Hypersensitivity Reactions (Lecture 29) PDF

Lecture (29); Hypersensitivity reactions (1) Hypersensitivity reactions (1) Objectives By the end of the lecture the student will be able to; Know the definitions of type I and type II hypersensitivity. Explain the underlying mechanisms of type I and type II hyperse...

Lecture (29); Hypersensitivity reactions (1) Hypersensitivity reactions (1) Objectives By the end of the lecture the student will be able to; Know the definitions of type I and type II hypersensitivity. Explain the underlying mechanisms of type I and type II hypersensitivity. List different examples of type I & type II hypersensitivity. Recognize the clinical manifestations of some examples of type I & type II hypersensitivity. www.vision.edu.sa Hypersensitivity reactions (1) Ag-Ab reaction Useful reaction, Harmful reaction, Against living irritants, Against living or non-living irritants, Resulting in their elimination. Resulting in tissue destruction. IMMUNITY HYPERSENSITIVITY www.vision.edu.sa Hypersensitivity reactions (1) Type I (immediate) hypersensitivity www.vision.edu.sa Hypersensitivity reactions (1) Type I (immediate) hypersensitivity Definition: Immediate hypersensitivity is a tissue reaction that occurs rapidly (typically within minutes) after the interaction of antigen with IgE antibody that is bound to the surface of mast cells in a sensitized host. www.vision.edu.sa Hypersensitivity reactions (1) The reaction is initiated by entry of an antigen, which is called an allergen because it triggers allergy.  Many allergens are environmental substances that are harmless for most persons on exposure.  Some people apparently inherit genes that make them susceptible to allergies.  This susceptibility is manifested by the propensity of such persons to mount strong T-helper 2 cell (Th2) responses and, subsequently, to produce IgE antibody against the allergens. www.vision.edu.sa  Hypersensitivity reactions (1) Sequence of Events in Immediate Hypersensitivity (Mechanism): Introduction of the antigen (Ag) for the 1st time: Activation of T-helper 2 (Th2) cells and production of IgE antibody. The Th2 cells secrete several cytokines; including IL-4, IL-5, and IL-13, which are responsible for all reactions of immediate hypersensitivity.  IL-4 stimulates IgE class switching in B cells to secrete IgE antibody.  IL-5 activates eosinophils that are recruited to the reaction.  IL-13 acts on epithelial cells and stimulates mucus secretion. IgE become fixed to the surface of mast cells. www.vision.edu.sa Hypersensitivity reactions (1) Sequence of Events in Immediate Hypersensitivity (Mechanism): Re-exposure to the same Ag: Reaction of Ag with IgE on the surface of mast cells. Liberation of histamine and other chemical mediators from mast cells, as well as generation of leukotrienes and prostaglandins, leading to;  Vasodilatation.  Bronchospasm.  ↑ mucus secretion.  Allergic inflammation (rich in eosinophils). www.vision.edu.sa Hypersensitivity reactions (1) Sequence of events in type I hypersensitivity www.vision.edu.sa Hypersensitivity reactions (1) Examples: Systemic reaction; Anaphylactic shock, e.g. penicillin injection or bee venom. Local reaction (Atopy); e.g. allergic rhinitis (hay fever) and bronchial asthma.  The term “atopy” is used to imply familial predisposition to such localized reactions, or genetic tendency to develop allergic disease. www.vision.edu.sa Hypersensitivity reactions (1) Anaphylactic shock  Within minutes of the exposure in a sensitized host; itching, urticaria, and skin erythema appear.  This is followed by respiratory difficulty caused by bronchoconstriction and accentuated by hypersecretion of mucus.  Laryngeal edema may occur, leading to upper airway obstruction.  In addition, the musculature of the entire GIT may be affected; leading to vomiting, abdominal cramps, and diarrhea.  Without immediate intervention, there may be systemic vasodilation with a fall in blood pressure (anaphylactic shock). www.vision.edu.sa Hypersensitivity reactions (1) Type II hypersensitivity www.vision.edu.sa Hypersensitivity reactions (1) Type II hypersensitivity Also called cytotoxic or antibody-mediated hypersensitivity. Definition: A Type of hypersensitivity caused by antibodies directed against target antigens on the surface of cells. www.vision.edu.sa Hypersensitivity reactions (1) Mechanism:  Ag: component of cell membrane, or hapten which attached to cell membrane e.g. drug.  Hapten is a small molecule that only becomes immunogenic when combined with a host protein carrier.  Ab: IgG or IgM.  Ag–Ab reaction can cause a disease by the following mechanisms; 1. Targeting cells for phagocytosis; e.g. autoimmune thrombocytopenia and autoimmune hemolytic anemia. 2. Activating the complement system leading to inflammation; e.g. Goodpasture syndrome. 3. Interfering with normal cellular functions; e.g. Grave’s disease. www.vision.edu.sa Hypersensitivity reactions (1) 1. Targeting cells for phagocytosis When circulating cells, such as RBCs or platelets, are opsonized and coated with autoantibodies, with or without complement proteins, the cells become targets for phagocytosis by neutrophils and macrophages. These phagocytes express receptors for IgG antibodies and for breakdown products of the C3 complement protein, and use these receptors to bind and ingest opsonized particles. Opsonized cells are usually eliminated in the spleen, and this is why splenectomy is of clinical benefit in autoimmune thrombocytopenia and some forms of autoimmune hemolytic anemia. www.vision.edu.sa Hypersensitivity reactions (1) www.vision.edu.sa  Hypersensitivity reactions (1) 2. Activating the complement system leading to inflammation  Ag–Ab reaction activates the complement system.  Products of complement activation serve several functions, one of which is to recruit neutrophils and monocytes, triggering inflammation in tissues.  Example; Goodpasture syndrome. www.vision.edu.sa  Hypersensitivity reactions (1) Goodpasture syndrome  Autoimmune disease.  Auto-antibodies attack basement membranes of kidney glomeruli and lung alveoli.  Clinical manifestations:  Nephritis.  Lung hemorrhage. www.vision.edu.sa Hypersensitivity reactions (1) 3. Interfering with normal cellular functions In Graves disease, antibodies against the Thyroid-Stimulating Hormone (TSH) receptor stimulate thyroid epithelial cells to secrete thyroid hormones, resulting in hyperthyroidism. www.vision.edu.sa Hypersensitivity reactions (1) www.vision.edu.sa Thank You www.vision.edu.sa