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VETERINARY PARASITOLOGY (3+2) General Veterinary Parasitology © (Unit-I) @ Course Instructor @ Assistant Professor M.V. Se., PhD Department of Veterinary Parasitology oO Dr. Madhurendra Bachan @ Hypersensitivity Classification of Hypersensitivity based on the time duration taken to react Immediate Hypersensitivity: Q refer to anaphylactic reactions within the humoral branch initiated by antibody or antigen- antibody complexes as immediate hypersensitivity, because the symptoms are manifest within minutes or hours after a sensitized recipient encounters antigen. Delayed-type hypersensitivity (DTH): QO Here symptom arises taking more time after exposure (It may takes days) Forms of hypersensitive reaction Based on differences in the effector molecules generated in the course of the reaction it may classified into Immediate hypersensitive reactions Here different antibody isotypes induce different immune effector molecules. oOo Example: v IgE antibodies induce mast-cell degranulation with release of histamine and other biologically active molecules. v IgG and IgM antibodies, induce hypersensitive reactions by activating complement. The effector molecules in the complement reactions are the membrane-attack complex (MAC) and such complement split products as C3a, C4a, and CSa. Delayed-type hypersensitivity reactions Q) Here the effector molecules are various cytokines secreted by activated Ty or Tc cells. © IgE-Mediated (Type I) Hypersensitivity QO) Induced by certain types of antigens referred to as allergens QO An allergen induces a humoral antibody response by the same mechanisms as described for other soluble antigens, resulting in the generation of antibody-secreting plasma cells and memory cells. QO) What distinguishes a type I hypersensitive response from a normal humoral response is that the plasma cells secrete IgE QO This class of antibody binds with high affinity to Fc receptors on the surface of tissue mast cells and blood basophils. QO) Mast cells and basophils coated by IgE are said to be sensitized. OQ A later exposure to the same allergen cross-links the membrane-bound IgE on sensitized mast cells and basophils, causing degranulation of these cells. The pharmacologically active mediators released from the granules act on the surrounding tissues. QO Principal effects: Vasodilation and Smooth-muscle contraction- may be either systemic or localized, depending on the extent of mediator release. Allergen General mechanism underlying a type I hypersensitive reaction Q Exposure to an allergen activates B cells to form IgE secreting plasma cells. UO) Secreted IgE molecules bind to IgE specific Fe receptors on mast cells and blood basophils. Second exposure to the allergen leads to crosslinking of the bound IgE, triggering the release of pharmacologically mediators, vasoactive amines, from mast cells and basophils. Q) The mediators cause smooth-muscle contraction, increased vascular permeability, and vasodilation. Several Pharmacologic Agents Mediate Type I Reactions QO These pharmacologically active agent/mediators released during mast-cell or basophil degranulation QO Act on: local tissues as well as on populations of secondary effector cells (Eosinophils, Neutrophils, T lymphocytes, monocytes, and platelets). The mediators thus serve as an amplifying terminal effector mechanism. QO When generated in response to parasitic infection: these mediators initiate beneficial defence processes, including vasodilation and increased vascular permeability, which brings an influx of plasma and inflammatory cells to attack the pathogen. QO) When generated against the inappropriate antigens (eg. allergens): results in unnecessary increases in vascular permeability and inflammation whose detrimental effects. o Re & Allergies to Parasites Beneficial role of the IgE—mast cell—-eosinophil system in immunity to parasitic worms was first observed in the self-cure phenomenon. Helminths preferentially stimulate IgE responses, and helminth infestations are commonly associated with many of the signs of allergy and anaphylaxis Example: Animals with tapeworms may show respiratory distress or urticaria. Anaphylaxis may be provoked by rupture of a hydatid cyst during surgery or Through transfusion of blood from a dog infected with Dirofilaria immitis to a sensitized animal. Vv v Vv v Classification of mediators classified as either primary or secondary Primary mediators produced before degranulation and are stored in the granules. Primary mediators are histamine, proteases, eosinophil chemotactic factor, neutrophil chemotactic factor, and heparin. Secondary mediators released by the breakdown of membrane phospholipids during the degranulation process. The secondary mediators include platelet-activating factor, leukotrienes, prostaglandins, bradykinins, and various cytokines. Principal mediators involved in type I hypersensitivity Mediator Effects Primary Histamine Increased vascular permeability; smooth-muscle contraction Serotonin Increased vascular permeability; smooth-muscle contraction Eosinophil Chemotactic factor (ECF-A) Eosinophil chemotaxis Neutrophil Chemotactic Facor (NCF-A) Neutrophil chemotaxis Proteases Bronchial mucus secretion; degradation of blood- vessel basement membrane; generation of complement split products HISTAMINE (Primary Mediators) Major component of mast-cell granules Once released from mast cells, histamine initially binds to specific receptors on various target cells. Three types of histamine receptors are found » HI receptor » H2 receptor » H3 receptor These receptors have different tissue distributions and mediate different effects when they bind histamine. Most of the biologic effects of histamine in allergic reactions are mediated by the binding of histamine to HI receptors (induces contraction of intestinal and bronchial smooth muscles, increased permeability of venules, and increased mucus secretion by goblet cells) Interaction of histamine with H2 receptors increases vascular permeability and dilation and stimulates exocrine glands. Binding of histamine to H2 receptors on mast cells and basophils suppresses | histamine exerts negative feedback on the release of mediators. LEUKOTRIENES AND PROSTAGLANDINS (Secondary mediators) Leukotrienes >» mediate bronchoconstriction, » increased vascular permeability, and > mucus production. Prostaglandin » causes bronchoconstriction QO The contraction of human bronchial and tracheal smooth muscles appears at first to be mediated by histamine, but, within 30-60 s, further contraction is mediated by the leukotrienes and prostaglandins. QO In humans, the leukotrienes are thought to contribute to the prolonged bronchospasm and "6 of mucus seen in asthmatics. Type I Reactions Can Be Systemic or Localized SYSTEMIC ANAPHYLAXIS Q) Systemic anaphylaxis is a shock-like and often fatal state whose onset occurs within minutes of a type | hypersensitive reaction. LOCALIZED ANAPHYLAXIS Q) In localized anaphylaxis, the reaction is limited to a specific target tissue or organ, often involving epithelial surfaces at the site of allergen entry. Example: Allergic rhinitis (hay fever), asthma, atopic dermatitis (eczema), and food allergies. Late-Phase Reactions Induce Localized Inflammatory Reactions As a type I hypersensitive reaction begins to subside, mediators released during the course of the reaction often induce localized inflammation called the late-phase reaction. Late-phase reaction begins to develop 4-6 h after the initial type I reaction and persists for 1-2 days. The reaction is characterized by infiltration of neutrophils, eosinophils, macrophages, lymphocytes, and basophils. The localized late-phase response also may be mediated partly by cytokines released from mast cells. Both TNF-a and IL-1 increase the expression of cell-adhesion molecules on venular endothelial cells, thus facilitating the build-up of neutrophils, eosinophils, and monocytes that characterizes the late-phase response. 
