Which hypersensitivity reactions involve antibodies

Although more research is necessary, some experts suggest that this reaction may actually be a subset of type 2 rather than a type on its own.

In type 3 hypersensitivity , antigens and antibodies form complexes in the skin, blood vessels, joints, and kidney tissues. These complexes cause a series of reactions that lead to tissue damage. Type 3 hypersensitivity reactions can lead to :. There are many treatment options available, depending on the severity and presentation of the hypersensitivity response.

Typically, treatment involves controlling the underlying condition. This may involve immunosuppression with systemic glucocorticoids and disease-modifying drugs. Unlike the other types, type 4 hypersensitivity reactions are cell-mediated. Instead of antibodies, white blood cells called T cells control type 4 hypersensitivity reactions.

Experts can further subdivide these reactions into type 4a, type 4b, type 4c, and type 4d based on the type of T cell involved and the reaction it produces. Some common causes of type 4 hypersensitivity reactions include exposure to poison ivy , certain metals, and drugs such as antibiotics or anticonvulsants. Diagnosing contact dermatitis is often achievable using a skin biopsy and skin patch tests. A doctor is likely to use a chest X-ray when diagnosing tuberculin-type hypersensitivity.

Granulomatous-type hypersensitivity is more challenging to diagnose, and a doctor may consider using any of the following to make an assessment:. Treatment varies from case to case. With contact dermatitis, for example, a doctor may prescribe topical steroids. However, with tuberculin-type hypersensitivity, the doctor will use a normal procedure for tuberculosis.

Common treatments for tuberculin-type hypersensitivity include:. Treatment for granulomatous-type hypersensitivity can also include steroid therapy, but treatments vary depending on the condition that comes from the reaction.

For example, a doctor may prescribe methotrexate as steroid treatment if a person presents with pulmonary sarcoidosis. Although hypersensitivity reactions are allergic reactions, some people may experience a non-immune anaphylactic reaction to certain drugs or foods. Some people may call this a nonallergic drug hypersensitivity reaction or refer to it as a pseudoallergic, idiosyncratic, or anaphylactoid reaction.

These reactions are often hard to distinguish from allergic reactions, but they noticeably cause symptoms directly, without the release of antibodies or T cells.

Contact dermatitis e. Eosinophil recruitment and activation release cytokines and pro-inflammatory chemicals. Chronic asthma and chronic allergic rhinitis. Cell- associated antigen. Austrian pediatrician Clemans von Pirquet — first described allergy mechanisms, including type III serum sickness. The device Pirquet used was similar to the tine test device with four needles seen in Figure 1 5. The tips of all the needles in the array are coated with tuberculin, a protein extract of TB bacteria, effectively introducing the tuberculin into the skin.

One to 3 days later, the area can be examined for a delayed hypersensitivity reaction, signs of which include swelling and redness. As you can imagine, scarification was not a pleasant experience, [9] and the numerous skin punctures put the patient at risk of developing bacterial infection of the skin. A positive test, which is indicated by a delayed localized swelling at the injection site, does not necessarily mean that the patient is currently infected with active TB. Because type IV delayed-type hypersensitivity is mediated by reactivation of memory T cells, such cells may have been created recently due to an active current infection or years prior if a patient had TB and had spontaneously cleared it, or if it had gone into latency.

However, the test can be used to confirm infection in cases in which symptoms in the patient or findings on a radiograph suggest its presence. Skip to content Learning Objectives Identify and compare the distinguishing characteristics, mechanisms, and major examples of type I, II, III, and IV hypersensitivities In Adaptive Specific Host Defenses , we discussed the mechanisms by which adaptive immune defenses, both humoral and cellular, protect us from infectious diseases.

Type I hypersensitivity reactions involve immunoglobulin E IgE antibody against soluble antigen, triggering mast cell degranulation. Type II hypersensitivity reactions involve IgG and IgM antibodies directed against cellular antigens, leading to cell damage mediated by other immune system effectors.

