Multiple Chemical Sensitivities Addendum to Biologic Markers in Immunotoxicology (1992) / Chapter Skim
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Antigen Specific and Antigen Non-Specific Immunization
Antigen Specific and Antigen Non-Specific Immunization
Pages 77-88
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From page 77... ...
.. The word Hypersensitivity in the multiple chemical hypersensitivity epithet means quite different things to those depending on whether they be toncolog~sts or immunologists The term unfortunately prejudices immunologists because hypersensitivity has very prease connotations based on several decades of molecularly oriented studies which concluded that classical immunological reactions are the result of highly specific molecular interactions between precisely defined prosthetic groups on antigens (epitopes)
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From page 78... ...
The amino acid sequence of a polypeptide determines how that peptide will fold three-dimensionally ~ space and that degree of folding is the antibody characteristic which allows the complementary fit of its homologous antigen.
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From page 79... ...
ON ~-NO, p monontltoootl.~e 200 ~0 O.S Fig. 2 When serological studies are Wended quantitatively, affinity constants can be obtained using equil~num dialysis methods.
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From page 80... ...
The numbers refer to the amino acid position in the heavy ~ or light (L) chain reppec~vely which is in closest approbation with the My polar forces on the haptenic molecule.
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From page 81... ...
81 that recognizes specific antigens also can be sUmulated non-specificaDy to carry out its effects independently of antigens. Knowledge emanating from studies of such matters as the plethora of pytokines required for immunology reactions, the many forces involved in ping and tran~dadng immune recognition into inflammation, the pharmacology of immune reactions, the ability of some very important immunological cells to recognize foreiguness in an antigen-~dependent manner (e.g., OK cells)
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From page 82... ...
Even for antigen specific responses, it has been pointed out by Warren and Chedid (19~ that if immunology is defined as the bodys reaction to fores insult, then one must also consider such non-antigen specific, Educed responses as the involvement of endothelial cells, activation of the complement and procoagalation cascades, vascular changes, pytokine generation, lysosomal enzyme release, the generation of toxic oxygen radicals, arachidon~c acid metabolism, even the effect of ~nterleu~n 1 ~1) on the hypothalamus, among many others (Table 3~.
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From page 83... ...
When an environmental stimulus Is additionally required to express the abnormal gene action, as ~ Me case of cutaneous photosensitization In certain porphyrins, clinical manifestations might be erroneously considered immune In origin, but the mteres~g thing here is the requirement for two separate signals. In addition to genetic factors, other conditions which are known to alter pharmacologic reactivity to substances are age, presence of concurrent disease, nutritional status, hormone levels, diurnal vanabon ~ drug disposition or sensitivity, environmental factors that induce or inhibit Hug metabolism, and effiacngy of repair mech~ms (Nebert and Weber, 1990~.
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From page 84... ...
by which this altered reactivity might occur and among them proposed are that certain viruses, notably respiratory syn~tial virus, may enhance IgE syntheses and mediator release from basophiis either directly or through the action of }nterferon i rom virus-shmulated lymphocytes. The viruses may also interfere with beta-adrenergic fulletion either by directly inhibiting such function, by passively allowing the mast cell to promote more mediator release, or by enhancing cholinerg~c stimulation of airways smooth muscle.
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From page 85... ...
Viruses may diminish beta-adrenerg~c function Could establish a permissive situation promoting mast cell mediator release 4. Viruses promote choliner~c-dependent responses Not In smooth muscle directly, but in inflammatory cell mediator release Se Viruses affect peptider~c responses Damage airway epithelillm Affect bronchodilator effects of LPO products Unopposed constriction of Substance P Infection inhibits SP degrading enzyme HYPOTHETICAL SCENARIO Inflammatory granulocytes, altered by infection Recruited to the airways Enhanced mediator release u' sim Leads to airway hyperresponsiveness Must take place in the generally-predisposed life.
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From page 86... ...
lee endotomn-induced Shwartzman reaction can be manifest either a dermal or systemic fo~m -- both lead to increased target organ hyperreactiv~ty following exposure to the second stimulus and thus meets the definition of altered reactivity. Neither Is antigen specific reaction because the two doses do not need to be antige~caRy replated, the time between sensitization and provocation Is too short to Educes antigen specific reactivity, and the increased sensitivity does not last more than a few days.
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From page 87... ...
1990. Respiratory infections: Their role In anway responsiveness and the pathogenesis of diseases and asthma.
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