Immune complex

Previous calorimetric investigations have shown large increases in heat production when aerobic metabolism was stimulated in erythrocytes [13,46] and leukocytes [47]. 

During defined experimental conditions, antigens and their corresponding specific rabbit antisera, were found to activate the metabolism of human blood cells, when heat production was measured [48J. In this study no attempt was made to identify the blood cells responsible for heat production. An increase was observed from the normal basal heat production of blood of about 60 pW to about 200 pW cm-. Sensitivity, specificity and reproducibility of the measurements were very good. 

In further investigations, simultaneous measurements of heat production were carried out in whole blood and isolated populations of blood cells and plasma, mixed with immune complexes [49]. Granulocytes were found to be the main source of heat production. Also mononuclear cells were activated when exposed to immune complexes, but their activation level was signiHcantly lower than for granulocytes. No increase of heat production was observed when the other blood cells and plasma were mixed with immune complexes. Binding of antigen-antibody complexes to granulocytes and subsequent activation of cell metabolism appears to be mediated by Fc and C3b receptors on the cell surface. 

Granulocyte activation has also been studied by microcalorimclry, stimulating cell phagocytosis with bacteria and latex particles [47] and yeast [50]. Other investigators have stimulated granulocytes with phorbol-12-myristale-13-acetate (51,52,53]. 

An elaborate study [51] was carried out where calorimetric values were correlated to the enthalpy change of aerobic and anaerobic metabolism during phagocytosis heat production was measured simultaneously with oxygen and glucose consumption as well as carbon dioxide, lactic acid and ATP production. 

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It was established that Ab to Klebsiella pneumoniae didn t demonstrate the cross-reactivity to antigens of the relative bacterial species so, it could be considered that antibodies investigated was highly specific only to the own antigen. The physical-chemical characteristics of the immunological interaction such as constants of formation of Ag-Ab complex were obtained. The binding constants of immune complex were Ka =(9.7 l.l)-10 and Ka,=(1.7+0.3)T0 (mg/ml)f... 

An affinity sorbent based on WPA-PG carrying immobilized human IgG was applied to the isolation of the first component of the complement (Cl) from human serum and for its separation into subcomponents Clr, Cls and Clq by the one-step procedure [126,127]. Cl was quantitatively bound to the sorbent at 0 °C. The activities of subcomponents Clq and Clr2r2 in the unbound part of the serum were found to be 0.8% and 3.3% of the initial activities in serum. This fraction, therefore, could be used as a R1 reagent for determining the hemolytic activity of Cl. Apparently, the neighboring macromolecules of immobilized IgG resemble to some extent an immune complex, whereas Cl formation is facilitated due to the mobility of polymer chains with the attached IgG macromolecules (Cl is usually dissociated in serum by 30%). After activation of bound Cl by heating (30 °C, 40 min) the activated subcomponent Clr is eluted from the sorbent. Stepwise elution with 0.05 mol/1 EDTA at pH 7.4 or with 0.05 mol/1 EDTA + 1 mol/1 NaCl at pH 8.5 results in a selective and quantitative elution of the activated subcomponent Cls and subcomponent Clq. 

A cascade of proteins of the immune response that can be triggered by antigen-antibody complexes and by the innate immune system (e.g. exposure to microbial polysaccharides) to raise the immune response. Complement proteins can detect and bind to foreign material or immune complexes and label them for phagocytosis. They can also cause inflammation by directly degranulating mast cells and releasing chemokines to recruit other immune cells into the affected area. 

Serum sickness is an inflammatory condition caused by the deposition of immune complexes in blood vessel walls and tissues. 

A Type III allergic reaction occurs when antibodies of the immunoglobulin G class (IgG) form immune complexes which are slowly eliminated and thus may elicit an inflammatory reaction by binding to the Fey receptors of leukocytes resulting in their activation. 

Imidazoline Receptor Immediate Early Genes Immune Complexes Immune Defense Immune System Immunity... 

