Immunologically mediated disorder

Piperidinyl derivatives, (II), (HI), and (IV), prepared by Brough (2), Baxter (3), and Thom (4), respectively, were effective in modulating immunologically mediated disorders and used in the treatment of psoriasis, atopical dermatitis, contact dermatitis, and other eczmatous dermatitides. 

Numerous metals are responsible for immunologically mediated disorders in humans. 

Hussain R, Poindexter RW, Ottesen EA Control of allergic reactivity in human filariasis. Predominant localization of blocking antibody to the IgG4 subclass. J Immunol 1992 148 2731-2739. Creticos PS Immunological changes associated with immunotherapy in Greenberger PA (ed) Immunotherapy of IgE-Mediated Disorders. 

S.2.2.9. Markers of immune activation and process. Acting with TNF-a-mRNA, sICAM-1, IL-lO-mRNA, and sTNF-R, these proteins and nucleic acids can be used as markers of the immunologically mediated inflammatory process seen in multiple sclerosis (M4). This disorder is associated with deregulation of cytokine expression, especially in regard to TNF-a. 

Immunologically mediated hypersensitivity disorders are referred to as allergy, a term that unfortunately is not always used in this strict sense. This... 

Intolerance. Non-immunologically mediated adverse reactions. In food intolerances, these may be due to pharmacological properties of food constituents, metabolic disorders, or responses of unknown etiology. 

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, represents a heterogeneous group of disorders resulting from repeated exposure to a variety of organic particles, which provokes, in a susceptible host, an immunologically mediated inflammation of the small airways and lung parenchyma (1). 

The most frequent skin disorder, which affects about 2% of the world s population is psoriasis. The thickened, scaly patches can cover much of the skin and become disabling. The inflammation and excessive epidermal growth are usually a T-cell mediated immunologic response to antigenic stimuli.P u v However, there is a hereditary form.31 Other common skin disorders include actinic keratosis induced by light and cancer. 

The supplementary presence of viruses, bacteria, air pollutants or microparticles can further trigger or support such inflammation. Cytotoxic mediators of the late phase of inflammation are additionally responsible for disorders of the mucociliary transport system, epithelial damage and dysfunction of the immunological mucosa defense against viruses and bacteria. 

There is indirect evidence of sex differences in immunology. Women have a higher incidence of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. The influence of sex hormones on the immune system may provide insight into these immunological disorders. For example, estrogen stimulates both humoral and cell-mediated immunity, whereas testosterone has the opposite effect (126). Therefore, it is not surprising that there is sex-dependent variability in response to immunosuppressive agents. 

Many reactions to beta-lactam antibiotics are clearly not immune mediated. These include bleeding disorders, neurotoxicity, and most cases of diarrhea. In addition, many reactions, the pathogenesis of which is still being discussed, clearly depend on the daily and the cumulative dose of beta-lactam antibiotics and hence the duration of treatment. Although the rare, but well-understood, immune hemolysis after penicillin is seen mostly with high-dose and long-term treatment, dose dependency and time dependency point to direct toxicity rather than to immunological mechanisms. Indeed, direct toxic effects of beta-lactam antibiotics on eukaryotic cells and specific interactions with receptor proteins and enzymes have been shown (4) and may underlie particular reactions. 

Mechanisms of non-immediate reactions are unclear but may be immunological and non-immunological. Delayed reactions of the IgE type are known (131). Aminopenicillins seem to be an important cause of non-immediate reactions (132-134). The morbilliform rash that begins 1-10 days after amoxicillin can be caused by a delayed cell-mediated immune reaction (135) as can fixed drug eruptions (136,137), toxic epidermal necrolysis (138-140), bullous erythroderma (141), and contact eczema (142). Investigation of these disorders should include delayed readings of skin tests (135). In patients with chronic urticaria, penicillin allergy was demonstrated by cutaneous tests. 

These differences between BN and LEW rats in susceptibility to metal-induced autoimmunity and nephropathy are associated with intrinsic differences in the immune system of these two strains. Indeed, from an immunological point of view, the balance between "type 1" (Thl/Tcl) and "type 2" (Th2/Tc2) cells is opposite in BN and LEW rats. BN rats are susceptible to "type 2"-mediated immunological disorders, to which the LEW strain is resistant. Conversely, "type l"-mediated organ-specific autoimmune disease are easily induced in LEW, but not in BN rats [155]. These immunological features depend on inherent properties of T lymphocytes. In vitro and in vivo studies have shown an inherent bias in T lymphocytes (CD4 and CDS) from BN and from LEW rats to produce respectively "type 2" (IL-4, IL-5, IL-13) and "type 1" (IFN-y cytokines [156-158]. The difference in susceptibility to metal-induced autoimmunity and nephropathy of BN and LEW strains provides a unique tool to study their genetic control. 

Allergic Asthma. It is the basic term for asthma mediated by immunological mechanisms. When there is evidence of IgE-mediated mechanisms the term IgE-mediated asthma is recommended. IgE antibodies can initiate both an immediate and a late asthmatic reaction. However, as in other allergic disorders, T-cell-associated reactions seem to be of importance in the late and delayed reactions. Depending on the duration of symptoms, asthma can be referred to as either intermittent or persistent (as recommended in the document Allergic Rhinitis and Its Impact on Asthma [3]). 

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