HCV (hepatitis C virus) has a high propensity to persist and to cause chronic hepatitis C, eventually leading to cirrhosis. Since HCV itself is not cytopathic, liver damage in chronic hepatitis C is commonly attributed to immune-mediated mechanisms. HCV proteins interact with several pathways in the host's immune response and disrupt pathogen-associated pattern recognition pathways, interfere with cellular immunoregulation via CD81 binding and subvert the activity of NK (natural killer) cells as well as CD4 + and CD8 + T-cells. Finally, HCV-specific T-cells become increasingly unresponsive and apparently disappear, owing to several possible mechanisms, such as escape mutations in critical viral epitopes, lack of sufficient help, clonal anergy or expansion of regulatory T-cells. The role of neutralizing antibodies remains uncertain, although it is still possible that humoral immunity contributes to bystander damage of virally coated cells via antibody-dependent cellular cytotoxicity. Cytotoxic lymphocytes kill HCV-infected cells via the perforin/granzyme pathway, but also release Fas ligand and inflammatory cytokines such as IFNγ (interferon γ). Release of soluble effector molecules helps to control HCV infection, but may also destroy uninfected liver cells and can attract further lymphocytes without HCV specificity to invade the liver. Bystander damage of these non-specific inflammatory cells will expand the tissue damage triggered by HCV infection and ultimately activate fibrogenesis. A clear understanding of these processes will eventually help to develop novel treatment strategies for HCV liver disease, independent from direct inhibition of HCV replication.

Abs (antibodies) are complex glycoproteins that play a crucial role in protective immunity to malaria, but their effectiveness in mediating resistance can be enhanced by genetically engineered modifications that improve on nature. These Abs also aid investigation of immune mechanisms operating to control the disease and are valuable tools in developing neutralization assays for vaccine design. This review explores how this might be achieved.

Oxidized low-density lipoprotein (OxLDL) and autoantibodies to OxLDL (aOxLDL) are implicated in the development of atherosclerosis. The objective of this study was to determine the importance of these factors in hypertension, a major risk factor for atherosclerosis. Samples were obtained from 111 men with established hypertension (diastolic pressure >95 mmHg) from the Swedish component of an ongoing hypertension study (European Lacidipine study on Atherosclerosis, ELSA) and from 75 normotensive control men, who were from a Swedish population-screening programme (diastolic pressure <80 mmHg). The presence of carotid atherosclerosis and the intima-media thicknesses were determined by ultrasonography. A monoclonal antibody to OxLDL, EO6, was used to determine oxidation epitopes in LDL. aOxLDL of IgG and IgM subclass were tested by ELISA against OxLDL. Hypertensive men had increased OxLDL levels compared with normotensives ( P =0.002), whereas autoantibodies tested were largely similar between groups. There was no association between the antibodies tested, or OxLDL and carotid atherosclerosis. Age was not associated with OxLDL or aOxLDL measurements. Taken together, our findings indicate that OxLDL is elevated in hypertensive men, which may predispose to atherosclerosis in hypertension. In contrast, aOxLDL levels were unchanged and the role of aOxLDL may depend on disease stage and/or type.

Paraneoplastic neurological syndromes are rare non-metastatic complications of cancer that have an immune-mediated aetiology. The central and peripheral nervous systems are considered to be immune-privileged sites, since the presence of the ‘blood-brain/nerve barrier’ means that antigens sequestered within the nervous system do not normally induce an immune response. Aberrant expression of a neuronal antigen by a tumour arising outside this barrier can lead to the breakdown of immune tolerance to the nervous system. However, in many cases the immune mechanisms that result in neurological dysfunction remain poorly defined. Furthermore, aberrant expression of neuronal antigens can be detected in many tumours that are not complicated by non-metastatic neurological syndromes. This review article examines current concepts in the immunopathogenesis of paraneoplastic neurological syndromes.

