Hypersensitivity (Chapter 14) PDF

6/27/2024 Hypersensitivity CHAPTER 14 Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOO...

6/27/2024 Hypersensitivity CHAPTER 14 Preamble PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the details needed for the Unit exam Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES Unit Objectives are your study guide (not this PowerPoint) Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! 1  6/27/2024 Chapter Overview Immunologic Introduction to Hypersensitivity mechanisms, clinical hypersensitivity categories examples, treatment, laboratory testing Hypersensitivity Exaggerated immune response to a typically harmless antigen Results in tissue injury and disease Type I Four categories of Type II hypersensitivity: Type III Type IV 2  6/27/2024 Hypersensitivity (continued) Immediate reactions Delayed reactions Develop minutes to hours after antigen Develop 24 to 48 hours after antigen exposure exposure Type I, type II, type III Type IV Hypersensitivity Four categories of classification Type I Hypersensitivity – cell bound antibodies react with antigen to release physiologically active substances Type II Hypersensitivity – free antibody reacts with antigen associated with cell surfaces Type III Hypersensitivity – antibody reacts with soluble antigen to form complexes that participate in tissues. Type IV Hypersensitivity – Delayed Hypersensitivity – not seen until 24-48 hours – different from other three in that sensitized T-cells not antibody 3  6/27/2024 Hypersensitivity Type I Type II reactions reactions Cell-bound antibody Free antibody reacts reacts with antigen to with antigen release associated with cell physiologically surfaces. active substances. Complement plays a Complement is not major role in involved in type I producing tissue reactions. damage in type II reactions. Hypersensitivity Type III Type IV hypersensitivity hypersensitivity Differs from the other Antibody reacts with three, because sensitized T soluble antigen to form cells rather than antibody complexes that precipitate are responsible for the in the tissues. symptoms that develop. Complement plays a major Complement is not role in producing tissue involved in type IV damage in Type III reactions. reactions. 4  6/27/2024 Type I Hypersensitivity Also known as anaphylactic hypersensitivity Typically thought of as “allergies” Commonly occur within minutes after exposure to an allergen Key components IgE Mast cells Basophils Eosinophils Sensitization Phase APCs process allergens and present them to Th cells. Th2 cells induce production of allergen-specific IgE. IgE binds to FceRI receptors on mast cells and basophils. 5  6/27/2024 Activation Phase Allergen cross-links adjacent cell-bound IgEs. Mast cells and basophils degranulate. Chemical mediators are released and bind to target organs. Allergy symptoms are produced. Type I Mediators released PREFORMED/PRIMARY NEWLY FORMED Histamine Platelet activating Heparin factor (PAF) Eosinophil chemotactic factor Prostaglandin (PG) D2 of anaphylaxis (ECF-A) Leukotrienes (LT) Neutrophil chemotactic factor B4, C4, D4 and E4 Proteases Cytokines 6  6/27/2024 Common Allergens Pollen Mold spores Animal dander Dust mites Certain foods (peanuts, Insect venom Certain drugs (penicillin) Latex shellfish, dairy products) Clinical Manifestations of Type I Hypersensitivity Rhinitis (“hay fever”) Allergic asthma Food allergies Urticaria (“hives”) Wheal and flare Eczema Systemic anaphylaxis A potentially fatal reaction 7  6/27/2024 Treatments for Type I Hypersensitivity Avoidance of allergens Drug therapy Antihistamines, bronchodilators, mast cell stabilizers, corticosteroids, epinephrine Monoclonal anti-IgE antibody Allergy immunotherapy (AIT) Administer gradually, increasing doses of allergen Testing for Type I Hypersensitivity: In Vivo Skin Tests Percutaneous or intradermal Process Apply a panel of allergens to separate sites on the skin. Wait 15 to 20 minutes. Positive test = wheal and flare at the site of application 8  6/27/2024 In Vitro Tests: Allergen-Specific IgE Testing RAST (radioallergosorbent test)was the first type of test to be used for specific IgE Enzyme methods are now used to detect IgE to a specific allergen in patient serum. In Vitro Tests: Total IgE RIST (Radioimmunosorbent test) was the first type of test method for Total IgE. Enzymes are now used to detect the total concentration of IgE in patient serum. 