Accumulation of immune complexes in tissue leads to tissue damage mediated by other immune system effectors. Type IV hypersensitivity reactions are T-cell—mediated reactions that can involve tissue damage mediated by activated macrophages and cytotoxic T cells. Type I Hypersensitivities When a presensitized individual is exposed to an allergen , it can lead to a rapid immune response that occurs almost immediately.

Figure Selected Preformed Components of Mast Cell Granules Granule Component Activity Heparin Stimulates the generation of bradykinin, which causes increased vascular permeability, vasodilation, bronchiole constriction, and increased mucus secretion Histamine Causes smooth-muscle contraction, increases vascular permeability, increases mucus and tear formation Serotonin Increases vascular permeability, causes vasodilation and smooth-muscle contraction Table B cells also process and present the same allergen epitope to T H 2 cells, which release cytokines IL-4 and IL to stimulate proliferation and differentiation into IgE-secreting plasma cells.

The IgE molecules bind to mast cells with their Fc region, sensitizing the mast cells for activation with subsequent exposure to the allergen. With each subsequent exposure, the allergen cross-links IgE molecules on the mast cells, activating the mast cells and causing the release of preformed chemical mediators from granules degranulation , as well as newly formed chemical mediators that collectively cause the signs and symptoms of type I hypersensitivity reactions.

Type I Hypersensitivities Common Name Cause Signs and Symptoms Allergy-induced asthma Inhalation of allergens Constriction of bronchi, labored breathing, coughing, chills, body aches Anaphylaxis Systemic reaction to allergens Hives, itching, swelling of tongue and throat, nausea, vomiting, low blood pressure, shock Hay fever Inhalation of mold or pollen Runny nose, watery eyes, sneezing Hives urticaria Food or drug allergens, insect stings Raised, bumpy skin rash with itching; bumps may converge into large raised areas Table Describe the differences between immediate and late-phase type I hypersensitivity reactions.

List the signs and symptoms of anaphylaxis. Micro Connections The Hygiene Hypothesis In most modern societies, good hygiene is associated with regular bathing, and good health with cleanliness. Type II Cytotoxic Hypersensitivities Immune reactions categorized as type II hypersensitivities , or cytotoxic hypersensitivities, are mediated by IgG and IgM antibodies binding to cell-surface antigens or matrix-associated antigens on basement membranes. Figure 1 5.

Complement-mediated hemolysis of fetal erythrocytes results in a lack of sufficient cells for proper oxygenation of the fetus. What happens to cells that possess incompatible antigens in a type II hypersensitivity reaction? Describe hemolytic disease of the newborn and explain how it can be prevented.

Subcategory Antigen Effector Mechanism Examples 1 Soluble antigen Activated macrophages damage tissue and promote inflammatory response Contact dermatitis e. Describe the three subtypes of type IV hypersensitivity. Explain how T cells contribute to tissue damage in type IV hypersensitivity. The tine test is considered less reliable than the Mantoux test. Strayer et al eds.

Fitzsimmons et al. Okada et al. Vamvakas, M. Previous: Chapter Diseases of the Immune System. Next: Share This Book Share on Twitter. Signs and Symptoms. Inhalation of allergens. Systemic reaction to allergens. Hay fever. Runny nose, watery eyes, sneezing. Hives urticaria. References Mandallaz et al.. Bird-egg syndrome. Cross-reactivity between bird antigens and egg-yolk livetins in IgE-mediated hypersensitivity.

International Archives of Allergy and Applied Immunology. Relationship of Dust Mites and Crustaceans. Updated: July 13, Accessed: April 17, Urticaria and angioedema. Allergy Asthma Clin Immunol. Anaphylaxis and Anaphylactoid Reactions: Diagnosis and Management.

American Journal of Therapeutics. Am Fam Physician. J Allergy Clin Immunol. Mechanisms of allergen-specific immunotherapy. Figure 4. Blood from a type A donor is administered to a patient with type B blood. The anti-A isohemagglutinin IgM antibodies in the recipient bind to and agglutinate the incoming donor type A red blood cells. The bound anti-A antibodies activate the classical complement cascade, resulting in destruction of the donor red blood cells. Many different types of erythrocyte antigens have been discovered since the description of the ABO red cell antigens.

