Hypersensitivity CPMS Hypersensitivity • The immune response has been described as a defense mechanism by which the body rids itself of potentially harmful antigens. • In some cases, however, this process can end up causing damage to the host. When this type of reaction occurs, it is termed hypersensitivity, which can be defined as a heightened state of immune responsiveness. • British immunologists P. G. H. Gell and R. R. A. Coombs devised a classification system for such reactions based on four different categories. Type I hypersensitivity • Also called Immediate hypersensitivity • The key reactant present in type I is IgE. • The distinguishing feature of type I hypersensitivity is the short time lag, usually seconds to minutes, between exposure to antigen and the onset of clinical symptoms. • Antigens that trigger formation of IgE are called atopic antigens, or allergens. Atopy refers to an inherited tendency to respond to naturally occurring inhaled and ingested allergens with continued production of IgE. Type I hypersensitivity • Carl Wilhelm Prausnitz and Heinz Küstner were the first researchers to show that a serum factor was responsible for type I reactions. It was the first observance of Passive cutaneous anaphylaxis. • Passive cutaneous anaphylaxis occurs when serum is transferred from an allergic individual to a nonallergic individual, and then the second individual is challenged with specific antigen Type I hypersensitivity IgE attaches to the cell membrane of mast cells or basophils, and they become the receptors for the allergen. After binding has occurred, the cells elaborate the substances (histamine) that cause the allergic reaction. Type I hypersensitivity • Mast cells and Basophils • Mast cells are the principle effector cells of immediate hypersensitivity, and they are derived from precursors in the bone marrow that migrate to specific tissue sites to mature. • Typically have more histamine content than basophils. • Basophils represent approximately 1 percent of the white blood cells in peripheral blood. They have a half-life of about 3 days. They contain histaminerich granules and high-affinity receptors for IgE, just as in mast cells. Type I hypersensitivity Mediators released from granules • Can be classified into two: Preformed or Newly synthesized Mediator Preformed Histamine Action Smooth muscle contraction, vasodilation, increased vascular permeability ECF-A Chemotactic for eosinophils Neutrophil Chemotactic factor Chemotactic for neutrophils Proteases Convert C3 to C3b, mucus production, activation of cytokines Type I hypersensitivity Mediators released from granules • Can be classified into two: Preformed or Newly synthesized Mediator Platelet activating Newly synthesized factor Action Platelet aggregation Prostaglandin Vasodilation; increased vascular permeability Leukotrienes Chemotactic for neutrophils, eosinophils Type I hypersensitivity • Anaphylaxis is the most severe type of allergic response, because it is an acute reaction that simultaneously involves multiple organs. • Anaphylactic reactions are typically triggered by glycoproteins or large polypeptides. Typical agents that induce anaphylaxis include venom from bees, wasps, and hornets; drugs such as penicillin; and foods such as shellfish, peanuts, or dairy products. • Clinical signs of anaphylaxis begin within minutes after antigenic challenge and may include bronchospasm and laryngeal edema, vascular congestion, skin manifestations such as urticaria (hives) and angioedema, diarrhea or vomiting, and intractable shock because of the effect on blood vessels and smooth muscle of the circulatory system. Type I hypersensitivity Common Examples: • Anaphylaxis • Hay Fever • Food Allergies • Asthma • Bee stings Special Tests for Type I hypersensitivity • Competitive Radioimmunosorbent Test (RIST) • Non-competitive RIST • Non-competitive Radioallergosorbent test (RAST) Type II hypersensitivity • The reactants responsible for type II hypersensitivity, or cytotoxic hypersensitivity, are IgG and IgM. • They are triggered by antigens found on cell surfaces. These antigens may be altered self-antigens or heteroantigens. • Best example: Transfusion reactions Type II hypersensitivity • Transfusion reactions happen when incompatible RBCs are given to the patient, resulting in an immune response. • Can be classified as either acute (patient has preformed antibodies) or delayed (patient has not yet encountered the antigen) • Most acute hemolytic transfusion reactions produce intravascular hemolysis while delayed reactions produce extravascular hemolysis Type II hypersensitivity • Other examples of type II hypersensitivity • Hemolytic Disease f the Fetus and Newborn • Autoimmune hemolytic anemia • Organ specific autoimmune diseases such as Goodpasture syndrome Type III hypersensitivity • Type III hypersensitivity reactions are similar to type II reactions in that IgG or IgM is involved and destruction is complement mediated. However, in the case of type III diseases, the antigen is soluble. When soluble antigen combines with antibody, complexes are formed that precipitate out of the serum • Example: • Arthus reaction • Serum sickness • Autoimmune diseases (SLE, RA) Arthus reaction A localized type III reaction that is rare in humans. Type IV hypersensitivity • Type IV hypersensitivity differs from the other three types of hypersensitivity in that sensitized T cells, usually a subpopulation of Th1 cells, play the major role in its manifestations. Antibody and complement are not directly involved. • Best example: • Contact Dermatitis • Pneumonitis • Tuberculin test Type V hypersensitivity? • This is an additional type that is sometimes (often in the UK) used as a distinction from type 2. • Instead of binding cell surface components, the antibodies recognise and bind to cell surface receptors, which either prevents the intended ligand from binding with the receptor or mimics the effects of the ligand, thus impairing cell signaling. • Examples • Graves’ disease • Myasthenia gravis END