Hypersensitivity Reactions (Immunology) PDF

‫كلية الطب‬ Hypersensitivity Reactions Lectures 7&8 Dr. Sozan Mohamed Fadl Head of Microbiology & Immunology Unit  Objectives By the end of this lecture, you should be able to: Define hypersensitivity Compare between the four types of hype...

‫كلية الطب‬ Hypersensitivity Reactions Lectures 7&8 Dr. Sozan Mohamed Fadl Head of Microbiology & Immunology Unit  Objectives By the end of this lecture, you should be able to: Define hypersensitivity Compare between the four types of hypersensitivity Explain the mechanism of each type Outline the link between hypersensitivity and the autoimmune diseases Hypersensitivity Reaction: is an exaggerated immune response to exogenous or endogenous (self) antigens. Types of antigens: Infection: bacterial, viral, fungal, ……… Harmless substances: Animals' wool, drugs, plant pollens, metals, dust, foods: egg, fruits, peanuts, seafood, … Self antigen: autoimmunity. Stages: Sensitization phase: asymptomatic first contact with an antigen. Effector phase: symptomatic phase during second and repeated exposure to the same antigen.  Types of Hypersensitivity According to mechanism of action there are four types: ACID: Type I (Allergy, atopy or immediate hypersensitivity) Type II (Cytotoxic hypersensitivity). Type III (Immune complex hypersensitivity). Type IV (Delayed or Cell-mediated hypersensitivity). NB: Types I, II, III are antibody-mediated, while type IV is cell-mediated.  Type-I: Immediate Hypersensitivity Reaction  Immediate: symptoms appear after 15-30 minutes to of allergen exposure. Could be delayed to 6-24 hours.  Also known as allergy or atopy.  Against exogenous antigens, so it does not cause autoimmune diseases. Examples: o Localized reaction: Urticaria Allergic rhinitis Asthma. Drugs allergy e.g., penicillin, sulfonamides, … Allergic conjunctivitis o Systemic reaction (Anaphylaxis): low blood pressure and airway obstruction can be fatal Mechanism of Type I Hypersensitivity Reaction: 1. First exposure (Sensitization phase): Plasma cells→ produce specific IgE IgE bind to its Fcε receptors on the mast cells & the basophils. 2. Second and repeated exposure: 1. Early reaction: the allergen bind to its specific IgE on the mast cells→ degranulation and release of inflammatory mediators: tryptase, histamine & prostaglandin, …...  Effect of histamine and the other mediators: o Itching (pruritic) o Vasodilation→ increased vascular permeability→ edema, erythema, hypotension. o Contraction of bronchial and intestinal muscles 2. Late reaction: attraction of eosinophils→ tissue damage. Urticaria Angioedema Allergic Conjunctivitis  SDL: Anaphylaxis: (type I hypersensitivity reaction) https://next.amboss.com/us/article/rq0f-S?q=Anaphylaxis :Definitions Anaphylaxis: a severe type-1 hypersensitivity reaction that can be life-threatening. Anaphylactic shock: a shock that results from anaphylaxis. Etiology: Younger patients: …………… Older patients: ……………………. Hospitalized patients: ………………… Management: Administer …………… intramuscular. Once stabilized, give ………….. & …………………  Type II Hypersensitivity Known as Cytotoxic Hypersensitivity. Lead to cells destruction Types of Antigens:  Exogenous: drug that had bind to a cell membrane.  Endogenous: part of a cell membrane→ autoimmune disease. Mechanism: IgM or IgG bind to the cell membrane leading to cells destruction by: o Opsonization & phagocytosis. o Natural killer cells (NK) activation. o Complement activation and cell lysis by MAC. ADCC Clinical Examples on Type II Hypersensitivity: 1) Anti-AB antibodies (IgM)→ Blood transfusion reaction 2) Anti-Rh factor antibodies (IgG)→ Hemolytic disease of the fetus and newborn (Rh incompatibility). 