Hypersensitivity Reactions PDF

4/4/2023 Objectives: HYPERSENSITIVITY 1 2 3 REACTIONS D...

4/4/2023 Objectives: HYPERSENSITIVITY 1 2 3 REACTIONS Detail the Evaluate the role Provide a Kristin Butler, MPH, MLS (ASCP)CM mechanisms and of antibodies, presumptive LSU Health Shreveport manifestations of macrophages, diagnosis, given the 4 types of lymphocytes, clinical CLPC Seminar, Spring 2023 hypersensitivity neutrophils, and manifestations and reactions. complement in lab results. each reaction. 1 2 What is the basic immune response? What is Hypersensitivity ? Heightened state of immune responsiveness An exaggerated response to a harmless antigen Can result in tissue damage, disease, and even death Clinical manifestations: contain, fight, expel Common allergens: dust, pollen, animal dander, plant materials, metals, foods, medications 3 4 How do allergic reactions manifest? Hypersensitivity Classification Allergic rhinitis Upper resp tract Sneezing, watery eyes Type I → Anaphylaxis, immediate Asthma Type II → Cell bound Ag Lower resp tract Pneumonitis Type III → Immune complex GI tract Abdominal cramping Type IV → Delayed hypersensitivity Nausea, vomiting, diarrhea Contact dermatitis Skin Erythema Anaphylaxis The term “allergy” refers to Types I & IV Circulation Shock 5 6 1  4/4/2023 Type I Hypersensitivity What happens? First…SENSITIZATION Immediate hypersensitivity reaction Initial exposure: Anaphylaxis, shock IgE synthesized Binds to mast cells and Short lag time between exposure to Ag and onset of basophils in smooth symptoms, about 2 – 30 minutes muscle, blood vessels, and mucosal linings via IgE dependent FceR1 receptors Triggered by allergen Continued production in atopy 7 8 What happens? What happens when a mast cell Next…ACTIVATION detonates? Subsequent exposure: Cross-linking of IgE on mast cells & basophils Degranulation releases mediators 9 10 Within Early phase Mediators 30-60 mins What’s the big deal about histamine? Histamine Mucus production, airway constriction, increased blood flow, movement of fluid into tissues, GI symptoms Eosinophil chemotactic factor of anaphylaxis (ECF-A) Attracts eosinophils Induces expression of eosinophil receptors for C3b Heparin, neutrophil chemotactic factors, & various proteases 11 12 2  4/4/2023 6-8 hours Late phase Mediators later Late phase allergic reaction Prostaglandin 6 – 8 hrs following Ag exposure Enhances affects of histamine → bronchial constriction Major role in chronic conditions & vasodilatation Additional mediators released Eosinophilia Leukotrienes ↑ vascular permeability, bronchoconstriction ↑ mucous secretion in airways Chemotactic for eosinophils & neutrophils Platelet activating factor (PAF), IL-4 & other cytokines 13 14 Common causes of Type I Reactions Clinical manifestations of Type I Varies from local skin reaction to anaphylaxis Symptoms depend on exposure, dosage, route of transmission, frequency of exposure 15 16 Localized reactions Anaphylaxis Majority of Type I reactions Most severe allergic response Involves multiple organs Most allergens inhaled Death may result from asphyxiation Upper resp → allergic rhinitis Commonly induced from: Lower resp → allergic asthma Insect bites Drugs (PCN) Others are from skin contact Food Pet dander → urticaria (hives) Latex Insect bite → angioedema 17 18 3  4/4/2023 Clinical signs of Anaphylaxis Oral allergy syndrome Constriction and tightening Pollen food syndrome of airways Appears to be food allergy → closely Swollen lips, tongue, throat connected to type of pollen and/or seasonal allergies Shock, with severe drop in Eat certain fruit or veggie → mouth itches BP or tingles Rapid pulse Due to cross-reactivity of proteins Dizziness, lightheadedness, Symptoms don’t last long loss of consciousness Rarely advance to hives, nausea, or anaphylaxis 19 20 If you are Birch Ragweed Mugwort allergic to: Grasses “Red Meat Allergy” pollen pollen pollen You may Apples Bananas Tomato Apples Sudden allergy to red meat also have Carrots Melons Melons Carrots Connected with bite from the lone star tick a reaction Celery Tomato Oranges Celery to: Peaches Cucumber Kiwi Saliva of tick contains alpha-gal – a sugar found only in animal meat Pears Zucchini Peanuts Kiwi Spices IgE produced (sensitization) to “foreign” sugar Hazelnuts At next meal of red meat (activation), type I Almonds hypersensitivity to alpha-gal in the meat Symptoms appear 4-6 hours after eating red meat http://www.mayoclinic.com/health/food-allergy/DS00082/DSECTION=symptoms Hives to anaphylaxis 21 22 Why must I have Skin testing for Type I Hypersensitivity allergies? In vivo response to allergens Cutaneous Prick test Genetics Simplistic method Particular MHC haplotypes Stop antihistamines have strong Th2 response Very sensitive test 48 – 72 hours prior Genetic variations that Specific to particular Ag encode for cytokines → Examines final reaction of patient to an allergen promote IgE response Small sample of allergen