The second most frequently described RBC antigens are Rh factors , named after the rhesus macaque Macaca mulatta factors identified by Karl Landsteiner and Alexander Weiner in The Rh system of RBC antigens is the most complex and immunogenic blood group system, with more than 50 specificities identified to date. In contrast to the carbohydrate molecules that distinguish the ABO blood groups and are the targets of IgM isohemagglutinins in HTRs, the Rh factor antigens are proteins.

As discussed in B Lymphocytes and Humoral Immunity , protein antigens activate B cells and antibody production through a T-cell—dependent mechanism, and the T H 2 cells stimulate class switching from IgM to other antibody classes. Although this primary antibody response can cause an HTR in the transfusion patient, the hemolytic reaction would be delayed up to 2 weeks during the extended lag period of a primary antibody response B Lymphocytes and Humoral Immunity.

Furthermore, the rapid secondary antibody response would provide even more anti-Rh factor antibodies for the HTR. Rh factor incompatibility between mother and fetus can also cause a type II hypersensitivity hemolytic reaction, referred to as hemolytic disease of the newborn HDN.

This exposure will usually occur during the last trimester of pregnancy and during the delivery process. These antibodies can cross the placenta from mother to fetus and cause HDN, a potentially lethal condition for the baby. Prior to the development of techniques for diagnosis and prevention, Rh factor incompatibility was the most common cause of HDN, resulting in thousands of infant deaths each year worldwide.

Additional doses may be administered after events that may result in transplacental hemorrhage e. However, the mother will need to be retreated with Rho D immune globulin during that pregnancy to prevent a primary anti-Rh antibody response that could threaten subsequent pregnancies.

Complement-mediated hemolysis of fetal erythrocytes results in a lack of sufficient cells for proper oxygenation of the fetus. The results reveal that Kerry has proteinuria abnormal protein levels in the urine , hemoglobinuria excess hemoglobin in the urine , and a low hematocrit RBC count. These tests suggest that Kerry is suffering from a mild bout of hemolytic anemia. The physician suspects that the problem might be autoimmune, so she refers Kerry to a rheumatologist for additional testing and diagnosis.

Type III hypersensitivities are immune-complex reactions that were first characterized by Nicolas Maurice Arthus — in To produce antibodies for experimental procedures, Arthus immunized rabbits by injecting them with serum from horses. However, while immunizing rabbits repeatedly with horse serum, Arthus noticed a previously unreported and unexpected localized subcutaneous hemorrhage with edema at the site of injection.

This reaction developed within 3 to10 hours after injection. This localized reaction to non-self serum proteins was called an Arthus reaction. An Arthus reaction occurs when soluble antigens bind with IgG in a ratio that results in the accumulation of antigen-antibody aggregates called immune complexes.

A unique characteristic of type III hypersensitivity is antibody excess primarily IgG , coupled with a relatively low concentration of antigen, resulting in the formation of small immune complexes that deposit on the surface of the epithelial cells lining the inner lumen of small blood vessels or on the surfaces of tissues. This immune complex accumulation leads to a cascade of inflammatory events that include the following:.

Activation of coagulation pathways also occurs, resulting in thrombi blood clots that occlude blood vessels and cause ischemia that can lead to vascular necrosis and localized hemorrhage. Systemic type III hypersensitivity serum sickness occurs when immune complexes deposit in various body sites, resulting in a more generalized systemic inflammatory response.

These immune complexes involve non-self proteins such as antibodies produced in animals for artificial passive immunity see Vaccines , certain drugs, or microbial antigens that are continuously released over time during chronic infections e. The mechanisms of serum sickness are similar to those described in localized type III hypersensitivity but involve widespread activation of mast cells, complement, neutrophils, and macrophages, which causes tissue destruction in areas such as the kidneys, joints, and blood vessels.

