Buy the Book PDA Download

Update Me E-mail alerts The Merck Manual Minute

Print This Topic Email This Topic

Allergic and other hypersensitivity disorders are exaggerated or inappropriate immune reactions.

Classification

The Gell and Coombs classification delineates 4 types of hypersensitivity reaction. Hypersensitivity disorders often involve more than 1 type.

Type I: Type I reactions (immediate hypersensitivity) are IgE-mediated. Antigen binds to IgE (which is bound to tissue mast cells and blood basophils), triggering release of preformed mediators (eg, histamine, proteases, chemotactic factors) and synthesis of other mediators (eg, prostaglandins, leukotrienes, platelet-activating factor, cytokines). These mediators cause vasodilation, increased capillary permeability, mucus hypersecretion, smooth muscle spasm, and tissue infiltration with eosinophils, type 2 helper T cells (T_H2), and other inflammatory cells. Type I reactions underlie atopic disorders (eg, allergic asthma, rhinitis, conjunctivitis) and latex and some food allergies.

Type II: Type II reactions result when antibody binds to cellular or tissue antigens or to a molecule coupled to a cell or tissue. The antigen-antibody complex activates cells that participate in antibody-dependent cell-mediated cytotoxicity (eg, NK cells, eosinophils, macrophages), complement, or both. The result is cell and tissue damage. Disorders involving type II reactions include hyperacute graft rejection of an organ transplant, Coombs'-positive hemolytic anemias, Hashimoto's thyroiditis, and anti-glomerular basement membrane disease (eg, Goodpasture's syndrome).

Type III: Type III reactions cause acute inflammation in response to circulating antigen-antibody immune complexes deposited in vessels or tissue. These complexes can activate the complement system or bind to and activate certain immune cells, resulting in release of inflammatory mediators. Consequences of immune complex formation depend in part on the relative proportions of antigen and antibody in the immune complex. Early, there is excess antigen with small antigen-antibody complexes, which do not activate complement. Later, when antigen and antibody are more balanced, immune complexes are larger and tend to be deposited in various tissues (glomeruli, blood vessels), causing systemic reactions. The isotype of induced antibodies changes, and glycosylation of the complex's components contributes to the clinical response. Type III disorders include serum sickness, SLE, RA, leukocytoclastic vasculitis, cryoglobulinemia, hypersensitivity pneumonitis, bronchopulmonary aspergillosis, and several types of glomerulonephritis.

Type IV: Type IV reactions (delayed hypersensitivity) are T cell–mediated. There are 4 subtypes based on the T-cell subpopulation involved:

• IVa: Type 1 helper T cells
• IVb: Type 2 helper T cells
• IVc: Cytotoxic T cells
• IVd: IL-8-secreting T cells

These cells, sensitized after contact with a specific antigen, are activated by reexposure to the antigen; they damage tissue by direct toxic effects or through release of cytokines, which activate eosinophils, monocytes and macrophages, neutrophils, or killer cells depending on type. Disorders involving type IV reactions include contact dermatitis (eg, poison ivy), hypersensitivity pneumonitis, allograft rejection, TB, and many forms of drug hypersensitivity.

Autoimmune disorders: Immune system reactions directed against intrinsic body components can lead to autoimmune disease (see Table 1: Allergic and Other Hypersensitivity Disorders: Putative Autommune Disorders).

Table 1
Putative Autommune Disorders Disorder Mechanism or Evidence Highly probable* Autoimmune Addison's disease Antibody and possibly cell-mediated adrenal cytotoxicity Autoimmune hemolytic anemia Phagocytosis of antibody-sensitized RBCs Autoimmune thrombocytopenic purpura Phagocytosis or lysis of antibody-sensitized platelets Goodpasture's syndrome Anti-basement membrane antibody Graves' disease TSH-receptor antibody (stimulatory) Hashimoto's thyroiditis Cell- and antibody-mediated thyroid cytotoxicity Insulin resistance Insulin-receptor antibody Myasthenia gravis Acetylcholine receptor antibody Pemphigus Epidermal acantholytic antibody SLE Circulating and locally deposited immune complexes Type 1 diabetes Cell- and antibody-mediated islet cell antibodies Probable* Adrenergic drug resistance (in some patients with asthma or cystic fibrosis) β-adrenergic receptor antibody Bullous pemphigoid IgG and complement in basement membrane Glomerulonephritis Glomerular basement membrane antibody or immune complexes Infertility (some cases) Antispermatozoal antibodies Mixed connective tissue disease Antibody to extractable nuclear antigen (ribonucleoprotein) Pernicious anemia Antiparietal cell, microsomes, and intrinsic factor antibodies Polymyositis Nonhistone ANA RA Immune complexes in joints Systemic sclerosis with anticollagen antibodies Nucleolar and other nuclear antibodies Sjögren's syndrome Multiple tissue antibodies, a specific nonhistone anti–SS-B antibody Possible* Chronic active hepatitis Smooth muscle antibody Endocrine gland failure Specific tissue antibodies (in some cases) Post-MI, cardiotomy syndrome Myocardial antibody Primary biliary cirrhosis Mitochondrial antibody Urticaria, atopic dermatitis, asthma (some cases) IgG and IgM antibodies to IgE Vasculitis Ig and complement in vessel walls, low serum component (in some cases) Vitiligo Melanocyte antibody Many other inflammatory, granulomatous, degenerative, and atrophic disorders No reasonable alternative explanation *Likelihood of being an autoimmune disorder. ANA = antinuclear antibody; TSH = thyroid-stimulating hormone.

Last full review/revision September 2008 by Peter J. Delves, PhD

Content last modified September 2008