 IgE causes immediate (type I) hypersensitivities › Characterized by immediate reaction of the sensitized individual  Generally within minutes of exposure  Tendency to have type I hypersensitivities is inherited › Reactions occur in at least 20% to 30% of population

 Sensitization occurs when antigen makes contact with some part of body and induces response  IgE antibodies bind to receptors on mast cells and basophiles › Antigen readily bonds to cells fixed with IgE antibodies  Within seconds, mast cells degranulate releasing mediators that initiate immune reaction including hives, hay fever and anaphylaxis

 Localized anaphylaxis › Most allergic reactions are local anaphylaxis  Hives  Allergic skin condition characterized by formation of wheal and flare rash  Hay fever  Allergic condition caused by inhaled antigen  Condition marked by itching teary eyes, sneezing and runny nose  Asthma  Respiratory allergy  Allergic mediators attracted to inflamed respiratory tract  Results in increased mucous secretion and bronchi spasm

 Generalized anaphylaxis › Rare, but more serious › Antigen enters bloodstream and becomes widespread  Reactions affect almost entire body  Can induce shock › Massive release of mediators causes extensive blood vessel dilation and fluid loss  Causes fall in pressure leading to blood flow insufficiency

 Immunotherapy › General term for techniques used to modify immune system for favorable effect › Procedure is to inject individual with extremely dilute suspension of allergen  Called desensitization or hyposensitization › Concentration of allergen gradually increased over time  Individual gradually becomes less sensitive

 Immunotherapy › Second therapeutic procedure is injection of antibodies to bind IgE  Essentially anti-IgE antibodies › Most IgE are bound to mast cells and basophiles  Engineered anti-IgE created  rhuMab = r ecombinant hu man M onoclonal a nti b ody

 Complement-fixing antibodies react with cell surface antigens causing cell injury or death  Cells can be destroyed in type II reactions through complement fixation and antibody-dependent cellular cytotoxicity (ADCC)  Examples of type II hypersensitivities are › Transfusion reactions › Hemolytic disease of the newborn

 Transfusion reactions › Normal red blood cells have different surface antigens  Antigens differ from person to person  People are designated type A, B, AB or O › Transfused blood that is antigenically different can be lysed by recipient immune cells › Cross-matching blood is used to ensure compatibility between donor and recipient › Antibody-coated cells removed by phagocyte system › Symptoms include low blood pressure, pain, nausea and vomiting

 Hemolytic disease of the newborn › Basis of disease is incompatibility of Rh factor between mother and child  Rh factor RBC cell surface antigen  Rh positive = Rh antigen present  Rh negative = Rh antigen missing  Anti-Rh antibodies form in Rh negative mother pregnant with Rh positive fetus  First Rh positive fetus unharmed  Second Rh positive fetus provokes strong secondary immune response  IgG antibodies of secondary response cross placenta causing extensive damage to fetal red blood cells

 Immune complexes consist of antigen and antibody bound together  Usually adhere to Fc receptors on cells › Complexes are destroyed and removed  Certain instances complexes persist in circulation or at sites of formation › Initiate blood clotting mechanism › Activate complement contributing to inflammation  Complexes commonly deposited in skin, joints and kidney  Complexes also cause disseminated intravascular coagulation (DIC) › Clots in small vessels  Leads to system failure

 Delayed hypersensitivities caused by cell- mediated immunity › Slowly developing response to antigen  Reactions peak in 2 to 3 days instead of minutes  T cells are responsible for reactions › Reactions can occur nearly anywhere in the body  Delayed hypersensitivity reactions responsible for contact dermatitis, tissue damage, rejection of tissue grafts and some autoimmune diseases

 Tuberculin skin test › Test involves introduction of small quantities of protein antigens from tubercle bacillus into skin › In positive skin test injection site reddens and gradually thickens  Reaction reaches peak in 2 to 3 days › Reactions result from sensitized T cells, release of cytokines and influx of macrophages

 Contact hypersensitivities › Mediated by the T cells  T cells release cytokines  Cytokines initiate inflammation that attracts macrophages  Macrophages release mediators to add to inflammation › Common examples of contact allergies include  Poison ivy and poison oak  Nickel in metal jewelry  Chromium salts in leather  Latex products

 Major drawback to graft transplantation is possible immunological rejection › Differences between donor and recipient tissues basis for rejection › Rejection is predominantly type IV reaction  Killing of graft cells occurs through complex combination of mechanisms › Contact with sensitized cytotoxic T cells and natural killer cells  Combination of agents commonly used to prevent graft rejection › Cyclosporin A › Steroids › Basiliximab  Monoclonal antibody preparation  Blocks binding of immune mediators

 Body usually recognizes self antigens › Destroys lymphocytes that would destroy self › Malfunction in immune recognition basis for autoimmunity  Autoimmune diseases may result from reactions to antigens that are similar to self antigens  Autoimmunity may occur after tissue injury › Self antigens released from injured organ  Autoantibodies form and interact with injured tissues and cause further damage

 Spectrum of autoimmune diseases › Reactions occur over spectrum  Organ-specific to widespread responses › Organ-specific  Thyroid disease  Only thyroid is affected › Widespread response  Lupus  Autoantibodies made against nuclear constituents of all body cells  Rheumatoid arthritis  Immune response made against collagen in connective tissue  Myasthenia gravis  Autoantibody-mediated disease  Antibody to acetylcholine receptor proteins

 Treatment of autoimmune diseases › Treatment aimed at:  Killing dividing cells  Immunosuppressant  Controlling T cell signaling  Cyclosporin  Anti-inflammatory medications  Cortisone-like steroids  Replacement therapy  Insulin

 Immunodeficiency disorders are marked by the body’s inability to make and sustain an adequate immune response  Two basic types of disorders › Primary or congenital  Inborn as a result of genetic defect or developmental abnormality › Secondary or acquired  Can be acquired as result of infection or other stressor

 Primary immunodeficiencies › Generally rare › Examples  Agammaglobulinemia  Few or no antibodies produced  Occurs in 1 in 50,000 people  Severe combined immunodeficiency disorder (SCID)  Neither B nor T lymphocytes are functional  Occurs in 1 in 500,000 live births  Selective IgA deficiency  Little or no IgA produced  Most common disorder  One in 333 to 700 people

 Secondary immunodeficiencies › Result from environmental, rather than genetic factors  Malignancies, advanced age certain infections, immunosuppressive drugs and malnutrition are just a few › Often results from depletion of certain cells of the immune system  Syphilis, leprosy and malaria affect T-cell population and macrophage function  Malignancies of lymphoid system decrease antibody- mediated immunity › Most serious widespread immunodeficiency is AIDS  Destroys helper T cells  Inhibits initiation of cellular and antibody-mediated immunity