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Although different models for rheumatoid arthritis have been studied, the pathogenesis in humans remains unknown. A possible mechanism is the crossreactivity between bacterial components and the target-tissue, the cartilage. The existence of this crossreactivity is supported by various data from clinical and experimental studies. Here we provide direct evidence that priming in vivo with cell wall fragments of Streptococcus pyogenes or Escherichia coli can induce a cellular and humoral anti-cartilage response in Balb/c mice in vitro. T cells isolated from these mice can be stimulated in vivo to proliferate by a variety of antigens among which arc the priming bacterium, an unrelated bacterium, small bacterial components and diverse antigens of cartilagenous origin. In bacterium-primed mice antibodies were also detected that displayed a reactivity to cartilage extract besides the reactivity to bacteria. A crossreactive response occurred in vivo in certain circumstances; a delayed type hypersensitivity reaction could be elicited in cell-wall-primed mice by challenge with cartilage extract. For the expression of this crossreactive response in vivo however, it was obligatory to attenuate the mouse's suppressor-circuit. In this paper we would suggest a mechanism for the pathology of chronic arthritis, based on repeated challenges with different bacterial stimuli. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease ( COPD) is characterized by an abnormal innate immune response. We have investigated the changes in the innate immune response of COPD alveolar macrophages exposed to both cigarette smoke and Toll-like receptor ( TLR) stimulation. COPD and control alveolar macrophages were exposed to cigarette smoke extract ( CSE) followed by TLR-2, -4 and -5 ligands [ Pam3 CSK4, lipopolysaccharide ( LPS) and phase I flagellin ( FliC), respectively] or non-typeable Haemophilus influenzae ( NTHi). CSE exposure suppressed TLR-induced tumour necrosis factor ( TNF)-α, interleukin ( IL)-6, IL-10 and regulated on activation, normal T cell expressed and secreted (RANTES) production in both COPD and control alveolar macrophages, but had no effect on interleukin 8 ( CXCL8) production. Similarly, CSE suppressed NTHi-induced TNF-α but not NTHi-induced CXCL8 production in COPD alveolar macrophages. Gene expression analysis showed that CSE suppressed LPS-induced TNF-α transcription but not CXCL8 transcription in COPD alveolar macrophages. The dampening effect of CSE on LPS-induced cytokine production was associated with a reduction in p38, extracellular signal regulated kinase (ERK) and p65 activation. In conclusion, CSE caused a reduced innate immune response in COPD alveolar macrophages, with the exception of persistent CXCL8 production. This could be a mechanism by which alveolar macrophages promote neutrophil chemotaxis under conditions of oxidative stress and bacterial exposure. [ABSTRACT FROM AUTHOR]

Epidemiological data have indicated that some infections are associated with a low risk of allergic diseases, thus supporting the idea (hygiene hypothesis) that the microbial load is an important environmental factor conferring protection against the development of allergies. We set out to test the hygiene hypothesis in a unique epidemiological setting in two socio-economically and culturally markedly different, although genetically related, populations living in geographically adjacent areas. The study cohorts included 266 schoolchildren from the Karelian Republic in Russia and 266 schoolchildren from Finland. The levels of total IgE and allergen-specific IgE for birch, cat and egg albumen were measured. Microbial antibodies were analysed against enteroviruses (coxsackievirus B4), hepatitis A virus, Helicobacter pylori and Toxoplasma gondii. Although total IgE level was higher in Russian Karelian children compared to their Finnish peers, the prevalence of allergen-specific IgE was lower among Russian Karelian children. The prevalence of microbial antibodies was, in turn, significantly more frequent in the Karelian children, reflecting the conspicuous difference in socio-economic background factors. Microbial infections were associated with lower risk of allergic sensitization in Russian Karelian children, enterovirus showing the strongest protective effect in a multivariate model. The present findings support the idea that exposure to certain infections, particularly in childhood, may protect from the development of atopy. Enterovirus infections represent a new candidate to the list of markers of such a protective environment. However, possible causal relationship needs to be confirmed in further studies. [ABSTRACT FROM AUTHOR]

