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3 Biologic Markers for Immune-Mediated Disease
Pages 33-52

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From page 33... ... Hypersensitivity reactions are also the most common type of immunoto~ ty associated with chemises in the environments Despite the relatively high morbidity and long history of these disorders (particularly in the workplaces, much of the pathophysiology has only recently been established, and many questions remain to be answered. Progress ~ addressing this important health problem has been impaired by the slow development of appropriate ammal models. Read the entire page →
From page 34... ... The final category of hypersensitive lung disease includes disorders associated with cellular ~mmu~ty, one example of which is chronic beryllium leg disease. Occupational Asthma aIld Rhinitis Asthma and rhinids are common reactions to inhaled environmental plant =d :`nimal allergens. Read the entire page →
From page 35... ... The Initial sensitization, after exposure of the mucosa to a chemical ~ ought to occur ~ lymph nodes that dry the lung or airways. After ~mmn~tion' B cells that produce specific IgE can be found ~ mucosal tissues. Read the entire page →
From page 36... ... Some of these antigens have adjuvant properties that could be ""portent in the induction of these reactions (Bice et al., 1977~. The Induction of immunity to these AIRS IN IMAf IJNOTOXICOLOGY antigens IS not understood, but it seems likely that antigens deposited in the lower respiratory tract are phago~zed by neutrophils or alveolar macrophages and carried via the lymphatics to the 1ung-assomated lymph nodes (Harmsen et al., 198S, 1987~. Read the entire page →
From page 37... ... EXPOSURE THROUGH INGESTION Adverse reactions to the ingestion of foods have been documented (Metcalfe, 1989~. When the pathogenesis of these reactions involves an immunologic response to a component of food, the reaction Is called food hypersensitivity (Anderson, 1986~. Read the entire page →
From page 38... ... Cell-mediated imm~ is responsible for allergic contact dermatitis and photocontact dermatitis. The third form of allergic dermatitis Is contact urticaria, ~ transient wheal-and-flare response caused by IgE antibody reactions. Read the entire page →
From page 39... ... The clinical characteristics of photocontact dermatitis closely resemble those of allergic contact dermatitis. Ibe major difference Is that photocontact dermadtis requires sunlight In addition to skin exposure to a sensitizing chemical, for initial 39 sensitization and for subsequent elicitation of skin responses. Read the entire page →
From page 40... ... , and super dioxide (330 ppm) have been shown to enhance sensitization of ovalb',min in guinea pigs (] Read the entire page →
From page 41... ... The mechanisms by which inhaled pollutants apparently en hanced the immune recognition of allergens are not understood BIOLOGIC MARKERS OF HYPERSENSlTIVlTY History and Clinical Signs As with the diagnoses of many diseases, a good Story and physical examination are often the most useful masticators for hyper sens~ ty disorders and are therefore useful ~ supporting the establishment of biologic markers. A thorough history should provide information about the extent and duration of the exposure and, perhaps, about the im munogen. Read the entire page →
From page 42... ... Antibody produced to inhaled antigens can be identif~ed in the blood of most individuals exposed to large quantities of antigens, but levels of specific antibody frequently do not correlate tenth disease (Pepys, 1986~. In Vitro Assays for Cellular Immunity Lymphocyte stimulation and other in vitro assays for cellular immunity can be used as indicators of cellular immune-mediated reactions. Read the entire page →
From page 43... ... Immune responses produced in target tissues (skin and limed should have responses that are comparable to those In humans. There are significant differences in the immunologic and inflammatory responses in various laboratory animals that have made it difficult to interpret data obtained from the vanes of animals models used previously. Read the entire page →
From page 44... ... Numerous species, including monkeys, mice, ram bits, dogs, and rats, have been used to mvesiigate contact sensitivity. The guinea pig produces a reaction histolog~caDy and morphologically similar to Hat absented in h~a:r~ {Mekon and Clam an, 1986~. Read the entire page →
From page 45... ... Because the guinea pig is considered a sensitive mammal for hypersensitivity responses, special studies often use this model, with erythema, edema, urticana, pulmonary distress, and other clinical signs of anaphylacdc shock as indicators of a hypersensitive reaction (Karol, 1988~. In some species, adjuvants are used to increase the probability Read the entire page →
From page 46... ... Guinea pigs have been used in risk assessment for more than 20 years. Table 3-1 shows approaches available to demonstrate contact hypersensitivity. Read the entire page →
From page 47... ... lMMUNE-MEDLATED DISEASE DERMIS ~~~ ~ T-DTH 47 � Antigen/Hapten _ (Chemical) ~~ CAM We Langerhans EPIDERMIS ~~ ~~ ~~~ ce I Is 4, CIRCULATION DERMIS ~ ~ Antigen-bearing i, Langerhans cell Afferent Lymphatic ~ (as) Read the entire page →
From page 48... ... 48 8 72 hours 1ater Time Line ~ ~ I I I I I I I I I I I I ~ I I I I I I I I I I ~ I I ~ ~ J I ~ I I I I I I I I Day O 7 14 21 28 35 40 45 FIGURE ~2 Schematic representation of selected methods for detecting chemicals produang contact hypersens~y. Read the entire page →
From page 49... ... Efforts are under way in many laboratories to develop and validate more quantitative nin~munolog~caDy basedn assays for spades other than the Guinea pig. ~ Volvo m~e assays being examined include the ear swelling, cellular influx, and local lymph node proliferation and infiltration tests. Read the entire page →
From page 50... ... The role of pulmonary inflation pros duced by inhaled chemicals in the induction of asthma should be ~nvesUgated. Local Versus Systemic Immunity The role of locally produce'd IRE, as opposed to systemic IgE, In the induction of clinical symptoms should be addressed, since clinical responses do not always correlate tenth the levels of systemic IgE. Read the entire page →
From page 51... ... Is it possible that they provide immune protection by assisting in tile recognition and eli~nination of offending antigens? Local Versus Systemic Immunize Systemic immune responses can be measured in patients with hypersensitivity disorders. Read the entire page →
From page 52... ... Data are needed to illuminate the effects of particle composition on the induction of sensitivity "d clinical disease. Chemical Haptens Additional data are needed on the mech~sms involved in the induction of ~mm~W to chemical haptens, such as TDI and beryllium. Read the entire page →

From page 33...

... Hypersensitivity reactions are also the most common type of immunoto~ ty associated with chemises in the environments Despite the relatively high morbidity and long history of these disorders (particularly in the workplaces, much of the pathophysiology has only recently been established, and many questions remain to be answered. Progress ~ addressing this important health problem has been impaired by the slow development of appropriate ammal models.

3 Biologic Markers for Immune-Mediated Disease Pages 33-52

3 Biologic Markers for Immune-Mediated Disease
Pages 33-52