OpenStax Anatomy and Physiology
The word “hypersensitivity” simply means sensitive beyond normal levels of activation. Allergies and inflammatory responses to nonpathogenic environmental substances have been observed since the dawn of history. Hypersensitivity is a medical term describing symptoms that are now known to be caused by unrelated mechanisms of immunity. Still, it is useful for this discussion to use the four types of hypersensitivities as a guide to understand these mechanisms.
Immediate (Type I) Hypersensitivity
Antigens that cause allergic responses are often referred to as allergens. The specificity of the immediate hypersensitivity response is predicated on the binding of allergen-specific IgE to the mast cell surface. The process of producing allergenspecific IgE is called sensitization, and is a necessary prerequisite for the symptoms of immediate hypersensitivity to occur. Allergies and allergic asthma are mediated by mast cell degranulation that is caused by the crosslinking of the antigen-specific IgE molecules on the mast cell surface. The mediators released have various vasoactive effects already discussed, but the major symptoms of inhaled allergens are the nasal edema and runny nose caused by the increased vascular permeability and increased blood flow of nasal blood vessels. As these mediators are released with mast cell degranulation, type I hypersensitivity reactions are usually rapid and occur within just a few minutes, hence the term immediate hypersensitivity.
Most allergens are in themselves nonpathogenic and therefore innocuous. Some individuals develop mild allergies, which are usually treated with antihistamines. Others develop severe allergies that may cause anaphylactic shock, which can potentially be fatal within 20 to 30 minutes if untreated. This drop in blood pressure (shock) with accompanying contractions of bronchial smooth muscle is caused by systemic mast cell degranulation when an allergen is eaten (for example, shellfish and peanuts), injected (by a bee sting or being administered penicillin), or inhaled (asthma). Because epinephrine raises blood pressure and relaxes bronchial smooth muscle, it is routinely used to counteract the effects of anaphylaxis and can be lifesaving. Patients with known severe allergies are encouraged to keep automatic epinephrine injectors with them at all times, especially when away from easy access to hospitals.
Allergists use skin testing to identify allergens in type I hypersensitivity. In skin testing, allergen extracts are injected into the epidermis, and a positive result of a soft, pale swelling at the site surrounded by a red zone (called the wheal and flare response), caused by the release of histamine and the granule mediators, usually occurs within 30 minutes. The soft center is due to fluid leaking from the blood vessels and the redness is caused by the increased blood flow to the area that results from the dilation of local blood vessels at the site.
Type II and Type III Hypersensitivities
Type II hypersensitivity, which involves IgG-mediated lysis of cells by complement proteins, occurs during mismatched blood transfusions and blood compatibility diseases such as erythroblastosis fetalis (see section on transplantation). Type III hypersensitivity occurs with diseases such as systemic lupus erythematosus, where soluble antigens, mostly DNA and other material from the nucleus, and antibodies accumulate in the blood to the point that the antigen and antibody precipitate along blood vessel linings. These immune complexes often lodge in the kidneys, joints, and other organs where they can activate complement proteins and cause inflammation.
Delayed (Type IV) Hypersensitivity
Delayed hypersensitivity, or type IV hypersensitivity, is basically a standard cellular immune response. In delayed hypersensitivity, the first exposure to an antigen is called sensitization, such that on re-exposure, a secondary cellular response results, secreting cytokines that recruit macrophages and other phagocytes to the site. These sensitized T cells, of the Th1 class, will also activate cytotoxic T cells. The time it takes for this reaction to occur accounts for the 24- to 72-hour delay in development.
The classical test for delayed hypersensitivity is the tuberculin test for tuberculosis, where bacterial proteins from M. tuberculosis are injected into the skin. A couple of days later, a positive test is indicated by a raised red area that is hard to the touch, called an induration, which is a consequence of the cellular infiltrate, an accumulation of activated macrophages. A positive tuberculin test means that the patient has been exposed to the bacteria and exhibits a cellular immune response to it.
Another type of delayed hypersensitivity is contact sensitivity, where substances such as the metal nickel cause a red and swollen area upon contact with the skin. The individual must have been previously sensitized to the metal. A much more severe case of contact sensitivity is poison ivy, but many of the harshest symptoms of the reaction are associated with the toxicity of its oils and are not T cell mediated.
Betts, J. G., Young, K. A., Wise, J. A., Johnson, E., Poe, B., Kruse, D. H., … DeSaix, P. (n.d.). Anatomy and Physiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/anatomy-and-physiology