B1b lymphocytes confer T cell-independent long-lasting immunity

Many microbial pathogens employ antigenic variation as a strategy to evade the immune system, posing a challenge in vaccine development. To understand the requirements for immunity against such pathogens, we studied Borrelia hermsii, a relapsing fever bacterium. We found that mice deficient in T, follicular B, marginal zone B, or B1a lymphocytes resolved B. hersmii bacteremia and became resistant to reinfection. The resolution of bacteremia coincided with an expansion and persistence of B1b lymphocytes, and purified B1b lymphocytes from convalescent wild-type or TCR-betaxdelta-/- mice conferred immunity to Rag1-/- mice. The B1b lymphocytes in the reconstituted Rag1-/- mice provided long-lasting immunity by rapidly generating B. hermsii-specific IgM but not IgG upon bacterial challenge. Unmutated IgM is sufficient to eliminate B. hermsii, because AID-/- mice deficient in somatic hypermutation and class switch recombination efficiently resolved all bacteremic episodes. These data demonstrate that B1b lymphocytes can provide long-lasting T cell-independent IgM memory.     

Functional interactions among neurons in inferior temporal cortex of the awake macaque

Summary Functional interactions among inferior temporal cortex (IT) neurons were studied in the awake, fixating macaque monkey during the presentation of visual stimuli. Extracellular recordings were obtained simultaneously from several microelectrodes, and in many cases, spike trains from more than one neuron were extracted from each electrode by the use of spike shape sorting technology. Functional interactions between pairs of neurons were measured using cross-correlation. Discharge patterns of single neurons were evaluated using auto-correlation and PST histograms. Neurons recorded on the same electrode (within about 100 n) had more similar stimulus selectivity and were more likely to show functional interactions than those recorded on different electrodes spaced about 250 to 500 microns apart. Most neurons tended to fire in bursts tens to hundreds of milliseconds in duration, and asynchronously from the stimulus induced rate changes. Correlated neuronal firing indicative of shared inputs and direct interactions was observed. Occurrence of shared input was significantly lower for neuron pairs recorded on different electrodes than for neurons recorded on the same electrode. Direct connections occurred about as often for neurons on different electrodes as for neurons on the same electrode. These results suggest that input projections are usually restricted to less than 500 m patches and are then distributed over greater distances by intrinsic connections. Measurements of synaptic contribution suggest that typically more than 5 near-simultaneous inputs are required to cause an IT neuron to discharge.     

The Genetic Link Between Diabetes and Atherosclerosis

Epidemiological studies have indicated that the risk of atherothrombotic coronary artery disease (CAD) is higher in patients with diabetes, but these results have not been consistently observed across clinical trials. To address this apparent discrepancy, we can apply the results of genome-wide association studies (GWAS) to provide a better understanding of the shared genetic architecture of diabetes and atherothrombotic CAD. For instance, a large GWAS has identified 16 novel loci that are associated with both diabetes and atherothrombotic CAD. These genetic variants may also be used to assess potential causal relationships reported in observational studies and clinical trials through Mendelian randomization analyses. For example, several Mendelian randomization analyses have shown that diabetes is associated with CAD independent of other risk factors (odds ratio [OR]: 1.63, 95% confidence interval [CI]: 1.23–2.07; P = 0.002). Furthermore, Mendelian randomization analyses can provide more insight into the perceived risk of diabetes among patients without diabetes receiving statin therapy. Here, genetically lower activity of HMG-CoA reductase (HMGCR) was associated with a modest increase in diabetes (OR per allele: 1.02, 95% CI: 1.00–1.05). These results highlight the biological mechanisms that link diabetes with the use of statins. In addition, this work illustrates the great potential value of genetic studies to clarify the mechanistic relationships among atherosclerotic vascular disease, dysglycemia, and diabetes. More research is needed to delineate and subsequently better understand the genetic links between diabetes and atherosclerosis.     

Near‐complete aortic mechanical valve dehiscence due to endocarditis reinfection

Prosthetic valve infective endocarditis (IE) is one of the most serious postimplantation complications. Prosthetic aortic valve IE constitutes 1%–6% of all prosthetic valve IE cases. We present a dramatic echocardiographic case of prosthetic aortic valve IE leading to near‐complete valve dehiscence. Echocardiographic evidence of prosthetic aortic valve rocking motion is indicative of significant dehiscence. Aside from IE, other causes and risk factors for prosthetic aortic valve dehiscence include inflammatory and autoimmune vasculitides, concomitant ascending aorta aneurysm, and aortic root calcification.     

Cytokine levels and phagocytic activity in patients with Alzheimer's disease

BACKGROUND: Clinical observations indicate that patients with Alzheimer's disease show a greater susceptibility to infections. One possible explanation is that this predisposition is due to alterations in their immune system. OBJECTIVE: To investigate this assumption, pro- and anti-inflammatory cytokines, as well as the phagocytic activity and superoxide anion generation was examined in aged individuals with and without Alzheimer's disease. METHODS: The production of IL-1beta, IL-2, IL-6, TNFalpha and IL-10 by peripheral blood mononuclear cells from 12 patients with Alzheimer's disease was compared with that of 12 age-matched individuals without any signs of dementia and 12 middle-aged healthy volunteers who served as an additional control. The engulfing capacity of the phagocytic cells was detected by counting cells containing latex beads and the number of particles internalized by each individual cell. RESULTS: The secretion of IL-2 was markedly low in the demented patients, compared with both elderly and middle-aged subjects. IL-1beta and TNFalpha production was similar in the individuals of the 3 groups. The production of IL-6 and IL-10 was significantly lower when compared to that of the middle-aged, but did not differ between the elderly patients with and without dementia. The phagocytic function of both polymorphonuclear cells and monocytes was decreased in individuals of the elderly groups with a low number of engulfed latex particles by each individual polymorphonuclear cell. The production of superoxide anions was increased only by monocytes from the elderly groups. CONCLUSIONS: The results suggest that although the impaired immune function in patients with Alzheimer's disease is related to the aging process, the significant low IL-2 production in these patients may play a role in their increased susceptibility to infections.