Antibodies complement binding

Type II reactions are produced by IgG (or IgM) antibody. The drug or hapten that elicited the antibody response binds to target cells. When antibody binds the drug, complement activation destroys the cell. Blood dyscrasias such as thrombocytopenia and hemolytic anemia are the most common examples of type II reactions. 

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. 

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. 

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. 

Paparounas K, O Hanlon GM, O Leary CP, Rowan EG, Willison HJ (1999) Anti-ganglioside antibodies can bind peripheral nerve nodes of Ranvier and activale the complement cascade without inducing acute conduction block in vitro (see comments). Brain 122 807-816. 

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. 

The classical pathway of complement activation is closely linked to acquired immunity because it is initiated by antigen-antibody complexes binding to Cl, the first component of this pathway. Antigen-antibody complexes that... 

Hyperacute rejection may occur when preformed donor-specific antibodies are present in the recipient at the time of the transplant and may be evident within minutes of the transplant procedure. Hyperacute rejection can be induced by immunoglobulin G (IgG) antibodies that bind to antigens on the vascular endothelium, such as class I MHC, ABO, and vascular endothelial cell antigens. Tissue damage can be mediated through antibody-dependent, cell-mediated cytotoxicity or through activation of the complement cascade. The ischemic damage to the microvasculature rapidly produces tissue necrosis. 

Infliximab (Remicade) is a mouse-human chimeric monoclonal antibody that binds to soluble and membrane-bound TNF-a and inhibits binding with its receptors. Infliximab is a complement-fixing antibody that induces complement-dependent and cell-mediated lysis when bound to cell-surface-bound TNF-a. It also induces proinflammatory cytokines, such as IL-1 and IL-6, and enhances leukocyte migration. Infliximab is FDA approved for the treatment of Crohn s disease and rheumatoid arthritis, but it is also in phase trials for the treatment of psoriasis. 

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