Hypersensitivities

NISAR ALI MSC Microbiology

emailNisar4044@yahoo.com

University of Swat

Hypersensitivities Undesirable reactions produced by the normal immune system. Hypersensitivity is an exaggerated immune response that results in tissue damage and is manifested in the individual on a second or subsequent contact with an antigen. Hypersensitivity reactions can be classified as either immediate or delayed. Obviously immediate reactions appear faster than delayed ones, but the main difference between them is the nature of the immune response to the antigen. Allergy Allergies, also known as allergic diseases, are a number of conditions caused by hypersensitivity of the immune system to something in the environment that usually causes little or no problem in most people. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptoms may include red eyes, an itchy rash, runny nose, shortness of breath, or swelling. Food intolerances.

General Features

1.Hypersensitivity reactions can be elicited by exogenous environmental antigens or endogenous self antigens.2.Results from failure of normal regulation of immune response.3.Development of hypersensitivity diseases is often associated with the inheritance of particular susceptibility genes.

Types Of HypersensitivityHypersensitivity reactions are divided according to mechanism of action into four groups:1-Type I (Immediate hypersensitivity).2-Type II (Cytotoxic hypersensitivity).3-Type III (Immune complex hypersensitivity).4-Type IV (Cell-mediated or Delayed hypersensitivity).5-Type V (Stimulatory Type) Jones-Mote Reaction (or) Cutaneous Basophil Hypersensitivity

Type I Hypersensitivity (IGE DEPENDENT) A type I hypersensitive reaction is induced by certain types of antigens referred to as allergens, and has all the hallmarks of a normal humoral response. Allergic reactions occur when an individual who has produced IgE antibody in response to an innocuous antigen (allergen) subsequently encounters the same allergen. Type I, or anaphylactic, reactions often occur within 2 to 30 minutes after a person sensitized to an antigen is re-exposed to that antigen.

Antigen-induced mediator release from mast cell

PHASES OF TYPE I Hypersensitivity REACTION

IMMEDIATE REACTION LATE-PHASE REACTIONManifested in minutes Manifested in 2-24 hours

laterSubsides in few hours May last for several daysRelease of mast cell•Histamine•Leukotrienes: C4, D4•Prostaglandins: D2

Tissue infiltration by:•Neutrophils•Eosinophils•Basophils•Monocytes•CD4+ T Cells

Effects•Vasodilation•Increase Vascular Permeability•Bronchoconstriction•Mucus-secretion

•Epithelial injury by inflammatory response

Type II Hypersensitivity (Cytolysis And Cytotoxic).These reactions involve a combination of IgG (or IgM) antibodies with an antigenic determinants on the surface of cells. Antibody can activate the complement system, creating pores in the membrane of a foreign cell, or it can mediate cell destruction by antibody dependent cell-mediated cytotoxicity (ADCC). Type II hypersensitivity is generally, called cytolytic or cytotoxic reactions because it results in the destruction of host cells, either by lysis or toxic mediators. Type II hypersensitive reactions involve antibody-mediated destruction of cells

Type II hypersensitivity

Type III Hypersensitivity—Immune Complex- Mediated Type III reactions involve antibodies against soluble antigens circulating in the serum. The antigen-antibody complexes are deposited in organs and cause inflammatory damage. The tissue damage that results from the deposition of immune complexes is caused by the activation of complement, platelets and phagocytes; in essence, an acute inflammatory response

Immune complex-mediated hypersensitivity. (1) Immune complexes on the basement membrane of the wall of a blood vessel, where they; (2) activate complement and attract inflammatory cells such as neutrophils to the site. (3) The neutrophilis discharge enzymes as they react with the immune complexes, resulting in damage to tissue cells

Type IV Hypersensitivity—Delayed HypersensitivityType IV hypersensitivity reactions (delayed hypersensitivity) constitute one aspect of cell-mediated immune response and are caused mainly by T cells. These are typically provoked by intracellular microbial infections or haptens like simple chemicals applied on the skin, evolve slowly and consist of a mixed cellular reaction involving lymphocytes and macrophages in particular. It is named delayed hypersensitivity because it appears in 24 to 48 hours after the presensitized host encounters the antigen, while immediate hypersensitivity reactions develop in 1/2 to 12 hours. A major factor in the delay is the time required for the participating T cells and macrophages to migrate to and accumulate near the foreign antigens. The T cells involved in delayed type hypersensitivity reactions are primarily TD cells. In some types of hypersensitivities resulting in tissue damage, Tc cells may also participate.

Type IV (delayed or cell-mediated) hypersensitivity

Type V: Hypersensitivity (Stimulatory Type) Jones-Mote Reaction (or) Cutaneous Basophil Hypersensitivity This is an antibody-mediated hypersensitivity and is a modification of type II hypersensitivity reaction. Antibodies interact with antigens on cell surface which leads to cell proliferation and differentiation instead of inhibition or killing. Antigen-antibody reaction enhances the activity of affected cell. Example of Grave’s disease: Thyroid hormones are produced in excess quantity in grave’s disease. Long acting thyroid stimulating (LATS) antibody is an autoantibody to thyroid membrane antigen. It is presumed that LATS combines with a TSH receptor on thyroid cell surface and brings about the the same effect as TSH resulting in excessive secretion of thyroid hormone.