergen. The first symptoms to appear vary according to the type of allergen and the site of entry.
One of the mediators, histamine, is a key player in the early stages. In fact, histamine alone can cause much of the initial allergic impact. Many of the characteristic signs and symp¬toms of allergy can be mimicked by giving histamine infusions to animals, and can be blocked by antihistamines. Itchiness occurs when histamine stimulates nerve endings. Histamine and other substances relax smooth muscle around blood vessels.
At the same time, both histamine and leukotrienes make the lining of blood vessels contract, enlarging the gaps between cells, so that fluid leaks out into surrounding tissues, causing swelling and inflammation. Mediators can also make airway muscles contract, leading to wheezing and difficulty breathing, or they can act on the digestive tract, causing nausea and diarrhea.
In the case of rhinoconjunctivitis (nasal and eye inflamma¬tion), airborne allergens such as ragweed pollen interact with IgE antibodies on mast cells in the linings of the nose and eyes, causing fluid leakage and increased mucus secretion. Likewise, the touch of an allergen may activate mast cells in the skin, causing blood-vessel expansion and leakiness, with consequent swelling and hives.
Allergens that are absorbed into the bloodstream can travel to sites far from the point of entry, causing more severe allergic symptoms all over the body; this is most common with drug, insect-venom and food allergies. For example, when a food allergen enters the body it activates mast cells all along the digestive tract, from mouth to intestines, leading to swelling and tingling of the lips, mouth and throat. Sudden smooth-muscle contraction of the intestines can cause nausea, vomiting and diarrhea.
The allergen may also trigger blood-vessel dilation throughout the body, with a dramatic drop in blood pressure, and allergic shock. Activation of mast cells in the airways may produce constriction and asphyxiation (choking). So many changes all at once, in so many systems, can lead to anaphylaxis, a severe, systemic (multisystem) reaction that’s potentially fatal. Such cases need immediate epinephrine (adrenalin) injection.
Type II and In Antibody-mediated, Non-IgE Hypersensitivity While type I allergy is triggered by IgE antibodies, type II and type III allergies involve other immune-system components. In a healthy immune response, foreign antigens are cleared by one of several mechanisms.
A little damage to bystander cells is inevitable. But type II and III allergic reactions may, for unknown reasons, actually work against the body. Otherwise healthy tissues can become targets of destruction by an antibody attack. Part of the body’s organs or tissues may be altered, perhaps leading to autoimmune diseases such as rheumatoid arthritis, lupus erythematosus and some thyroid diseases. Diabetes mellitus results when the antibody attack destroys the insulin-producing cells of the pancreas. Similarly misplaced attacks may play a role in multiple sclerosis.
Type II, or antibody-mediated Cytotoxic Hypersensitivity
Often directed against foreign antigens lodged in or on the body’s cells. For example, small molecules such as antibiotics can become absorbed onto the red blood cells, triggering antibody action against the drug. The antibodies may bind to the blood cells and destroy them, resulting in hemolytic anemia. In Goodpasture’s syndrome, antibodies are directed against the kidneys and lungs, leading to kidney damage and lung disease.
Type III hypersensitivity, or immune-complex-mediated hypersensitivity
This type involves antibody-antigen complexes that are too large to be engulfed and destroyed by leukocytes, and are deposited in tissues where they stimulate destructive inflam¬mation. If these complexes enter the blood, they can lodge in narrow passages and filtration sites such as the lungs, kidney, joints, arteries and skin, causing great damage and resulting in autoimmune diseases such as rheumatoid arthritis.
The air sacs of the lungs (alveoli) can become hugely inflamed in this way, causing extrinsic allergic alveolitis, a type III hypersensi¬tivity sometimes experienced by farmers, vets or animal fanciers.
Type IV, Delayed Hypersensitivity (DTH)
The first signs of type IV hypersensitivity usually appear 24 to 72 hours after exposure to an allergen, as opposed to the seconds or minutes taken for a type I allergy to appear. Type IV reactions often result from exposure to antigens such as nickel, cosmetic ingredients, poison ivy, latex additives and formaldehyde. The characteristic itching, rash, redness and swelling surface two to three days after contact. These reac-tions involve special immune-system T-cells found in the skin and lungs.
Once the triggering antigen is removed, the reaction slowly fades and the skin eruptions vanish. However, type IV aller-gies can be most uncomfortable and unsightly, and if the sites become infected they can lead to serious complications.
If the eruptions are chronic or lingering, they can cause scarring and granulomas (internal scar tissue and bumps) near or at the affected site. Therapy for delayed hypersensitivity is avoidance of triggers and relief of the inflammation, usually with corticosteroids. Drugs that suppress the immune system, such as cyclosporin, are also occasionally used for severe cases.