December 24th, 2018

(This section of the book is taken from this summers autoimmunity series)

Programming the newborn's immune system to recognize self tissue from a foreign invader is the first critical stage of normal life after birth and breastfeeding initiation occurs.

Reality check - what is the problem? It is simple, humans are suffering from diseases of immune dysfunction, inflammation and self-attack at alarming rates with no signs of abating. It is all starting in the earliest days of life and we need to understand the risks before we can make good choices.



Before we understand abnormal, what is normal?
Normal functioning immune systems correctly identify pathogens and foreign invaders killing them while leaving our well functioning cells alone to work for us. The immune system also correctly identifies food, animal and plant proteins as benign. This process is called tolerance.
I know that in book terms, your child was just born, however, let us briefly rewind time to go back to the beginning again for a better understanding.
While you are conceiving of and producing your little beautiful baby, he or she is a 50% split amalgam of genes from mom and dad. While pregnant, mom's immune system loves the babies genes that are hers but not dad's genes. Therefore, mom's immune system has to go through a process of shifting away from targeting dad's foreign DNA by altering the function of her immune warriors to prevent a spontaneous abortion. If this occurs correctly, then you are born naturally. Mothers are active living creatures with their own load of bacteria in their intestines, on their skin, vagina and placenta. These bacteria start the process of programming the newborn's innate and adaptive immune systems in the placenta to know friendly bacteria from troublemakers. When the infant is born they hopefully slide through the vaginal canal and pick up more bacteria only to immediately latch on to the breast and acquire yet more friends.

These bacteria begin the process of teaching the immune system how to act. This is the key point: the child's immune system is actually programming itself to tolerate these bacteria and to not respond negatively. This is the beginning of tolerance. If this process gets disrupted for any reason, tolerance can be broken and this is thought to be one of the main break points for the beginning of inflammation, allergy and autoimmune dysfunction for the child.

The mission critical cells in this tolerance process are the Treg cell and the dendritic cell. We will discuss these cells because they will be important in how we can overcome disease risk and hopefully live well.

Defined as: The regulatory T cells, formerly known as suppressor T cells, are a sub population of T cells or thymic cells which modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Tregs are immunosuppressive and generally suppress or down regulate induction and proliferation of effector T cells. (Corthay et. al. 2009)

If this cell is turned on appropriately, then the system maintains a normal response to immune activation. In other words, if for some reason your immune system starts to fight a pathogen, these Treg cells are necessary to dampen the fighters and prevent local damage when the pathogen is killed.

An analogy for this response is: imagine the army is fighting a war and the war is over, however, the GI's are still hanging around the city and they decide to go to bar for little relaxation. Invariably, they get rowdy and start to destroy stuff. The military police are called in to stop the fracas and calm the situation returning the army back to stand down mode. The Tregs are our military police and we need them!

The second important cell, the dendritic cell, is a class of immune cell located in the intestinal lining whose primary job is to taste protein fragments of bacteria, food and anything in the intestinal lumen and decide if they are friend or foe. The immune system historically is set up so that the dendritic cells learn from everything that they see. (Banchereau et. al. 1998)

Think about an industrial assembly line. If a product specialist is checking the production line and finds a defective product, they immediately remove it, look for more defects and then shut down the line if more are found.
This is ideally and simplistically what the dendritic cell does. It is on the look out for specific trouble makers. If it finds them, it starts a chain of events that will cause the pathogen to die. (Raker et. al. 2015)

What is the process by which tolerance develops normally from an epigentic perspective?

A study looking at asthma risk in Amish and Hutterite populations and the induction of immune tolerance was published in 2016. These two populations are genocentric-farming enclaves in the United States. The major difference between these communities is that the Amish children live on the farm where the Hutterites live around the farm and do not have much exposure to the animals. What the study found was profound for our understanding of disease development. The children from the youngest ages in the Amish households were exposed to large volumes of animal based and soil based bacteria that prevented the onset of allergic disease. Conversely, the Hutterite children had little exposure to animal bacteria and had a 30%+ risk of asthma and allergy. (Stein et. al. 2016)
The hypothesis from this study is that the bacteria from the animal exposure induced immune tolerance by selecting for a stable human microbiome which maintains an educated and functional immune system. This fits nicely into the biome depletion theory which notes that the lack of microbial exposure is the major root cause of disease. (Parker et. al. 2010)
Whether it be via animal exposure, vaginal delivery, breastfeeding, benign parasite ingestion, or other non deadly microbial exposure, as babies and young children we need more time spent with microbes to keep our immune system functional and tolerant.

To put this into perspective, we hypothesize that we have been a culture of cleanliness for far too long and this is clearly putting us all at risk for disease. We all would benefit from more exposure to animal and soil based microbes from the earliest ages. We need to be outside in nature as much as possible.

 

Dr. M

Corthay T Regulator Cells Article
Banchereau Nature Article
Raker Frontiers in Immunology Article
Proal Current Opinions in Rheumatology Article
Parker EvMed Review Article
Stein NEJM Article

 

Autoimmunity and allergy defined:

In Immunological terms, autoimmunity and allergy are conditions in which one's own tissues are subject to the deleterious effects of actions of the immune system. This is when a specific antibody and/or cell-mediated immune response targets the body's own native tissues (autoimmunity) or a benign protein from a food, pollen or animal (allergy), for example, instead of a pathogen.

What this means is that our immune system loses the ability to discern our native cells or these benign proteins from pathogens and subsequently attacks these cells inappropriately leading to tissue damage that we see and feel as disease. This can happen at any age, but emerging evidence is teaching us that the early years are critical at setting the system up for long term success or failure.