Complement binding

DNA viruses modulate the host immune response, e.g., most likely the etiologic agent of Kaposfs sarcoma, KSHV (human herpes vims —8), has captured complement-binding proteins, three cytokines (two macrophage inflammatory proteins and interleukin 6), bcl-2, interferon regulatory factors, interleukin 8 receptor. Certain retroviruses... 

Fc fragment (for Fragment, crystallizable) A region of an antibody (IgG molecule) composed of two heavy chains on the C-terminal side. Fc has many effector functions (e.g., binding complement, binding to cell receptors on macrophages and monocytes, etc.) and serves to distinguish one class of antibody from another. 

Adhesion proteins belonging to this group contain a lectin-like domain, a single EGF repeat, and a number of repeats of a protein domain related to the complement binding protein motif (LI). Like most other adhesion proteins, selectins are transmembrane proteins. Selectins bind to carbohydrate groups using... 

FIGURE 6.10 Complement fixation assay. Left Antigen is present in the patient s serum, then the complement is completely utilized and SRBC lysis is minimal. Right Antigen is not present in the patient s serum, then the complement binds anti-SRBC antibody and lysis of the SRBCs ensues. SRBC, sheep red blood cells. 

Foremost among these assays is the Raji cell assay developed by The-ofilopoulos and co-workers (T15). The Raji cell line, derived from a patient with Burkitt s lymphoma, lacks surface immunoglobulin, has Fc receptors that bind monomeric IgG only weakly, and possesses numerous receptors for Clq, C3b/C4b, C3d, and other complement components (G23, S4, S27, S28, T8, T12). Immune complexes which have fixed complement bind to... 

In most of 19 renal specimens from autopsies of intravenous diamorphine users there was severe lymphomono-cytic glomerulonephritis as a result of activation of the classical pathway of the complement binding system (40). This could have been a result of diamorphine itself, adulterants, or active hepatitis B and/or C infection. 

Fig. 7. Schematic representation of the domain organizadon, as well as ligand-, receptor-, and co-receptor-binding preferences of the semaphorins and their neuronal receptors. The individual domains are labeled. PSI, Plexin/Semaphorin//ntegrin domain IPX, /mmunoglobulin-like domain found in Plexins (and Met) and in some Transcription factors CUB, domain homologous to complement-binding factors Clr and Cls FV/VIII, domain homologous to coagulation factor V and VIII (also known as F5/8 type C or discoidin domain) MAM, Meprin/A5/fi domain SP, Sex-Plexin domain. Semaphorins, plexins and scatter-factor receptors (MET) share a common semaphorin domain (black heptagon).

Monoclonal The preclinical testing strongly depends on the type of product, intended frequency antibodies of application, dose, intended clinical therapeutic or diagnostic effect and should be decided on a case by case basis. Complement-binding and cross-reactivity with human tissue should be tested. 

When foreign cells enter the human body they are captured by antibodies, which attach themselves to the cell membrane surface. Complement binds to these antibodies in a specific order, after which the target cells are lysed. Because the liposome bilayer is structurally similar to the cell wall, complement can be used to completely lyse antibody-bound liposomes. Attention has to be paid to the fact that although complement is specific, some liposomes are susceptible to complement lysis, without being bound to an antibody. Most liposome immunoassays are homogeneous complement-based assays. 

A method for predicting the safety of transfusion is based on the use of cells labeled with radioactive chromium (74). After the administration of several milliliters of the labeled blood, the survival of erythrocytes in the recipient s circulation is examined poor survival in vivo indicates that transfusion with these erythrocytes will be hazardous (75,76). There are two types of survival curve for incompatible erythrocytes. A curve described by a single exponential function is seen with most potent IgG antibodies that do not bind complement, including anti-D, anti-C, and anti-K, antibodies. Clearance described by more than one exponential is observed with complement-binding antibodies (77). In the latter there is a slowing of erythrocyte destruction 5-20 minutes after injection... 

In the serum of three patients with acute hypersensitivity reactions to penicillamine, complement-binding antibodies against penicillamine were detected (349). Patients with Wilson s disease are not known to have an abnormal immune status. The striking variability of penicUlamine-induced pathology, including autoimmune reactions such as SLE, is also seen in patients with Wilson s disease, but the proportion of these patients in whom withdrawal is necessary is smaller, about 2-8% (72,79,80,350). 

Monoclonal antibodies can vary tremendously in terms of isotype, construction (animal derived, chimeric, humanized, bound to toxin), ability to activate complement, binding avidity, target specificity, and whether it binds and blocks or binds and activates the receptor. Monoclonal antibodies may be directed toward soluble or membrane bound receptors or receptor ligands, tumor antigens, growth factor or their receptors. Therefore toxicity and side effects are equally variable [68]. 

In general, complement-binding monoclonal antibodies are more likely to cause a first dose response and cytokine release and potentially renal failure. 

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