Overreactions To Antigens: Allergy/Hypersensitivity
An allergy or hypersensitivity is an exaggerated immune response that injures or inflames tissues.

There are four categories of hypersensitivity reactions: type I (atopy & anaphylaxis), Type II (cytotoxic), Type III (immune complex reactions), and Type IV (delayed hypersensitivity reactions).

Antigens which trigger hypersensitivity reactions can be either exogenous (originate outside the host) or endogenous (involve the host's own tissue).

Type I Allergic Reactions: Atopy and Anaphylaxis
Type I hypersensitivity reactions result from excessive IgE production in response to an exogenous antigen.

The two kinds of type I hypersensitivites are atopy, a chronic, local allergy; and anaphylaxis, a systemic, potentially fatal allergic response.

The predisposition to type I hypersensitivities is inherited, but age, geographic locale, and infection also influence allergic response.

Type I allergens include inhalants, ingestants, injectants, and contactants.

The portals of entry for type I antigens are the skin, respiratory tract, gastrointestinal tract, and the genitourinary tract.

Type I hypersensitivities are set up by a sensitizing dose of allergen and expressed when a second provocative dose triggers the allergic response. The time interval between the two can be many years.

The primary participants of type I hypersensitivities are IgE, basophils, mast cells, and agents of the inflammatory response.

Allergies are diagnosed by a variety of in vitro and in vivo tests that assay specific cells, IgE, and local reactions.

Allergies are treated by medications which interrupt the allergic response at certain points. Allergic reactions can often be prevented by desensitization therapy.

Type II Hypersensitivities: Reactions That Lyse Foreign Cells
Type II hypersensitivity reactions occur when preformed antibodies react with foreign cell-bound antigens. The most common type II reactions occur when transfused blood is mismatched to the recipient's ABO type. The donor cells are destroyed by complement fixation of host IgG and IgM to ABO antigen sites.

Type II hypersensitivities are set up by RBC antigens preformed antibody against A and B, or against other cell-bound antigens following prior exposure.

Complement, IgG, and IgM antibodies are the primary mediators of type II hypersensitivities.

Type II hypersensitivities can also occur when Rh- mothers are sensitized to Rh+ RBCs of their unborn babies and the mother's anti-Rh antibodies cross the placenta, causing hemolysis of the newborn's RBCs. This is called hemolytic disease of the newborn, or erythroblastosis fetalis.

The concepts of universal donor (type O) and universal recipient (type AB) apply only under emergency circumstances. Cross-matching donor and recipient blood is always done to determine which transfusions are safe to perform.

Type III Hypersensitivities: Immune Complex Reactions
Type III hypersensitivities are induced when a profuse amount of antigen enters the system and results in large quantities of antibody formation.

Type III hypersensitivity reactions occur when large quantities of antigen react with host antibody to form large, soluble immune complexes that settle in tissue cell membranes, causing chronic destructive inflammation. The reactions appear hours or days after the antigen challenge.

The mediators of type III hypersensitivity reactions include soluble IgA, IgG, or IgM, and agents of the inflammatory response.

The two kinds of type III hypersensitivities are local (Arthus) reactions and systemic (serum sickness). Arthus, or local, reactions occur at the site of injected drugs or booster immunizations. Systemic reactions occur when repeated antigen challenges cause systemic distribution of the immune complexes and subsequent inflammation of joints, lymph nodes, and kidney tubules.

Autoimmune hypersensitivity reactions occur when autoantibodies or host T cells mount an abnormal attack against self-antigens. Autoimmune antibody responses can be either local or systemic type II or type III hypersensitivity reactions. Autoimmune T cell responses are type IV hypersensitivity reactions.

Susceptibility to autoimmune disease appears to be influenced by gender and by genes in the MHC complex.

Autoimmune disease may be an excessive response of a normal immune function, the appearance of sequestered antigens, ``forbidden'' clones of lymphocytes which react to self antigens, or the result of alterations in the immune response caused by infectious agents, particularly viruses.

Examples of autoimmune diseases include systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus, myasthenia gravis, and multiple sclerosis.

Type IV Hypersensitivities: Cell Mediated (Delayed ) Reactions
Type IV hypersensitivity reactions occur when cytotoxic T cells attack either self tissue or transplanted foreign cells. Type IV reactions are also termed delayed hypersensitivity reactions because they occur hours to days after the antigenic challenge.

Type IV hypersensitivity reactions are mediated by T lymphocytes and are carried out against foreign cells showing both a foreign MHC and a non-self receptor site.

Examples of type IV reactions include the tuberculin reaction, contact dermatitis, and mismatched organ transplants (host rejection and GVHD reactions).

The four classes of transplants or grafts are determined by the degree of MHC similarity between graft and host. From most to least similar these are: autografts, isografts, allografts, and xenografts.

Graft rejection can be minimized by tissue matching procedures, immunosuppressive drugs, and use of tissues which do not provoke a type IV response.

Immunodeficiency Diseases: Hyposensitivity of the Immune System
Immunodeficiency diseases occur when immune response is reduced or absent.

Primary immune diseases are genetically induced deficiencies of B cells, T cells, thymus gland, or combinations of these. Secondary immune disease are caused by either infection, organic disease, chemotherapy, or radiation.

The most well-known infection-induced immunodeficiency is AIDS.

Cancer: Cells Out of Control
Cancer is caused by genetic transformation of normal host cells into malignant cells. These transformed cells perform no useful function, but instead grow unchecked and interfere with normal tissue function.

Benign tumors are self contained, slow growing, and do not differ greatly from their tissues of origin.

Malignant tumors are invasive, fast growing, very different from their tissues of origin and metastasize into organs remote from the site of origin.

Possible causes of cancerous transformation include irregularities in mitosis, genetic damage, activation of oncogenes, and infection by retroviruses.

Cytotoxic T cells, NK cells, LAK cells, and macrophages identify and destroy transformed cancerous cells by recognizing and attaching to foreign surface markers on the transformed cells.

Cancerous cells survive when these mechanisms fail.