Immune system development

“For an immune system to work properly, it needs to be confronted by an infection in the first year of life,” says Greaves. Without that confrontation with an infection, the system is left unprimed and will not work properly.”

And this issue is becoming an increasingly worrying problem. Parents, for laudable reasons, are raising children in homes where antiseptic wipes, antibacterial soaps and disinfected floorwashes are the norm. Dirt is banished for the good of the household.

In addition, there is less breast feeding of infants and a tendency for them to have fewer social contacts with other children. Both trends reduce babies’ contact with germs. This has benefits – but also comes with side effects. Because young children are not being exposed to bugs and infections as they once were, their immune systems are not being properly primed.

“When such a baby is eventually exposed to common infections, his or her unprimed immune system reacts in a grossly abnormal way,” says Greaves. “It over-reacts and triggers chronic inflammation.”

From https://www.theguardian.com/science/2018/dec/30/children-leukaemia-mel-greaves-microbes-protection-against-disease, about how childhood leukemia develops.  Also impacts Type I diabetes, allergies, and other auto-immune disorders.

Inflammation and Depression

This is not some new-agey crap.  It’s from NIH.

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

 

Here’s the abstract:

Abstract

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.

 

Depression is a devastating disorder, afflicting up to 10% of the adult population in the United States and representing one of the leading causes of disability worldwide¹. Although effective treatments are available, approximately one third of all patients with depression fail to respond to conventional antidepressant therapies², further contributing to the global burden of the disease. Accordingly, there is a pressing need for new conceptual frameworks for understanding the development of depression to develop better treatments. In this Review, we outline emerging data that point to the immune system — and, in particular, the inflammatory response — as a potentially important contributor to the pathophysiology of depression. We first consider the origins of this notion from an evolutionary perspective, examining the advantages of depressive behaviours in the context of host immune responses to pathogens, predators and conspecifics in ancestral environments. The pivotal role of psychosocial stress in the modern world are then examined, highlighting inflammasome activation and immune cell trafficking as novel mechanisms by which stress-induced inflammatory signals can be transmitted to the brain. Neurotransmitters and neurocircuits that are targets of the inflammatory response are also explored followed by an examination of brain–immune interactions as risk and resilience factors for depression. Finally, these interactions are discussed as a foundation for a new era of therapeutics that target the immune system to treat depression, with a focus on how immunological biomarkers can be used to personalize care.

And a fun graphic with a lot of technical terms:

Vagus Nerve

The Chopra Center has posted information on how to improve Vagal Tone, which can help reduce inflammation.

Read the whole article for the what and why, but here’s the how:

How to Perform Abdominal Massage

This abdominal massage technique is easy to do at home in just a few minutes. It is best to perform this practice on an empty stomach, a few hours after eating. Start slowly and see how your body responds.

1. Lie down on a comfortable floor mat or on a bed.
2. Place your hand below your sternum or breastbone. Make gentle downward stroking movements—moving your hand down toward your abdomen. Repeat this movement for a few minutes, cycling one hand over the other in a backward bike-pedaling–like motion.
3. Next, use your fingertips to make small circular motions on your abdomen. Start massaging the sides of your abdomen and slowly work your way inward and downward. Go progressively deeper, using a firm but comfortable amount of pressure. Continue this abdominal massage for several minutes.
4. End your practice with a few minutes of a gentle reclined two-knee spinal twist pose (Supta Matsyendrasana). This restorative yoga posture improves digestion and encourages an opening within the fascia and diaphragm to help you deepen your breath and induce an anti-inflammatory relaxation response.
   • Lying on your back, exhale as you press your lower back lightly into the floor or bed.
   • Breathe here for a few moments as your lower back opens.
   • When you are ready, gently contract your abdominal muscles as you inhale and bend your knees toward your chest.
   • Exhale and bring your arms out to your side with your palms toward the floor, even with your shoulders.
   • On a slow inhale, lift your heels a bit higher than your knees, and then as you exhale slowly lower both legs to the left toward the floor.
   • Keep your knees at the level of your hips and your feet and knees stacked together. Rest in this posture for 30 to 60 seconds.
   • Continue taking slow, deep breaths as you gently twist from side to side, moving with your breath.