9  6/27/2024 Type I Hypersensitivity Animation Type II Hypersensitivity Cell destruction Key Also known as components = antibody- Inhibition of IgG and IgM Effects of the mediated cytotoxic directed antibodies: cell function against a cell hypersensitivity surface antigen Increase in cell function 10  6/27/2024 Cell Damage in Type II Hypersensitivity Activation of classical pathway of complement and cell lysis Opsonization and phagocytosis of the cell Antibody-dependent cell- mediated cytotoxicity (ADCC) Clinical Examples of Type II Hypersensitivity Transfusion reactions Hemolytic disease of the newborn (HDN) Autoimmune hemolytic anemia Warm reactive antibodies Cold agglutinins Paroxysmal cold hemoglobinuria Anti-GBM disease Hashimoto’s disease 11  6/27/2024 Hemolytic Disease of the Newborn (HDN) Pregnant woman produces antibodies to Rh antigens (usually RhD) on fetal RBCs. Cold Agglutinins Agglutinins are antibodies that cause the red blood cells to clump together. Cold agglutinins are active at cold temperatures. Febrile (warm) agglutinins are active at normal body temperatures. Cold agglutinins react best with red blood cells at temperatures below 37oC. Cold agglutinins that are active in vitro up to a temperature of 30oC or more are generally associated with harmful effects blocking of small vessels on exposure to cold red cell agglutination production of hemolytic anemia. 12  6/27/2024 COLD AGGLUTININ SYNDROME Can be seen in two clinical settings: Chronic cold agglutinin syndrome usually has a gradual onset and chronic course. Usually seen in the elderly The agglutinins usually contain monoclonal kappa light chains. This condition may also be due to the presence of a lymphoma in some individuals. Post-infectious cold agglutinin syndrome Commonly follows infection with Mycoplasma pneumoniae or infectious mononucleosis. Those affected with cold agglutinin syndrome, in addition to a high titer of cold agglutinins, are also found to have large amounts of C3d, resulting in a positive direct antiglobulin test. COLD AGGLUTININS: Mycoplasma pneumoniae MYCOPLASMA PNEUMONIAE INFECTION Cold agglutinins are found in approximate 55% of patients Subclinical hemolysis is common; some have episodes of hemolytic anemia. Cold agglutinin occurs in the 2nd or 3rd week after onset; hemolysis is rapid Abnormal IgM cold agglutinins, with anti-I specificity increase in titer, reaching a peak at day 12 to 15, then rapidly decreasing after day 20. Patients may recover from the respiratory infection, then become ill again. Symptoms: Increasing pallor, jaundice ,splenomegaly; some have hemoglobinuria Rare cases, gangrene may result from exposure to the cold. If hemolytic anemia occurs, proceeds at an alarming rate and may be fatal. 13  6/27/2024 COLD AGGLUTININS: Infectious Mononucleosis INFECTIOUS MONONUCLEOSIS Cold agglutinins of anti-i specificity are frequently present as a transient phenomenon with IM. 50% of patients with the disease have anti-i present Antibody is normally detectable in vitro up to a temperature of about 25oC In patients who developed a hemolytic syndrome (less than 1%), the antibody was found to be active in vitro up to a temperature of at least 28oC Direct Antiglobulin Test (DAT) Detects RBCs coated with complement components or IgG antibody. Patient RBCs are incubated with a poly-specific anti-human Ig directed against IgG and C’. If positive (agglutination), the test is repeated with mono-specific anti-IgG, anti-C3b, and anti-C3d. 14  6/27/2024 Indirect Antiglobulin Test Positive test = RBC Process agglutination Incubate reagent RBCs with patient Tests patient serum at 37oC; wash serum for to remove excess. Coombs’ test antibodies to Add anti-human RBC antigens. globulin. Type II Animation 15  6/27/2024 Type III Hypersensitivity Complex-mediated hypersensitivity Key components are IgG and IgM directed against a soluble antigen. Small