Biologic Markers in Immunotoxicology (1992) / Chapter Skim
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7 Human Immune-System Biologic Markers of Immunotoxicity
7 Human Immune-System Biologic Markers of Immunotoxicity
Pages 99-112
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From page 99... ...
T cells consist of an array of subtypes of cells: those that mediate important nnmunoregulatory funcdons, such as help or suppression; those involved ~ effecter functions, such as the direct destruction of andgen-beanug cells; and those that make soluble products caDed lymphokines. Together, these T cells play a central role ~ delayed hypersensitive or cellular immune response.
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From page 100... ...
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From page 101... ...
Patient tenth the W~skott-AIdrich syndrome can have normal immunoglobulin levels yet lack isohemag(lutinins as an indicator of their antibodyde6~cient state. Other natural antibodies that can be assayed include heterolysins (e.g., against sheep or rabbit red blood cells)
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From page 102... ...
A white blood celB count and differential should be obtained, and the absolute lymphocyte count should be calculated by multiplying the total white cell count by the percentage of lymphocytes. Children have higher absolute lymphocyte counts than adults do, so age must be considered ~ evaluating lymphocyte slumbers.
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From page 103... ...
Thus, describing CDl cods as helper cells and CD cells as suppressor-cytoto~nc cells us not justified More important, it has become clear that the CD4 cells and CDS cells recognize foreign antigens In the context of distinct major histocompatibility antigens. CD4 cells recognize antigen ~ the association with class II MHC human leukocyte anthem, ~A-D)
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From page 104... ...
As noted before, all patients should have an absolute peripheral white blood cell count as well as a differential test to define the prm portions of the white blood cell types. Lympho~tope~ can be associated with primary immunodefic~engy diseases but can also occur secondarily to viral infections, malnutntion, stress, and autoimmune diseases or to hematopoietic malignancy.
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From page 105... ...
OPPORTtJN~S FOR DEVELOPMENT OF BIOLOGIC MARKERS THAT ASSESS THE Ertt;CT OF IMMUNOTOXICANIS Primary Humoral Immune Responses Although the tests for hum oral, cellular, and nonspecific ~ uniq have been of great value in studying profound hereditary munodeficienc`,r states, they are not sensitive enough to me~y detect modest ~mmunodefic~ency in populations of individuals exposed to immunoto~nc agents. Furthermore, the available tests usually are directed toward evaluating a complete immune respollse, such as cell-mediated may, without defining the nature of the immune
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From page 106... ...
This section discusses the scientific basis for finding biologic markers that can be used In access the effects of toxic agents on the immune system. The primary response to KLH is one such marker.
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From page 107... ...
The cell surface expression and subsequent release into the body fluids, including serum, of soluble IL-2 receptors appear to be a consequence of cellular activation of various cell types that could play a role In the regulation of the immune response. Thus, the analysis of serum levels of ILL receptors and other activation antigens could provide a new approach to the in viva analysis of lymphopyte activation.
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From page 108... ...
The penpheral-blood mononuclear cells can be assessed for the patient's capacity to generate self-HLA-restricted, cell-mediated pytotoner to viral antigens. When this am preach is used In patients with common variable hypog~mmagIob''1inemia' the capaaty to produce virus-specific self-restricted CIL is vanable but usually relatively norms.
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From page 109... ...
109 All tests should be performed once or twice a year by a physician on persons who are suspected of exposure to ~mmunotomcants so that latency and changes over time can be assessed. Finally, aliquots of fresh serum and pelleted white blood cells should be stored at -70°C for each ~ndindual studied at each time.
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From page 110... ...
Although the tests for hum oral, cellular, and Ilonspedfic immunity have great value in studies of profound hereditary immunodeficien~y states, they have not been evaluated for their ability to detect more modest ~mmunodefic~enmes that might be observed In individuals exposed to immunosuppressive immunotomc agents. Therefore, the tests for jmmune-system biologic markers that have been proposed here for risk assessment should be validated prospectively In populations exposed to putative ;mmunotoxicants and in control groups for their ability to predict the development of disease associated pith immunodeficienc~r.
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From page 111... ...
Biolog~c marker tests that focus on the ability to develop a primary response to a new antigen should be developed and valiStem Such tests could be more sensitive than are the available tests that examine 111 secondary recall responses. Furthermore, a · · · — test reqmr~g a primary immune response pelts an analysis of the events of antigen processing and recognition.
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