Guinea Pig Inhalation Tests

The guinea pig model reproduces the characteristics of pulmonary allergic hypersensitivity and airway inflammation observed in humans. Inhalation is the exposure route for the sensitization and the elicitation phases. Like the human response, the guinea pig smooth muscle responds to histamine and other pharmaceutical mediators. In addition, both immediate and late-onset responses can be demonstrated (Griffiths-Johnson and Karol, 1991). Therefore, results of inhalation studies in guinea pigs can...

Evaluating Immune System Status Immunotoxicity

Because xenobiotics have multiple effects on the immune system, it is difficult to arrive at a concise definition for immunotoxicity. However, the U.S. FDA considers an immunotoxic effect to be any change in the structure or function of the immune system that is permanent or reversible. This definition has been embraced by most immunotoxicologists because it considers all possible outcomes of interactions between the immune system and xenobiotics. The interaction between xenobiotics (e.g.,...

Evaluation ofthe Immune System

The choice for experimental animal is the species that absorbs, metabolizes, distributes, and excretes (ADME) the test chemical in a manner similar to humans. Often, the ADME ofthe test chemical is unknown before testing. Here, mice, rats, or dogs are used because there are methods available to detect effects on the immune response. Regulatory agencies require testing in both the rat and the mouse because validated testing methods are available. Route and...

Common IgEMediated Allergic Reactions

Reactions to penicillin are common in 1 to 10 of patients taking the drug. The Th2 response is directed toward metabolic products of the drug. The most common antigen is the penicilloyl derivative reacted with e amino groups in lysine residues of proteins. A second antigen is created when the thiazilidine ring of penicillic acid is opened to create penamaldic acid. The acid can form disulfide linkages with proteins Symptoms, occurring 10-14 days following treatment, can be distinctly different....

Exogenous And Endogenous Antigens

Most exogenously synthesized immunogens are derived from bacteria, viruses, and fungi infecting the host. Viruses such as influenza have several different immunogenic molecules. Because the virus leaves the cell by a process of budding, the envelope surrounding the virus often contains glycoproteins and lipoproteins from the host's cell membrane. These immunogenic molecules con- Table 1. Position of Immunodominant T-cell Epitopes and Amphipathic Segments in Selected Proteins Table 1. Position...

Animal Models of Autoimmunity

Norway rats immunized with nontoxic concentrations of mercuric chloride HgCl2 develop a disease characterized by Th2-cell-dependent B-cell stimulation. Stimulation culminates in the production of autoantibodies directed toward DNA, glomerular basement membrane, collagen IV, thyroglobulin, and myeloperoxidase. The autoimmune disease is characterized by an autoimmune glomerulonephritis and immune complex vasculitis. Humans exposed to mercury develop the same kidney...

Selective IgA Deficiency

IgA deficiency is the most common of all immunodeficiencies. Depending on the country, the incidence is between 1 400 and 1 3000. There is an increased incidence oflgA deficiency in subjects with defects in chromosome 18, connatal rubellasyndrome, andataxia telangiectasia Mietens, 1983 . Associatedwith the deficiency are recurrent bacterial infections, bronchitis, sinusitis, pneumonia, allergies, and autoimmune diseases Schaffer etal., 1991 . B-cell differentiation arrest preventing isotypic...

Mutations in HLA Class IIAntigens

IDDM, also known asjuvenile or type I diabetes, occurs in only 0.2 of all diabetes. Usually, the disease begins early in life with a peak age of onset of 11 to 12 years. Destruction of insulin-producing ft cells is related to both cytotoxic T cells and an antibody response. There is a strong association between the presence of cis-dimers of HLA-DQ and IDDM in all ethnic groups studied Todd, 1990 . Evidence suggests that a single amino acid substitution at position 57 in the B-chain is...

Early Asthmatic Reactions in the Lung

Asthma is a disease characterized by partial airway obstruction that is reversible either spontaneously or with treatment. Up to 80 of patients with asthma have positive skin tests to common aeroallergens such as pollens or grasses. Over 75 of asthmatic patients have associated rhinitis Nelson, 1985 . When exposed to the allergen for the second time, histamine, heparin, and trypase are extruded from the mast cells or basophils within 15-20 min. The preformed mediators have diverse biological...

Immune Effector Cells Lymphocytes

Two pools of lymphocytes are found in the body. The largest pool resides in the secondary lymphoid organs such as the spleen and lymph nodes. Lymphocytes in these organs are usually undergoing stimulation and differentiation. Resting lymphocytes in the peripheral blood represent the smallest pool. At any point in time, only 2 of the total lymphocyte pool circulates in the peripheral blood Anonymous, 1995a . The number of lymphocytes in the peripheral blood varies with the species. In humans,...

Sequestered Antigens

Tissue antigens, sequestered behind anatomic barriers, do not contact T cells when the repertoire of self' antigens are determined. Sequestered antigens are found in tissues such as the eye and testis. T cells are not rendered tolerant or anergic to the sequestered antigens. When antigens from these immunologically privileged sites contact immunocompetent cells, induction of an autoimmune disease results. Sequestered antigens come into contact with the immune system following trauma to an...