Section 2 Hypersensitivity Reactions

Type I hypersensitivity (Anaphylactic type) Immediate hypersensitivity reaction, resulting from release of pharmacologically active mediators.

Activation of mast cells in type I hypersensitivity and release of their mediators. ECF, eosinophil chemotactic factor; NCF, neutrophil chemotactic factor; PAF, platelet-activating factor. (From Robbins Basic Pathology ,2003） Slide 7.9

(2) Tissue reactions: variable in severity Mildest may be only edema. Reaction is triggered by mast cells, basophils. If inflammatory cells are present, many are eosinophils.

(3) Diseases ① Urticaria and angioneurotic edema ② Asthma ③ Hay fever ④Insect allergy: serious or fatal anaphylaxis may follow. Edema of larynx, with airway obstruction may occur.

2. Type II Hypersensitivity Cytolytic or cytotoxic reactions (1) Mechanism: ① Complement-dependent reactions Transfusion reactions Erythroblastosis fetal Autoimmune hemolytic anemia Certain drug reactions

②Antibody-dependent cell-mediated cytotoxicit (ADCC). May be relevant to: Graft rejection The destruction of targets too large to be phagocytosed, such as parasites or tumor cells.

③Antibody-mediated cellular dysfunction Myasthenia gravis: muscle weakness Graves’ disease: hyperthyroidism

Schematic illustration of three different mechanisms of antibody-mediated injury in type Ⅱ hypersensitivity. A, Complement-dependent reactions that lead to lysis of cells or render them susceptible to phagocytosis. (From Robbins Basic Pathology ,2003） Slide 7.10

Antibody-dependent cell-mediated cytotoxicity (ADCC) Antibody-dependent cell-mediated cytotoxicity (ADCC). IgG-coated target cells are killed by cells that bear Fc receptors for IgG (e.g., NK cells, macrophages). . (From Robbins Basic Pathology ,2003） Slide 7.11

Antireceptor antibodies disturb the normal function of receptors Antireceptor antibodies disturb the normal function of receptors. In this example, acetylcholine receptor antibodies impair neuromuscular transmission in myasthenia gravis. (From Robbins Basic Pathology ,2003） Slide 7.12

3. Type Ⅲ Hypersensitivity (Immune complex-mediated) (1) Reaction types ① Arthus reaction ② serum sickness ③ Collagen diseases

(2) Toxic complex diseases: ① Acute glomerulonephritis ② Systemic lupus erythematosus ③ Necrotizing angiitides ④ Rheumatoid arthritis ⑤ Progressive systemic sclerosis ⑥ Dermatomyositis etc.

Schematic illustration of the three sequential phases in the induction of systemic type Ⅲ (immune complex) hypersensitivity. (From Robbins Basic Pathology ,2003） Slide 7.13

Schematic representation of the pathogenesis of immune complex-mediated tissue injury. The morphologic consequences are depicted as boxed areas. . (From Robbins Basic Pathology ,2003） Slide 7.14

(From Robbins Basic Pathology ,2003） Immune complex vasculitis. The necrotic vessel wall is replaced by smudgy, pink “fibrinoid” (Dr. Trace Worrell) (From Robbins Basic Pathology ,2003） Slide 7.15

4. Type Ⅳ Hypersensitivity (Cell-Mediated ) Delayed hypersensitivity reaction (1) Tissue reaction: Consist of parenchymal destruction associated with perivascular lymphocytic and macrophage reaction.

(2) Diseases: ① Chronic active hepatitis ② Viral exanthem(皮疹） ③ Contact dermatitis ④ Graft rejection ⑤ Inflammatory bowel disease.

Delayed hypersensitivity in the skin Delayed hypersensitivity in the skin. Immunoperoxidase staining reveals a predominantly perivascular cellular infiltrate that marks positively with anti-CD4 antibodies. ( Dr. Louis Picker) . (From Robbins Basic Pathology ,2003） Slide 7.16

(From Robbins Basic Pathology ,2003） A section of a lymph node shows several granulomas, each made up of an aggregate of epithelioid cells and surrounded by lymphocytes. The granuloma in the center shows several multinucleate giant cells. ( Dr. Trace Worrell) (From Robbins Basic Pathology ,2003） Slide 7.17

Schematic illustration of the events that give rise to the formation of granuloma in type Ⅳ hypersensitivity reactions. Note the role played by T cell-derived cytokines. . (From Robbins Basic Pathology ,2003） Slide 7.18