Disorders in Immunity

Categories of Hypersensitivity

Hypersensitivities are categorized by the mechanism of immune reaction, and are labeled types I through IV. Major categories of B cell–mediated hypersensitivity include type I (common allergy), type II (cytotoxic antibody dependent), and type III (immune complex formation). Type IV reactions are T cell-mediated rather than antibody-mediated.

Hypersensitivity reactions are inappropriately strong immune responses to antigens, which results in damage to the host. An antigen is a specific portion of a foreign particle that activates an immune response. When an antigen comes from the environment, it is considered an allergen. An allergen is an antigen with an environmental origin and the capacity to elicit a type I hypersensitivity response with immunoglobulin E (IgE). An allergic response does not necessarily trigger all of the different parts of the immune response. Allergens include things such as mold spores, pet dander, foods (e.g., nuts and fish oil), medications (e.g., penicillin and sulfa drugs), and pollen. IgE is an antibody that recognizes specific antigens such as allergens. If an immune response is mounted against the host's own body cells and tissues, it is described as autoimmunity. If the immune system produces antibodies against antigens from another individual of the same species, it is described as alloimmunity. Alloimmunity can occur if the wrong blood type is used during a transfusion or after organ transplantation because of the protein incompatibility between blood and the patient.

The mechanism of immune reaction is used to categorize hypersensitivities, labeled types I through IV. This classification system is useful for categorizing different conditions and quickly differentiating the mechanistic basis for them. Hypersensitivities are not mutually exclusive; more than one type may manifest simultaneously or in conjunction with other disease processes.

Type I hypersensitivity involves the production of immunoglobulin E (IgE) and B cell antibodies against the antigen. Examples of type I hypersensitivity are allergic rhinoconjunctivitis (hay fever) and anaphylaxis, a severe and rapidly developing allergic reaction.

Type II hypersensitivity involves a tissue-specific immune response with localized targeting of immune action. Autoimmune hemolytic anemia (a group of disorders where the body destroys red blood cells faster than it makes them) and myasthenia gravis (an autoimmune neuromuscular disease that causes weakness in the skeletal muscles) are type II hypersensitivities.

Type III reactions involve the formation of an immune complex (also called an antigen-antibody complex), which is the molecule formed from the binding of an antibody to an antigen. Rheumatoid arthritis and lupus are immune complex reactions. Type II and type III hypersensitivities both involve immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies.

Type IV hypersensitivity is T cell mediated and has lymphocytes that mature in the thymus gland rather than antibody mediated. Examples of type IV hypersensitivity include poison ivy dermatitis and type I diabetes mellitus.

Hypersensitivity Type and Associated Immune Mediators

Hypersensitivity Type Immune Mediators Description Examples
I: Allergy
  • Immunoglobulin E (IgE)
Allergic response occurs within minutes. Free antigens cross-link IgE on mast cells and basophils, causing release of biomolecules.
  • Allergic rhinoconjunctivitis
  • Anaphylaxis
  • Asthma
II: Cytotoxic antibody dependent
  • Immunoglobulin M (IgM) 
  • immunoglobulin G (IgG) complement
Antibodies (IgM or IgG) target cells (self or foreign) for destruction by cytotoxic T cells or by complement.
  • Hemolytic anemia
  • Myasthenia gravis
  • Rheumatic heart disease
  • Red blood cell rejection by transfusion donors
  • Hemolytic disease of the newborn (HDN)
III: Immune complex formation
  • Immunoglobulin G (IgG)
  • Complement
  • Neutrophils
Antibody (IgG) binds to antigens, forming an immune complex that can be deposited in vessel walls, initiating local inflammation.
  • Rheumatoid arthritis
  • Lupus
  • Serum sickness
IV: T cell mediated
  • Helper T cells
Memory helper T cells activate macrophages and cause an inflammatory response that can lead to tissue damage.
  • Poison ivy dermatitis
  • Type I diabetes mellitus
  • Transplant rejections

Hypersensitivity types I through IV are mediated through specific immune proteins and cells. The body responds to the activation of a particular immune mediator. Multiple diseases can develop from each specific hypersensitivity type.

Hypersensitivity reactions require sensitization, or previous exposure to the antigen that induces an adaptive response. The immune system must be exposed to the antigen in order to develop antibodies or T cells specific to it. The individual is sensitized when antibodies or T cells are produced in sufficient quantities to elicit an immune response upon repeated exposure to the antigen. For some antigens and some people, sensitization happens quickly and in response to a small exposure. In other circumstances, the immune system requires multiple exposures to the antigen in order to sensitize. In either case, once sensitized, the immune system reacts to the antigen in a disproportionate manner that results in tissue damage.

Hypersensitivity reactions are mediated through B cell antibodies, T cells, and other leukocytes (white blood cells) and proteins. Stem cells give rise to cells that eventually become mature blood cells and the cells of the immune system. This is a process known as hematopoiesis. Stems cells are found in the bone marrow of the skull, ribs, pelvis, sternum, and femurs of adults. Two lineages of blood cells arise from stem cells—the lymphoid line, which produces B cells and T cells, and the myeloid line, which leads to the production of monocytes (macrophage precursors), mast cells, basophils, neutrophils, eosinophils, megakaryocytes (which eventually become platelets), and red blood cells. New cells are continually being generated to replace old cells, with approximately 1% of the body's total blood cells begin replaced daily.

Specifically, red blood cells, platelets, macrophages, and granulocytes (neutrophils, eosinophils, and basophils) are produced within the bone marrow. In addition to hematopoiesis, the bone marrow also removes defective red blood cells from circulation and is the location where B cells mature, differentiate, and become immunocompetent. The thymus, spleen, and lymph nodes produce lymphocytes (B cells and T cells). Precursors of T cells become immunocompetent in the thymus. Similarly, monocytes migrate to and mature in the spleen, liver, and lymph nodes.

Differentiation of Hematopoietic Stem Cells

Hematopoietic stem cell in bone marrow differentiate into different immune and blood cells. Type I, II, and III hypersensitivity reactions of the immune system are B cell-mediated, whereas type IV hypersensitivity is T cell-mediated. Key myeloid cells in the allergic (type I) response are mast cells, basophils, neutrophils, and eosinophils.