Immune complex diseases

Hypersensitivity to foreign epitopes Anti-idiotypic response to normal cells Immune complex disease Potential MPS toxicity D. Specific specificity... 

Hultman, P., and Enestrom, S., Dose-response studies in murine mercury-induced autoimmunity and immune-complex disease. Toxicol. Appl. Pharmacol., 113, 199, 1992... 

Regarding the cellular phenomenon giving the autoimmune disease in Balb mice, the importance of T cells in the induction of the immune-complex disease was found while in another strain, SJL mice, a polyclonal B cell activation was obtained however, the importance of T cells could not be excluded [209],... 

In summary, these are the clinically relevant questions about the immunogenicity of rDNA species-specific proteins will antibody be induced in the recipient that will neutralize the therapeutic effect or lead to immune complex disease What is the class (e.g., IgG or IgE) and specificity (i.e., reactivity against specific protein or contaminant) of the antibody induced The former antibody type could potentially neutralize the product and produce immune complex disease, while the latter could result in an anaphylaxis response. It is possible that the antibody induced is of insignificant health consequence, and its presence is known only because of improvements made in the sensitivity of detection methods with the introduction of the enzyme-linked immunosorbent (ELISA) assay. 

CH50 determinations can be used to analyze the total serum complement and are useful for monitoring immune complex diseases (Sullivan, 1989) activation of complement (Table 15.13) in the presence of autoantibodies is indicative of immune complex diseases and autoimmunity. The various components of the complement system (C3, C4) can also be measured to assess the integrity of the system. For instance, low serum concentrations of C3 and C4, with a concomitant decrease in CH50 may indicate activation of complement, while a low C4 alone is a sensitive indicator of reduced activation of the complement system. Since C3 is used as an alternate complement pathway, it usually measures high. Therefore, a low C3 with a normal C4 may indicate an alternate pathway of activation. 

Finally, platelets can be activated by immune complexes following binding of immunoglobulin G (IgG) Fc domains to platelet Fey RII. This process involves tyrosine phosphorylation of a motif designated as ITAM (immunoreceptor tyrosine-based motif) found on the cytoplasmic domain of platelet Fey RII receptors (73). This may play a role in immune complex diseases, particularly in heparin-induced thrombocytopenia. 

Bacillus Calmette-Guerin (BCG) and its active component, muramyl dipeptide, have been shown to have aspecific immunostimulant activity. It is mainly used for the local treatment of bladder cancer. It binds to fibronectine in the bladder epithelium. Hypersensitivity reactions and immune complex disease are its major adverse reactions. 

The newer derivatives seem less likely to cause hypersensitivity reactions, perhaps because the protein adducts generated are shorter lived. All four types of hypersensitivity reaction have been observed with penicillin. Thus, high doses may cause hemolytic anemia and immune complex disease and cell-mediated immunity may give rise to skin rashes and eruptions, and the most common reactions are urticaria, skin eruptions, and arthralgia. Antipenicillin IgE antibodies have been detected consistently with an anaphylactic reaction. The anaphylactic reactions (type 1 see above), which occur in 0.004% to 0.015% of patients, may be life threatening. 

In the last decade, numerous new techniques have been developed for the detection and quantitation of immune complex material in tissue and biological fluids. In many respects, clinical studies using these techniques have substantiated the primary pathogenic role of immune complexes in a variety of human diseases. At the same time, these studies have reaffirmed the notion that immune complexes occur frequently in the course of an immune response or as an epiphenomenon unrelated to pathogenesis, and that, despite the presence of immune complexes, typical clinical manifestations of immune complex disease may be an unusual event. 

With respect to studies in animal models which dissect the mechanisms of formation, localization, and fate of immune complexes, the mechanisms by which they elicit an inflammatory response, and their biologic activities, we provide little more than summary information required to understand the concept of immune complex disease and the principles of the tests. For more detailed information, the reader is referred to several excellent reviews (C14, H2, Til, Ul, W12). 

The deposition of immune complexes along vascular basement membranes and the ensuing inflammatory response are the hallmark of immune complex disease. The distribution of deposition by and large determines the clinical features of the disease. In the human, factors governing the localization of immune complexes are incompletely understood, though it is presumed that blood flow physiology plays a role. Areas of relatively high-... 

As larger amounts of complexes are infused into experimental animals, the rate of clearance slows and vascular lesions appear, presumably as a result of overload (B9, HI, H2). Similar phenomena may occur in man, and impaired clearance has been demonstrated in several diseases associated with manifestations of immune complex deposition including systemic lupus erythematosus (F9, H8, K9, L19, P2), primary biliary cirrhosis (G19), Sjogren s syndrome (H9), and dermatitis herpetiformis (L6). Impaired clearance may be a result of circulatory overload by immune complexes, or a primary defect in mononuclear phagocytic system function may contribute or predispose to immune complex deposition (A15, A16, HI). However, impaired clearance, as currently measured, is neither a prerequisite nor a consistent consequence of immune complex disease. 

Animal models of disease, whether naturally occurring or artificially induced, provide valuable insights into human disease and allow rigidly controlled studies that are not possible in humans. Probably the most intensively studied model of an immune complex disease is the spontaneous lupuslike disease that occurs in certain inbred strains of mice, especially the (NZB x NZW) F, hybrid. Its study has provided insights with respect to genetic predisposition (H25), the role of endogenous retroviruses (D8), the influence of sex hormones (R9), the identification of T suppressor cell abnormalities (T3), and the propensity to form certain autoantibodies, especially to double-stranded DNA (S36) and to the RNA-protein complex, Sm (E2). Though animal studies are not the subject of this review, we emphasize that the entire concept and framework by which we view immune complex disease in humans are based on initial observations in animals. 

The extravalvular manifestations of infective endocarditis have many clinical features of an immune complex disease and immunologic studies of... 

L15, Ol, W32). Remission of immune complex disease and circulating immune complex levels after successful therapy of the tumor provides further evidence of a cause and effect relationship (H23). 

H20. Henson, P. M., and Cochrane, C, G., Acute immune complex disease in rabbits. The role of complement and of a leucocyte-dependent release of vasoactive amines from platelets. /. Exp. Med. 133, 554-571 (1971). 

IgG immune response immune complex disease IgE hypersensitivity... 

Severe complications connected with cholera (or combined) immunization are extremely rare and the causal relation is always doubtful. However, when they do occur they constitute a contraindication to further administration. There are occasional reports of neurological and psychiatric reactions (SED-8, 706) (SEDA-1, 246), Guillain-Barre syndrome (SEDA-1, 246), myocarditis (154,155), myocardial infarction (SEDA-3, 261), a syndrome similar to immune complex disease (156), acute renal insufficiency accompanied by hepatitis (157), and pancreatitis (158). 

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