Try out this simple practice for accessing the power of your vagus nerve. Perform these techniques for a few minutes once or twice a day for several weeks.

 

Another study on dietary fat

From The Lancet:

 

Background

The relationship between macronutrients and cardiovascular disease and mortality is controversial. Most available data are from European and North American populations where nutrition excess is more likely, so their applicability to other populations is unclear.

Methods

The Prospective Urban Rural Epidemiology (PURE) study is a large, epidemiological cohort study of individuals aged 35–70 years (enrolled between Jan 1, 2003, and March 31, 2013) in 18 countries with a median follow-up of 7·4 years (IQR 5·3–9·3). Dietary intake of 135 335 individuals was recorded using validated food frequency questionnaires. The primary outcomes were total mortality and major cardiovascular events (fatal cardiovascular disease, non-fatal myocardial infarction, stroke, and heart failure). Secondary outcomes were all myocardial infarctions, stroke, cardiovascular disease mortality, and non-cardiovascular disease mortality. Participants were categorised into quintiles of nutrient intake (carbohydrate, fats, and protein) based on percentage of energy provided by nutrients. We assessed the associations between consumption of carbohydrate, total fat, and each type of fat with cardiovascular disease and total mortality. We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random intercepts to account for centre clustering.

…

Interpretation

High carbohydrate intake was associated with higher risk of total mortality, whereas total fat and individual types of fat were related to lower total mortality. Total fat and types of fat were not associated with cardiovascular disease, myocardial infarction, or cardiovascular disease mortality, whereas saturated fat had an inverse association with stroke. Global dietary guidelines should be reconsidered in light of these findings.

 

and

 

Research in context

Evidence before this study

We did a systematic search in PubMed for relevant articles published between Jan 1, 1960, and May 1, 2017, restricted to the English language. Our search terms included “carbohydrate”, “total fat”, “saturated fatty acid”, “monounsaturated fatty acid”, “polyunsaturated fatty acid”, “total mortality”, and “cardiovascular disease”. We searched published articles by title and abstract to identify relevant studies. We also hand-searched reference lists of eligible studies. We considered studies if they evaluated association between macronutrient intake and total mortality or cardiovascular disease. The studies cited in this report are not an exhaustive list of existing research. Existing evidence on the associations of fats and carbohydrate intake with cardiovascular disease and mortality are mainly from North America and Europe.

Added value of this study

Current guidelines recommend a low fat diet (<30% of energy) and limiting saturated fatty acids to less than 10% of energy intake by replacing them with unsaturated fatty acids. The recommendation is based on findings from some North American and European countries where nutrition excess is of concern. It is not clear whether this can be extrapolated to other countries where undernutrition is common. Moreover, North American and European populations consume a lower carbohydrate diet than populations elsewhere where most people consume very high carbohydrate diets mainly from refined sources. Consistent with most data, but in contrast to dietary guidelines, we found fats, including saturated fatty acids, are not harmful and diets high in carbohydrate have adverse effects on total mortality. We did not observe any detrimental effect of higher fat intake on cardiovascular events. Our data across 18 countries adds to the large and growing body of evidence that increased fats are not associated with higher cardiovascular disease or mortality.

Implications of all the available evidence

Removing current restrictions on fat intake but limiting carbohydrate intake (when high) might improve health. Dietary guidelines might need to be reconsidered in light of consistent findings from the present study, especially in countries outside of Europe and North America.

The study appears mainly to have been funded by Canadian health organizations.

Cancer Vaccine

This latest great report on a cancer cure comes from Stanford Medicine, which I consider a reputable source.

 

Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers at the Stanford University School of Medicine.

The approach works for many different types of cancers, including those that arise spontaneously, the study found.

The researchers believe the local application of very small amounts of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation.

“When we use these two agents together, we see the elimination of tumors all over the body,” said Ronald Levy, MD, professor of oncology. “This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”

One agent is currently already approved for use in humans; the other has been tested for human use in several unrelated clinical trials. A clinical trial was launched in January to test the effect of the treatment in patients with lymphoma.

Here’s how it works:

Levy’s method works to reactivate the cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site. (A microgram is one-millionth of a gram). One, a short stretch of DNA called a CpG oligonucleotide, works with other nearby immune cells to amplify the expression of an activating receptor called OX40 on the surface of the T cells. The other, an antibody that binds to OX40, activates the T cells to lead the charge against the cancer cells. Because the two agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are “prescreened” by the body to recognize only cancer-specific proteins.

Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.

The approach worked startlingly well in laboratory mice with transplanted mouse lymphoma tumors in two sites on their bodies. Injecting one tumor site with the two agents caused the regression not just of the treated tumor, but also of the second, untreated tumor. In this way, 87 of 90 mice were cured of the cancer. Although the cancer recurred in three of the mice, the tumors again regressed after a second treatment. The researchers saw similar results in mice bearing breast, colon and melanoma tumors.

“I don’t think there’s a limit to the type of tumor we could potentially treat, as long as it has been infiltrated by the immune system.”

Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals’ life span, the researchers found.

Finally, Sagiv-Barfi explored the specificity of the T cells by transplanting two types of tumors into the mice. She transplanted the same lymphoma cancer cells in two locations, and she transplanted a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the growth of the colon cancer cells.

“This is a very targeted approach,” Levy said. “Only the tumor that shares the protein targets displayed by the treated site is affected. We’re attacking specific targets without having to identify exactly what proteins the T cells are recognizing.”

So we can’t all go get a shot and never get cancer.  But if a tumor is detected, and this works out in trials, we could get a shot and all of that type of cancer within our body would be killed by our own T cells.  If we got some other cancer, we would have to go get another shot for that one.

 

Gut Biome and Exercise

From New York Times:

(Researchers) began by recruiting 32 men and women who did not exercise. About half were obese and the rest of normal weight.

The scientists took blood and fecal samples and tested everyone’s aerobic fitness. Then they had the men and women begin supervised workouts, during which their efforts increased over time from about 30 minutes of easy walking or cycling to about an hour of vigorous jogging or pedaling three times per week.

The volunteers were asked not to change their normal diets.

After six weeks, the scientists collected more samples and retested everyone, and then asked the volunteers to stop exercising altogether.

Six weeks later, the tests were once again repeated.

The subsequent analysis showed that the volunteers’ gut bugs had changed throughout the experiment, with some increasing in numbers and others declining. The researchers also found changes in the operations of many microbes’ genes. Some of those genes were working harder now, while others had grown silent.

Most of these changes were not shared from one person to the next. Everyone’s gut responded uniquely to exercise.

But there were some similarities, the researchers found. In particular, they noted widespread increases in certain microbes that can help to produce substances called short-chain fatty acids. These fatty acids are believed to aid in reducing inflammation in the gut and the rest of the body. They also work to fight insulin resistance, a precursor to diabetes, and otherwise bolster our metabolisms.

Most of the volunteers had larger concentrations of these short-chain fatty acids in their intestines after exercise, along with the microbes that produce them.

These increases were greatest, though, among the volunteers who had begun the experiment lean compared to those who were obese, the scientists found.

And perhaps not surprisingly, almost all of the changes in people’s guts dissipated after six weeks of not exercising. By and large, their microbiomes reverted to what they had been at the study’s start.

Still, the study’s overall results suggest that even a few weeks of exercise can alter the makeup and function of people’s microbiomes, says Jeffrey Woods, a professor of kinesiology and community health at the University of Illinois who conducted the study, along with his doctoral student Jacob Allen (now a postdoctoral researcher at Ohio State University) and others.

In theory, Dr. Woods continues, these changes could contribute to some of the broader health benefits of exercise, such as its ability to reduce inflammation throughout the body.

“But more studies need to be done to prove this,” he says.

This is really interesting because it gives a physical reason for why exercise helps reduce diabetes.  Also more info on the biome.

Vaccines and why the anecdotes?

Just saw this paper dated 2008 from NIH titled  “Genetics and the myth of vaccine encephalopathy”

It talks about the anecdotes of children receiving vaccines and then within one to 14 days, seemingly regressing and becoming autistic.  It turns out there is an explanation for this:  Vaccines can cause fevers.  A very small number of people have either genetic defects/mutations (which happen during development – not inherited) or mitochondrial disorders.  These already existing issues lead to autism, triggered by a fever.  So the person would have become autistic when triggered by a fever, whether that fever was caused by a vaccine or some other (inevitable) cause.