HYPERSENSITIVITY

INTRODUCTION
WHAT IS HYPERSENSITIVITY?
Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. The immune system is amazingly good at protecting the body against the numerous pathogens that challenge us, but immunity also makes mistakes that can cause serious health problems. A common mistake begins when the immune system recognizes a foreign protein that does not pose any threat, sometimes raising a violent immune response. The immune system will recognize selfproteins and begin to attack the bodys own tissues.

TYPES OF HYPERSENSITIVITY
Allergic reactions can be immediate or delayed and the rate and types of reaction indicate different immune responses. Peter Gell and Robert Comb developed a system in 1963 to classify these different reactions. Nearly 40 years ago they proposed a classification scheme which defined 4 types of hypersensitivity reactions. Type I Immediate or IgE mediated hypersensitivity Type II Antibody dependent -IgG Type III Immune Complex-Mediated Type IV Cell mediated or delayed type hypersensitivity (DTH) The first three are mediated by antibody and the fourth one is by T-Cells.

TYPE-I HYPERSENSITIVITY REACTION

The hypersensitivity reactions may be either local or systemic systemic anaphylaxis : It is a shock-like and often fatal state whose onset occurs within minutes of a type-I hypersensitive reaction. Localized Anaphylaxis In localized anaphylaxis, the reaction is limited to a specific target tissue or organ often involving epithelial surfaces at the site of allergen entry. The tendency to manifest localized anaphylactic reactions is inherited and is called atopy. Atopic allergies which afflict at least 20% of the population in developed countries, include a wide range of IgEmediated disorders, including allergic rhinitis, asthma.

Allergic Rhinitis
It is the most common atopic disorder, affecting 10% of the US prop.. It is commonly known as hay fever. This results from the reaction of airborne allergens with sensitized mast cells in conjunctivae and nasal mucosa to induce the release of pharmacologically active mediators from mast cells. These mediators then cause localized vasodilation and increased capillary permeability. Symptoms -watery exudation of the conjucative, nasal mucosa and upper respiratory tract, as well as sneezing and coughing. s

Asthma Asthma is triggered by degranulation of mast cells with release of mediators, but instead of occurring in nasal mucosa the reaction develops in the lower respiratory tract. The resulting contraction of the bronchial smooth muscles leads to bronchoconstriction. Asthmatic patients may have abnormal level of receptors for neuropeptides. E.g., asthmatic patients have increased expression of receptors for substance P a peptide that contracts smooth muscles, and decreased expression of receptors for vasoactive intestinal peptide which relax smooth muscle.

Methods to Detect Type I Hypersensitivity Reactions

1. skin testing. 2. Radioimmunosorbent test (RIST) can quantify nanogram amounts of total serum IgE. 3. Radioallergosorbent test (RAST)

Steps for controlling

The obvious first step in controlling type I hypersensitivity is to avoid contact with known allergens. .Removal of house pets, dust control measures, or avoidance of offending foods can eliminate a type I response. Immunotherapy with repeated injections of increasing doses of allergens (hyposensitization) has been reduce the severity of type I reaction or even eliminate them completely Such repeated introduction of allergen by subcutaneous injections appears to cause a shift toward IgG production or to induce T-cell-mediated suppression that turns off the IgE response. In this situation, the IgG antibody is referred to as blocking antobidy because it competes for the allergen, binds to it, and forms a complex that can be removed by phagocytosis: as a result the allegen is not available crosslink the IgE on the most cell membranes and allergic symptoms decrease.

TYPE II ANTOBODY-MEDIATED CYTOTOXIC HYPERSENSITIVITY Type II hypersensitivity reactions antibody-mediated destruction of cells. involve

HEMOLOGIC DISEASE OF THE NEWBORN IS CAUSED BY TYPE II REACTIONS

TYPE III IMMUNE COMPLEX MEDIATED HYPERSENSITIVITY

Type III hypersensitivity reaction is mediated by immune complexes essentially of IgG antibodies with soluble antigens. It occurs when antigens and antibodies are present in roughly equal amounts, causing extensive cross-linkings. Large immune complexes that cannot be cleared are deposited in vessel walls and induce an inflammatory response. The reaction can take hours, days or even weeks to develop. Type III reactions can be localized or can also be generalized.

TYPE III REACTIONS - LOCALIZED

Injection of an antigen intradermally or subcutaneously into an animal that has high levels of circulating antibody specific for that antigen leads to the formation of localized immune complexes, which mediate on acute Arthus reactions with in 4-8 hrs. As the reaction develops, localized tissue and vascular damage results in an accumulation of fluid (edema) and red blood cells (erythema) at the site.

TYPE-III REACTIONS (GENERLIZED)

When large amounts of antigen enter the bloodstream and bind to antibody, circulating immune complexes can form. If antigen is in excess, small complexes from, because these are not easily cleared by the phagocytic cells. They can cause tissue damaging. Now these generalized reaction are observed after the administration of antitoxins containing foreign serum, such as horse antitetanus. In such cases the recipient of a foreign serum protein. These antibodies then form circulating immune complexes with the foreign serum antigens. With in days or weeks after exposure to foreign serum antigens, an individual begins to manifest a combination of symptoms that are called serum sickness.

TYPE IV CELL MEDIATED OR DELAYED TYPE HYPERTENSITIVITY

It is called cell mediated because it is characterized by cell mediated response rather than antibodies as in other types of hypersensitivity reactions. Specifically, the T lymphocytes are involved in the development of the sensitivity. T lymphocytes are white blood cells in the body. After exposure to antigens, through a series of biochemical events the T-cells will be activated. By releasing some chemicals T cells activate other white blood cells to mount on immune response. The entire cascade of reactions take 2-3 days to develop

PHASE OF DTH SENSITIZATION PHASE

EFFECTOR PHASE

A prolonged DTH response can lead to formation of a granuloma, a nodule-like mass . Lytic enzymes released from activated macrophages in a granuloma can cause extensive tissue damage.