抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

The Design and Analysis of Experiments

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Attachment--and loss.

In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

/pdf/from-inflammation-to-sickness-and-depression-when-the-immune-maw2hn72o8.pdf

From inflammation to sickness and depression: when the immune system subjugates the brain

Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression

https://stevebmd.files.wordpress.com/2011/04/cytokines-sing-the-blues2006.pdf

Cytokines sing the blues: inflammation and the pathogenesis of depression

Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.

The role of inflammation in depression: from evolutionary imperative to modern treatment target

Context Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse, and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants. Objectives To determine whether inhibition of the inflammatory cytokine tumor necrosis factor (TNF) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP), TNF, and its soluble receptors, predicts treatment response. Design Double-blind, placebo-controlled, randomized clinical trial. Setting Outpatient infusion center at Emory University in Atlanta, Georgia. Participants A total of 60 medically stable outpatients with major depression who were either on a consistent antidepressant regimen (n = 37) or medication-free (n = 23) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method. Interventions Three infusions of the TNF antagonist infliximab (5 mg/kg) (n = 30) or placebo (n = 30) at baseline and weeks 2 and 6 of a 12-week trial. Main Outcome Measures The 17-item Hamilton Scale for Depression (HAM-D) scores. Results No overall difference in change of HAM-D scores between treatment groups across time was found. However, there was a significant interaction between treatment, time, and log baseline hs-CRP concentration (P = .01), with change in HAM-D scores (baseline to week 12) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less. Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response (≥50% reduction in HAM-D score at any point during treatment) of 62% (8 of 13 patients) in infliximab-treated patients vs 33% (3 of 9 patients) in placebo-treated patients (P = .19). Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders (P  Conclusions This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers. Trial Registration clinicaltrials.gov Identifier: NCT00463580.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/1356541/yoa120056_31_41.pdf

A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression The Role of Baseline Inflammatory Biomarkers

OBJECTIVE: Previous theories have emphasized the role of excessive glucocorticoid activity in the pathology of chronic stress. Nevertheless, insufficient glucocorticoid signaling (resulting from de...

http://sites.oxy.edu/clint/physio/article/theroleofinsufficientglucocorticoidsignalinginstressrelateddisorders.pdf

Charles L. Raison

Papers

Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression

Cytokines sing the blues: inflammation and the pathogenesis of depression

The role of inflammation in depression: from evolutionary imperative to modern treatment target

A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression The Role of Baseline Inflammatory Biomarkers

When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders