4 Types of Hypersensitivity Reactions

Hay Fever
Hay fever is a type I hypersensitivity reaction.

Martin Leigh/Photodisc/Getty Images

Our immune system works continuously to keep us healthy and protect us against bacteria, viruses, and other germs. Sometimes, however, this system becomes too sensitive, causing hypersensitivity reactions that can be harmful or even deadly. These reactions are the result of exposure to some type of foreign antigen either on or in the body.

Hypersensitivity reactions are categorized into four major types: type I, type II, type III, and type IV. Type I, II, and III reactions are the result of antibody actions, while type IV reactions involve T cell lymphocytes and cell-mediated immune responses.

Type I Hypersensitivity Reactions

Hay Fever and Pollen
This image is depicting hay fever showing pollen grains (yellow) entering the nasal cavity (left) of a hay fever sufferer. The symptoms are caused by a massive release of the chemical histamine in the body in response to the pollen. Claus Lunau/Science Photo Library/Getty Images

Type I hypersensitivities are immune reactions to allergens. Allergens can be anything (pollen, mold, peanuts, medicine, etc.) that triggers an allergic reaction in some individuals. These same allergens do not normally cause problems in most individuals.

Type I reactions involve two types of white blood cells (mast cells and basophils), as well as immunoglobulin E (IgE) antibodies. Upon the initial exposure to an allergen, the immune system produces IgE antibodies which bind to the cell membranes of mast cells and basophils. The antibodies are specific to a particular allergen and serve to detect the allergen upon subsequent exposure.

A second exposure results in a rapid immune response as IgE antibodies attached to mast cells and basophils bind allergens and initiate degranulation in the white blood cells. During degranulation, mast cells or basophils release granules that contain inflammatory molecules. The actions of such molecules (heparin, histamine, and serotonin) result in allergy symptoms: runny nose, watery eyes, hives, coughing, and wheezing.

Allergies can range from mild hay fever to life-threatening anaphylaxis. Anaphylaxis is a serious condition, resulting from inflammation caused by histamine release, that impacts the respiratory and circulatory systems. The systemic inflammation results in low blood pressure and blockage of air passages due to swelling of the throat and tongue. Death may occur quickly if not treated with epinephrine.

Type II Hypersensitivity Reactions

Red Blood Cell Agglutination
This image shows type A blood (A antigen) that was agglutinated (clumped) by mixing the blood with a serum containing anti-A antibody. An antigen-antibody reaction agglutinated the red blood cells forming a large clump. Ed Reschke/Photolibrary/Getty Images

Type II hypersensitivities, also called cytotoxic hypersensitivities, are the result of antibody (IgG and IgM) interactions with body cells and tissues that lead to cell destruction. Once bound to a cell, the antibody initiates a cascade of events, known as complement, that causes inflammation and cell lysis. Two common type II hypersensitivities are hemolytic transfusion reactions and hemolytic disease of newborns.

Hemolytic transfusion reactions involve blood transfusions with incompatible blood types. ABO blood groups are determined by the antigens on red blood cell surfaces and the antibodies present in blood plasma. A person with blood type A has A antigens on blood cells and B antibodies in blood plasma. Those with blood type B have B antigens and A antibodies. If an individual with type A blood were given a blood transfusion with type B blood, the B antibodies in the recipients plasma would bind to the B antigens on the red blood cells of the transfused blood. The B antibodies would cause the type B blood cells to clump together (agglutinate) and lyse, destroying the cells. Cell fragments from the dead cells could obstruct blood vessels leading to damage of the kidneys, lungs, and even death.

Hemolytic disease of newborns is another type II hypersensitivity that involves red blood cells. In addition to A and B antigens, red blood cells may also have Rh antigens on their surfaces. If Rh antigens are present on the cell, the cell is Rh positive (Rh+). If not, it is Rh negative (Rh-). Similar to ABO transfusions, incompatible transfusions with Rh factor antigens can lead to hemolytic transfusion reactions. Should Rh factor incompatibilities occur between mother and child, hemolytic disease could occur in subsequent pregnancies.