antigen–antibody complexes precipitate out and deposit in tissues. C’ binds; vasodilation and vasopermeability increase. Macrophages and neutrophils migrate to the affected areas and release their lysosomal enzymes, resulting in tissue damage. Arthus Reaction Skin reaction caused by type III hypersensitivity Localized inflammation characterized by redness and edema Peaks at 3 to 8 hours 16  6/27/2024 Serum Sickness Generalized type III hypersensitivity reaction Caused by passive immunization of humans with animal serum Produces antibodies against the foreign animal proteins in patients. Causes immune complexes to form and deposit in tissues. Symptoms: headache, fever, nausea, joint pain, rashes, and lymphadenopathy Other Conditions Associated With Type III Hypersensitivity Some autoimmune diseases (e.g., Reactions to bee systemic lupus stings erythematosus and rheumatoid arthritis) Sequelae to Drug reactions (e.g., infections (e.g., post- penicillin) streptococcal glomerulonephritis) 17  6/27/2024 Laboratory Testing–Type III Hypersensitivity Testing for ANAs Fluorescent staining of tissue sections to detect deposited immune complexes Testing for rheumatoid factor (an anti-IgG) Testing complement levels May be decreased in the serum during periods of high disease activity. Type III Animation 18  6/27/2024 Type IV Hypersensitivity Cell-mediated hypersensitivity Th1 cells and macrophages are involved. APCs present antigen to naïve T helper cells, which differentiate into Th1 cells. Th1 cells release cytokines that attract and activate macrophages. Macrophages induce inflammation. Cytotoxic T lymphocytes are recruited and destroy target cells. Hypersensitivity peaks 48 to 72 hours after antigen exposure. Clinical Examples of Type IV Hypersensitivity Infections with intracellular pathogens Mycobacterium tuberculosis, Mycobacterium leprae, Pneumocystis carinii, Leishmania species, herpes simplex virus Contact dermatitis 19  6/27/2024 Clinical Examples of Type IV Hypersensitivity (continued) Hypersensitivity pneumonitis Allergic diseases of the lungs Caused by inhalation of bacterial and fungal spores Examples: Farmer’s lung disease, bird breeder’s lung disease, humidifier lung disease Contact Dermatitis Low-molecular-weight compounds contact the skin and act as haptens to sensitize Th1 cells. Examples include poison ivy, poison oak, nickel salts, materials in cosmetics and hair dyes, and latex. Skin eruptions with erythema, swelling, and papules are produced. 20  6/27/2024 Skin Testing for Delayed Hypersensitivity Patch test Antigen applied to skin surface Test for contact dermatitis (+) test = redness with papules or tiny blisters Skin testing for immunodeficiency Inject common antigens intradermally Skin Testing for Delayed Hypersensitivity (continued) Antigen injected intradermally Test for tuberculosis exposure (PPD) or T- cell function (+) test = induration Mantoux method 21  6/27/2024 Interferon Gamma Release Assays (IGRA) Measure production of IFN-γ by patient T cells stimulated with MTB antigens Quantiferon TB Gold Plus assay Patient blood is incubated in special tubes with MTB antigens. Plasma is tested for IFN-γ by ELISA. T-SPOT-TB test Patient mononuclear cells are incubated with MTB antigens and tested for IFN-γ by ELISpot. Type IV Animation 22  6/27/2024 Summary - Type I Hypersensitivity Release of mediators from IgE- sensitized mast cells and basophils occurs after cross-linking by allergen. Summary - Type II Hypersensitivity Cell destruction is caused by antibody and complement, opsonization, or ADCC. Antibody binds to cell receptor and stimulates or inhibits cell function. 23  6/27/2024 Summary - Type III Hypersensitivity Antigen– antibody complexes activate complement. Neutrophils are recruited and release lysosomal enzymes that cause tissue damage. Summary - Type IV Hypersensitivity Antigen-sensitized Th1 cells release cytokines. Recruit macrophages. Induce inflammation. Activate Tc cells to cause direct cell damage. 24  6/27/2024 Postamble READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. USE THE UNIT OBJECTIVES AS A STUDY GUIDE All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives 25