As a result of tissue destruction, symptoms of serum sickness include chills, fever, rash, vasculitis, and arthritis. Development of glomerulonephritis or hepatitis is also possible. Autoimmune diseases such as systemic lupus erythematosus SLE and rheumatoid arthritis can also involve damaging type III hypersensitivity reactions when auto-antibodies form immune complexes with self antigens. These conditions are discussed in Autoimmune Disorders. Figure 6. Type III hypersensitivities and the systems they affect.

Antibacterial sera are much less commonly used now than in the past, having been replaced by toxoid vaccines. However, a diphtheria antitoxin produced in horses is one example of such a treatment that is still used in some parts of the world.

Although it is not licensed by the FDA for use in the United States, diphtheria antitoxin can be used to treat cases of diphtheria, which are caused by the bacterium Corynebacterium diphtheriae. Serum sickness can occur when the patient develops an immune response to non-self horse proteins. Immune complexes are formed between the horse proteins and circulating antibodies when the two exist in certain proportions. These immune complexes can deposit in organs, causing damage such as arthritis, nephritis, rash, and fever.

Serum sickness is usually transient with no permanent damage unless the patient is chronically exposed to the antigen, which can then result in irreversible damage to body sites such as joints and kidneys. Kerry does not make it to the rheumatologist.

She is quickly rushed to the emergency department, where her primary care physician relates her medical history and recent test results. The emergency department physician calls in the rheumatologist on staff at the hospital for consultation. Based on the symptoms and test results, the rheumatologist suspects that Kerry has lupus and orders a pair of blood tests: an antinuclear antibody test ANA to look for antibodies that bind to DNA and another test that looks for antibodies that bind to a self-antigen called the Smith antigen Sm.

Type IV hypersensitivities are not mediated by antibodies like the other three types of hypersensitivities. Rather, type IV hypersensitivities are regulated by T cells and involve the action of effector cells.

These types of hypersensitivities can be organized into three subcategories based on T-cell subtype, type of antigen, and the resulting effector mechanism. The sensitization step involves the introduction of antigen into the skin and phagocytosis by local antigen presenting cells APCs. Upon subsequent exposure to the antigen, these sensitized memory T H 1 cells release cytokines that activate macrophages, and activated macrophages are responsible for much of the tissue damage.

Examples of this T H 1-mediated hypersensitivity are observed in tuberculin the Mantoux skin test and contact dermatitis , such as occurs in latex allergy reactions. In the second type IV subcategory, CD4 T H 2-mediated reactions result in chronic asthma or chronic allergic rhinitis. In these cases, the soluble antigen is first inhaled, resulting in eosinophil recruitment and activation with the release of cytokines and inflammatory mediators. In the third type IV subcategory, CD8 cytotoxic T lymphocyte CTL -mediated reactions are associated with tissue transplant rejection and contact dermatitis.

Figure 7. Exposure to hapten antigens in poison ivy can cause contact dermatitis, a type IV hypersensitivity. However, sensitization stimulates helper T cells, leading to production of memory helper T cells that can become reactivated on future exposures. This lesion, which will persist until the allergen is removed, can inflict significant tissue damage if it continues long enough.

Austrian pediatrician Clemans von Pirquet — first described allergy mechanisms, including type III serum sickness. The device Pirquet used was similar to the tine test device with four needles seen in Figure 8. The tips of all the needles in the array are coated with tuberculin, a protein extract of TB bacteria, effectively introducing the tuberculin into the skin. One to 3 days later, the area can be examined for a delayed hypersensitivity reaction, signs of which include swelling and redness.

Figure 8. The tine test is considered less reliable than the Mantoux test. As you can imagine, scarification was not a pleasant experience, [10] and the numerous skin punctures put the patient at risk of developing bacterial infection of the skin.

A positive test, which is indicated by a delayed localized swelling at the injection site, does not necessarily mean that the patient is currently infected with active TB. Because type IV delayed-type hypersensitivity is mediated by reactivation of memory T cells, such cells may have been created recently due to an active current infection or years prior if a patient had TB and had spontaneously cleared it, or if it had gone into latency.

However, the test can be used to confirm infection in cases in which symptoms in the patient or findings on a radiograph suggest its presence.