In the case of an Rh- mother with an Rh+ child, exposure to the child's blood during the final trimester of pregnancy or during childbirth would induce an immune response in the mother. The mother's immune system would build up antibodies against the Rh+ antigens. If the mother became pregnant again and the second child was Rh+, the mother's antibodies would bind to the babies Rh+ red blood cells causing them to lyse. To prevent hemolytic disease from occurring, Rh- mothers are given Rhogam injections to stop the development of antibodies against the blood of the Rh+ fetus.

Type III Hypersensitivity Reactions

Arthritis X-ray
Arthritis is an inflammation of the joints. This colored X-ray shows the hands of an 81 year old female patient with rheumatoid arthritis. Credit: Science Photo Library/Getty Images

Type III hypersensitivities are caused by the formation of immune complexes in body tissues. Immune complexes are masses of antigens with antibodies bound to them. These antigen-antibody complexes contain greater antibody (IgG) concentrations than antigen concentrations. The small complexes can settle on tissue surfaces, where they trigger inflammatory responses. The location and size of these complexes make it difficult for phagocytic cells, like macrophages, to remove them by phagocytosis. Instead, the antigen-antibody complexes are exposed to enzymes that break down the complexes but also damage underlying tissue in the process.

Immune responses to antigen-antibody complexes in blood vessel tissue causes blood clot formation and blood vessel obstruction. This can result in inadequate blood supply to the affected area and tissue death. Examples of type III hypersensitivities are serum sickness (systemic inflammation caused by immune complex deposits), lupus, and rheumatoid arthritis.

Type IV Hypersensitivity Reactions

Skin Rash
Contact dermatitis is a type IV hypersensitivity that results in severe skin rash. Smith Collection/Stone/Getty Images

Type IV hypersensitivities do not involve antibody actions but rather T cell lymphocyte activity. These cells are involved in cell mediated immunity, a response to body cells that have become infected or carry foreign antigens. Type IV reactions are delayed reactions, as it takes some time for a response to occur. Exposure to a particular antigen on the skin or an inhaled antigen induces T cell responses that result in the production of memory T cells.

Upon subsequent exposure to the antigen, memory cells induce a quicker and more forceful immune response involving macrophage activation. It is the macrophage response that damages body tissues. Type IV hypersensitivities that impact the skin include tuberculin reactions (tuberculosis skin test) and allergic reactions to latex. Chronic asthma is an example of a type IV hypersensitivity resulting from inhaled allergens.

Some type IV hypersensitivities involve antigens that are associated with cells. Cytotoxic T cells are involved in these types of reactions and cause apoptosis (programmed cell death) in cells with the identified antigen. Examples of these types of hypersensitivity reactions include poison ivy induced contact dermatitis and transplant tissue rejection.

Hypersensitivity Reactions Key Takeaways

  • Hypersensitivity reactions are exaggerated immune responses to allergens.
  • There are four types of hypersensitivity reactions. Types I through III are mediated by antibodies, while type IV is mediated by T cell lymphocytes.
  • Type I hypersensitivities involve IgE antibodies that initially sensitize an individual to an allergen and provoke a quick inflammatory response upon subsequent exposure. Allergies and hay fever are both type I.
  • Type II hypersensitivities involve the binding of IgG and IgM antibodies to antigens on cell surfaces. This induces a cascade of events that leads to cell death. Hemolytic transfusion reactions and hemolytic disease of newborns are type II reactions.
  • Type III hypersensitivities result from the formation of antigen-antibody complexes that settle on tissues and organs. In an attempt to remove these complexes, underlying tissue is also damaged. Serum sickness and rheumatoid arthritis are examples of type III reactions.
  • Type IV hypersensitivities are regulated by T cells and are delayed reactions to antigens associated with cells. Tuberculin reactions, chronic asthma, and contact dermatitis are examples of type IV reactions.

    Sources

    • "Hypersensitivity Reactions." Microbiology and Immunology Online, www.microbiologybook.org/ghaffar/hyper00.htm.
    • Parker, Nina, et al. Microbiology. OpenStax, Rice University, 2017.