1. Two-dimensional immunoelectrophoresis and conventional sodium dodecyl sulphate-polyacryl-amide gel electrophoresis was performed on various mixtures of purified α 1 -antitrypsin (α 1 AT) and leucocyte elastase (LE). 2. The results confirm that α 1 AT inhibits LE by the formation of enzyme-inhibitor complexes demonstrable by both techniques. 3. The complexes break down with time and are not affected by pH in the presence of excess α 1 AT. However, the breakdown is more rapid in the presence of excess enzyme only at pH values where LE remains active. The resultant products of the complex breakdown include inactivated LE and α 1 AT that has undergone limited proteolysis. 4. It is concluded that the presence or absence of α 1 AT-enzyme complexes as demonstrated by two-dimensional immunoelectrophoresis must be interpreted with caution when studying α 1 AT function in lung secretions. The absence of such complexes does not mean that previous interaction with enzyme has not occurred, thereby accounting for a reduction in α 1 AT inhibitory capacity.

1. The quantification of α 1 -antitrypsin (α 1 AT) by standard immunological techniques is altered by interaction of the protein with leucocyte elastase. 2. The results obtained for α 1 -antitrypsinleucocyte elastase mixtures in the presence of a functional excess of the inhibitor were relatively accurate for the first 6 h. However, continued incubation for more than 24 h led to a major over-estimation of the α 1 AT as the result of breakdown of the enzyme-inhibitor complex releasing a partially proteolysed form of the inhibitor. 3. In the presence of excess enzyme up to a twofold overestimation of α 1 AT occurred within 1 h and the degree of overestimation increased with time (up to threefold at 24 h). This was eventually associated with the presence of only a partially proteolysed form of α 1 AT (mol wt. ⋍ 50000). 4. Different results for each sample were obtained when different polyclonal antisera were used to quantify the α 1 AT. 5. Complete inactivation of α 1 AT by oxidation resulted in little change in the immunological quantification of the protein. However, further addition of H 2 O 2 led to a progressive underestimation of the α 1 AT. 6. The effect of physicochemical alteration on the immunological quantification of α 1 AT by different antisera should be borne in mind for all studies assessing this protein in lung secretions.

1. Antibodies against angiotensin II were purified by affinity chromatography. 2. When injected intravenously into rats, the antibody distributed in the extracellular space with a half-time of 11 h and a distribution volume of about 10 ml/100 g body weight. The antibody was eliminated with a half-time of 7 days. 3. Plasma angiotensin II concentrations increased about 100-fold the control values 7 min after antibody injection and declined in parallel with the antibody concentration. It was calculated that only about 1–4% of the binding capacity of the antibody was occupied by angiotensin throughout the experiment. 4. Since the plasma renin concentration was normal, except during the short initial phase of stimulation, it is concluded that upon antibody injection the renin-angiotensin system rapidly, reached an equilibrium, with concentrations of free angiotensin close to or identical with normal concentrations.

1. Intravascular coagulation has been assessed by following the catabolism of 131 I-fibrinogen in relation to 125 I-labelled antigen disposal during anaphylaxis and acute and chronic serum sickness glomerulonephritis in rabbits. 2. As a result of antigen challenge early in the bovine serum albumin (BSA) immunization schedule, in vivo formation of immune complexes caused platelet damage, intravascular coagulation shown as ‘rebound defibrination’ (that is a transient fall of labelled fibrinogen), and also activation of kinins and of fibrinolysis. 3. ‘Rebound defibrination’ was associated with precipitating antibody to BSA, with rapid removal of antigen, and with the appearance of fibrin microthrombi in the renal glomeruli. It also appeared to be related to the development of proliferative glomerular histology. Further, inhibition of fibrinolysis before antigen challenge may lead to patchy renal cortical infarction. 4. Florid ‘rebound defibrination’ occurred in animals with anaphylaxis and was accompanied by obstruction of the vasculature of lungs and kidneys by fibrin. These animals had high levels of precipitating antibody. 5. Animals which developed chronic proteinuria late in immunization had relatively more non-precipitating antibody to BSA and showed slower removal of antigen, no rebound effect and thus normal fibrinogen catabolism. Glomerular histology showed little proliferative response. 6. Long-term horse serum injection produced glomerulonephritis accompanied by fibrinoid vasculitis, and accelerated fibrinogen catabolism.