injected Highly allergic individuals Compare each area to controls are more prone to Th2 stimulation and have higher Tests several allergens on large area (arm or back) levels circulating IgE Positive reaction = redness/edema @ 15-30 mins 23 24 4  4/4/2023 Skin testing for Type I Hypersensitivity Lab tests for Type I Hypersensitivity RIST (Radioimmunosorbent test) Total IgE level Noncompetitive immunoassay 25 26 Lab tests for Type I Hypersensitivity Treatment of Type I Hypersensitivity RAST (Radioallergosorbent test) Avoidance Antigen specific IgE Antihistamines Noncompetitive immunoassay Bronchodilators Inhaled corticosteroids Epinephrine Hyposensitization Anti-IgE monoclonal Ab Singulair 27 28 Hyposensitization Anti-IgE monoclonal antibody Allergy shots Combines with IgE at same site that IgE would bind Immunotherapy to receptors on mast cells Useful when typical allergy meds don’t work Alleviates allergic symptoms NOT A CURE! Severe-persistent asthma Alters body’s immune response to allergens IgG response Omalizumab (Xolair) Buildup of IgG to allergen IgG binds to the offending antigen before it reaches IgE coated mast cells 29 30 5  4/4/2023 Singulair Type II Hypersensitivity Montelukast sodium Cell bound antigens Leukotriene receptor antagonist Triggered by Ag on cell surface Binds to leukotriene receptors on airway muscle Antibody dependent cellular cells, macrophages, eosinophils, and myeloid stem cytotoxicity (ADCC) cells Inhibits bronchoconstriction IgG and IgM bind to surface Ag Decreases mean peripheral eosinophil count C’ and phagocytosis activated 31 32 Mechanism of action Type II outcomes Ab coats cell surface 1) Destruction of cell = lysis → C’ activated Hemolytic disease of fetus/newborn (HDFN) → cell lysis Blood transfusion reaction, autoimmune hemolytic anemias → opsonization → phagocytosis 2) Function of cell is inhibited Myasthenia gravis Results in cell damage, Goodpasture’s destruction, and dysfunction 3) Function of cell increased beyond normal Graves disease 33 34 Type III Hypersensitivity Type III Outcomes Immune complex dependent 1) Arthus reaction – after vaccination 2) Serum sickness – after antitoxins, some meds Ab combines with soluble Ag → immune complex 3) Autoimmune diseases – rheumatoid arthritis formation Deposit in tissue (joints, lungs, skin, kidneys) Activate C’ Influx of inflammatory cells Prolongs total inflammatory response 35 36 6  4/4/2023 Arthus reaction Serum Sickness Local immune complex Reaction to specific immune formation globulins or medications Residual Ab bind to Ag Esp to antitoxins produced in components animals Complement binds to complex Usually due to Ab to some Inflammation, swelling, redness animal protein Neutrophils attracted and cause tissue damage Same mechanism as Arthus reaction, but systemic Sometimes seen after booster manifestation vax (Dtap) 37 38 Autoimmune diseases Type IV Hypersensitivity Rheumatoid arthritis Delayed hypersensitivity Systemic lupus erythematosus Mediated by Th1 cells and cytotoxic T-cells Ab and C’ are not directly involved Immune complex deposition triggers inflammation and Initial sensitization phase → memory T cells tissue destruction about 1-2 weeks after 1st exposure Significant cause of morbidity Subsequent exposure → cell-mediated response and mortality about 48-72 hours after exposure 39 40 Mechanism of action Type IV Outcomes Antigen forms complex with skin proteins 1) Contact dermatitis APC presents Ag to Th1 Activated Th1 cells 2) Hypersensitivity Release cytokines pneumonitis Recruit neutrophils Activate macrophages 3) TB skin testing Activate cytotoxic T-cells Results in tissue damage 41 42 7  4/4/2023 Contact dermatitis Contact dermatitis Common causes: Allergen combines with host protein and stimulates an immune response Poison ivy, oak, sumac Intensity of reaction depends on concentration of Nickel allergen and degree of sensitization Rubber Takes 48 – 72 hours for reaction to manifest Cosmetics Mild to severe localized inflammation Topical medications May last 3 – 4 weeks Latex Redness, blisters, itching, peeling 43 44 iPhone vs BlackBerry Patch testing for contact dermititis When wedding rings Non-absorbent adhesive patch containing allergen attack Area is read at 48 hours Final evaluation after 4 – 7 days Also available for certain industries Side effects vary 45 46 Hypersensitivity pneumonitis TB skin testing Allergic diseases of the lungs Mantoux test Caused by inhalation of bacteria, fungi, or chemicals Purified protein derivative (PPD) Examples: Farmer’s lung, bird breeder’s lung, PPD of M.tuberculosis injected intradermally humidifier lung disease Test reading at 48-72 hours Positive reaction indicates TB exposure 47 48 8  4/4/2023 Comparison of hypersensitivity reactions Thank you for listening! Kristin Butler, MPH, MLS (ASCP)CM LSU Health Shreveport 318-813-2919 [email protected] https://microbenotes.com/hypersensitivity-introduction-causes-mechanism-and-types/ 49 50 9