3) Autoimmune diseases:  Anti-acetylcholine receptor→ Myasthenia gravis disease (muscle weakness and paralysis).  Drug induced autoimmune hemolytic anemia e.g., penicillin.  Type III Hypersensitivity  Known as immune complex hypersensitivity.  The antigens are soluble → formation immune complexes. Types of Allergen:  Exogenous: drugs.  Endogenous: soluble self antigen→ autoimmune diseases. Mechanism: - IgG antibodies bind to antigens in circulation (immune complexes). - Immune complexes deposit in the tissues specially the vessels and activate the complement, and the neutrophils→ inflammation e.g., vasculitis. Clinical Examples on Type III Hypersensitivity: 1- Arthus reaction: localized in skin. Intradermal injection of tetanus or diphtheria vaccines → local skin lesion. 2- Serum sickness: systemic reaction Intravascular drugs injection→ fever, skin rash, joints pain. 3- Some autoimmune diseases: Systemic lupus erythematosus (SLE). Antinuclear antibody (ANA) against DNA, RNA, histones, …….  SLE Arthus Reaction  Type IV Hypersensitivity Known as cell mediated or delayed hypersensitivity. peaks 48-72 hours after exposure to antigens. Types of antigens: Intracellular pathogens e.g., mycobacteria, viruses, …. Metals and chemicals. Self antigens Cells involved: CD4+ T helper-1 Macrophages CD8+ T cytotoxic cells Clinical examples of type IV hypersensitivity: Contact dermatitis: nickel, cosmetics, plants e.g., ivy. Granulomatous formation: o Tuberculosis o Tuberculin (Mantoux) skin test. Some autoimmune diseases: o Diabetes type-1 o Multiple sclerosis. Drug induced rash: following amoxicillin administration for infectious mononucleosis. Contact Dermatitis Contact dermatitis: Tuberculin test  1 3 3 4 Type Immunoglobulins Cells & Examples mediators Type-1 IgE Mast cells Urticaria Immediate Basophils Allergic rhinitis Eosinophils Asthma. Drugs allergy -Histamine Allergic conjunctivitis -Prostaglandin Anaphylaxis -Tryptase Type-2 IgM or IgG Phagocytes Hemolytic transfusion cytotoxic NK cells reaction Complement Hemolytic disease of the fetus and newborn Myasthenia gravis. Drug induced hemolytic anemia Type Immunoglobulins Cells & Examples mediators Type-3 IgG Complement Arthus reaction Immune- Neutrophils Serum sickness complex Systemic lupus erythematosus (SLE) Type-4 ---- TH-1 (CD4+) Contact dermatitis Delayed T cytotoxic Mantoux tuberculin or cell cells (CD8+) skin test mediated Macrophages Multiple sclerosis Type-1 diabetes mellitus Drug reactions Disease name Antigen Affected organs Asthma SLE Arthus reaction Serum sickness Myasthenia gravis Transfusion reaction Hemolytic fetus anemia What is the type of hypersensitivity in multiple sclerosis? A. Anaphylaxes B. Cytotoxic C. Immune complexes D. Cell mediated Which of these is an example of type-II hypersensitivity reaction? E. Asthma F. Contact dermatitis G. Blood transfusion reaction H. Systemic lupus erythematosus. A 4-month-old boy is brought to the physician because of a painful lesion on his right leg. Yesterday, he received his scheduled childhood immunizations, including the second dose of the diphtheria, tetanus, and acellular pertussis vaccine. Physical examination shows an ulcer over the right thigh. Skin biopsy shows localized edema, skin necrosis, neutrophilic infiltration, and complement deposition. Which of the following is the most likely cause of his symptoms? A. Dermal mast cell activation B. Immune complex deposition C. Attack of cell membrane antigens. D. T lymphocyte-mediated hypersensitivity Are you allergic to something? Share your story with us  :Reference n Basic Immunology Functions and Disorders of :the Immune System 6th edition :Chapter 11- Hypersensitivity reactions: Pages 218 to 234.Lippincott’s Immunology 3rd edition :Chapter 14- Hypersensitivity reactions: Pages 207-224