Leukocyte Trafficking and Migration
For the immune system to work properly, leukocytes need to be able to detect pathogens and move to appropriate locations. This session discussed work about how regulators and consequences of the movement of immune cells. The first presentation (Stress-induced Redistribution of Immune Cells: From Barracks, to Boulevards, to Battlefields) by Firdaus Dhabhar laid out the movement of immune cells in response to stress.
Generally, leukocytes reside in “barracks” such as lymph nodes. This allows them to be exposed to many different cells and have a good chance of recognizing pathogens. Dr. Dhabhar presented data that when stressed, immune cells leave the “barracks” and migrate to locations in the body likely (evolutionarily) to be compromised such as the skin (imagine if you were running from a tiger, the skin would be the most likely to be compromised by damage or infection first). Immune cells move via the blood vessels, the “boulevards”. The data presented demonstrated that shortly (around 30 minutes) after a stressor, there are elevated levels of leukocytes in the peripheral blood; however, after 1-2 hours, levels begin to fall. Rather than indicating that immune cells are dying or returning to the “barracks”, this is because they are going into the skin, the likely “battlefields”. This is demonstrated first by the time course of the levels of leukocytes in peripheral blood peaking and then falling off. Corresponding to the fall off, there are increased reactions to skin tests, suggesting a localized increased immune reaction where it would be expected—in the skin (for example, see his 1999 paper, Enhancing versus suppressive effects of stress hormones on skin immune function). Suzi Hong talked about Mechanisms of Immune Cell Mobilization During Stress and presented data implicating the sympathetic nervous system and particularly an adrenergic mechanism involved in cell trafficking. E. S. Wohleb presented data suggesting that repeated social defeat (an aggressive mouse is placed in a cage with other mice for two hours and they are repeatedly defeated) increases migration of immune cells into the prefrontal cortex and this mediates the relationship of social defeat with anxiety-like behaviors in a mouse model.
Promoting Stress Resistance and Stress Resilience
This session examined processes presumably downstream of stress. The basic model was stress to inflammation to outcomes. Then interventions that alter stress should putatively change inflammation and have some effect on the outcome.
Michael Irwin talked about sleep and inflammation (Behavioral Control of Inflammation: Promoting Well-Being in Aging). Sleep disturbances are a sign of depression, but there is also evidence that they increase risk for depression or recurrence of a depressive episode. This effect may be mediated by sleep disturbances (“stress”) leading to increased inflammation, and inflammation induces so-called sickness behaviors that include many of the symptoms of depression. Dr. Irwin presented data that sleep disturbances drive change in TNF-α and IL-6 as well as gene expression and NFκB. The effect on inflammation is more robust in females, possibly explaining differences in rates of depression between males and females. A Tai Chi intervention in older adults reduced levels of IL-6 and improved sleep quality (moderated by initial severity), although it did not have effects on other measures of inflammation. Unclear what is special about IL-6. One implication is that it may be valuable to focus and treat people with sleep disturbances as people at risk for depression. Cognitive Behavioral Therapy (CBT) is effective for insomnia.
Charles Raison talked about an intervention to increase stress resilience called Cognitively-Based Compassion Training (CBCT; Compassion Training as a Pathway to Stress Resilience: Effects Along the Mind-Body Continuum). He presented data comparing inflammatory responses to the Trier Social Stress Test (a task that involves social evaluative threat and stress) in participants who either received CBCT or a control condition. CBCT reduced the inflammatory response to the TSST, and this was stronger for people who practiced it more.
Carissa Low (Stress, coping, and inflammation in adolescents) presented data that approach-oriented coping in adolescents interacted with stress (low/high) to predict levels of inflammation. Specifically, use of approach-oriented coping was more beneficial for people with high stress. T. Pace (Engagement with Cognitively-Based Compassion Training is associated with reduced salivary C-reactive protein and cortisol from before to after training in foster care program adolescents) talked about how CBCT is helpful for youth in foster care and (as in Dr. Raison’s presentation) there are practice effects. That is the more youth reported practicing and using CBCT, the more they benefited from the intervention (practice negatively related to C-reactive protein; CRP). CRP was measured in saliva at Salimetrics.
A Tutorial on 21st Century Molecular Biology: A Role in PNI Research?
The four talks in this session were A Primer on Molecular Biology by Herbert Mathews, Genomic Approaches in PNI by Steve Cole, The basics of miRNA: A Newly Appreciated genetic Modulator by Erick Tatro, and Strengths and Limitations of Current Molecular Analysis Approaches by Matthew McQueen. The first over viewed how DNA is stored, transcribed, and translated. There was also some discussion of factors that can regulate transcription for example in the promoter region of a gene, and this type of topic was discussed further in Erick Tatro’s talk. Steve Cole described an interesting approach to using genomics data. Basically if you have two groups (say people with high and low social support), you can measure gene expression, and use analytic methods to find differences in expression between the two groups. Next, look up all the genes that are differentially expressed between groups and see if those cluster on a few functions (such as regulation of NFκB). This can be stronger than the candidate gene approach, and by looking up all genes differentially expressed, you avoid biasing yourself to only look at genes you recognize. The final talk by Matthew McQueen discussed some of the problems in working with genome wide association studies (GWAS) analytically, primarily related to multiple comparisons and trying to find a signal out of all the noise when you may only have a few thousand subjects and have 22 thousand some genes (i.e., curse of dimensionality).
There was a presentation session on Infection, Cognition & Mental Health. Although I attended it, I struggled to really understand it (it was both mechanistic and dealing with neural anatomy, which I am not too familiar with). At the end of the day, there was a trainee dinner and an early investigator social, both of which I heard were pretty good (though I did not go to either). From what I heard, the trainee dinner was nicer than the early investigator social.