Microbiology 14 - Hypersensitivity Reactions.pdf

Microbiology Immunology Hypersensitivity Reactions Microbiology| Hypersensitivity Reactions Contents : Type I Hypersensitivity 4 Type II Hypersensitivity 11 Transfusion Reactions 15 Microbiology| Hypersensitivity Reactions Hypersensitivity refers to excessive, undesirable (damaging, discomfort-produ...

Microbiology Immunology Hypersensitivity Reactions Microbiology| Hypersensitivity Reactions Contents : Type I Hypersensitivity 4 Type II Hypersensitivity 11 Transfusion Reactions 15 Microbiology| Hypersensitivity Reactions Hypersensitivity refers to excessive, undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction. Frequently, a particular clinical condition (disease) may involve more than one type of reaction. Microbiology| Hypersensitivity Reactions Type I Hypersensitivity : Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity. The reaction may involve skin (urticaria and eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis). Microbiology| Hypersensitivity Reactions The reaction may cause a range of symptoms from minor inconvenience to death. The reaction usually takes 15 - 30 minutes from the time of exposure to the antigen, although sometimes it may have a delayed onset (10 - 12 hours). Immediate hypersensitivity is mediated by IgE. The primary cellular component in this hypersensitivity is the mast cell or basophil. The reaction is amplified and/or modified by platelets, neutrophils and eosinophils. A biopsy of the reaction site demonstrates mainly mast cells and eosinophils. Microbiology| Hypersensitivity Reactions The mechanism of reaction involves preferential production of IgE, in response to certain antigens (often called allergens). The precise mechanism as to why some individuals are more prone to type-I hypersensitivity is not clear. However, it has been shown that such individuals preferentially produce more of TH cells that secrete IL-4, IL-5 and IL-13 which in turn favor IgE class switch. IgE has very high affinity for its receptor on mast cells and basophils. Microbiology| Hypersensitivity Reactions Microbiology| Hypersensitivity Reactions The allergen that induce the production of specific IgE Ab in human they could be: Plant pollens, mold spores House dust, house dust mites Animal hair, feather Food (milk, egg, fish, peanut, chocolate) Insect venom Drugs and chemical Note: Diagnostic tests for immediate hypersensitivity include skin (prick and intradermal) tests, IgE antibodies are measured against the suspected allergens by enzyme immunoassay (ELISA). Microbiology| Hypersensitivity Reactions Therapeutic measures : Avoidance of the responsible allergen (environmental control). It is easily accomplished with food allergen, but may be difficult with inhaled allergen. Hypo sensitization involves injecting the patient overtime with gradually increasing doses of the responsible allergen. This stimulates the production of IgG blocking Ab which react with offending allergen and prevent its combining with IgE Ab on the mast cell. Microbiology| Hypersensitivity Reactions Symptomatic treatment is achieved with anti-histamines which block histamine receptors. Late onset allergic symptoms, particularly bronchoconstriction is treated with (Singulair, Accolate) Symptomatic, although short term, relief from bronchoconstriction is provided by bronchodilators (inhaler) such as (Terbutaline, Albuterol). Thophylline is also used to relieve bronchopulmonary symptoms. Microbiology| Hypersensitivity Reactions Type II Hypersensitivity : Type II hypersensitivity is also known as cytotoxic hypersensitivity and may affect a variety of organs and tissues. Microbiology| Hypersensitivity Reactions The antigens are normally endogenous, although exogenous chemicals which can attach to cell membranes can also lead to type II hypersensitivity. The reaction time is minutes to hours. Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement. Phagocytes and NK cells may also play a role. Microbiology| Hypersensitivity Reactions Pathogenesis mechanism: The combination of IgG or IgM with Ag (epitopes) on cell surface or tissue may lead to one of the following destructive process: Lysis or inactivation of the target cell by activation of the complement system. Lysis or inactivation of target cells by antibody dependent cytotoxicity (ADCC) through the action of NK cells. Phagocytosis of the target cells with or without complement (either directly through antibody FC receptor present on phagocyte or by immune adherence where C3b have receptors on phagocytic cells). Microbiology| Hypersensitivity Reactions Clinical examples of Type II responses include: Certain autoimmune diseases where Ab’s produced vs membrane Ag’s: Grave’s Disease – Ab’s produced vs thyroid hormone receptor. Myasthenia Gravis – Ab’s produced vs acetylcholine receptors. Autoimmune hemolytic anemia – Ab’s produced vs RBC membrane Ag’s. Hemolytic Disease of the Newborn Hyperacute graft rejection Blood Transfusion reactions, Graft rejection Microbiology| Hypersensitivity Reactions Transfusion reactions : Produced by mismatched blood types. Destroys foreign RBC by complement-mediated lysis triggered by IgG. Produces fever, intravascular clots, lower back pain, Hgb in urine. Microbiology| Hypersensitivity Reactions Hemolytic Disease of the Newborn : Occurs via maternal IgG Ab’s crossing the placenta. In severe cases causes erythroblastosis fetalis. Most commonly develops in Rh- mother with Rh+ fetus. Exposure to Rh+ fetal RBC’s stimulates prod of memory/plasma. Activation of memory cells in subsequent pregnancy stimulate IgG Ab’s which can cross the placenta. mild-severe hemolytic anemia ensues along with bilirubin which affects the brain/CNS. Microbiology| Hypersensitivity Reactions Treatment centers on anti-Rh antibodies (Rhogam). Mothers can be tested for anti-Rh antibodies to check for a rise in titre. Isolated fetal RBC’s can be checked for anti-Rh IgG w/ Coombs test. Drug-induced hemolytic anemia Drugs such as aspirin and antibiotics can bind to the surfaces of RBC’s. Such complexes can trigger Ab-mediated cell lysis by complement activation.