Perifascicular capillaries are closer to aggregates of antibody-secreting cells (B-lymphocytes) situated in perimysial connective tissue and therefore are most severely affected by antibody-dependent cytotoxic reactions. Immune-complex deposition occurs at a higher level in the vascular tree (i.e., at arteriolar level) and this may cause fluctuations in perfusion pressure. Perifascicular capillaries are most distal from the head of vascular pressure and therefore most likely to suffer from periodic anoxia. 

There are also other immimological mechanisms, especially via IgG or IgM antibodies with immune complex formation, which can lead to similar clinical conditions [20, 34, 42] as has been shown in dextran anaphylaxis (table 1). Triggering of mast cells and basophils leads to release of various vasoactive mediators, among which histamine was the first recognized in 1908 (fig. 3,4) [6]. 

Fig. 2. IgG-mediated systemic versus local anaphylaxis, a IgG-mediated systemic anaphylaxis. When allergen-IgG immune complexes are formed in the circulation, basophils immediately capture them through IgG receptors on their surface and are activated to release PAF, that in turn act on vascular endothelial cells, leading to increased vascular permeability, b Passive cutaneous anaphylaxis. When allergen-IgG immune complexes are formed in the skin, they stimulate tissue-resident mast cells to release chemical mediators such as histamine, leading to local inflammation. 

The first component of complement is Cl. This is a complex of three molecules designated Clq, Clr and Cls. The classical pathway is only initiated by an immune complex (antibody bound to antigen) when Clq binds to the Fc portion of the complexed antibody (IgM or IgG). The binding of Clq activates the Clr and Cls molecules associated with it to yield activated Cl which now cleaves C4 and then C2 (subunits of... 

Immune complexes enhancement (Nicolosi et al., 1993). Reduction of serum cholesterol and LDL-C elevation of HDL-C (Seetharamiah and Chandrasekhara, 1989 Raghuram et al, 1989 Rukmini and Raghuram, 1991 Lichtenstein et al., 1994 Sugano and Tsuji, 1997). Hypolipidemic effect (Lichtenstein et al., 1994). 

Immune complex enhancement. Beta-cells activation and Increased insulin production (Btuni, 1988). Neuro-regulatory effect (Nakazawa et al., 1977 Btuni, 1988 Hiraga et al., 1993). 

Fc receptor up-regulation on macrophages (enhancing activity of immune complex clearance)... 

Combination of circulating antigens and antibodies to form immime complexes is a normal phenomenon, and normally this immune complex eliminates by... 

Fig. 1 Immune complex binding activity of pectic polysaccharides (Reproduced with permission from reference 6. copyright 1994 Carbohydrate polymer).

Fig. 5 Effect of GL-4IIb2 and periodate oxdization product on FcR mediated immune complex binding to macrophages...

It has been pointed out that some of the histopatholog-ical changes in rheumatoid synovitis are similar to those noted adjacent to atherosclerotic plaques. For example, accumulation of mononuclear cells at the extraluminal surface of endothelial cells in the adventitia and the deposition of immune complexes have been reported in both diseases (Rothschild and Masi, 1982). 

Antibodies to very low density lipoprotein (VLDL) and LDL have been detected in the serum of patients with RA, but not control groups (Lazarevic et al., 1993). In these studies, 38% of patients with active RA tested positive for anti-VLDL/LDL antibodies whilst these autoantibodies were not detected in patients with psoriatic arthritis, osteoarthritis or healthy subjects. Lipoproteins were found in the dissociated components of circulating immune complexes in the serum of 30% of the RA patients. It was concluded that dyslipoproteinaemia in some RA patients may be due to an autoimmune component of the disease. 

Mulligan, M.S., Hevel, J.M., Morletta, M.A. and Ward, P.A. (1991). Tissue injury caused by deposition of immune complexes is L-aiginine dependent. Proc. Natl. Acad. Sci. USA 88, 6338-6342. 

Mulligan, M.S., Moncada, S. and Ward, P.A. (1992). Protective eflfect of inhibitors of nitric oxide synthase in immune complex-induced vasculitis. Br. J. Pharmacol. 107, 1159-1162. 

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