Soluble antigenic preparations of Veillonella parvula and Bacteroides gingivalis were separated by SDS-PAGE and used after electroblotting and solubilization for in vitro lymphocyte stimulation in 13 patients with severe periodontitis and 12 controls. The cellular responses of controls and patients to V. parvula antigens were represented by four main proliferation-inducing fractions with 74-66, 52- 46, 22-19 and 12 kD mol, wt. These fractions induced slightly enhanced DNA synthesis in lymphocytes from eight patients who failed to respond to whole antigenic extract. Lymphocyte samples from Veillonella whole extract unresponsive patients were also examined for in vitro proliferation by B. gingivalis fractions. Almost all stimulatory activities could be classified into five regions of 84-74, 35-31, 28-25, 17-15 and 12 kD. [ABSTRACT FROM AUTHOR]

In the first step of the present study we re-examined the question whether HLA class I molecules isolated from human lymphocytes can bind to intact bacteria. HLA antigens were isolated from the lymphoblastoid cell line HOM-2 and incubated with the bacteria Yersina enterocolitica. Significant binding of antigens to the bacteria was detected whether the antigens were solubilized in the detergent NP 40, reconstituted in liposomes or presented as papain cleaved molecules. Next, we studied the specificity of the binding. We compared the ability of NP 40 solubilized HLA antigens derived from four different cell lines, expressing different HLA-A, -B and -C antigens, to bind to nine different strains of bacteria. Remarkably, few differences were found in that each strain of bacteria bound 10-30% of the HLA antigens derived from any of the four cells lines. Further, after a sample of HLA antigens had been incubated with one strain of bacteria, the unbound HLA antigens would fail to bind to another strain. The conclusions are as follows. First, we have confirmed a previous report that HLA class I antigens could bind to bacteria. Second, binding to bacteria is mediated through the extracellular portion of the HLA molecules which is not affected by papain cleavage. Third, it is the non-polymorphic areas of the HLA antigens which are responsible, because antigens purified from cell lines with different HLA-A, -B and -C allotypes have similar binding ability. Lastly, the binding of bacteria to HLA antigens is a universal phenomenon which does not distinguish one strain of bacteria from another. [ABSTRACT FROM AUTHOR]

The study of antibody responses in the intestine has been greatly hampered by lack of reproducible sensitive assays. An assay for measuring antibody against bacteria capable of regularly detecting gut antibody in gastroenteritis is described. It is based on absorption of antibody onto bacteria and measurement of the amount of antibody bound using radiolabelled anti-immunoglobulin antibody. Anti-light chain antibody is used to detect all classes of antibody as well as partially degraded antibody which retains the capacity to bind; anti-alpha and anti-gamma antibody is used to measure IgA and IgG antibody. The sensitivity of the assay depends on the use of anti-immunoglobulin antibody purified by affinity chromatography and allows measurement of nanogram amounts of antibody. Its specificity and kinetics are described and the particular advantages it provides in the measurement of antibacterial antibody in the intestine are discussed. [ABSTRACT FROM AUTHOR]

The sera of seventy-two patients with ITP were tested for their inhibitory activity on the agglutination of IgG-coated particles by RF or Clq. The majority (83%) displayed an inhibitory effect toward both agglutinators, whereas 17% were found to contain endogenous RF. A negative correlation was observed between the number of platelets and the titres of inhibitory factors. Some sera were fractionated by gel filtration. The inhibitory factors and sometimes trace amounts of IgG were distributed over several peaks eluted before monomeric 7S IgG. The IgG detected in the heavy fractions of two ITP sera corresponded to antigen-antibody complexes as shown by dissociation experiments at acid pH. In all ITP sera analysed by chromatography, DNA has been detected in the heavy fractions and appears to be the antigen of certain complexes. The sera from forty-two patients with ITP were analysed by counter-electrophoresis for the presence of viral antigens. HBs antigen was detected in twenty sera, EBV antigen in five, and adenovirus antigen in six. [ABSTRACT FROM AUTHOR]