The maternal immune system is challenged with paternal antigens through exposure to trophoblast tissue and fetal cells crossing the placenta into the maternal circulation. The dose of antigen, the manner of presentation (cellular, subcellular, or soluble), and the nature of the antigen all determine the type of response that will be elicited. It is also clear that complex maternal immunologic responses, including antibodies to red blood cell antigens, HLA-A, HLA-B, HLA-C, and HLA-D antigens, and cell-mediated responses such as proliferation, lymphokines, cytotoxicity, and suppressor cells, are generated to a variety of paternal antigenic determinants. The fact that some of these reactions are detected in vitro in the absence of maternal serum, but not in its presence, suggests that the local milieu is important in influencing their expression in vivo. For example, such factors as hormones (cortisol, progesterone, and estrogen), pregnancy-associated glycoproteins (alpha 2-macroglobulin and beta 1-glycoprotein) and AFP, which have immunosuppressive properties, may all serve nonspecifically to inhibit and decrease the general tone of maternal immunologic responses, particularly at the placental interface, where many of these factors are present in high concentrations. However, these nonspecific factors may not be sufficient to prevent presensitized effector lymphocytes from continuing an ongoing rejection process, as is often the case in the chronic rejection of an allograft. For this purpose, specific enhancing antibodies would play an important role by blocking maternal responses or protecting the fetus. There may be a subtle balance created on the trophoblast cell surface between specific antibodies and trophoblast or embryonic alloantigens, resulting in limited expression of antigens capable of inducing rejection reactions. This could favor the production of blocking antibodies and/or T-suppressor cells, as opposed to cytotoxic antibody and killer cells. In fact, low levels of antigen density on the cell surface favor a blocking effect by IgG rather than cytotoxicity. Blocking or enhancing antibodies can exert their effect on maternal immunologic responses in several ways. They could block the afferent limb by combining with antigen and preventing sensitization or increasing the level of sensitivity. An example of the latter would be the coating of fetal cells that enter the maternal circulation. Enhancing antibodies could work directly on the effector cells to suppress their function. The antibody itself, or more likely antigen-antibody complexes, may be important in this regard.(ABSTRACT TRUNCATED AT 400 WORDS)

In summary, the term adverse drug reaction is used to designate any type of undesirable and unintended response to a drug and can be broadly classified on the basis of either the presence or absence of an immune mechanism. Allergic reactions (immune) constitute only 5% to 10% of adverse drug reactions. Drug intolerance (nonimmune) constitutes the rest of these reactions. Many of these latter reactions are mild and self-limited, and many drug intolerances cannot be exactly characterized. Of those reactions in which an immune mechanism has been indicated or reactions that clinically appear to be "allergiclike," a limited number of in vivo (eg, skin tests) or in vitro (eg, RAST, IgE-ELISA, other antibody, or cell-mediated assays) tests have proved helpful in the diagnosis. Best studied are adverse reactions to aspirin, penicillin, insulin, and RCM. The principal treatment of all adverse drug reactions is to avoid the drug that has been specifically identified as being responsible for the previous reaction. In cases where avoidance is not possible, desensitization is an alternative (eg, penicillin and insulin). Prophylactic treatment of patients who had previously demonstrated a drug intolerance reaction (eg, systemic RCM reaction) with medication--particularly type I activation--may be helpful in some patients.