Hypersensitivity

Introduction the immune response uses multiple strategies to reduce damage to self by turning off responses when pathogen is cleared and avoiding reactions to self antigens. However, these checks and balances can break down, leading to immune-mediated reactions that are more detrimental than protective.

Introduction What is the Hypersensitivity ? Hypersensitivity refers to excessive, reactions produced by the normal immune system. Hypersensitivity reactions are harmful antigen-specific immune responses , occur when an individual who has been primed by an innocuous antigen subsequently encounters the same antigen , produce tissue injury and dysfuntion

Hypersensitivity reactions Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction. Frequently, a particular clinical condition (disease) may involve more than one type of reaction.

TYPE I Hypersensitivity OR (IgE-mediated) is also known as immediate or anaphylactic hypersensitivity. The reaction may involve skin (urticaria and eczema), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis). The reaction may cause a range of symptoms from minor inconvenience to death. The reaction usually takes 15 - 30 minutes from the time of exposure to the antigen.

TYPE I Hypersensitivity Immediate hypersensitivity is mediated by IgE. The primary cellular component in this hypersensitivity is the mast cell or basophil. Healthy individuals generate IgE antibodies only in response to parasitic infections. However, some people referred to as atopic , are predisposed to generate IgE antibodies against common environmental antigens (Plant pollens – Foods- Drugs- Insect products).

Type I reactions occur in two phases - Sensitization phase First contact with allergens - Challenge phase Subsequent contact with allergens

Mediators

Mediators involved in the allergic response : Hypersensitivity Reactions Mediators involved in the allergic response : Performed mediators Newly formed mediators (membrane-derived) Histamine & serotonin Bronchoconstriction Increased vascular permiability Neutrophil & eosinophil chemotactic factors(NCF and ECF) Induce inflammatory cell infiltration Leukotrine (LT) B4: Chemoattractant LTC4,-D4,-E4(slow-reacting substance of anaphylaxis SRS-A): Sustained bronchoconstriction and edema Prostaglandins & thromboxanes: Platelet-activating factor (PAF) Prolonged air way hyperactivity

Allergy: Rhinitis, Eczema & Conjunctivitis Normal nose

TYPE II Hypersensitivity is also known as ( cytotoxic hypersensitivity). the antibodies (IgM & IgG) produced by the immune response bind to antigens on the patient's own cell surfaces (antibody-mediated). Antibody bound to a cell-surface antigen can induce death of the antibody-bound cell

Mechanism of killing targeted cells : 1) Certain immunoglobulin subclasses can activate the complement system. 2) antibodies can mediate cell destruction by antibody dependent cell-mediated cytotoxicity (ADCC), in which cytotoxic cells bearing Fc receptors bind to the Fc region of antibodies on target cells and promote killing of the cells. 3) antibody bound to a foreign cell also can serve as an opsonin. (molecule that enhances phagocytosis by marking an antigen for an immune response)

Transfusion Reactions Transfusion reactions are an example of type II hypersensitivity, on the membrane of red blood cells are encoded by genes with several allelic forms. An individual with a particular allele of a blood-group antigen can recognize other allelic forms in transfused blood as foreign. Blood types are referred to as A, B, or O, and the antigens that are associated with the blood types are identified as A, B, and H.

The Table shows that the plasma of individuals with a given blood type, such as A, have antibodies against the alternative blood type, anti-B antibody. These antibodies are presumed to arise in response to microorganisms and ingested foodstuffs that have antigenic determinants very similar to blood group antigens. Individuals with type AB cells have plasma with no antibodies to either A or B antigens. Type O individuals have antibodies against both A and B antigens.

Transfusion Reactions When the antibodies directed toward ABH antigens are termed Isohemagglutinins For example, If a type A individual is transfused with blood containing type B cells, a transfusion reaction occurs in which the preexisting anti-B isohemagglutinins bind to the B blood cells and mediate their destruction by means of complement-mediated lysis. Individuals with blood type O express only the H antigen. Although they can donate blood to anyone.

Hemolytic Disease of the Newborn Hemolytic disease of the newborn develops when maternal IgG antibodies specific for fetal blood-group antigens cross the placenta and destroy fetal red blood cells. An Rh- mother fertilized by an Rh+ father is in danger of developing a response to the Rh antigen and rejecting an Rh+ fetus. at the time of delivery, separation of the placenta from the uterine wall allows larger amounts of fetal umbilical cord blood to enter the mother’s circulation. These fetal red blood cells stimulate Rh-specific B cells to mount an immune response.

Hemolytic Disease of the Newborn Hemolytic disease of the newborn caused by Rh incompatibility in a second or later pregnancy can be almost entirely prevented by administering antibodies against the Rh antigen to the mother at around 28 weeks of pregnancy and within 24 to 48 hours after the first delivery.

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